The research work presented herein addresses the problem of the mathematical modelling of fire and fire-sprinkler scenarios. This involved the numerical simulation of two-phase, three-dimensional, buoyant, turbulent, recirculating flows. The simulations were carried out in two successive and distinct stages.

The first stage dealt with the modelling of buoyant hot turbulent gas flows generated by a fire within room-sized compartments. These single phase studies were based on the field modelling approach to fire simulation.

The second part of the study involved the introduction of the cold water droplets through a single sprinkler head, thus, extending the scenario into the more complex two-phase regime. This led to expanding the single-phase fire model to take account of two concurrently present phases, ie. gas/liquid. The strategy used to model the twophase process was the Eulerian-Eulerian technique or volume-fraction method. In order to take into account the physics involved in this process, interphase friction or drag was considered. Furthermore, due to the large difference in temperatures between the hot gases and the cold water droplets it was necessary to introduce interphase heat transfer. Due to the subsequent evaporation of the water droplets interphase mass transfer was also accounted for.

Models for both steady-state and time-dependent situations were developed, whereby experimental results of transient fire-sprinkler tests were used for validation. The simulations performed indicated the creation of extremely complex flow fields within the compartments both prior and during sprinkler activation. Phenomena such as the significant cooling of the hot combustion gases caused by the active sprinkler and the evaporation of water droplets have also been predicted. This has been verified by the experimental data. Thus, it can be concluded that the models outlined herein are capable of simulating the complex two-phase fire-sprinkler scenarios.

The need for subsequent investigative studies into such areas as the effect of using different auxiliary relationships eg. heat transfer, sprinkler characteristics and gridspacing has been highlighted. In order to complete the validation process, further experimental data needs to be made available.

This two-phase technique has proven to be very computationally intensive with simulations requiring days of CPU time. 'Mis is clearly unacceptable. However, it is
suggested that parallel computing technology may provide a means for reducing the CPU time involved to hours.

It can be concluded that though the model developed requires further investigation and refinements, it provides a basis for a practical and useful fire engineering tool.


BACKGROUND
HIV infection has often been linked to faster immune aging. We sought to determine whether or not treatment-naïve spontaneous HIV-1 controllers (HICs) and ART-exposed patients differ with regard to the expression of cell senescence markers.

METHODS
Eighty-eight chronically infected HICs and ART-exposed patients (median time since infection: 15 years) with an undetectable plasma HIV RNA load (for at least the previous two years) were included. We used flow cytometry to measure immunosenescence markers (KLRG-1 and CD57) expression in fresh blood samples collected from patients and healthy donors.

RESULTS
For the CD8 T cell population as a whole, the ART-exposed but not the HIC patients exhibited a much higher proportion of KLRG-1 and CD57 CD8 T cells than HDs. For the CD8 T cell subsets, HICs had a lower proportion of CD57 effector CD8 T cells than ART patients or HDs, whereas the proportions of KLRG-1 effector were similar. A similar trend was observed for terminal effectors. No impact of age, gender or standard parameters of infection (CD4 percentage, protective HLA allele, viral blips) was observed. The difference in the proportion of CD57 cells between HIC and ART was observed more specifically in long-term infected patients (>20 years). However, when considering the CD57 effector memory and effector subsets, the cytotoxic granule content was greater in HICs than in ART.

CONCLUSION
The proportion of CD57 effector CD8 T cells is lower in HICs than in ART-exposed patients. This profile may be beneficial by ensuring limited senescence associated with consistent cytotoxic potential.


Purpose of review—To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIVinfected individuals, and the potential of earlier cART initiation to reduce this risk. Recent findings—Factors leading to increased risk of non-AIDS defining malignancies (NADM) in particular remain poorly understood. Immunodeficiency appears to be key, whereas evidence is emerging that a direct pro-oncogenic effect of HIV, activated inflammatory and coagulation pathways, and cART toxicity may also contribute. By reducing HIV replication, improving immune function and limiting chronic inflammation, cART initiation at higher CD4+ cell counts may therefore reduce NADM risk. However, cART only partly normalizes enhanced inflammation and coagulation seen during HIV infection and conflicting laboratory and epidemiological data have been reported as to if (and how) cART affects NADM risk. Furthermore, secondary analyses of randomized controlled trials comparing early versus delayed cART initiation were inconclusive. Summary—Continuous epidemiological surveillance is warranted to monitor trends in cancer incidence among HIV-infected individuals and to better understand the impact of earlier cART on NADM risk. The role of adjuvant anti-inflammatory or anti-thrombotic therapies to reduce cancer risk deserves further investigation.


Background . Physician leadership is essential for the strengthening of health systems, especially in underserved settings such as sub-Saharan Africa. To be effective, leaders must be perceived as such by their community. It is unknown how perceptions of physician leadership in Botswana compare with those of the Canadian Medical Education Directives for Specialists (CanMEDS) Physician Competency Framework, which is used to shape the training of Botswana's future physicians. Objective . To examine if the perceived competencies of physician leadership in Botswana are  specifically named in the CanMEDS Framework and thereby inform Botswana's graduate medical education. Methods . We conducted focus groups discussions with nurses, interns, medical officers and specialists at Princess Marina Hospital and Nyangabgwe Referral Hospital. Key questions focused on describing the qualities of physician leadership. For data analysis we used inductive content coding and comparison with the CanMEDS frameworks. Results . Forty-eight clinicians participated and 111 unique codes were assigned to 503 comments.  Eighty-four per cent of comments corresponded to the CanMEDS 2005 competencies; many were  captured within the competencies of the medical expert (13.0%), communicator (17.8%), collaborator (15.6%), scholar (14.9%) and professional (31.3%) roles. About 5% of comments mapped to the draft CanMEDS 2015 update, and 11.5% were not specifically described in either version of CanMEDS, including charisma and decisiveness. Conclusion . The CanMEDS frameworks specifically address most of the competencies perceived as important for physician leadership in Botswana. Additional perceptions were identified that may require the attention of existing and aspiring physician leaders and their teachers to ensure they attain and maintain their effectiveness as leaders.


Most studies in social sciences have been gender blind, and this blindness hinders attempts to understand the causal mechanisms that create and maintain social patterning in outcomes. It is important to examine the differences and similarities between men and women and focus attention on both potential explanations for socio-economic gradients in various social, political and economic outcomes as well as on potential explanations for gender differences in these outcomes. Also, most of these studies and more so African economics research use examples and mathematical models developed in different environments that are not easily understood by non economists. The outcomes of the research may not necessarily fit into the African environment and may also impact differently on men and women.This paper uses desktop research and proposes gender mainstreaming and Africanise economics research.


We present an analysis of young stellar object (YSO) candidates towards the LDN 1188 molecular cloud. The YSO candidates were selected from the WISE all-sky catalogue, based on a statistical method. We found 601 candidates in the region, and classified them as Class I, Flat, and Class II YSOs. Groups were identified and described with the Minimal Spanning Tree (MST) method. Previously identified molecular cores show evidence of ongoing star formation at different stages throughout the cloud complex.


Cocaine use has increased rapidly over the past few years. This has led to an increase in the number and variety of cocaine-related conditions for which medical attention is sought. Among these have been several cases of intracranial hemorrhage. Four cases reported in the literature and 6 from our own institution are presented here. They represent different diagnoses including hemorrhage from aneurysms and arteriovenous malformations, hemorrhage into a tumor, and spontaneous hemorrhage with no underlying lesion with and without preexisting hypertension. Analysis of these cases suggests that the hypertension induced by cocaine secondary to sympathetic stimulation may be the common factor. Cocaine may also cause arterial spasm. Although the pathophysiology has not been entirely resolved, the clinical significance of this association is clear. Intracranial hemorrhage should be considered in the differential diagnosis whenever a patient presents with an acute alteration in neurologic examination associated with cocaine use.


THIS IS YOUR LIFE Paul Cobley Marcello Barbieri (ed), Introduction to Biosemiotics: The New Biological Synthesis, Dordrecht, Springer, 2007; xii + 530pp, £54.00. 'The over-arching context for bisoemiotics is our biosphere, in the sense of the organic whole of living matter', wrote Thomas A. Sebeok in 2001, 'and Earth', he went on, 'is the only geosphere which contains living matter. Because there can be no semiosis without interpretability - surely life's cardinal propensity - semiosis presupposes the axiomatic identity of the semiosphere with the biosphere'.1 Thus stated, this has been the general programme for biosemiotics in the last fifteen to twenty years. Yet, this is not an easy thesis to grasp, particularly for those who have retreated into the comfort of a view of the world as comprised solely of different combinations of power and endless language games. It is for this reason that biosemiotics has thus far failed to see itself at the centre of a sustained academic publishing enterprise, despite the commitment and endeavour of a range of embattled multi- and trans-disciplinary scholars. And it is for this reason that Barbieri's volume constitutes a major achievement. With the arrival of this Introduction, particularly in its open demonstration of a diverse range of opinion within the field, biosemiotics has reached a defining moment. (One is tempted to say that it has 'come of age', but this happened quite some time ago.) The book is not a single-author monograph, concise and aimed at absolute beginners. Instead, it consists of eighteen largely original contributions from major names in biosemiotics (Hoffmeyer, Kull, Barbieri, Markos), sympathetic major theoretical biologists (Pattee, Salthe) as well as at least one commentator who has come to biosemiotics from semiotics rather than in the reverse direction (Danesi). These contributions are divided into three sections: 'Historical background', 'Theoretical issues' and 'Biosemiotic research'. The volume is not comprehensive -1 would have liked to have seen contributions from, to name just a few appropriate living scholars, Terrence Deacon, Claus Emmeche, Timo Maran and S0ren Brier. However, there are always going to be quibbles of this kind with edited collections. So, it would be more evenhanded to say that this volume provides an invaluable overview in addition to a much-needed summing up of the biosemiotic enterprise. Let us sketch some of the issues raised by the thematic sections. The explicit 'summing up' is mainly to the fore in the first section on 'Historical background'. Favareau's essay, though seemingly bitty, amounts to a persuasive account of one of the leading trajectories in biosemiotics (if not semiotics generally). Ranging from Aristotle, through Poinsot to Sebeok and, then, Barbieri, with the help of Deely and by way of a coruscating account of the influence of Descartes on modern thought, its 68 pages are worth the (intellectual) admission price alone. Favareau's essay also hauls aloft the main issues and criticisms that biosemiotics has elicited, although in the historical section, it is Jamsa's review that actually looks at the marriage of Peircean theory and biology. Finally, Barbieri's essay in the same section is a 'revised repeat' (as they say in the description of updates on reality TV programmes) of his 2002 review of Kull's special von Uexkull issue of Semiotica. In their summing up, both Barbieri and Favareau suggest that biosemiotics is now a field which is more varied than it previously was when dominated by the rediscovery of von Uexkull; chiefly, the change in the field consists in the way that it has embraced the more mechanistic approach to semiosis of Barbieri himself, leading to a perspective within biosemiotics which is not geared towards explication of the dynamics and context-based nature of signs and texts but allows for understanding the workings of nature as code-based. The section on 'Theoretical issues' kicks off with Pattee's essay focusing on the 'symbolic control' of matter. …


