Assessing training and professional development needs of library staff. Report for National Library of Health

Urquhart, C., Spink, S. & Thomas, R., Assessing training and professional development needs of library staff. Report for National Library of Health. (2005). Aberystwyth: Department of Information Studies, University of Wales Aberystwyth Sponsorship: National Library for Health (NHS Information Authority)

Procurement of electronic content across the UK National Health Service and Higher Education sectors. Report to JISC executive and LKDN executive.

Spink, S., Urquhart, C., Cox, A. & Higher Education Academy - Information and Computer Sciences Subject Centre. (2007). Procurement of electronic content across the UK National Health Service and Higher Education sectors. Report to JISC executive and LKDN executive. Sponsorship: JISC/LKDN

Od "Subaltern studies" do "Provincializig Europe". Kilka postkolonialnych refleksji na temat historii

Tekst wskazuje II połowę XX wieku jako cezurę wyznaczającą kres dziewiętnastowiecznego pojęcia historii, służącego europejskim imperiom do uzasadnienia ekspansji kolonialnej. Na przykładzie kontrastu Indii i Zachodu dowodzi, że myślenie historyczne jest uwarunkowane kulturowo. Ruchy antykolonialne odwracają dyskurs kolonialny, czyniąc z niego argument dla szybkiej demokratyzacji społeczeństw, odbiegającej od modelu europejskiego za sprawą zredukowanej liczby etapów postępu cywilizacyjnego i rezygnacji z perspektywy historycznej. Seria Subaltern Studies podważa uniwersalność europejskiego modelu nowoczesności i jego adekwatność na terenach byłych kolonii po upadku zachodnich imperiów.

Os recetores da melatonina como novos alvos de fármacos antidepressivos

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Qualidade de vida relacionada com a saúde oral

Dissertação apresentada à Universidade Fernando Pessoa como parte dos requisitos para a obtenção do grau de Mestre em Psicologia, ramo de Psicologia Clínica e da Saúde

Mapping Parallel Iterative Algorithms onto Workstation Networks

For communication-intensive parallel applications, the maximum degree of concurrency achievable is limited by the communication throughput made available by the network. In previous work [HPS94], we showed experimentally that the performance of certain parallel applications running on a workstation network can be improved significantly if a congestion control protocol is used to enhance network performance. In this paper, we characterize and analyze the communication requirements of a large class of supercomputing applications that fall under the category of fixed-point problems, amenable to solution by parallel iterative methods. This results in a set of interface and architectural features sufficient for the efficient implementation of the applications over a large-scale distributed system. In particular, we propose a direct link between the application and network layer, supporting congestion control actions at both ends. This in turn enhances the system's responsiveness to network congestion, improving performance. Measurements are given showing the efficacy of our scheme to support large-scale parallel computations.

A Spectrum of TCP-Friendly Window-Based Congestion Control Algorithms

The increased diversity of Internet application requirements has spurred recent interests in transport protocols with flexible transmission controls. In window-based congestion control schemes, increase rules determine how to probe available bandwidth, whereas decrease rules determine how to back off when losses due to congestion are detected. The parameterization of these control rules is done so as to ensure that the resulting protocol is TCP-friendly in terms of the relationship between throughput and loss rate. In this paper, we define a new spectrum of window-based congestion control algorithms that are TCP-friendly as well as TCP-compatible under RED. Contrary to previous memory-less controls, our algorithms utilize history information in their control rules. Our proposed algorithms have two salient features: (1) They enable a wider region of TCP-friendliness, and thus more flexibility in trading off among smoothness, aggressiveness, and responsiveness; and (2) they ensure a faster convergence to fairness under a wide range of system conditions. We demonstrate analytically and through extensive ns simulations the steady-state and transient behaviors of several instances of this new spectrum of algorithms. In particular, SIMD is one instance in which the congestion window is increased super-linearly with time since the detection of the last loss. Compared to recently proposed TCP-friendly AIMD and binomial algorithms, we demonstrate the superiority of SIMD in: (1) adapting to sudden increases in available bandwidth, while maintaining competitive smoothness and responsiveness; and (2) rapidly converging to fairness and efficiency.

A Spectrum of TCP-friendly Window-Based Congestion Control Algorithms

The increasing diversity of Internet application requirements has spurred recent interest in transport protocols with flexible transmission controls. In window-based congestion control schemes, increase rules determine how to probe available bandwidth, whereas decrease rules determine how to back off when losses due to congestion are detected. The control rules are parameterized so as to ensure that the resulting protocol is TCP-friendly in terms of the relationship between throughput and loss rate. This paper presents a comprehensive study of a new spectrum of window-based congestion controls, which are TCP-friendly as well as TCP-compatible under RED. Our controls utilize history information in their control rules. By doing so, they improve the transient behavior, compared to recently proposed slowly-responsive congestion controls such as general AIMD and binomial controls. Our controls can achieve better tradeoffs among smoothness, aggressiveness, and responsiveness, and they can achieve faster convergence. We demonstrate analytically and through extensive ns simulations the steady-state and transient behavior of several instances of this new spectrum.

