NGR Tumor-Homing Peptides : Structural Requirements for Effective APN (CD13) Targeting

Acknowledgements We thank The Development Trust, University of Aberdeen, for financial support and a fellowship to M.P.

Last-step enzymatic [18F]-fluorination of cysteine-tethered RGD peptides using modified Barbas linkers

Acknowledgements We thank the Engineering and Physical Sciences Research Council, UK, for a research grant. Funded by Engineering and Physical Sciences Research Council, UK

Changes in [18F]Fluoro-2-deoxy-D-glucose incorporation induced by doxorubicin and anti-HER antibodies by breast cancer cells modulated by co-treatment with metformin and its effects on intracellular signalling

Peer reviewed

A two-step fluorinase enzyme mediated 18F labelling of an RGD peptide for positron emission tomography

Peer reviewed

Resist-substrate interface tailoring for generating high density arrays of Ge and Bi2Se3 nanowires by electron beam lithography

The authors report a chemical process to remove the native oxide on Ge and Bi2Se3 crystals, thus facilitating high-resolution electron beam lithography (EBL) on their surfaces using a hydrogen silsesquioxane (HSQ) resist. HSQ offers the highest resolution of all the commercially available EBL resists. However, aqueous HSQ developers such as NaOH and tetramethylammonium hydroxide have thus far prevented the fabrication of high-resolution structures via the direct application of HSQ to Ge and Bi2Se3, due to the solubility of components of their respective native oxides in these strong aqueous bases. Here we provide a route to the generation of ordered, high-resolution, high-density Ge and Bi2Se3 nanostructures with potential applications in microelectronics, thermoelectric, and photonics devices.                         

Scaling limits of a model for selection at two scales

The dynamics of a population undergoing selection is a central topic in evolutionary biology. This question is particularly intriguing in the case where selective forces act in opposing directions at two population scales. For example, a fast-replicating virus strain outcompetes slower-replicating strains at the within-host scale. However, if the fast-replicating strain causes host morbidity and is less frequently transmitted, it can be outcompeted by slower-replicating strains at the between-host scale. Here we consider a stochastic ball-and-urn process which models this type of phenomenon. We prove the weak convergence of this process under two natural scalings. The first scaling leads to a deterministic nonlinear integro-partial differential equation on the interval $[0,1]$ with dependence on a single parameter, $\lambda$. We show that the fixed points of this differential equation are Beta distributions and that their stability depends on $\lambda$ and the behavior of the initial data around $1$. The second scaling leads to a measure-valued Fleming-Viot process, an infinite dimensional stochastic process that is frequently associated with a population genetics.

Regulation of tail-anchored ubiquitin conjugating enzymes that are localised to the endoplasmic reticulum

The vast majority of secreted and membrane proteins are translated and folded at the endoplasmic reticulum (ER), where a sophisticated quality control mechanism ensures that only correctly folded proteins exit the ER and traffic to their final destinations. On the other hand, proteins that persistently misfold are eliminated through a process known as ER associated degradation (ERAD). This involves retrotranslocation of the misfolded protein through the ER membrane, and ubiquitination in advance of degradation by cytosolic proteasomes. The process of ERAD is best described in yeast where ubiquitin conjugating enzymes Ubc6p and Ubc7p function with a limited number of E3 ubiquitin ligases to ubiquitinate misfolded proteins. Interestingly, although the mechanistic principles of ERAD have been conserved through evolution, there is increasing evidence that homologues of the yeast enzymes have gained divergent roles and novel regulatory functions in higher eukaryotes, meaning that the process in humans is more complex and involves a larger repertoire of participating proteins. Two homologues of Ubc6p have been described in humans, and have been named as Ubc6 (UBE2J2) and Ubc6e (UBE2J1). However, little work has been done on these enzymes and thus our main objective of this study was to progress the functional characterisation of these ERAD E2 conjugating enzymes. Our studies included a detailed analysis of conditions whereby these proteins are stabilised and degraded. We’ve also explored the different molecular signalling pathways that induced changes on their steady state protein levels. Furthermore, Ubc6e has a phosphorylatable serine residue at position 184. Thus, our studies also involved delineating the signalling kinases that phosphorylate Ubc6e and examining its function in ERAD. Our studies confirm that the E2 Ubc enzymes are regulated posttranslationally and may have important implications in the regulation of ERAD.

Conjuring Canadas: Historians and the Quest to Define a Canadian Nation and its Past, 1920-1967

This dissertation examines the various ways in which Canadian historical researchers confronted the “Canada question,” namely the challenge of defining the basis of a unified national community. In doing so, it follows the scholarship and activities of a network of historians and intellectuals centred on the Canadian Historical Review, a quarterly publication founded in 1920. This study examines their scholarship with the aim of identifying not only the various solutions they posed to the problem, but also the philosophical undercurrents that informed their reasoning in the process. It also traces the rise of a rival network in the Revue d’histoire de l’Amérique française, a French-language historical publication founded in 1947 that by its very existence posed a significant challenge to the definition of the nation at the core of the Canadian Historical Review. This dissertation argues that the network bound together by the Review was engaged in a hegemonic project, one that sought to present a particular definition of Canada through a historical narrative that rested upon a liberal logic. Yet the greatest sustained challenge they faced in this endeavour emerged from Francophone historical scholars, who, although proposing vastly different Canadas to those imagined at the Canadian Historical Review, came under the sway of a number of liberal currents of thought as well. A detailed summary of the key traits of these liberal Canadas is found in the conclusion.