Background To comply with an action plan patients need to recall information accurately. Little is known about how well patients recall consultations, particularly telephone consultations increasingly used to triage acute problems. Purpose of study This was an exploratory study to measure how accurately patients recall the content of face-to-face and telephone consultations and what factors may be associated with accurate recall. Study design In Scotland in 2008, the advice (diagnoses; management plan(s); and safety-netting arrangements) given in audio recorded face-to-face and telephone consultations was compared with the advice recalled by patients at interview approximately 13 days later. Patients also performed a memory test. Interactions were sought between accurate recall, consultation type, and factors postulated to influence recall. Results Ten general practitioners (GPs) and 175 patients participated; 144 (82%) patients were interviewed. Patients recalled most important components of telephone and face-to-face consultations equally accurately or with only minor errors. Overall, patients presenting multiple problems (p<0.001), with brain injury (p<0.01) or low memory score (p<0.01) had reduced recall. GPs rarely used strategies to improve recall; however, these were not associated with improved recall. Conclusions Contrary to previous hospital based research, patients tended to remember important components of both face-to-face and telephone consultations—perhaps reflecting the familiar, less anxiety provoking environment of primary care. The unsuccessful use of strategies to improve recall may reflect selective use in cognitively impaired patients. Clinicians should compensate for situations where recall is poorer such as patients presenting multiple problems or with brain injury. Patients might be advised to restrict the number of problems they present in any one consultation.


In recent years the regularity method has been used to tackle many embedding problems in extremal graph theory. This thesis demonstrates and develops three different techniques which can be used in conjunction with the regularity method to solve such problems. These methods enable us to prove an approximate version of the well-known Sumner's universal tournament conjecture, first posed in 1971, which states that any tournament G on 2n − 2 vertices contains a copy of any directed tree T on n vertices. An analysis of the extremal cases then proves that Sumner's universal tournament conjecture holds for any sufficiently large n. Our methods are also applied to the problem of obtaining hypergraph analogues of Dirac's theorem. Indeed, we show that for any k \(\geqslant\) 3 and any 1 \(\leqslant\) \(\ell\) \(\leqslant\) k − 1 with k - \(\ell\)\(\nmid\)k, any k-uniform hypergraph on n vertices with minimum degree at least \(\frac{n}{\lceil k / (k - \ell) \rceil (k - \ell)}\) + o(n) contains a Hamilton \(\ell\)-cycle. This result confirms a conjecture of Han and Schacht, and is best possible up to the o(n) error term. Together with results of Rodl, Rucinski and Szemeredi, this result asymptotically determines the minimum degree which forces an \(\ell\)-cycle for any \(\ell\) with 1 \(\leqslant\)\(\ell\)\(\leqslant\) k − 1.


Whereas gender, race and ethnicity have been placed at the very center of the rediscovery of European Union anti-discrimination law in the last decades, religion seems to stand in the backyard of the European Union Agenda. Efforts to tackle discrimination based on religious belief have not yet invested all areas of European Union anti-discrimination law, whose preference has been progressively devoted to other factors, even by leaving religion aside from the material scope of the Race Directive 43/2000/CE. The Employment Equality Directive, in fact, only prohibits discrimination on grounds of religion and belief in the fields of employment and occupation, vocational training, membership of employer and employee organizations, though refraining from following the Race Directive approach as to the width of protection. Freedom of religion within the European Union is then enshrined under Article 10, Freedom of thought, conscience and religion, of the European Union Charter of Fundamental Rights together with the general guarantee of non-discrimination under Article 21 and that of cultural religious and linguistic diversity set forth under Article 22. On the Council of Europe side, the European Convention – through Article 9, 14 and, to some extent, 1, Protocol no. 12 – and the European Court of Human Rights (ECtHR) have instead played a prominent role in addressing issues pertaining to freedom of religion, although generally disregarding the discriminatory implications of the scrutinized cases. Reference is made to the ECtHR consistent case-law on: proselytism (see Kokkinakis v. Greece); religious communities and their legal recognition (see Hasan and Chaush v. Bulgaria, Metropolitan Church of Bessarabia and Others v. Moldova); religious holydays (Francesco Sessa v. Italy, ); religious symbols in the public sphere (see Leyla Sahin v. Turkey, S.a.s. v. France; Eweida and others v. the United Kingdom; Hamidovic v. Bosnia Herzegovina); disposal of public services in the interest of religious communities (Izzetin Dogan v. Turkey). The European Union Charter of Fundamental Rights, together with the above mentioned Articles of the European Convention of Human Rights, set therefore the framework where to situate the lines of intervention towards discrimination on account on religion in european multicultural and multi-religious society. Moving ahead and beyond the existing legal background on religious anti-discrimination law, the presentation intends to discuss and compare the European Union Court of Justice (ECJ) and the European Court of Human Rights (ECtHR) approaches towards discrimination claims on religious ground, by highlighting weaknesses and challenges faced by the principle of equality and non-discrimination on account of religious belief at the european level. As to the method, the proposed analysis, through selected case studies, will address and disclose achievements and perspectives in the fight against discrimination based on religious belief by looking at the following issues: the notion of religion with specific reference to its overlapping relationship with that of ethnicity; the notions and implications of direct and indirect discrimination; the collective or "group" resonance of discrimination on account of religious belief. The parallel and combined investigation of the EU Court of Justice (see Achbita v. G4S and Bougnaoui v. Micropole) and the ECtHR case-law will thus offer an insight into the unsolved questions behind the understanding and the legal awareness towards discrimination based on religion. The presentation will eventually bring about: the urge to challenge western countries approach to anti-discrimination strategies by acknowledging the inadequate realization of existing measures and suggesting diverse mechanisms which might embrace a focus on minorities' rights as an additional tool to overcome discrimination; the adequacy of approaching anti-discrimination claims by interlacing religion and ethnicity; the challenges encountered by anti-discrimination law and Courts' dependence on the so-called comparator methodology.


Since 2001, the Kingdom of Saudi Arabia has been fighting domestic terrorism and adopting policies and strategies in countering radicalism and terrorism. How effective are these policies, strategies, and tactics in combating terrorist ideology, reducing the number of terrorist activists and sympathizers, as well as preventing terrorist acts in the Kingdom? Although the government's roles and efforts in counterterrorism programs are fruitful and advantageous, further strategic actions are necessary.


Platelet-rich fibrin (PRF) is a natural fibrin meshwork material with multiple functions that are suitable for tissue engineering applications. PRF provides a suitable scaffold for critical-size bone defect treatment due to its platelet cytokines and rich growth factors. However, the structure of PRF not only promotes cell attachment but also, due to its density, provides a pool for cell migration into the PRF to facilitate regeneration. In our study, we used repeated freeze drying to enlarge the pores of PRF to engineer large-pore PRF (LPPRF), a type of PRF that has expanded pores for cell migration. Moreover, a biodegradable Mg ring was used to provide stability to bone defects and the release of Mg ions during degradation may enhance osteoconduction and osteoinduction. Our results revealed that cell migration was more extensive when LPPRF was used rather than when PRF was used and that LPPRF retained the growth factors present in PRF. Moreover, the Mg ions released from the Mg ring during degradation significantly enhanced the calcium deposition of MC3T3-E1 preosteoblasts. In the present study, a bone substitute comprising LPPRF combined with a Mg ring was demonstrated to have much potential for critical-size bone defect repair.


The main indicator for the presence of an ancient settlement at a certain location is the find of pottery fragments. With regard previously to the sites of continental Croatia, it has been the practice to date fragments to a broad period of 'medieval times'. This volume marks the first full-scale attempt to closely examine 10th to 13th Croatian pottery typologically and chronologically. As well as pottery analysis, data obtained from cemeteries and Romanesque architectural remains, as well as other types of finds such as coin hoards and swords, were included in the study. This, and information taken from historical sources, has considerably increased the available knowledge on the organization of settlements in the Sava-Drava interfluves during the period of 10th to 13th centuries.