SymbolDesign: A User-centered Method to Design Pen-based Interfaces and Extend the Functionality of Pointer Input Devices

A method called "SymbolDesign" is proposed that can be used to design user-centered interfaces for pen-based input devices. It can also extend the functionality of pointer input devices such as the traditional computer mouse or the Camera Mouse, a camera-based computer interface. Users can create their own interfaces by choosing single-stroke movement patterns that are convenient to draw with the selected input device and by mapping them to a desired set of commands. A pattern could be the trace of a moving finger detected with the Camera Mouse or a symbol drawn with an optical pen. The core of the SymbolDesign system is a dynamically created classifier, in the current implementation an artificial neural network. The architecture of the neural network automatically adjusts according to the complexity of the classification task. In experiments, subjects used the SymbolDesign method to design and test the interfaces they created, for example, to browse the web. The experiments demonstrated good recognition accuracy and responsiveness of the user interfaces. The method provided an easily-designed and easily-used computer input mechanism for people without physical limitations, and, with some modifications, has the potential to become a computer access tool for people with severe paralysis.

Integrated magnetic components for high-power high-current dc-dc converters

This thesis is focused on the design and development of an integrated magnetic (IM) structure for use in high-power high-current power converters employed in renewable energy applications. These applications require low-cost, high efficiency and high-power density magnetic components and the use of IM structures can help achieve this goal. A novel CCTT-core split-winding integrated magnetic (CCTT IM) is presented in this thesis. This IM is optimized for use in high-power dc-dc converters. The CCTT IM design is an evolution of the traditional EE-core integrated magnetic (EE IM). The CCTT IM structure uses a split-winding configuration allowing for the reduction of external leakage inductance, which is a problem for many traditional IM designs, such as the EE IM. Magnetic poles are incorporated to help shape and contain the leakage flux within the core window. These magnetic poles have the added benefit of minimizing the winding power loss due to the airgap fringing flux as they shape the fringing flux away from the split-windings. A CCTT IM reluctance model is developed which uses fringing equations to accurately predict the most probable regions of fringing flux around the pole and winding sections of the device. This helps in the development of a more accurate model as it predicts the dc and ac inductance of the component. A CCTT IM design algorithm is developed which relies heavily on the reluctance model of the CCTT IM. The design algorithm is implemented using the mathematical software tool Mathematica. This algorithm is modular in structure and allows for the quick and easy design and prototyping of the CCTT IM. The algorithm allows for the investigation of the CCTT IM boxed volume with the variation of input current ripple, for different power ranges, magnetic materials and frequencies. A high-power 72 kW CCTT IM prototype is designed and developed for use in an automotive fuelcell-based drivetrain. The CCTT IM design algorithm is initially used to design the component while 3D and 2D finite element analysis (FEA) software is used to optimize the design. Low-cost and low-power loss ferrite 3C92 is used for its construction, and when combined with a low number of turns results in a very efficient design. A paper analysis is undertaken which compares the performance of the high-power CCTT IM design with that of two discrete inductors used in a two-phase (2L) interleaved converter. The 2L option consists of two discrete inductors constructed from high dc-bias material. Both topologies are designed for the same worst-case phase current ripple conditions and this ensures a like-for-like comparison. The comparison indicates that the total magnetic component boxed volume of both converters is similar while the CCTT IM has significantly lower power loss. Experimental results for the 72 kW, (155 V dc, 465 A dc input, 420 V dc output) prototype validate the CCTT IM concept where the component is shown to be 99.7 % efficient. The high-power experimental testing was conducted at General Motors advanced technology center in Torrence, Los Angeles. Calorific testing was used to determine the power loss in the CCTT IM component. Experimental 3.8 kW results and a 3.8 kW prototype compare and contrast the ferrite CCTT IM and high dc-bias 2L concepts over the typical operating range of a fuelcell under like-for-like conditions. The CCTT IM is shown to perform better than the 2L option over the entire power range. An 8 kW ferrite CCTT IM prototype is developed for use in photovoltaic (PV) applications. The CCTT IM is used in a boost pre-regulator as part of the PV power stage. The CCTT IM is compared with an industry standard 2L converter consisting of two discrete ferrite toroidal inductors. The magnetic components are compared for the same worst-case phase current ripple and the experimental testing is conducted over the operation of a PV panel. The prototype CCTT IM allows for a 50 % reduction in total boxed volume and mass in comparison to the baseline 2L option, while showing increased efficiency.

