Some close-in gaseous exoplanets are nearly in Roche lobe contact, and previous studies show that tidal decay can drive hot Jupiters into contact during the main sequence of their host stars. Improving on a previous model, we present a revised model for mass transfer in a semidetached binary system that incorporates an extended atmosphere around the donor and allows for an arbitrary mass ratio. We apply this new formalism to hypothetical, confirmed, and candidate planetary systems to estimate mass-loss rates and compare with models of evaporative mass loss. Overflow may be significant for hot Neptunes out to periods of similar to 2 days, while for hot Jupiters, it may only be important inward of 0.5 days. We find that CoRoT-24 b may be losing mass at a rate of more than an Earth mass in a gigayear. The hot Jupiter WASP-12 b may lose an Earth mass in a megayear, while the putative planet PTFO8-8695 orbiting a T Tauri star might shed its atmosphere in a few megayears. We point out that the orbital expansion that can accompany mass transfer may be less effective than previously considered because the gas accreted by the host star removes some of the angular momentum from the orbit, but simple scaling arguments suggest that the Roche lobe overflow might remain stable. Consequently, the recently discovered small planets in ultrashort periods (< 1 day) may not be the remnants of hot Jupiters/Neptunes. The new model presented here has been incorporated into Modules for Experiments in Stellar Astrophysics (MESA).

This thesis explores the role mutualist pollinators and their symbionts play in the genetic structuring and speciation of their host plants along an elevational gradient in Papua New Guinea. Using the fig and fig-wasp mutualism as a model system, we employed high-throughput sequencing techniques to explore fine-scale population genomics of both fig and wasps along their elevational range. We found there to be clear lowland and highland clustering of tree populations along the gradient, often with a mid-elevation contact zone. In the case of the pollinating wasps, we retrieved the same clustering except in this case, the genetic difference between clusters was high enough as to consider them as separate species. This result supports evidence from other studies challenging the cospeciation paradigm of one wasp species per fig species. In addition, we explore ecological traits which may promote, or at least, maintain, reproductive isolation between fig (sub)species along with behavioural preference tests from pollinating wasps. In order to further investigate the mechanisms promoting wasp speciation along the gradient, we describe Wolbachia infection status as well as strain type. Wolbachia-induced cytoplasmic incompatibility (CI) is often invoked as a possible speciation agent since it can rapidly provoke and maintain reproductive isolation between otherwise freely interbreeding insect populations. Finally, we explore non-pollinating fig wasp (NPFW) diversity along the gradient for a subset of our focal species. Our study reveals that there is a tight relationship between NPFW diversity and host species, and a mid-elevation peak.

Regulation of the actin cytoskeleton is key to cellular function and underlies processes including cell migration, mitosis and endocytosis. Motile cells send out dynamic actin protrusions that enable them to sense and interact with their environment, as well as generating physical forces. Linking of the actin cytoskeleton to the cell membrane is essential for the formation of these protrusions. The proteins that are thought to fulfil such a role have a membrane interacting domain (such as the PH domain in lamellipodin, or I-BAR protein in IRSp53) and a domain which interacts with actin regulatory proteins (such as the SH3 domain of IRSp53, which binds Ena and VASP). I investigated the contribution of the F-BAR protein Toca-1 in linking actin polymerisation to membranes, by characterising a new protein-protein interaction and the interaction of Toca-1 with giant unilamellar vesicles. FBP17, a homologue of Toca-1, can oligomerise to form 2D flat lattices and 3D tubules on membranes. Proteins of the Toca-1 family have previously been implicated in actin polymerisation in cell-free systems and during endocytosis. However, there is emerging evidence that Toca-1 family proteins could also be involved in the formation of outward facing protrusions, lamellipodia and filopodia. In an in vitro system that recapitulates the formation of filopodia-like structures (FLS) on supported lipid bilayers, Toca-1 is recruited early, suggesting a Toca-1 scaffolding mechanism could precede the recruitment of other actin regulators. One prediction of this model is that Toca-1 would bind proteins previously implicated in filopodia formation, such as formins. I found that extracts depleted of Toca-1 binding partners no longer forms filopodia-like structures and subsequently optimised pull-down assays to identify Toca-1 binding partners by mass-spectrometry. I identified four formins, Diaph1, Diaph3, FHOD1 and INF2, and as well as the actin elongation factors and filopodia proteins, Ena and VASP. I further characterised these interactions and found that Toca-1 binds Ena and VASP via its SH3 domain. The interaction is