CLINICAL PRESENTATION & EXAM: A twenty-two year old collegiate triple jumper presents with tenderness over the tibial shaft along the medial border. During the evaluation the athlete cannot recall a specific incident that caused the pain, but notes that it has been ongoing for a few weeks. Initially achy pain was present during activity, but developed to a sharp and unusual pain while at rest. Percussion test, bump test, and squeeze test are used during the physical examination to detect possible fractures. ANATOMY & PATHOLOGY: The tibia is located in the lower leg along with the fibula. The tibia is the larger of the two bones and responsible for absorbing majority of the forces when performing weightbearing activities. Increase stress and overloading the tibia too quickly can cause micro-cracks in the bone. DIAGNOSTIC TESTING & CONSIDERATIONS: After the initial evaluations are performed, CT scans can be done to detect any cracks in the bone. It isn't uncommon for the plain films to be negative in the case of a stress fracture, even if the athlete presents with signs of a fracture. An MRI was ordered and the results showed a tibial stress fracture with a DBL (dreaded black line). TREATMENT & RETURN TO ACTIVITY: Conservative treatments did not prove to be a benefit, and the patient had to undergo two PRP injections. Tibial stress fractures that present with a DBL usually require surgery to be fixed. A rod would be implanted and used to absorb bodily stress. This method was not ideal seeing as the patient was a triple jumper and the rod would prevent her from performing at a high level. Athletic trainers must be knowledgeable in implementing different treatment options when rehabilitating their athletes if the decide to opt out of surgical intervention.


The governance challenges facing the International Monetary Fund (IMF) are not simply limited to representation and voice, and the associated question of quota allocation. The author identifies governance issues that hitherto remained largely ignored by the literature and policy-makers alike. Specifically, he examines the governance issues that arise when (i) one or more shareholders hold controlling voting blocks, and (ii) principal-agent problems exist between the Executive Board and the Managing Director. Furthermore, these typical governance issues are compounded by the specific characteristics of IMF governance, such as consensus decision making, the lack of clear fiduciary duty on the part of the Executive Board, and the lack of separation between the Executive Board and the Managing Director. The author then attempts to quantify the extent to which the IMF's governance structure deviates from corporate best practice. Unsurprisingly, he finds that the IMF does not follow best practice. The author offers several proposals for governance reforms, including that the IMF should implement a form of "constrained discretion." Under this framework, the Executive Board would set the objectives and rules for the IMF on an annual basis. The Managing Director and the staff would be free to pursue these objectives, conditional on the rules. These respective reforms would improve accountability and hence the legitimacy of the IMF.


ABSTRACT The article analyses the history of translating film into ethnic minority languages in China. Using such sources as official regulations, newspapers, quantitative data, memoirs and oral history, the author examines China's film translation policies, translation institutions, and modes of translation with respect to minority languages. It will also shed light on the evolution of these trends of film translation into ethnic minority languages in China over time. It provides an overview of major events in the development of the practice of translating films into minority languages in China, from the 1950s to the present day. This overview can be divided into three periods based on the technological developments that shaped these practices: 1950s to 1965, 1965–2009, and 2009 to the present day. The first period is defined by the use of dubbing by major film studios and oral interpretation by mobile projectionists. The second period is defined by centralized production of magnetic dubbing tracks by film translation centres located in the regions where ethnic minorities live. The third period is defined by digital dubbing carried out by a coordinated national network of 11 film translation centres for ethnic minority languages.


The poems of Robert Bly are rooted deep in the earth. Snow and sunshine, barns and cornfields and cars on the empty nighttime roads, abandoned Minnesota lakes and the mood of America now these are his materials. He sees and talks clearly: he uses no rhetoric nor mannered striving for effect, but instead the simple statement that in nine lines can embody a mood, reveal a profound truth, illuminate in an important way the inward and hidden life. This is a poet of the modern world, thoroughly aware of the complexities of the moment but equally mindful of the great stream of life all life of which mankind is only a part."


This paper investigates the dynamics of the distribution of unconditional and conditional – on technology – wages in Europe, using both industry and individual level data for the period 1995-2007. We find that the unconditional wage distribution shows scant signs of polarization in Europe. On the other hand, the effect of technology is more nuanced. At the industry level, technological changes have an effect on polarization of jobs, but not on polarization of wages. At the individual level, we use a counterfactual distributional analysis which accounts for the heterogeneity of tasks across occupations, and we find only mild evidence of wage polarization. Technology affects the lower and upper part of the wage distribution in different ways, with service tasks affecting the lower quantiles and abstract tasks affecting the higher ones.


The proteasome plays a major role in non-lysosomal protein degradation pathways and inhibition of proteasomes became a valid therapeutic strategy for anti-cancer therapy in the recent years. Current efforts focus on the identification and development of second generation inhibitors with enhanced pharmacological properties. For this, improved structural knowledge and an advanced biochemical characterization of proteasome inhibition is necessary.
In this work, I present a reproducible and robust pipeline that enables the purification, crystallization, crystal handling and structure determination of the native 20S proteasome and 20S-inhibitor complexes. Crystal structures including four previously uncharacterized inhibitor complexes with clinically relevant inhibitors were elucidated at resolutions between 1.8 and 2.1 A. The improved resolutions allow to define the inhibition chemistry at atomic resolution. This led to revised descriptions of binding modes for epoxyketone and ketoaldehyde inhibitors, a redefinition of the proteasome active site, and a concept for future drug design.
Single particle electron cryomicroscopy (cryo-EM) was the method of choice when studying the influence of 20S core particle inhibition on the dynamic 26S holoenzyme. We determined structures of the 26S proteasome with and without inhibitor and report for the first time structural changes of 26S proteasomes upon inhibition. Drug binding limits the conformational space of the 19S regulatory particle and we identified an energy barrier that stabilizes the proteasome in a non-productive state. Here, we describe that core particle inhibition triggers a structural long-range allosteric regulation of the human 26S proteasome.
This thesis offers insights into the exact catalytic mechanism of peptide cleavage and proteasome inhibition in the human 20S proteasome and a detailed description of the proteolytic site. In addition, the structural impact of 20S inhibition on the human 26S proteasome was studied for the first time and the findings allow for a new way to screen and develop future allosteric proteasome inhibitors. A reproducible workflow to structurally study inhibitor-proteasome complexes by advanced protein complex purification combined with X-ray crystallography or single particle cryo-EM is presented.


Here we describe the role of the Cladosporium fulvum nitrogen response factor 1 (Nrf1) gene in regulation of the expression of avirulence gene Avr9 and virulence on tomato. The Nrf1 gene, which was isolated by a polymerase chain reaction-based strategy, is predicted to encode a protein of 918 amino acid residues. The protein contains a putative zinc finger DNA-binding domain that shares 98% amino acid identity with the zinc finger of the major nitrogen regulatory proteins AREA and NIT2 of Aspergillus nidulans and Neurospora crassa, respectively. Functional equivalence of Nrf1 to areA was demonstrated by complementation of an A. nidulans areA loss-of-function mutant with Nrf1. Nrf1-deficient transformants of C. fulvum obtained by homologous recombination were unable to utilize nitrate and nitrite as a nitrogen source. In contrast to what was observed in the C. fulvum wild-type, the Avr9 gene was no longer induced under nitrogen-starvation conditions in Nrf1-deficient strains. On susceptible tomato plants, the Nrf1-deficient strains were as virulent as wild-type strains of C. fulvum, although the expression of the Avr9 gene was strongly reduced. In addition, Nrf1-deficient strains were still avirulent on tomato plants containing the functional Cf-9 resistance gene, indicating that in planta, apparently sufficient quantities of stable AVR9 elicitor are produced. Our results suggest that the NRF1 protein is a major regulator of the Avr9 gene.


This research investigates the impact of the Indonesian family planning program on the labor force participation decisions and contraceptive choices of women. I develop a discrete choice dynamic structural model, where each married woman in every period makes joint choices regarding the method of contraceptive used and the sector of employment in which to work in order to maximize her expected discounted lifetime utility function. Each woman obtains utility from pecuniary sources, nonpecuniary sources, and choice-specific time shocks. In addition to the random shocks, there is uncertainty in the model as a woman can only imperfectly control her fertility. Dynamics in the model are captured by several forms of state and duration dependence. Women in this model make different choices due to different preferences, differences in observable characteristics, and realization of uncertainty. The choices made by a woman depend on the compatibility between raising children and the sector of employment (including wages). While making decisions regarding contraceptive use, a woman considers the trade-off between costs (monetary and nonmonetary) of having a child and the benefits from having one. The primary source of data for this study is the first wave of the Indonesia Family Life Survey (IFLS 1), a retrospective panel. In my research, I use the geographic expansion and the changing nature of the Indonesian family planning program as sources of exogenous variation to identify the parameters of the structural model. I estimate the model using maximum likelihood techniques with data from IFLS 1 for the periods 1979-1993. Structural model estimates indicate that informal sector jobs offer greater compatibility between work and childcare. Parameter estimates indicate that choices of contraception method and employment sector vary by exogenous characteristics.


Unconventional computation (UCOMP) is an important and emerging area of scientific research, which explores new ways of computing that go beyond the traditional model, as well as quantum- and brain inspired computing. Such alternatives may encompass novel substrates (e.g., DNA, living cells, or mixtures of the two) as well as new paradigms which, for example, support combined information processing and material production (as living systems do). UCOMP researchers draw inspiration from a wide and diverse range of sources, from physics, to chemistry, biology and ecology. The field is growing quickly, and has the potential to revolutionize not only our fundamental understanding of the nature of computing, but the way in which we solve problems, design networks, do industrial fabrication, make drugs or construct buildings. The problems we already face in the 21st century will require new and creative approaches, conceptual frameworks, mechanisms and perspectives. UCOMP offers one route towards this. TRUCE is a coordination action to help organize the international UCOMP community. The inherent diversity of the field has led to fragmentation, with many sub-fields developing in parallel. With large-scale project support now being offered by the European Commission, the time is precisely right to organize and coordinate the field at the European level. This coordination action will engage the European community (and beyond), construct the first UCOMP roadmap, reach out to a wider public beyond the scientific community, and build the foundations for a new, sustainable and coherent scientific discipline.