Characterization of TRAF6 mediated ubiquitination of presenilins and γ-secretase substrates

Post-translational modification of the γ-secretase protease complexes and their substrates has an important role in controlling receptor-initiated signalling events, which are critically important in the pathogenesis of cancer, inflammatory and Alzheimer’s disease. Our lab has previously characterised an interaction between TRAF6 and presenilin-1, which lead to the identification of interleukin-1 (IL-1) receptor type 1 (IL-1R1) and Toll-like receptor-4 (TLR4) as novel γ-secretase substrates. Subsequently our group showed that TRAF6 promoted ubiquitination and γ-secretase cleavage of IL-1R1. The aim of this project is to study the association between TRAF6 and the presenilins, the critical γ-secretase complex components, and to determine the functional importance of TRAF6-mediated ubiquitination of γ-secretase substrates. Firstly, we show that the full-length presenilins are novel substrates of TRAF6-mediated Lysine-63-linked polyubiquitination. Secondly, we show that co-expression of TRAF6 and the presenilins increases the stability and alters the turnover of the presenilins. Thirdly, we reveal that TRAF6-mediated ubiquitination of presenilin does not affect γ-secretase enzyme activity, but may regulate the full-length presenilin functions such as ER Ca2+ signalling. Previously, we have reported IL-1R1 as a novel substrate of TRAF6-mediated ubiquitination. In this study, we identified five lysine residues in the IL-1R1 intracellular domain targeted by TRAF6-mediated polyubiquitination. Furthermore, mutagenesis of these five lysine residues led to decreased IL-1R1 cell surface expression, precluded the ectodomain shedding and attenuated the responsiveness to IL-1β stimulation, demonstrating the critical role of TRAF6 in IL-1R1 trafficking.

An investigation on the use of SNR distributions for the optimisation of coarse-fine spectrum sensing for cognitive radio

This thesis investigates the optimisation of Coarse-Fine (CF) spectrum sensing architectures under a distribution of SNRs for Dynamic Spectrum Access (DSA). Three different detector architectures are investigated: the Coarse-Sorting Fine Detector (CSFD), the Coarse-Deciding Fine Detector (CDFD) and the Hybrid Coarse-Fine Detector (HCFD). To date, the majority of the work on coarse-fine spectrum sensing for cognitive radio has focused on a single value for the SNR. This approach overlooks the key advantage that CF sensing has to offer, namely that high powered signals can be easily detected without extra signal processing. By considering a range of SNR values, the detector can be optimised more effectively and greater performance gains realised. This work considers the optimisation of CF spectrum sensing schemes where the security and performance are treated separately. Instead of optimising system performance at a single, constant, low SNR value, the system instead is optimised for the average operating conditions. The security is still provided such that at the low SNR values the safety specifications are met. By decoupling the security and performance, the system’s average performance increases whilst maintaining the protection of licensed users from harmful interference. The different architectures considered in this thesis are investigated in theory, simulation and physical implementation to provide a complete overview of the performance of each system. This thesis provides a method for estimating SNR distributions which is quick, accurate and relatively low cost. The CSFD is modelled and the characteristic equations are found for the CDFD scheme. The HCFD is introduced and optimisation schemes for all three architectures are proposed. Finally, using the Implementing Radio In Software (IRIS) test-bed to confirm simulation results, CF spectrum sensing is shown to be significantly quicker than naive methods, whilst still meeting the required interference probability rates and not requiring substantial receiver complexity increases.

The role of presenilin 1 and presenilin 2 in IL-1β-, LPS- and TNFα- mediated signalling events

The importance of γ-secretase protease activities in development, neurogenesis and the immune system are highlighted by the diversity of its substrates and phenotypic characterization of Presenilin (PS)-deficient transgenic animals. Since the discovery of Amyloid precursor protein (APP) and it’s cleavage by γ-secretase complexes, over 90 other type I membrane proteins have been identified as γ-secretase substrates. We have identified interleukin-1 (IL-1) receptor type I (IL-1R1), toll-like receptor 4 (TLR4) and tumour necrosis factor-α (TNFα) receptor-1 (TNFR1) as novel substrates for - secretase cleavage, which play an important role in innate immunity. In this study, using PS-deficient cells and PS-knockout animal models we examined the role of PS proteins, PS1 and PS2, in IL-1R1-, TLR4- and TNFR1- mediated inflammatory responses. Data presented show that in response to IL- 1β, lipopolysaccharide (LPS) or TNFα, immortalised fibroblasts from PS2- deficient animals have diminished production of specific cytokines and chemokine, with differential reduction in nuclear factor-κB (NF-κB) and (mitogen activated protein kinase) MAPK activities. In contrast, no defect in the response to IL-1β, LPS or TNFα was observed in PS1-deficient immortalised fibroblasts. These observations were confirmed using bone marrow-derived macrophages from PS2-null mice, which also display impaired responsiveness to IL-1β- and LPS, with decreased production of inflammatory cytokines. Furthermore, in whole animal in vivo responses, we show that PS2-deficient animals display ligand (IL-1β, LPS and TNFα)-dependent alterations in the production of specific pro-inflammatory cytokines or chemokines. Importantly, this reduced responsiveness to IL-1β, LPS or TNFα is independent of γ- secretase protease activity and γ-secretase cleavage of TNFR1, IL-1R1 or TLR4. These observations suggest a novel γ-secretase-independent role of PS2 in the regulation of innate immune responsiveness and challenge current concepts regarding the regulation of IL-1β-, LPS- and TNFα-mediated immune signalling.

