Practical challenges in moving to Open Access: a focus on research funders and universities

At the Berlin7 conference in Paris on 3 December 2009 Knowledge Exchange provided a workshop on the practical challenges to be addressed in moving to Open Access. Presentations where provided by John Houghton and Alma Swan discussing the outcomes of studies on the costs and benefits of Open Access for institutions and the society as a whole. These were followed by presentations by two funding agencies on the results of financing publication costs both at an institutional and national level in Germany. Also the results of the Springer deal in the Netherlands where presented. The third section was focused on the results of implementing mandates both by funding bodies and institutions.

Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in one of several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 90% of cases are caused by 21-hydroxylase deficiency, and the severity of the resulting clinical symptoms varies according to the level of 21-hydroxylase activity. 21-Hydroxylase deficiency is usually caused by mutations in the CYP21A2 gene, which is located on the RCCX module, a chromosomal region highly prone to genetic recombination events that can result in a wide variety of complex rearrangements, such as gene duplications, gross deletions and gene conversions of variable extensions. Molecular genotyping of CYP21A2 and the RCCX module has proved useful for a more accurate diagnosis of the disease, and prenatal diagnosis. This article summarises the clinical features of 21-hydroxylase deficiency, explains current understanding of the disease at the molecular level, and highlights recent developments, particularly in diagnosis.

Focus giurisprudenziale. Sentenza 8/09/2015, Grande Camera della Corte di Lussemburgo, c.d. caso Taricco

Con sentenza Sez. 3 Num. 2210 Anno 2016 - Relatore: Scarcella Alessio - Data Udienza: 17/09/2015, la Cassazione, in una ipotesi di cd. “grave frode IVA”, ha disapplicato la specifica norma di cui all'ultima parte del terzo comma dell'art. 160 ed al secondo comma dell'art. 161 cod. pen. a seguito della sentenza della Corte di Giustizia U.E. dell'8 settembre 2015 (Grande Sezione), Taricco, causa C-105/14.

Achieving a strategic sales focus: contemporary issues and future challenges.

The main aim of this book is to consider how the sales function informs business strategy. Although there are a number of books available that address how to manage the sales team tactically, this text addresses how sales can help organizations to become more customer oriented. Many organizations are facing escalating costs and a growth in customer power, which makes it necessary to allocate resources more strategically. The sales function can provide critical customer and market knowledge to help inform both innovation and marketing. Sales are responsible for building customer knowledge, networking both internally and externally to help create additional customer value, as well as the more traditional role of managing customer relationships and selling. The text considers how sales organizations are responding to increasing competition, more demanding customers and a more complex selling environment. We identify many of the challenges facing organisations today and offers discussions of some of the possible solutions. This book considers the changing nature of sales and how activities can be aligned within the organization, as well as marketing sensing, creating customer focus and the role of sales leadership. The text will include illustrations (short case studies) provided by a range of successful organizations operating in a number of industries. Sales and senior management play an important role in ensuring that the sales teams' activities are aligned to business strategy and in creating an environment to allow salespeople to be more successful in developing new business opportunities and building long-term profitable business relationships. One of the objectives of this book is to consider how conventional thinking has changed in the last five years and integrate it with examples from sales practice to provide a more complete picture of the role of sales within the modern organization.

Formal and philological inquiries into the nature of interrogatives, indefinites, disjunction, and focus in Sinhala and other languages