Globally, there are social, economic and environmental challenges related to sustainable development; these challenges include climate change, the need to feed a rapidly increasing population, high rates of poverty and environmental degradation. These challenges have forced us to rethink the way in which development takes place, resulting in the emergence of the concept of a 'green economy'. A green economy results in improved human well-being and social equity, while significantly reducing risks to the environment. It is based on principles which integrate social, economic and environmental considerations. South Africa has adopted the principle of green economic growth, and agriculture is one of the sectors that will drive this growth. Agriculture could address some of the sustainable development problems, but there are challenges related to resource availability, environmental impacts of agriculture and climate change. For agriculture to support a green economy it has to be productive, contribute to economic growth and not undermine the environment, social and cultural systems. The information base and policies required to support a green economy in general, and/or an agriculture-supported green economy have not yet been developed, as the green economy is an emerging concept in South Africa as well as globally. The generation of such information requires analysis and synthesis of green economy principles and agricultural imperatives into generic principles and practices for facilitating agriculture's contribution to the green economy. In this paper, we conduct this analysis and synthesis and highlight the defining aspects of an agricultural green economy.


The application of neutron powder diffraction to the study of mineral behaviour at high temperature and high pressure is reviewed. The characteristics of neutrons that make them particularly amenable to such studies are outlined, and recent techno- logical developments in the attainment of extreme sample environments are discussed. These developments include the design of new high-pressure cells, hydrothermal cells, and furnaces that allow in situ diffraction under extreme conditions. The application of this technology to problems of order-disorder in minerals is illustrated in a series of recent examples.


Attempts to meet rising worldwide energy demands, often leads to the construction of hydrocarbonate pipelines over very long distances. Crossing seismic areas is often inevitable for such pipeline routes even though the design of new pipelines takes place within a stringent framework of regulations to protect the environment and avoid populated areas. In such cases, the potential for large ground differential movement due to fault activation often becomes the primary cause of pipeline failure. Buried steel pipelines deform to adapt to movement of the surrounding soil, so possible failure modes are tensile fracture of girth welds between adjacent pipeline parts, local buckling of the pipeline wall due to compressive strains, and upheaval buckling due to high compressive forces in the case of reverse-type faults. The latter is the dominant failure mode for relatively shallowly buried pipelines with low diameter-to-thickness ratio, but is not usually relevant for the relatively thin-walled pipelines used to transport fuel. Minimizing the consequences of induced large ground displacements on pipeline integrity is both an industrial and academic research topic of high priority. Among conventional mitigating measures, such as constructing a wider trench and backfilling with loose granular soil to reduce soil-pipeline friction, research is directed towards integrating flexible joints between adjacent steel parts in buried pipelines crossing areas prone to large ground displacements. This approach aims at concentrating strains at the joints, leaving the steel pipe virtually undeformed. Thus, the failure modes caused by high strain concentrations, i.e. tensile fracture of the welds and local shell buckling, are avoided. However, the introduction of flexible joints - acting as internal hinges and transforming the continuous pipeline to a segmented one - tends to decrease pipeline global stiffness and render them more susceptible to upheaval buckling, to the extent that it may become the dominant failure mode, even for deeply-buried pressurized pipelines with relatively high diameter-to-thickness ratios crossing reverse faults. This issue is investigated numerically by modeling the pipeline with beam-type finite elements, and the surrounding soil with nonlinear translational springs. The numerical models are calibrated by comparison to experimental tests. Numerical analyses incorporating geometrical nonlinearities as well as pipeline steel and soil nonlinearities are carried out in order to investigate upheaval buckling and post-buckling global behavior of pipelines with flexible joints at reverse fault crossings, and compare it to the aforementioned local - compressive or tensile - failure modes. Results indicate that during pipeline design a balance has to be struck between the advantages of using flexible joints to reduce strains and the limitation of hazard against failure due to upheaval buckling.


Martensitic stainless steel has a wide range of applications in steam generators and food industries like mixing blades due to high mechanical and good corrosion resistance. In this research, the effect of austenitizing temperatures (1040°C -1070°C), tempering temperatures (300, 400, 500, 600 and 700°C) and also the tempering times of (2 and 5 h) on microstructure and mechanical properties of martensitic stainless steel X20CrMoWV121(AISI 422) has been investigated. The results of the experiments showed that with increasing the austenitizing temperature from 1040 to 1070°C the impact energy is reduced, and the hardness and yield strength are increased. These changes are due to the increase in the austenite grain size. The secondary hardness occurs in the tempering temperature in range of 400-500°C.The results revealed that after tempering, an increase in hardness and strength and a reduction in toughness occurred in the samples. Also, with increase in the tempering time from 2 to 5 hours at 700°C, the toughness increased and hardness as well as strength were reduced due to the precipitation of the carbides.DOI: http://dx.doi.org/10.5755/j01.mech.22.6.13599


In this thesis, we investigate gender difference across Nordic mutual fund managers. We analyse a data set free of survivorship bias, consisting of 430 Nordic singlemanaged mutual funds in the period January 2005 to June 2017, where we look at differences in risk-adjusted performance, risk-taking behavior and investment style caused by the managers gender. Examining previous literature, we hypothesize that femaleand male mutual fund managers perform differently. Furthermore, we expect females to behave more risk-averse, and follow a different investment style than their male counterparts. By utilizing multiple methodologies to ensure robust results, we find no support for our hypotheses. Hence, we document that the mutual fund manager market in the Nordics is efficient with respect to that one cannot achieve abnormal returns by investing in funds based on the gender of the fund managers. Furthermore, our findings suggest that femaleand male mutual fund managers share the same investment style and risk propensity.


The ventral tegmental area (VTA) is thought to be involved in the addictive properties of many drugs, including cocaine. It has been hypothesized that cocaine exerts its actions in the VTA by blocking the reuptake of dopamine released from the dendrites of the A10 dopamine neurons, thus prolonging the actions of dopamine at D2 autoreceptors. However, cocaine also blocks the reuptake of the other monoamines, including serotonin (5-HT). Using intracellular recordings from midbrain dopamine neurons in a brain slice preparation, we have found that cocaine (0.1–10 microM) inhibited the GABAB IPSP in a dose- dependent manner. This effect was observed in the presence of the D2 dopamine receptor antagonists sulpiride (1 microM) and eticlopride (0.1 microM). 5-HT mimicked this effect, as did the selective 5-HT1D receptor agonist sumatriptan and the 5-HT-releasing agent fenfluramine. The actions of both 5-HT and cocaine were attenuated by the 5-HT1C/D antagonist metergoline. Pretreatment of slices with the 5-HT-depleting agent p-chloroamphetamine (pCA; 10 microM) abolished the inhibition of the GABAB IPSP by cocaine but failed to affect the actions of sumatriptan. We conclude that cocaine acts to modulate the GABA input to A10 dopamine neurons via inhibition of the 5-HT transporter, increasing the concentration of 5-HT at presynaptic 5-HT1D receptors. These actions of cocaine were apparent at lower concentrations than those required to act via inhibition of the dopamine transporter. This reduction of inhibitory synaptic input into the VTA would be expected to attenuate the GABA-mediated feedback inhibition from the nucleus accumbens, thus leading to increased activation of dopamine neurons.


Abstract. An Aerosol Chemical Speciation Monitor (ACSM, Aerodyne Research Inc.) was deployed at the Montseny (MSY; 41° 46'46" N, 02° 21'29" E, 720 m a.s.l.) regional background site in the western Mediterranean, Spain, from June 2012 to July 2013 to measure real-time inorganic (nitrate, sulfate, ammonium and chloride) and organic submicron aerosol concentrations. Co-located measurements, including real-time submicron particulate matter (PM1) and black carbon (BC) concentrations, and off-line PM1 chemical analysis were also carried out. This is one of the few studies that compare ACSM data with off-line PM1 measurements, avoiding the tail of the coarse mode included in the PM2.5 fraction. The ACSM + BC concentrations agreed with the PM1 measurements, and a strong correlation was found between the concentrations of ACSM species and the off-line measurements, although some discrepancies remain unexplained. Results point to a current underestimation of the relative ionization efficiency (RIE) established for organic aerosol (OA), which should be revised in the future. The OA was the major component of submicron aerosol (53% of PM1), with a higher contribution in summer (58% of PM1) than in winter (45% of PM1). Source apportionment of OA was carried out by applying positive matrix factorization (PMF), using the multilinear engine (ME-2) to the organic mass spectral data matrix. Three sources were identified in summer: hydrocarbon-like OA (HOA), low-volatile oxygenated OA (LV-OOA), and semi-volatile oxygenated OA (SV-OOA). The secondary OA (SOA; 4.8 μg m−3, sum of LV-OOA and SV-OOA) accounted for 85% of the total OA, and its formation during daytime (mainly SV-OOA) was estimated to be 1.1 μg m−3. In winter, HOA was also identified (12% of OA), a contribution from biomass burning OA (BBOA) was included and it was not possible to differentiate between two different SOA factors, but a single oxygenated OA (OOA) factor was resolved. The OOA contribution represented 60% of the total OA, with a degree of oxidation higher than both OOA summer factors. An intense wildfire episode was studied, obtaining a region-specific BBOA profile.