Evaluation of HER2, p53, bcl-2, topoisomerase II-alpha, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes.

BACKGROUND: Breast cancer is a heterogeneous disease. Predictive biological markers (BM) of responsiveness to therapy need to be identified. Evaluation of BM is mainly done at the primary site. However, in the adjuvant therapy of breast cancer, the main goal is control of micrometastases. It is still unknown whether heterogeneity in the expression of BM between the primary site and its micrometastases exists. OBJECTIVE: To evaluate the expression of some BM with potential predictive value from the primary breast cancer site and metastatic ipsilateral axillary lymph nodes. PATIENTS AND METHODS: Focality (percentage of positive cells) and intensity staining scores were evaluated for each marker. Freshly cut sections (4 microm) from embedded blocks of breast cancer fixed in formalin or bouin were put onto superfrost slides (Menzel-Gläser). Protein expression was evaluated immunohistochemically (IHC) using monoclonal antibodies against: topo II-alpha (clone KiS1, 1 microg/ml, Roche) with a trypsine pre-treatment (P); HSP27 (clone G3.1, 1/60, Biogenex), HSP70 (clone BRM.22, 1/80, Biogenex) and HER2 (clone CB11, 1/40, Novocastra; without P); p53 (clone D07, 1/750, Dako) and bcl-2 (clone 124, 1/60, Dako) with citrate buffer as P. RESULTS: Overall, the percentage of discordant marker status in the primary tumour and its metastatic lymph nodes was 2% for HER2, 6% for p53, 15% for bcl-2, 19% for topoisomerase II-alpha, 24% for HSP27 and 30% for HSP70. For the subgroup of patients with positive BM in the primary tumour, the percentage of discordance was 6% for HER2, 7% for p53, 14% for bcl-2, 19% for HSP70, 21% for topoisomerase II-alpha and 36% for HSP27. For the subgroup of patients with positive BM in the lymph nodes, the percentage of discordance was 9% for bcl-2, 15% for HER2 and p53, 21% for topoisomerase II-alpha, 22% for HSP27 and 25% for HSP70. CONCLUSIONS: 1) No biological marker had 100% concordant results. 2) Although some discordant cases might be explained by the limitations of the IHC technique, future studies aiming to evaluate the predictive value of BM in the adjuvant therapy of breast cancer should take into account a possible difference in BM expression between the primary and the metastatic sites.

Effect of insulin-like growth factor-I during preantral follicular culture on steroidogenesis, in vitro oocyte maturation, and embryo development in mice

Insulin-like growth factor-I (IGF-I) is involved in the regulation of ovarian follicular development and has been shown to potentiate the FSH responsiveness of granulosa cells from preantral follicles. The aim of the present study was to investigate the effect of IGF-I during preantral follicular culture on steroidogenesis, subsequent oocyte maturation, fertilization, and embryo development in mice. Preantral follicles were isolated mechanically and cultured for 12 days in a simplified culture medium supplemented with 1% fetal calf serum, recombinant human FSH, transferrin, and selenium. In these conditions, follicles were able to grow and produce oocytes that could be matured and fertilized. The first experiment analyzed the effect of different concentrations of IGF-I (0, 10, 50, or 100 ng/ml) added to the culture medium on the follicular survival, steroidogenesis, and the oocyte maturation process. The presence of IGF-I during follicular growth increased the secretion of estradiol but had no effect on the subsequent oocyte survival and maturation rates. In the second experiment, IGF-I (0 or 50 ng/ml) was added to the culture medium during follicular growth, oocyte maturation, or both, and subsequent oocyte fertilization and embryo development rates were evaluated. Oocyte fertilization rates were comparable in the presence or absence of IGF-I. However, the blastocyst development rate was enhanced after follicular culture in the presence of IGF-I. Moreover, the total cell number of the blastocysts observed after differential labeling staining was also higher when follicles were cultured or matured in the presence of IGF-I.