Psychological factors associated with self-management among adolescents with Type 1 diabetes: a review

This review aims to synthesise the literature examining the psychosocial variables related to self-management (insulin adherence, non-adherence and administration, blood sugar monitoring, dietary behaviour, exercise behaviour) in adolescents with type 1 diabetes.
A systematic search of three electronic databases was carried out and, after the application of eligibility criteria, 21 articles were assessed for quality prior to data extraction. Numerous psychological factors were found to be associated with self-management; however, correlations were typically small to moderate. The strongest associations were found between social anxiety and diet (among males); greater intrinsic motivation, conscientiousness and diet; and extraversion and exercise.

Barriers of sentiment : Identity -formation, -regulation and subjectification in preschools

This thesis studies preschool socialization in terms of identity -formation, -regulation, and subjectification. Both the methodology and theoretical backdrop draws on Critical Management Studies, and the contribution to research comes from studying a subject otherwise non-prioritized. I have performed a qualitative study entailing interviews of pedagogues and preschool chiefs working within the same company in the Stockholm region. The study indicate that preschool discourse emphasize the importance of social competences and rituals, and moreover that the institution also accentuates its role in setting the proper ‘preconditions’. Furthermore, the study demonstrates how pedagogues – using mechanisms such as individual discourses, the children’s agency, and the milieu – try to form individuals who are: social, independent, self-reliant, have a strong ‘self’, joyful towards learning, and ‘can do it themselves’. I make a liaison between the aforementioned ideals and certain trends discussed by managerial literature, like for instance currents towards: self-management, neo-normative control, self-entrepreneurial attitudes, ambidextrousness, and the ‘principle of potential’ (Costea et al., 2012; Fleming & Study, 2009; Holmqvist & Spicer, 2013; Maravelias, 2011; Pongratz & Voß, 2003). Finally the thesis concludes by firstly underscoring that the Discourse of for example ‘joyful learning’ and ‘independency’ in preschools tend to demolish physical modes of control in place of psychological ones; and secondly, by discussing historical practices, the thesis brings attention to a shift from safekeeping children to preparing them for industrial, urbanistic, and capitalistic social existence. 

Next-Generation Sequencing of Hereditary Hemochromatosis-Related Genes: Novel Likely Pathogenic Variants Found in the Portuguese Population

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1G>C)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5'-UTR of HAMP gene (c.-25G>A). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.

Give and You Shall Receive: Investing in the Careers of Women Professionals

Purpose – The purpose of this paper is to explore what organizations can do to facilitate the retention and advancement of women professionals into top leadership positions. A social exchange framework is applied to examine ways organizations can signal support for and investment in the careers of women professionals, and ultimately the long-term work relationship. Design/methodology/approach – This paper employed a qualitative methodology; specifically, semi-structured interviews with 20 women executives, in primarily the US hospitality industry, were conducted. The interviews were recorded, transcribed, and content analyzed. Findings – Organizations are likely to strengthen the retention of their female professionals if they signal support through purposeful, long-term career development that provides a sightline to the top, and ultimately creates more female role models in senior-level positions. Organizations can also signal support through offering autonomy over how work is completed, and designing infrastructures of support to sustain professionals during mid-career stages. Findings are used to present a work-exchange model of career development. Research limitations/implications – This research is an exploratory study that is limited in its scope and generalizability. Practical implications – The proposed work-exchange model can be used to comprehensively structures initiatives that would signal organizational support to – and long-term investment in – female professionals and enable them to develop their career paths within their organizations. Originality/value – Through offering a work-exchange model of career development, this paper identifies components of organizational support from a careers perspective, and highlights the factors that could potentially contribute to long-term growth and retention of women professional

Sesamoids of the metatarsophalangeal joint of the big toe: a sistematic review

Abstract: The first metatarsal sesamoid bones are not always taken into consideration when making a diagnosis, in pathologies that affect the region of the first metatarsal head. This is due to the insufficient knowledge of all the pathologies that can affect the sesamoids and the relative little incidence that they have. With the increment of sports activities, in particular the running, increasingly affects of the symptoms concerning this region are observed. Methods: A literature search was performed in 5 databases (Medline, PubMed, Scopus, Cochrane Library and BUCEA). The terms included in the search were: sesamoids, anatomy, biomechanics, sesamoids review and sesamoids pathology. In the initial search articles with no more than 10 years, only humans and revision texts are considered. Results: 24 articles were selected and include different pathologies with diagnosis using imaging tests and treatments, both conservative and surgical; as well as aspects from the biomechanics of the metatarsal-sesamoid joint. Conclusion: Sesamoids due of his anatomy, topography and function can be involved in a lot of pathologies; with similar signs and symptoms that can confuse the podiatry when he has to make a correct diagnosis or treatment.

Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015 : a systematic analysis for the Global Burden of Disease Study 2015

As doenças infeciosas e a história dos antibióticos

O presente trabalho aborda a história das principais doenças que assolaram a Europa desde a época medieval à época contemporânea, incluindo a referência às origens, às manifestações e ao tratamento. É igualmente abordada a questão do isolamento das substâncias ativas nas plantas medicinais e farmacológicas até à descoberta do primeiro antibiótico identificado pelo homem – a penicilina, por Alexandre Fleming – e a sua enorme importância no combate aos micro-organismos.