Leonhard-Marek, Sabine, Friederike Stumpff, Inge Brinkmann, Gerhard Breves, and Holger Martens. Basolateral Mg / Na exchange regulates apical nonselective cation channel in sheep rumen epithelium via cytosolic Mg . Am J Physiol Gastrointest Liver Physiol 288: G630–G645, 2005. First published November 18, 2004; doi:10.1152/ajpgi.00275.2004.—High potassium diets lead to an inverse regulation of sodium and magnesium absorption in ruminants, suggesting some form of cross talk. Previous Ussing chamber experiments have demonstrated a divalent sensitive Na conductance in the apical membrane of ruminal epithelium. Using patch-clamped ruminal epithelial cells, we could observe a divalent sensitive, nonselective cation conductance (NSCC) with K permeability Cs permeability Na permeability. Conductance increased and rectification decreased when either Mg or both Ca and Mg were removed from the internal or external solution or both. The conductance could be blocked by Ba , but not by tetraethylammonium (TEA). Subsequently, we studied this conductance measured as shortcircuit current (Isc) in Ussing chambers. Forskolin, IBMX, and theophylline are known to block both Isc and Na transport across ruminal epithelium in the presence of divalent cations. When the NSCC was stimulated by removing mucosal calcium, an initial decrease in Isc was followed by a subsequent increase. The cAMP-mediated increase in Isc was reduced by low serosal Na and serosal addition of imipramine or serosal amiloride and depended on the availability of mucosal magnesium. Luminal amiloride had no effect. Flux studies showed that low serosal Na reduced Mg fluxes from mucosal to serosal. The data suggest that cAMP stimulates basolateral Na /Mg exchange, reducing cytosolic Mg. This increases sodium uptake through a magnesium-sensitive NSCC in the apical membrane. Likewise, the reduction in magnesium uptake that follows ingestion of high potassium fodder may facilitate sodium absorption, as observed in studies of ruminal osmoregulation. Possibly, grass tetany (hypomagnesemia) is a side effect of this useful mechanism.


This paper argues that linguistic features common in discourse around Open Access Publishing are socially constructed in ways that lend themselves to implicit bias against the Open Access (OA) movement. These biases materialize through common linguistic practices such as de-centering OA and highlighting the uncertainty of OA Publishing, resulting in "patchy endorsements" of the status quo of Subscription Publishing. Following previous research that demonstrates how educational content on OA can lead to cognitive load and biases that reinforce the status quo in scholarly publishing, we analyze publicly available, online content from our own institutions with an eye towards how these biases manifest specifically in the practice of librarianship. Using examples from this analysis, we suggest strategies and intentional language that can be used by librarians and other OA advocates to counteract bias and shift towards a construction of OA Publishing as the status quo. While many strategies and difficult negotiations are needed to functionally establish OA as the default in scholarly publishing, language choice is a device through which advocates at any level can advance towards an open-centered culture.


Introduction: In order to practice evidence-based veterinary medicine, good quality clinical evidence needs to be produced, in order that it can be apprasied systematically by the EBVM network, and used by vets. There is very little good-quality veterinary evidence for most of the veterinary procedures carried out every day across the world. Very few, if any, individuals have all the necessary qualities (case-load, time, research expertise, financial support) to be able to systematically produce good-quality, and relevant, clinical research on their own, in a timely manner. The Association for Veterinary Soft Tissue Surgery (AVSTS) www.avsts.org.uk is an affiliate group with the British Small Animal Veterinary Association (BSAVA), and functions as a clinical network of like-minded individuals. In 2013 AVSTS sought to create a role for itself in facilitating the production (by its members) of multi-centre clinical research of relevance to its members. Materials and methods: Members of AVSTS were asked to join the AVSTS Research Cooperative (ARC), with a veterinary epidemiologist and an experienced multi-centre veterinary clinical researcher (to help with study design and statistical planning), and the Animal Health Trust clinical research ethics committee. An email list was established, and a page was set up on the AVSTS website, to allow information to be disseminated. The AVSTS spring and autumn meetings were used as a regular forum by ARC, to discuss its direction, to generate interest, to create and promote specific studies (in order to widen participation amongst different centres), and to update members about previous studies. Results: Membership of ARC has grown to 224 people, although the epidemiologist left. One multi-centre study has been published, two have been presented and await publication, one has been accepted for presentation, two other studies are gathering data at present, and further studies are in the pipeline. There has been interest from general practitioner members but as yet no studies of general practice procedures have been forthcoming. Discussion: Vets want to be involved with clinical research. ARC has had early successes and will continue to grow - though more work is needed to encourage general practitioner members. Multi-centre research allows more cases to be recruited more quickly, adding weight to studies and shortening the period of data-gathering. These initial retrospective studies have generated a committed core of individuals seeking to create prospective studies together. An online tool is planned, to facilitate real-time case-recruitment for prospective multi-centre studies including randomised controlled trials. Anyone can join ARC, please email email@example.com.


Industrial robots are finding their niche in the field of machining due to their advantages of high flexibility, good versatility and low cost. However, limited by the low absolute positioning accuracy, there are still huge obstacles in high precision machining processes such as grinding. Aiming at this problem, a compensation method combining analytical modeling for quantitative errors with spatial interpolation algorithm for random errors is proposed based on the full consideration of the source and characteristics of positioning errors. Firstly, as for the quantitative errors, namely geometric parameter and compliance error in this paper, a kinematics-based error model is constructed taking the coupling effect of errors into consideration. Then avoiding the impact of random errors, the extended Kalman filtering algorithm (EKF) is adopted to identify the error parameters. Secondly, based on the similarity principle of spatial error, spatial interpolation algorithm is used to model the residual error caused by temperature, gear clearance etc. Based on the spatial anisotropy characteristics of robot motion performance, an adaptive mesh division algorithm was proposed to balance the accuracy and efficiency of mesh division. Then, an inverse distance weighted interpolation algorithm considering the influence degree of different joints on the end position was established to improve the approximation accuracy of residual error. Finally, the rough-fine two-stage serial error compensation method was carried out. Experimental results show the mean absolute positioning accuracy is improved from 1.165 mm to 0.106 mm, which demonstrates the effectiveness of the method in this paper.


Applied Behavior Analysis (ABA) has addressed many problems of social significance. Illustrating one such problem, dental patients with special needs sometimes physically resist needed treatments. Treatment options include medications, mechanical or physical restraints, or attempts to overcome resistance behaviorally. This paper reviews alternative behavioral approaches to decreasing resistance and increasing cooperation. Common characteristics of effective treatments are outlined and their limitations discussed. Key words: behavioral dentistry, applied behavior analysis, alternatives to sedation I. INTRODUCTION Applied behavior Analysis (ABA) has always attempted to provide empirically-based solutions to problems of social significance in the real world. And, from its inception, ABA has specifically addressed behavior change in persons with special needs--e.g., children, the developmentally disabled and autistic, the mentally ill, persons with traumatic brain injury and other disabilities. One area that has received considerable (and cross-disciplinary) attention has been the fact that some children and adults with special needs exhibit physical resistance to daily oral hygiene and to needed dental treatments, especially when daily oral hygiene tasks are less than pleasant; and when those dental treatments are provided in strange and unfamiliar environments, and when the treatments themselves are inherently intrusive, aversive and painful (e.g., examinations, injections, extractions). The literature provides ample evidence that a behavioral approach to resistance to dental treatment can accomplish two important goals. First, a patient's physical resistance can be reduced during treatment, thus allowing that particular treatment to be completed. Second, and more importantly, a behavioral approach can transcend the immediate treatment situation and can be implemented in such a way that the individual actually learns to increase cooperation with dental treatment in the future, thus making later treatment easier. Concomitantly, at least some children and persons with special needs will gain in overall quality of life, increased oral hygiene skill levels, and self-control and in their ability to tolerate unpleasant situations.. In many cases and for many patients exhibiting mild to moderate physical resistance, it will be possible to complete dental treatment, even an extended series of treatments, by implementing one or more of the interventions described below. However, there will almost always be a minority of individuals who will not respond with cooperation even when multiple positive interventions are implemented. In some cases, this may be due to extreme resistance on the part of the patient; in other cases, it may be due to the inherently painful nature of the treatment. In these circumstances, we are faced with an interesting ethical dilemma. We know that the first rule of service provision is to do no harm. Sometimes that decision is clear-cut and easy to make (e.g., an impacted tooth needs to be extracted; an acute dental injury requires immediate treatment). When patients resist, however, the determination of harm is less obvious. On the one hand, we do avoid immediate harm by "fudging" oral hygiene skill training, and by avoiding treatment for the patient. But, over time, lack of daily hygiene and dental treatment results in increasingly poor oral hygiene, which may require more intrusive (i.e., an increased possibility of more intrusive, possibly dangerous, and certainly expensive) treatment in the future. The question is not whether we "do harm"; rather, the question is when harm will be done, and how best to minimize that harm. This is a particularly interesting question given that various regulatory agencies on the one hand require individuals with special needs to be provided with daily oral hygiene and with regular dental examinations and treatments as needed, and yet those same regulatory agencies also place significant impediments (and even negative consequences) in the way of such practices. …


mHealth (healthcare using mobile wireless technologies) has the potential to improve healthcare and the quality of life for elderly and chronic patients. Many studies from all over the world have addressed this issue in view of the aging population in many countries. However, there has been a lack of any consolidated evidence-based study to classify mHealth from the dual perspectives of healthcare and technology. This paper reports the results of an evidence-based study of mHealth solutions for chronic care amongst the elderly population and proposes a taxonomy of a broad range of mHealth solutions from the perspective of technological complexity. A systematic literature review was conducted over 10 online databases and the findings were classified into four categories of predominant mHealth solutions, that is, self-healthcare, assisted healthcare, supervised healthcare and continuous monitoring. The findings of the study have major implications for information management and policy development in the context of the Millennium Development Goals (MDGs) related to healthcare in the world.