In this thesis I examine a variety of linguistic elements which involve ``alternative'' semantic values---a class arguably including focus, interrogatives, indefinites, and disjunctions---and the connections between these elements. This study focusses on the analysis of such elements in Sinhala, with comparison to Malayalam, Tlingit, and Japanese. The central part of the study concerns the proper syntactic and semantic analysis of Q[uestion]-particles (including Sinhala "da", Malayalam "-oo", Japanese "ka"), which, in many languages, appear not only in interrogatives, but also in the formation of indefinites, disjunctions, and relative clauses. This set of contexts is syntactically-heterogeneous, and so syntax does not offer an explanation for the appearance of Q-particles in this particular set of environments. I propose that these contexts can be united in terms of semantics, as all involving some element which denotes a set of ``alternatives''. Both wh-words and disjunctions can be analysed as creating Hamblin-type sets of ``alternatives''. Q-particles can be treated as uniformly denoting variables over choice functions which apply to the aforementioned Hamblin-type sets, thus ``restoring'' the derivation to normal Montagovian semantics. The treatment of Q-particles as uniformly denoting variables over choice functions provides an explanation for why these particles appear in just this set of contexts: they all include an element with Hamblin-type semantics. However, we also find variation in the use of Q-particles; including, in some languages, the appearance of multiple morphologically-distinct Q-particles in different syntactic contexts. Such variation can be handled largely by positing that Q-particles may vary in their formal syntactic feature specifications, determining which syntactic contexts they are licensed in. The unified analysis of Q-particles as denoting variables over choice functions also raises various questions about the proper analysis of interrogatives, indefinites, and disjunctions, including issues concerning the nature of the semantics of wh-words and the syntactic structure of disjunction. As well, I observe that indefinites involving Q-particles have a crosslinguistic tendency to be epistemic indefinites, i.e. indefinites which explicitly signal ignorance of details regarding who or what satisfies the existential claim. I provide an account of such indefinites which draws on the analysis of Q-particles as variables over choice functions. These pragmatic ``signals of ignorance'' (which I argue to be presuppositions) also have a further role to play in determining the distribution of Q-particles in disjunctions. The final section of this study investigates the historical development of focus constructions and Q-particles in Sinhala. This diachronic study allows us not only to observe the origin and development of such elements, but also serves to delimit the range of possible synchronic analyses, thus providing us with further insights into the formal syntactic and semantic properties of Q-particles. This study highlights both the importance of considering various components of the grammar (e.g. syntax, semantics, pragmatics, morphology) and the use of philology in developing plausible formal analyses of complex linguistic phenomena such as the crosslinguistic distribution of Q-particles.

focus on fruits : 10 tips to help you eat more fruits

Eating fruit provides health benefits. People who eat more vegetables and fruits as part of an overall healthy diet are likely to have a reduced risk of some chronic diseases. Fruits provide nutrients vital for health, such as potassium, dietary fiber, vitamin C, and folate (folic acid). Most fruits are naturally low in fat, sodium, and calories. None have cholesterol. Any fruit or 100% fruit juice counts as a part of the Fruit Group. Fruits may be fresh, canned, frozen, or dried, and may be whole, cut-up, or pureed.

Contribution of plant phytochemicals to organic homeostasis: focus on the aging process and opportunistic infections

Aging process is conceived as a normal stage during human life cycle, but it is also considered a hot topic among scientists and medical community. Alarming rates of premature aging and oxidative stress-related diseases have increasingly affect human individuals. Stress, pollution and exposition to chemical substances are considered the main triggering factors for those conditions; in addition, they also suppress the immune system and, therefore, improve organic vulnerability and occurrence of opportunistic infections [I]. Apart from the associated morbidity and mortality, the increasing rates of antimicrobial resistance improve the severity of the clinical conditions [2]. Botanical preparations possess a multitude of bioactive properties, namely acting as antimicrobials, antioxidants, and homeostasis modulators. Thus, upcoming alternatives, mainly based in plant phytochemicals, are necessary to improve the wellbeing as also life expectancy of individuals. The present study aims to evaluate and to compare both antioxidant and antimicrobial properties of plant extracts rich in phenolic compounds. Among the tested plants, Glycyrrhiza glabra L. (licorice) evidenced the most pronounced free radicals scavenging and antimicrobial effects, followed by Salvia officina/is L. (sage), Thymus vulgaris L. (thyme) and Origanum vulgare L. (oregano). Eucalyptus globulus Labill. (blue gum) and Juglans regia L. (walnut) also showed a high effect, while Pterospartum tridentatum (L.) Willk. (carqueja) and Rubus ulmifolius Schott (elm leaf blackberry) displayed moderate effects, and lastly, Tabebuia impetigirwsa (Mart. ex DC) Standley (pau d'arco), Foeniculum vulgare Miller (fennel), Rosa canina L. (rose hips) and Matricaria recutita L. (chamomile) gave only slight effects. In general, the most pronounced bioactivities were observed in the plant preparations (infusion>decoction>hydromethanolic extract) with higher levels of phenolic compounds (both flavonoids and phenolic acids). The observed synergisms between the phenolic compounds present in the extracts highlight the use of phytochemicals as future health promoters. However, further studies are necessary to understand the effective mode of action of individual phenolic constituents as also the existence of polyvalence relationships between them.