direct and is strongly reduced if the proline-rich region in Ena is deleted. VASP was still able to bind without its proline rich region, suggesting there could be additional binding sites. I discovered that the binding of Ena and VASP was dependent on the clustering state of Toca-1, whilst the binding of the previously identified Toca-1 binding partner N-WASP was not. This further supports the importance of Toca-1 oligomerisation in actin polymerisation. I tested these interactions in the FLS system and found that increasing Toca-1 concentration leads to increased recruitment of N-WASP, as well as the novel binding partner Ena to the structures, whereas an increase in VASP was not observed. SH3-domain mediated interactions are required for Toca-1 recruitment to FLS, suggesting that its membrane and protein binding activities act cooperatively. I showed that unlike N-WASP, which promotes the formation of branched actin, Ena and VASP are not required for actin polymerisation on supported lipid bilayers, suggesting that they are redundant with other factors in the elongation step of FLS formation. Ena and VASP are known to be important for the formation of neuronal filopodia and so I began to further test the role of these interactions in a cellular context using a neuronal cell culture system. As well as recruiting protein binding partners, F-BAR family proteins are implicated in stabilising lipid microdomains and can induce the clustering of phosphoinositides. I investigated the role of Toca-1 in actin polymerisation on PI(4,5)P2-rich giant unilamellar vesicles (GUVs). Actin-rich tails formed on the GUVs only when excess Toca-1 was supplemented into the extracts, and I propose that this is due to lipid organisation by Toca-1. In summary, my work suggests a model in which Toca-1 clusters, stabilises the membrane lipids and recruits regulators of actin polymerisation, such as Ena. This mechanism could be used to link actin polymerisation to the membrane in cellular protrusions, such as filopodia.

Anaplastic Lymphoma Kinase (ALK) is a Receptor Tyrosine Kinase (RTK) and an oncogene associated with several human diseases, but its normal function in humans and other vertebrates is unclear. Drosophila melanogaster has an ALK homolog, demonstrating that the RTK has been conserved throughout evolution. This makes Drosophila a suitable model organism for studying not only Drosophila ALK function, but also to study mammalian forms of ALK. In Drosophila the ligand Jeb activates ALK, initiating signaling crucial for visceral mesoderm development. The activating ligand for mammalian ALK is unclear, and for this reason Drosophila was employed in a cross-species approach to investigate whether Drosophila Jeb can activate mouse ALK. Jeb is unable to activate mouse ALK, and therefore mouse ALK is unable to substitute for and rescue the Drosophila ALK mutant phenotype. This suggests that there has been significant evolution in the ALK-ligand relationship between the mouse and Drosophila. In humans ALK has recently been shown to be involved in the development of neuroblastoma, a cancer tumor in children. I have developed a Drosophila model for examining human gain of function ALK mutants found in neuroblastoma patients. The various ALK variants have acquired point mutations in the kinase domain that have been predicted to activate the RTK in a constitutive and ligand independent manner. When expressed in the fly eye, active human ALK mutants result in a rough eye phenotype, while inactive wild type ALK does not, due to the lack of an activating ligand in the fly. In this way  several of the ALK mutations identified in neuroblastoma patients could be confirmed to be activated in a ligand independent manner. Moreover, a novel ALK mutant; ALKF1174S, was discovered in a neuroblastoma patient and was in the Drosophila model shown to be a gain of function mutation, and a previously predicted gain of function mutation; ALKI1250T, was shown to be a kinase dead mutation. This fly model can also be used for testing ALK selective inhibitors, for identifying activating ligands for human ALK and for identifying conserved components of the ALK signaling pathway. Gut musculature development in Drosophila is dependent on ALK signaling, while somatic muscle development is not. Proteins of the Wasp-Scar signaling network regulate Arp2/3-complex mediated actin polymerization, and I have investigated their function in visceral and somatic muscle fusion. I found that Verprolin and other members of this protein family are essential for somatic but not visceral muscle development. Despite fusion defects in both tissues in Verprolin and other examined mutants, gut development proceeds, suggesting that fusion is not crucial for visceral mesoderm development. Hence the actin polymerization machinery functions in both somatic and visceral muscle fusion, but this process only appears to be essential in somatic muscle development. / Exploiting Drosophila as a model system for studying Anaplastic Lymphoma Kinase in vivo