Accurate numerical prediction of surface heat transfer in the presence of film cooling within aero-engine sub-components, such as blade effusion holes and combustor liners, has long been a goal of the aero-engine industry. It requires accurate simulation of the turbulent mixing and reaction processes between freestream and the cooling flow. In this study, the stress-blended eddy simulation (SBES) turbulence model is used together with the flamelet generated manifold (FGM) combustion model to calculate the surface heat flux upstream and downstream of an effusion cooling hole. The SBES model employs a blending function to automatically switch between Reynolds-averaged Navier–Stokes (RANS) and large eddy simulation (LES) based on the local flow features, and thus significantly reduces the computational cost compared to a full LES simulation. All simulations are run using ansys fluent®, a commercial finite-volume computational fluid dynamics (CFD) solver. The test case corresponds to an experimental rig run at Massachusetts Institute of Technology (MIT), which is essentially a flat plate brushed by a uniform freestream of argon with ethylene seeded inside, and is cooled by either a reacting air or a non-reacting nitrogen jet inclined at 35 deg to the freestream. Calculations are performed for both reacting and non-reacting jet cooling cases across a range of jet-to-stream blowing ratios and compared with the experimental data. The effects of mesh resolution are also investigated. Calculations are also performed across a range of Damköhler number (i.e., flow to chemical time ratio) from zero to 30, with unity blowing ratio, and the differences in the maximum surface heat flux magnitude in the reacting and non-reacting cases at a specific location downstream of the hole are investigated. Results from these analyses show good correlation with the experimental heat flux data upstream and downstream of the cooling hole, including the heat flux augmentation due to local reaction. Results from the Damköhler number sweep also show a good match with the experimental data across the range investigated.


Background Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a platform for other health services. However, each year millions of children worldwide, mostly from low- and middle-income countries (LMICs), do not receive the full series of vaccines on their national routine immunisation schedule. This is an update of the Cochrane review published in 2011 and focuses on interventions for improving childhood immunisation coverage in LMICs. Objectives To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunisation coverage in LMICs. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 4, part of The Cochrane Library. www.cochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 12 May 2016); MEDLINE In-Process and Other Non-Indexed Citations, MEDLINE Daily and MEDLINE 1946 to Present, OvidSP (searched 12 May 2016); CINAHL 1981 to present, EbscoHost (searched 12 May 2016); Embase 1980 to 2014 Week 34, OvidSP (searched 2 September 2014); LILACS, VHL (searched 2 September 2014); Sociological Abstracts 1952 - current, ProQuest (searched 2 September 2014). We did a citation search for all included studies in Science Citation Index and Social Sciences Citation Index, 1975 to present; Emerging Sources Citation Index 2015 to present, ISI Web of Science (searched 2 July 2016). We also searched the two Trials Registries: ICTRP and ClinicalTrials.gov (searched 5 July 2016) Selection criteria Eligible studies were randomised controlled trials (RCT), non-RCTs, controlled before-after studies, and interrupted time series conducted in LMICs involving children aged from birth to four years, caregivers, and healthcare providers. Data collection and analysis We independently screened the search output, reviewed full texts of potentially eligible articles, assessed risk of bias, and extracted data in duplicate; resolving discrepancies by consensus. We then conducted random-effects meta-analyses and used GRADE to assess the certainty of evidence. Main results Fourteen studies (10 cluster RCTs and four individual RCTs) met our inclusion criteria. These were conducted in Georgia (one study), Ghana (one study), Honduras (one study), India (two studies), Mali (one study), Mexico (one study), Nicaragua (one study), Nepal (one study), Pakistan (four studies), and Zimbabwe (one study). One study had an unclear risk of bias, and 13 had high risk of bias. The interventions evaluated in the studies included community-based health education (three studies), facility-based health education (three studies), household incentives (three studies), regular immunisation outreach sessions (one study), home visits (one study), supportive supervision (one study), information campaigns (one study), and integration of immunisation services with intermittent preventive treatment of malaria (one study). We found moderate-certainty evidence that health education at village meetings or at home probably improves coverage with three doses of diphtheria-tetanus-pertussis vaccines (DTP3: risk ratio (RR) 1.68, 95% confidence interval (CI) 1.09 to 2.59). We also found low-certainty evidence that facility-based health education plus redesigned vaccination reminder cards may improve DTP3 coverage (RR 1.50, 95% CI 1.21 to 1.87). Household monetary incentives may have little or no effect on full immunisation coverage (RR 1.05, 95% CI 0.90 to 1.23, low-certainty evidence). Regular immunisation outreach may improve full immunisation coverage (RR 3.09, 95% CI 1.69 to 5.67, low-certainty evidence) which may substantially improve if combined with household incentives (RR 6.66, 95% CI 3.93 to 11.28, low-certainty evidence). Home visits to identify non-vaccinated children and refer them to health clinics may improve uptake of three doses of oral polio vaccine (RR 1.22, 95% CI 1.07 to 1.39, low-certainty evidence). There was low-certainty evidence that integration of immunisation with other services may improve DTP3 coverage (RR 1.92, 95% CI 1.42 to 2.59). Authors' conclusions Providing parents and other community members with information on immunisation, health education at facilities in combination with redesigned immunisation reminder cards, regular immunisation outreach with and without household incentives, home visits, and integration of immunisation with other services may improve childhood immunisation coverage in LMIC. Most of the evidence was of low certainty, which implies a high likelihood that the true effect of the interventions will be substantially different. There is thus a need for further well-conducted RCTs to assess the effects of interventions for improving childhood immunisation coverage in LMICs. Interventions that will increase and sustain the uptake of vaccines in low- and middle-income countries What is the aim of this review? The aim of this Cochrane review was to evaluate the effect of different strategies to increase the number of children in low-and-middle-income countries who are vaccinated to prevent infection by a disease. Researchers in Cochrane collected and analysed all relevant studies to answer this question and found 14 relevant studies. Do strategies to improve childhood vaccination work? Giving information about vaccination to parents and community members, handing out specially designed vaccination reminder cards, offering vaccines through regular immunisation outreach with and without household incentives (rewards), identifying unvaccinated children through home visits and referring them to health clinics, and integrating vaccination services with other services may lead to more children getting vaccinated. However, offering parents money to vaccinate their children may not improve vaccination uptake. Most of these findings were of low-certainty, and we need more well-conducted research in this area. What was studied in the review? Millions of children in low-and-middle-income countries still die from diseases that could have been prevented with vaccines. There are a number of reasons for this. Governments and others have tried different strategies to increase the number of children vaccinated. What are the main results of the review? The review authors found 14 relevant studies from Georgia, Ghana, Honduras, India, Mali, Mexico, Nicaragua, Nepal, Pakistan, and Zimbabwe. The studies compared people receiving these strategies to people who only received the usual healthcare services. The studies showed the following: Giving information and discussing vaccination with parents and other community members at village meetings or at home probably leads to more children receiving three doses of diphtheria-tetanus-pertussis vaccine (moderate-certainty evidence). Giving information to parents about the importance of vaccinations during visits to health clinics combined with a specially designed participant reminder card and integration of vaccination services with other health services may improve the uptake of three doses of diphtheria-tetanus-pertussis vaccine (low-certainty evidence). Offering money to parents on the condition that they vaccinate their children may make little or no difference to the number of children that are fully vaccinated (low-certainty evidence). Using vaccination outreach teams to offer vaccination to villages on fixed times monthly may improve coverage for full vaccination (low-certainty evidence). How up-to-date is this review? The review authors searched for studies that were published up to May 2016.


This paper presents a framework for automatic service composition which combines a composition graph model with an Ant Colony Optimization metaheuristic to find the optimal composition solution. The composition graph model encodes all the possible composition solutions that satisfy a user request. The graph will be further used as the search space for the ant-inspired selection method targeting the identification of the optimal composition solution. To identify the optimal composition solution we define a fitness function which uses the QoS attributes and the semantic quality as selection criteria. The proposed composition framework has been tested and evaluated on an extended version of the SAWSDL-TC benchmark.


"A Dictionary of Biology" is an up-to-date reference work explains several thousand specialized words that allow for empirical approaches to the biological sciences. It includes more than bare definitions, including information about most of the things named so as to convey their significance in biological discussion. M. Abercrombie, C. J. Hickman, and M. L. Johnson in effect interpret this language as it is actually used, emphasizing customary usage rather than etymology.This comprehensive lexicon includes two thousand entries. Many unfamiliar terms, especially the rarer ones, are defined with the help of other technical terms, perhaps equally unfamiliar. This trick of dictionary-makers could only be avoided by giving a complete account of a large part of biology under each heading. Every biological technical term used in a definition is itself defined elsewhere in the dictionary; though some semi-technical terms, words that can be found in any English dictionary are omitted.The authors use codes throughout the dictionary to help the reader to interpret the use of a word such as whether it is used in relation to plants and animals only, whether the word is an adjective, and when a term is defined elsewhere and adds information to the current definition. The result is an invaluable guide for the layman, the student, and the scholar alike. It presents clear and authoritative explanations of the terms and will remain useful as a quick and concise source of reference.


A combination of zinc (Zn) and antimony (Sb) is considered to be one of the most promising alternatives to commercial carbon materials in Li-ion batteries (LIBs). This study reports a facile and scalable strategy to fabricate ZnSb2O6 nanoparticles, and the as-prepared sample exhibits advanced lithium storage properties in terms of high specific capacity (a reversible capacity of 512.7 mA h g−1 at 0.1 mA cm−2 (100 mA g−1) after 100 cycles), long cycle life and superior rate performance (a reversible capacity of 394.4 mA h g−1 at 0.5 mA cm−2 (500 mA g−1) after 300 cycles). The superior electrochemical performance is attributed to insertion processes and conversion and alloying reactions, as well as pseudocapacitive contribution. Full cells were also fabricated, which exhibited superior electrochemical performances.


How much of the combinatorial structure of a pointed polyhedron is contained in its vertex-facet incidences? Not too much, in general, as we demonstrate by examples. However, one can tell from the incidence data whether the polyhedron is bounded. In the case of a polyhedron that is simple and "simplicial," i.e., a d-dimensional polyhedron that has d facets through each vertex and d vertices on each facet, we derive from the structure of the vertex-facet incidence matrix that the polyhedron is necessarily bounded. In particular, this yields a characterization of those polyhedra that have circulants as vertex-facet incidence matrices.