Knowing What to Do: School Focus, Teacher Morale, and Teacher Turnover

This study explored how schools’ focus – the collective perception among teachers of clarity and consistency regarding school goals, expectations, and priorities – related to schoolwide morale and school turnover rates. I examined the hypothesis that focus attenuates the deleterious effects of student misconduct on teacher morale and the contributory role of student misconduct leading to teacher turnover. In addition, I examined climate strength regarding perceptions school focus as an indicator of focus itself, as well a potential moderating effect of climate strength on the magnitude of school focus-school morale and school focus-turnover relationships. Data from a national sample of middle and high schools (N schools = 348, N teachers = 11,376) were analyzed using school-level multiple regression models. Schools with higher focus had significantly higher morale, independent of related perceptions of administrative leadership. No significant relationship was found between school focus and school turnover rates. The hypothesized moderating effect of focus on student misconduct and morale was not supported, though there was a significant indication that focus attenuated the positive relationship between student misconduct and turnover. Climate strength of school focus ratings significantly correlated with focus scores, but did not moderate relationships between focus and predicted outcomes. Findings suggest that school-level focus does represent a characteristic of schools that has a meaningful positive relationship with teacher morale but do not necessarily clarify how that relationship manifests in schools or if that relationship presents an avenue for intervention.

Focus on sulfur count rates along marine sediment cores acquired by XRF Core Scanner

The aim of this study is to investigate the information provided by sulfur count rates obtained by X-ray fluorescence core scanner (XRF-CS) along sedimentary records. The analysis of two marine sediment cores from the Niger Delta margin shows that XRF-CS sulfur count rates obtained at the surface of split core sections with XRF-CS correlate with both direct quantitative pyrite concentrations, as inferred from X-ray powder diffraction (XRD) and sulfur determination by wavelength dispersive X-ray fluorescence (WD-XRF) spectrometry, and total dissolved sulfide (TDS) contents in the sediment pore water. These findings demonstrate the potential of XRF-CS for providing continuous profiles of pyrite distribution along split sections of sediment cores. The potential of XRF-CS to detect TDS pore water enrichments in marine sediment records, even a long time after sediment recovery, will be further discussed.

Development of a brand and implementation of a promotional campaign for the products of Ria de Aveiro focus on brand identity and brand positioning

Directed internship

A systems approach to cardiovascular health and disease with a focus on aortic wave dynamics

Cardiovascular diseases (CVDs) have reached an epidemic proportion in the US and worldwide with serious consequences in terms of human suffering and economic impact. More than one third of American adults are suffering from CVDs. The total direct and indirect costs of CVDs are more than $500 billion per year. Therefore, there is an urgent need to develop noninvasive diagnostics methods, to design minimally invasive assist devices, and to develop economical and easy-to-use monitoring systems for cardiovascular diseases. In order to achieve these goals, it is necessary to gain a better understanding of the subsystems that constitute the cardiovascular system. The aorta is one of these subsystems whose role in cardiovascular functioning has been underestimated. Traditionally, the aorta and its branches have been viewed as resistive conduits connected to an active pump (left ventricle of the heart). However, this perception fails to explain many observed physiological results. My goal in this thesis is to demonstrate the subtle but important role of the aorta as a system, with focus on the wave dynamics in the aorta.

The operation of a healthy heart is based on an optimized balance between its pumping characteristics and the hemodynamics of the aorta and vascular branches. The delicate balance between the aorta and heart can be impaired due to aging, smoking, or disease. The heart generates pulsatile flow that produces pressure and flow waves as it enters into the compliant aorta. These aortic waves propagate and reflect from reflection sites (bifurcations and tapering). They can act constructively and assist the blood circulation. However, they may act destructively, promoting diseases or initiating sudden cardiac death. These waves also carry information about the diseases of the heart, vascular disease, and coupling of heart and aorta. In order to elucidate the role of the aorta as a dynamic system, the interplay between the dominant wave dynamic parameters is investigated in this study. These parameters are heart rate, aortic compliance (wave speed), and locations of reflection sites. Both computational and experimental approaches have been used in this research. In some cases, the results are further explained using theoretical models.

The main findings of this study are as follows: (i) developing a physiologically realistic outflow boundary condition for blood flow modeling in a compliant vasculature; (ii) demonstrating that pulse pressure as a single index cannot predict the true level of pulsatile workload on the left ventricle; (iii) proving that there is an optimum heart rate in which the pulsatile workload of the heart is minimized and that the optimum heart rate shifts to a higher value as aortic rigidity increases; (iv) introducing a simple bio-inspired device for correction and optimization of aortic wave reflection that reduces the workload on the heart; (v) deriving a non-dimensional number that can predict the optimum wave dynamic state in a mammalian cardiovascular system; (vi) demonstrating that waves can create a pumping effect in the aorta; (vii) introducing a system parameter and a new medical index, Intrinsic Frequency, that can be used for noninvasive diagnosis of heart and vascular diseases; and (viii) proposing a new medical hypothesis for sudden cardiac death in young athletes.