Many animals live in societies of varying degrees of organization. Some individuals in these societies seem to sacrifice their own fitness to increase the fitness of some others. Understanding the forces that mould the evolution of such altruistic behaviour has become a dominant theme in modern evolutionary biology. Primitively eusocial polistine wasps provide excellent model systems to study the evolution of altruism as they show high degrees of plasticity in their behaviour. Different individuals in the same population pursue different social strategies such as nesting alpne or nesting in groups. When wasps nest in groups, usually only one individual becomes the egg layer, while die rest assume the role of sterile workers. Why do the workers not become solitary foundresses and rear their own offspring instead of working to rear the brood of another individual? Here I have used the tropical primitively eusocial wasp Ropalidia marginata to explore some factors that might potentially favour the worker strategy over the solitary founding strategy. Workers in multiple foundress nests may benefit by rearing brood more closely related to them than their own offspring would be. However, from previous work on this species it is known that relatedness between sisters is rather low and that workers therefore rear quite distantly related brood. Therefore, I have concentrated on factors other than genetic relatedness that might potentially favour the worker strategy. A total of 145 naturally initiated nests with different numbers of foundresses was monitored over a period of 16 months, and their productivities were compared. Although the total colony productivity increased, the per capita productivity did not increase with increasing foundress numbers. Colonies with larger foundress numbers did not produce significantly heavier progeny and did not produce them significantly faster than colonies with fewer individuals. The conspecific usurpers preferred to usurp single foundress colonies more often than multiple foundress colonies. Therefore, protection from conspecific usurpers might be an advantage of multiple foundress associations. About 10% of the multiple foundress nests experienced queen turnovers. This provides a finite chance to reproduce and gain some individual fitness for workers, at some future point of time. Wasps may not be similar in their reproductive abilities and those who are less fertile might be joining others who are more fertile. Testing such a hypothesis would require that individuals who have chosen to be subordinate cofoundresses in multiple foundress associations are forced to nest alone. During this study a total of 77 nests was monitored. Cofoundresses forced to nest alone had significantly lower productivity than natural solitary foundresses and also queens of multiple foundress nests who were forced to nest alone. This suggested that wasps are not similar either in their reproductive ability or brood rearing ability or both. To ascertain which of the factors was responsible for lower productivity in cofoundresses, productivity of wasps isolated into laboratory cages was compared. There was no significant difference in the productivity of isolated cofoundresses and isolated queens. This suggests that wasps are not subfertile per se but probably differ in their foraging and brood rearing abilities. The certainty with which resources are brought into the nest and therefore, the certainty with which the mean per capita productivity is attained, provides an automatic benefit of group living according to the central limit theorem. This prediction was also tested. The coefficient of variation of mean per capita productivity decreased significantly with increasing foundress numbers. Behavioural observations on another 36 colonies, with different number of adults, showed that the coefficient of variation of food brought to the nest and the rate at which larvae were fed, decreased significantly with increasing number of adults. A computer simulation was used to find out the effect of group size on the variance in feed larva. Assuming that larvae cannot be starved for too long and cannot utilize more than a certain amount of food at a time, the fitness of larvae was found to increase with an increase in the number of adults attending the nest. Previous work on R. marginata has been largely confined to postemergence colonies. An attempt was made to look at and compare social organization in preemergence colonies with that of postemergence colonies. It was found that the egg layer was not the most dominant animal in the well-established preemergence colonies. There were no detectable differences in the social organization of the preemergence colonies (of this study) with that of postemergence colonies of the earlier studies. Perhaps my conclusions drawn from studying preemergence colonies are therefore applicable more widely to the species. It can be concluded that the apparent increased fitness of the worker strategy over solitary foundress strategy does not come from any increase in per capita productivity, but comes instead from (i) the greater predictability with which the mean per capita productivity is attained in larger colonies, (ii) the lower probabilities of usurpation of larger colonies, (iii) queen turnovers that provide opportunities for workers in multiple foundress colonies to gain some direct individual fitness and (iv) the lower brood rearing abilities of workers in multiple foundress nests that make the worker strategy the best of a bad job.