This paper reports refinement studies on the temporal coupling scheme and time-stepping management of TRACE/S3K, a dynamically coupled code version of the thermal-hydraulics system code TRACE and the 3D core simulator Simulate-3K. The studies were carried out for two test cases, namely a PWR rod ejection accident and the Peach Bottom 2 Turbine Trip Test 2. The solution of the coupled calculation, especially the power peak, proves to be very sensitive to the time-step size with the currently employed conventional operator-splitting. Furthermore, a very small time-step size is necessary to achieve decent accuracy. This degrades the trade-off between accuracy and performance. A simple and computationally cheap implementation of time-projection of power has been shown to be able to improve the convergence of the coupled calculation. This scheme is able to achieve a prescribed accuracy with a larger time-step size.


To improve the quantity and impact of observations used in data assimilation, it is necessary to take into account the full, potentially correlated, observation error statistics. A number of methods for estimating correlated observation errors exist, but a popular method is a diagnostic that makes use of statistical averages of observation‐minus‐background and observation‐minus‐analysis residuals. The accuracy of the results it yields is unknown as the diagnostic is sensitive to the difference between the exact background and exact observation error covariances and those that are chosen for use within the assimilation. It has often been stated in the literature that the results using this diagnostic are only valid when the background and observation error correlation length‐scales are well separated. Here we develop new theory relating to the diagnostic. For observations on a 1D periodic domain we are able to the show the effect of changes in the assumed error statistics used in the assimilation on the estimated observation error covariance matrix. We also provide bounds for the estimated observation error variance and eigenvalues of the estimated observation error correlation matrix. We demonstrate that it is still possible to obtain useful results from the diagnostic when the background and observation error length‐scales are similar. In general, our results suggest that when correlated observation errors are treated as uncorrelated in the assimilation, the diagnostic will underestimate the correlation length‐scale. We support our theoretical results with simple illustrative examples. These results have potential use for interpreting the derived covariances estimated using an operational system.


Abstract Seven clinopyroxene compositions along the join M2LiM1AlTSi2O6 (spodumene) to M2LiM1Fe3+TSi2O6 (ferri-spodumene) were synthesized at 2 GPa, 800 °C under highly oxidizing conditions (using H2O2 fluid) in an end-loaded piston cylinder. In addition, the LiFe3+Si2O6 composition was also synthesized under the intrinsically reducing conditions in a piston cylinder, to check the effect of fO2 on iron speciation. The run products were characterized by field emission scanning electron microscope (FE-SEM), Rietveld refinements on XRPD synchrotron data, and space groups were assigned using SAED-TEM patterns. Run products are composed mainly of lithium clinopyroxene (Li-Cpx), plus minor amounts of hematite (magnetite under reducing condition) and corundum, as independently detected by image analysis (area%) and Rietveld refinements (wt%); moreover, Rietveld results were used to derive cell parameters, M1-site occupancy (Al vs. Fe3+), atomic positions, and average bond lengths of all these Li-Cpx indexed in the C2/c space groups according to SAED-TEM. Li-Cpx with Al and Fe3+ amounts close to 50:50 are actually slightly richer in Al apfu than nominal; the LiFe3+Si2O6 grown under very oxidized and reducing conditions have very similar cell parameters, indicating that fO2 is unable to induce a significant incorporation of Fe2+ in these Li-Cpx. The replacement of Al with Fe3+ induces a linear (%) increase of the cell edges following b > a > c, whereas β is roughly constant and the cell volume increases linearly. Furthermore, the substitution of Al with Fe3+ only weakly affects the T-O average length (<1%), whereas M2-O and M1-O bonds increase linearly of 2.3 and 5.0%, respectively. These new experimental data have been compared with other available on Li-, Na-, and Ca-Cpx, i.e., M2(Li,Na,Ca,Mg,Fe2+)M1(Mg,Fe2+Al,Ni,Cr,Ga,V,Fe3+,Mn,Sc,In)TSi2O6, to model lattice strain, bond lengths, steric effects, and phase transitions behaviors. The replacement of Al with progressively larger cations in LiM3+Si2O6 Cpx (M3+: Ni, Cr, Ga, V, Fe3+, Ti, Sc, and In) results in a linear increase following V > b > a > c, whereas β is roughly constant except for Ti-end-member and P21/c compositions. Lattice strains induced by X, T, and P for Li-Cpx in the C2/c stability field show that when the M1 site is progressively filled with a large cation, ε1 axis (ε1 > ε2 > ε3) increases along b, whereas ε2 and ε3 are nearly parallel to a and at about 30° from c. Conversely, T will provoke a similar enlargement of ε1 and ε2 along b and a edges, respectively, whereas ε3 is again oriented at about 30° from c; the increasing of P will instead shorten all strain tensor components (ε1, ε2, and ε3) with a similar percentage amount; notably, high-P is the only stress that induces a strain component to be almost parallel to c edge. Moreover, finite lattice strains and orientation in C2/c LiMe3+Si2O6 Li-Cpx induced by Me3+: Al-Fe3+, Fe3+-Sc, Sc-In are slightly different, with ε1 invariably lying along b; conversely, Li-Na cation substitution is completely different with the highest and lowest deformations on the ac plane and ε2 along b; ε3 vector is negative and oriented at about 30° from T-chains. The ideal replacement of Al with larger cations up to In in Li-Cpx induces the M1-O, M2-O, and T-O average bond lengths to increase by 10.6, 4.3, and <0.5%. Steric effects in LiM1Me3+Si2O6 and NaM1Me3+Si2O6 Cpx are significant and very similar, whereas several other Me1+ and Me2+ substitutions in Cpx at both the M1 and M2 site, keeping fixed the other site, display less or even the absence of steric effects. Our new data also better elucidate relationships between Li-Cpx composition, symmetry at room and non-ambient conditions and Tc. The aggregate cation radii at the M1 site does not exclusively control the stability of C2/c and P21/c polymorphs; instead valence electrons can profoundly favor the stabilization of a polymorph.


The coloured Petri net formalism has been recently used to analyse and optimise manufacturing systems making use of the state space (SS) analysis. This approach has great potential for scheduling and production planning purposes when it is properly implemented. In this article, an improved version of the algorithm known as the time line search for optimising the makespan of manufacturing models is presented. The algorithm has been developed for the use in a compact SS of coloured Petri net models in order to analyse the highest possible number of manufacturing configurations for the improvement of the makespan of a production system. The proposed algorithm can be used for the developing of decision support tools in manufacturing or operational decision-making.


In this paper we concern ourselves with the problem of obtaining high sequence rate sequential machines; machines which are constructed from realistic devices to operate at an input sequence rate which is independent of the machine complexity. To accomplish this result we have only to show a construction to realize acceptably synchronous devices from badly timed, restricted fan-in and fan-out devices. Once a complete set of synchronous devices is obtained, the results of Arden [1] and Arthurs [2] apply, and we know that any finite state machine has a realization using these devices which accepts input sequence members at a rate that is characteristic of the set of devices, not of the machine. The technique we propose for achieving this result is to produce a lattice of interconnected clock pulse sources called clock pulse propagators (CPP). These devices generate clock pulses which are acceptably synchronized with respect to the outputs of neighboring CPP's but are not required to be in synchronization with some machine-wide standard as in current practice. Once it is established that such a network is possible, techniques already known can be applied in the utilization of the clock pulses to synchronize logic and signals. Part I of the paper concerns the analysis of CPP networks and Part II1 covers the synthesis of sequential machines using CPP networks as clocking sources.


Numerous large clinical trials of cardiovascular risk lowering agents have been conducted in the hope of reducing the excess cardiovascular risk found in patients with diabetes mellitus. However, the relationship between glucose and cardiovascular disease remains complex and various areas require further study. Even in patients with diabetes, an individual's cardiovascular risk is highly variable depending on other clinical characteristics, the assumption that glucose is a continuous risk factor has often been based on weak evidence from relatively short studies, the effect of commonly used cardiovascular risk lowering agents often has unexpected effects on new-onset diabetes and statins have not yet been studied in detail, and whether glucose-lowering therapies actually reduce cardiovascular risk has remained a contentious issue despite the conduct of large clinical trials. Furthermore, the realisation that the combination of diabetes and chronic heart failure, a common complication of coronary disease, carries a particularly poor prognosis suggests that prediction of diabetes in this population may be clinically valuable.

Aims:
I aimed to address the following different, though related, questions regarding glucose and cardiovascular disease:
1. Are anticipated cardiovascular event rates in diabetes endpoint trials actually achieved? Is it possible to easily identify patients with diabetes that are at particular risk of events (information that is crucial to investigators who wish to design clinical trials)?
2. Is fasting glucose concentration independently and convincingly associated with increased risk of cardiovascular events in those without diabetes?
3. Do statins, the most commonly prescribed medications worldwide, have any influence on the risk of developing diabetes?
4. If statins do indeed affect new-onset diabetes, is there any evidence of a dose-dependent effect?
5. How effectively can clinicians predict the development of diabetes in chronic heart failure using commonly recorded clinical information?
6. Does intensive glucose-lowering therapy reduce the risk of cardiovascular events in patients with diabetes?

Methods:
To address these questions three approaches were used, namely (i) systematic review of previously published data from large cardiovascular endpoint trials conducted in patients with diabetes; (ii) analyses of existing datasets from two large clinical trials; (iii) meta-analyses of published and unpublished data from large clinical trials.