The mitogenome of Onchocerca volvulus from the Brazilian Amazonia focus

We report here the first complete mitochondria genome of Onchocerca volvulus from a focus outside of Africa. An O. volvulus mitogenome from the Brazilian Amazonia focus was obtained using a combination of highthroughput and Sanger sequencing technologies. Comparisons made between this mitochondrial genome and publicly available mitochondrial sequences identified 46 variant nucleotide positions and suggested that our Brazilian mitogenome is more closely related to Cameroon-origin mitochondria than West African-origin mitochondria. As well as providing insights into the origins of Latin American onchocerciasis, the Brazilian Amazonia focus mitogenome may also have value as an epidemiological resource.

Biochemical studies of postsynaptic density signaling proteins with a focus on synaptic GTPase activating protein and PDZ domains

Memory storage in the brain involves adjustment of the strength of existing synapses and formation of new neural networks. A key process underlying memory formation is synaptic plasticity, the ability of excitatory synapses to strengthen or weaken their connections in response to patterns of activity between their connected neurons. Synaptic plasticity is governed by the precise pattern of Ca²⁺ influx through postsynaptic N-methyl-D-aspartate-type glutamate receptors (NMDARs), which can lead to the activation of the small GTPases Ras and Rap. Differential activation of Ras and Rap acts to modulate synaptic strength by promoting the insertion or removal of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptors (AMPARs) from the synapse. Synaptic GTPase activating protein (synGAP) regulates AMPAR levels by catalyzing the inactivation of GTP-bound (active) Ras or Rap. synGAP is positioned in close proximity to the cytoplasmic tail regions of the NMDAR through its association with the PDZ domains of PSD-95. SynGAP’s activity is regulated by the prominent postsynaptic protein kinase, Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5), a known binding partner of CaMKII. Modulation of synGAP’s activity by phosphorylation may alter the ratio of active Ras to Rap in spines, thus pushing the spine towards the insertion or removal of AMPARs, subsequently strengthening or weakening the synapse. To date, all biochemical studies of the regulation of synGAP activity by protein kinases have utilized impure preparations of membrane bound synGAP. Here we have clarified the effects of phosphorylation of synGAP on its Ras and Rap GAP activities by preparing and utilizing purified, soluble recombinant synGAP, Ras, Rap, CaMKII, CDK5, PLK2, and CaM. Using mass spectrometry, we have confirmed the presence of previously identified CaMKII and CDK5 sites in synGAP, and have identified novel sites of phosphorylation by CaMKII, CDK5, and PLK2. We have shown that the net effect of phosphorylation of synGAP by CaMKII, CDK5, and PLK2 is an increase in its GAP activity toward HRas and Rap1. In contrast, there is no effect on its GAP activity toward Rap2. Additionally, by assaying the GAP activity of phosphomimetic synGAP mutants, we have been able to hypothesize the effects of CDK5 phosphorylation at specific sites in synGAP. In the course of this work, we also found, unexpectedly, that synGAP is itself a Ca²⁺/CaM binding protein. While Ca²⁺/CaM binding does not directly affect synGAP activity, it causes a conformational change in synGAP that increases the rate of its phosphorylation and exposes additional phosphorylation sites that are inaccessible in the absence of Ca²⁺/CaM.

The postsynaptic density (PSD) is an electron-dense region in excitatory postsynaptic neurons that contains a high concentration of glutamate receptors, cytoskeletal proteins, and associated signaling enzymes. Within the PSD, three major classes of scaffolding molecules function to organize signaling enzymes and glutamate receptors. PDZ domains present in the Shank and PSD-95 scaffolds families serve to physically link AMPARs and NMDARs to signaling molecules in the PSD. Because of the specificity and high affinity of PDZ domains for their ligands, I reasoned that these interacting pairs could provide the core components of an affinity chromatography system, including affinity resins, affinity tags, and elution agents. I show that affinity columns containing the PDZ domains of PSD-95 can be used to purify active PDZ domain-binding proteins to very high purity in a single step. Five heterologously expressed neuronal proteins containing endogenous PDZ domain ligands (NMDAR GluN2B subunit Tail, synGAP, neuronal nitric oxide synthase PDZ domain, cysteine rich interactor of PDZ three and cypin) were purified using PDZ domain resin, with synthetic peptides having the sequences of cognate PDZ domain ligands used as elution agents. I also show that conjugation of PDZ domain-related affinity tags to Proteins Of Interest (POIs) that do not contain endogenous PDZ domains or ligands does not alter protein activity and enables purification of the POIs on PDZ domain-related affinity resins.