Η αναδιοργάνωση του κυτταροσκελετού ακτίνης έχει κρίσιμο ρόλο στη διήθηση και τη μετάσταση των καρκινικών κυττάρων. Οι πρωτεΐνες κοφιλίνη και N-WASP συνδέονται με την ακτίνη και ρυθμίζουν τη δυναμική του κυτταροσκελετού, ενώ η πρωτεΐνη β-παρβίνη εντοπίζεται στις εστιακές συνδέσεις και διαμεσολαβεί τη σηματοδότηση διαμέσου των ιντεγκρινών με επίσης σημαντική επίδραση στον κυτταροσκελετό ακτίνης. Μεταβολή της έκφρασης των παραπάνω πρωτεϊνών έχει παρατηρηθεί σε διάφορα νεοπλάσματα στον άνθρωπο. Η παρούσα μελέτη επιχειρεί να προσδιορίσει το ρόλο τους στον καρκίνο του λάρυγγα. Για αυτό το λόγο μελετήθηκε με ανοσοϊστοχημεία η έκφραση των πρωτεϊνών κοφιλίνη, N-WASP β-παρβίνη σε 72 ιστικά δείγματα ασθενών με πλακώδες καρκίνωμα του λάρυγγα και αξιολογήθηκε η συσχέτιση της έκφρασης τους με κλινικές και παθολογοανατομικές παραμέτρους καθώς και με την επιβίωση. Θετική ανοσοϊστοχημικη έκφραση των πρωτεϊνών κοφιλίνη, N-WASP β-παρβίνη παρατηρήθηκε στο 86,1%, 93,1% και 94,4% των περιπτώσεων καρκινώματος του λάρυγγα αντίστοιχα, σε αντίθεση με τον παρακείμενο φυσιολογικό ιστό όπου η έκφραση ήταν ασθενής ή απούσα. Η κυταροπλασματική έκφραση της κοφιλίνης έδειξε τάση συσχέτισης με τα προχωρημένα στάδια της νόσου (p=0,063), ενώ η πυρηνική της έκφραση συσχετίστηκε σε στατιστικά σημαντικό βαθμό (p=0,031) με την προχωρημένη ηλικία (>65 ετών) των ασθενών. Η κυτταροπλασματική έκφραση του N-WASP ήταν μεγαλύτερη στα γλωττιδικά καρκινώματα (p=0,068) και συσχετίστηκε σε στατιστικά σημαντικό βαθμό με τα καλά διαφοροποιημένα καρκινώματα (p=0,031). Η κυτταροπλασματική έκφραση της β-παρβίνης συσχετίστηκε σε στατιστικά σημαντικό βαθμό (p=0,038) με τα προχωρημένα στάδια της νόσου. Παρόλο που οι ασθενείς με υψηλότερη έκφραση του N-WASP εμφάνιζαν καλύτερες επιβιώσεις, δεν επιβεβαιώθηκαν στατιστικά σημαντικές συσχετίσεις της έκφρασης των 3 υπό μελέτη πρωτεϊνών με την επιβίωση. Η αυξημένη έκφραση των πρωτεϊνών κοφιλίνη, N-WASP και β-παρβίνη στον καρκίνο του λάρυγγα μπορεί να υποδεικνύει την πιθανή συμμετοχή τους στην παθογένεση της νόσου. Ενώ η υψηλή έκφραση της κοφιλίνης και της β-παρβίνης φάνηκε να ευνοεί την προαγωγή/εξέλιξη του καρκίνου, τα αυξημένα επίπεδα της πρωτεΐνης N-WASP συσχετιστήκαν με ευνοϊκούς προγνωστικούς παράγοντες. / Actin cytoskeleton dynamics are critically implicated in cancer invasion and metastasis. Actin binding proteins cofilin and N-WASP regulate actin filament turnover and the focal adhesion protein β-parvin mediates integrin signaling to actin cytoskeleton. Altered expression of these proteins has been implicated in human malignancies. This study addresses their role in human laryngeal cancer. Protein expression of cofilin, N-WASP and β-parvin were investigated by immunohistochemistry in 72 FFPE samples of human laryngeal squamous cell carcinoma. Correlations with clinicopathological data and survival were evaluated. Positive immunostaining of cofilin, N-WASP and β-parvin were observed in 86.1%, 93,1% and 94,4% cases respectively, in contrast to the weak or absent staining at the non neoplastic adjacent mucosa. Cytoplasmic cofilin immunoreactivity tended to correlate with advanced disease stage (p=0.063), while its nuclear immunoreactivity correlated significantly with advanced (>65 years) patient age (p=0,031). N-WASP immunoreactivity was higher in glottic laryngeal carcinomas (p=0.068) and significantly correlated with low grade tumors (p=0.031). Expression of β-parvin also correlated significantly with advanced disease stage (p= 0.038). Although patients with high N-WASP expression showed higher survival rates no statistical significant correlation between cofilin, N-WASP or β-parvin immunoreactivity and survival was found. Overexpression of cofilin, N-WASP and β-parvin may be implicated in human laryngeal carcinogenesis. While high expression of cofilin and β-parvin seems to favor tumor progression increased levels of N-WASP associated with favorable prognostic factors.