Results and interpretation:
1. In a systematic review of 29 trials with 116,790 patients with diabetes, it was apparent that the majority of large cardiovascular endpoint trials conducted in patients with diabetes vastly overestimated the likely cardiovascular event rates in initial power calculations. Introduction of (i) previous history of cardiovascular disease and/or (ii) presence of proteinuria, as binary trial inclusion criteria, provides a simple and effective way to identify patients at high risk, something that is sought after for appropriate clinical trial power calculations.
2. In a population of 6,447 men without diabetes at baseline, impaired fasting glycaemia was not associated with increased risk of cardiovascular events over 15 years. Similarly, when baseline fasting glucose values <7.0mmol/L were split into quintiles, patients in the highest quintile were at similar risk of all vascular endpoints to those in the lowest. By contrast, impaired fasting glycaemia was a powerful risk factor for developing diabetes.
3. A meta-analysis of published and unpublished data from most large placebo- and standard care-controlled statin trials, which included data for 91,140 trial participants without diabetes at baseline, revealed that statin therapy is associated with a 9% higher risk for developing diabetes.
4. A subsequent meta-analysis of unpublished data from five large trials comparing intensive statin therapy with moderate dose therapy found that intensive statin therapy increases the risk of developing diabetes by 12% compared to moderate dosing, in keeping with a dose-dependent effect. While statin therapy remains effective at reducing cardiovascular risk it appears that patients on statin therapy, especially those on intensive regimens, should be considered for diabetes screening.
5. In an analysis of data for 1,620 patients with chronic heart failure and no diabetes at baseline studied for 2.8 years, the strongest predictors of new-onset diabetes were similar to those in the general population. In particular, the combination of HbA1c and body mass index provided a c-statistic of 0.79.
6. In a meta-analysis of published data for 33,040 patients with diabetes who participated in clinical trials comparing intensive glucose-lowering therapy with standard therapy, non-fatal myocardial infarctions were reduced by 17% on intensive therapy but no other cardiovascular endpoints were reduced. Death rates were similar in both groups.

Conclusion:
While diabetes is associated with excess cardiovascular risk, risk varies considerably depending on other risk factors. Glucose is, at best, a weak risk factor in those without diabetes, and glucose-lowering in patients with diabetes has only yielded a modest reduction in non-fatal myocardial infarctions but not other events; by contrast, measures of glycaemia are powerful predictors of new-onset diabetes in patients with and without chronic heart failure. Finally, the relationship between glucose and vascular disease is further complicated by the fact that numerous medications designed to reduce cardiovascular risk appear to have surprising effects on the risk of developing diabetes.


Design verification testing of a new multi-channel antenna and receiver system is a significant and challenging undertaking. This paper describes a unique method for creating an intermediate system test prior to conducting outdoor field testing, or anechoic chamber testing. By substituting a Rotman lens for a multi-channel antenna, a slate of receiver and processing algorithm tests can be performed using multi-static signals in a closed loop setting without the need for an antenna test chamber. The Rotman lens can simulate multiple simultaneous angles of arrival of signals through an antenna array without the effects of clutter, multi-path, and other environmental interference.


Global warming is an ongoing issue, which will require continuous dialogue for years to come among scientists, engineers, policy-makers, investors and the public. This opinion paper argues that the better we understand the issue, the wider the public awareness is and the wiser we will be in planning ahead to minimise or prevent the adverse impacts and save the earth for the long run.


The microwave reflection type sensor using microstrip disk antenna is developed. The
purpose of developing the sensor is to monitor the fresh concrete hardening and to
determine concrete curing point.
The structure of microstrip disk antenna is divided into three parts i.e. radiation
surface, substrate and ground plane. This antenna is developed from polytetra
fluoroethlene (PTFE) or random micro fibre glass substrate (RTD 5880) with dielectric
constant &r = 2.2. The RTD 5880 substrate is selected based on its suitability to operate
at the resonant frequency of 10.7 GHz.
In developing the microstrip antenna, parameters such as radius of disk, resonant
frequency, resistance at resonance, total quality factor, efficiency and bandwidth has to
be taken into consideration. The difference between calculation and experimental
results of the resonant frequency and resistance at resonance is about 5%.
The measurements on fresh concrete and concrete curmg are done in via two
techniques namely contact and non-contact. The samples were prepared based on water to cement ratio 0.5, 0.55 and 0.6. These samples are left to dry in natural condition and
at room temperature for 1, 3, 7, 14 and 28 days.
The results of both techniques showed that reflection from non-contact technique have
readings higher than 100 mW and was more stable compared to contact technique. The
non-touching technique was also easy to manage when applied to fresh concrete
compared to the touching technique.
Studies had shown that the power reflection is inversely proportional with concrete
curing time. Significant power reflection reduction had occurred during the first three
days of curing process. This phenomena was due to accelerated hydration process that
happening inside the concrete during that period. As the curing process resumed,
hydration process slowed down then reaching approximately a constant rate. It is
during this period that the concrete had hardened and gained its strength.
Realising the relationship between microwave, moisture content inside the concrete and
concrete strength, the microwave moisture sensor is developed to measure the water or
moisture content. This approach can be utilized as a technique in non-destructive
testing for concrete to monitor concrete hardening process and predict the anticipated
concrete strength in order to fulfill design requirements


This paper aims to encourage greater reflexivity about the limits of prejudice reduction as a model of social change, particularly when applied to societies characterised by historically entrenched patterns of inequality. We begin by outlining some underlying values and assumptions of this model. We then elaborate how our research on political attitudes in post-apartheid South Africa has led us to question, qualify and sometimes reject those assumptions and move towards a 'contextualist' perspective on the efficacy of different models of social change. We agree that the project of getting us to like one another may be
crucial for producing change in some contexts. In other contexts, however, it is an epiphenomenon that distracts psychologists from the main causes of, and solutions to, problems such as race, class, or gender discrimination. In still others, with an irony that is evidenced increasingly by research, prejudice reduction may actually contribute to the very problem it is designed to resolve. That is, it may diminish the extent to which social injustice is acknowledged, rejected and challenged.


Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we screened patients with PHS and GCPS for GLI3 mutations. The patient group consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We detected 47 pathological mutations (among 60 probands); when these were combined with previously published mutations, two genotype-phenotype correlations were evident. First, GCPS was caused by many types of alterations, including translocations, large deletions, exonic deletions and duplications, small in-frame deletions, and missense, frameshift/nonsense, and splicing mutations. In contrast, PHS was caused only by frameshift/nonsense and splicing mutations. Second, among the frameshift/nonsense mutations, there was a clear genotype-phenotype correlation. Mutations in the first third of the gene (from open reading frame [ORF] nucleotides [nt] 1-1997) caused GCPS, and mutations in the second third of the gene (from ORF nt 1998-3481) caused primarily PHS. Surprisingly, there were 12 mutations in patients with GCPS in the 3' third of the gene (after ORF nt 3481), and no patients with PHS had mutations in this region. These results demonstrate a robust correlation of genotype and phenotype for GLI3 mutations and strongly support the hypothesis that these two allelic disorders have distinct modes of pathogenesis.


Functional genomics technologies have been widely adopted in the biological research of both model and non-model species. An efficient functional annotation of DNA or protein sequences is a major requirement for the successful application of these approaches as functional information on gene products is often the key to the interpretation of experimental results. Therefore, there is an increasing need for bioinformatics resources which are able to cope with large amount of sequence data, produce valuable annotation results and are easily accessible to laboratories where functional geno-mics projects are being undertaken. We present the Blast2GO suite as an integrated and biologist-oriented solution for the high-throughput and automatic functional annotation of DNA or protein sequences based on the Gene Ontology vocabulary. The most outstanding Blast2GO features are: (i) the combination of various annotation strategies and tools controlling type and intensity of annotation, (ii) the numerous graphical features such as the interactive GO-graph visualization for gene-set function profiling or descriptive charts, (iii) the general sequence management features and (iv) high-throughput capabilities. We used the Blast2GO framework to carry out a detailed analysis of annotation behaviour through homology transfer and its impact in functional genomics research. Our aim is to offer biologists useful information to take into account when addressing the task of functionally characterizing their sequence data.


The objective of this research is to unveil the dynamics of technological innovation in planned economies in transition. It is proposed in the thesis that all innovation systems in the world, in fact, consist of certain configurations of market and hierarchy. These systems have always been shifting from one existing market-hierarchy mix to a new one, which is expected to be more conducive to technological innovation and economic development. Current reforms in many planned economies in transition reflect this theoretical proposition. A research framework is constructed to include three main dimensions for the study of a specific innovation system, i.e. Arrangements, Achievements and Actors. China, which has undergone reforms since 1978, is chosen as the empirical basis of the research. The research examined technology policy and technological innovation in China between 1978 to 1988. The thesis starts from Arrangements - R&D System in China and Its Reform. The thesis illustrates reforms in the R&D system in relation to government technology policy. There exist coherent government efforts to promote innovations through various plans, and the planning process incorporates both market and command elements. The institutional structure of Chinese R&D system remains still vertically departmentalised, but horizontal links are created through the market. Secondly, Achievements - Performance of Chinese R&D System is assessed through patterns of technological innovation. Data from National Awards for S&T Progress (1978-1988) are included in a substantial database, which is used to generate patterns of technological innovation and patterns of innovating organisations. These patterns were presented and interpreted in relation to geographical differences, sectoral differences, typological differences, forms of co-operation and the impacts of S&T policy and reform. The third dimension is study on Actors - Innovation in Applied R&D institutes. Through semi-structured interviews and questionnaire survey, internal structure and research management are analysed in the light of ongoing reforms. The reform of R&D funding system greatly affected the way applied R&D institutes operate. Both organisational and individual incentives for innovating are increasingly associated with economic or material benefits. The research suggests there is a need to put reforms in the R&D system into a wider societal and political context. Some general attributes of applied R&D institutes are also discussed in the thesis.