The aim of this thesis is to assess how the configuration of linear and non-linearwind resource grids impacts the optimization.Three different software tools are used for this study: WAsP (linear model) includedin WindPRO, and WindSim (a non-linear model) - a CFD tool, and WindPRO forthe optimization. With the same configuration for wind resources, WAsP andWindSim will run to calculate the wind resource grids, .rsf or .wrg format, whichwill be compared in the post processing tab of WindPRO (from CFD interface).Using different optimization algorithms, the results from two software will becompared. The test site is flat terrain in the sea with no complexity (0,0002roughness and no orography or obstacle), and the chosen turbine here is Enercon40.3 (55m hub height, with the rated power at 14 m/s), and the wind is coming fromone direction, in our case North, which means sector 0.After comparison of the resource files from linear and non-linear wind resourcegrids, the optimization and comparison is ran for the two wind resource grids (linearand non-linear). The results of the optimization are also compared with optimizationresults of Eftun Yilmaz’s thesis (Eftun Yilmaz, 2013). We can see from the resultsthat WindSim gives almost 40% bigger values for the production. The results arecomparable with findings of Eftun Yilmaz thesis.

Cdc42 is a member of the Rho family of small GTPases, which, together with its homologues RhoA and Rac1, controls a multitude of cellular functions via the actin cytoskeleton. Cdc42 exerts its effects on the cytoskeleton via effector proteins of the Wiskott-Aldrich Syndrome (WASP) family and the Transducer of Cdc42-dependent Actin assembly (TOCA) family. The WASP family and their activation by Cdc42 have been thoroughly studied in vitro and are well understood. Conversely, understanding of the TOCA family remains limited by a lack of biochemical, biophysical and structural insight. An investigation of the TOCA1-Cdc42 interaction is described here, revealing a relatively low affinity interaction with a dissociation constant in the micromolar range. This is 10-100x weaker than other Rho-effector interactions and suggests that TOCA1 must first be co-localised with Cdc42 to achieve stable binding in vivo. The solution NMR structure of the Cdc42 binding HR1 domain of TOCA1 provides the first structural data on this protein and reveals some interesting structural features that may relate to binding affinity and specificity. A structural model of the Cdc42-HR1 complex provides further insight into differential specificities and affinities of GTPase-effector interactions. NMR and actin polymerisation assays provide insight into the pathway of Cdc42/TOCA1/WASP-dependent actin assembly, suggesting unidirectional displacement of TOCA1 by N-WASP. A comparison of the Cdc42- TOCA1 model with an NMR structure of Cdc42 in complex with the GTPase binding domain of WASP reveals a possible mechanism by which an ‘effector handover’ from TOCA1 to N-WASP could take place. Small GTPases such as Cdc42 are lipid modified and membrane anchored via their C- termini in vivo, so in vitro studies using truncated, unmodified GTPases are limited in their biological interpretation. This project also aimed to develop methods to study full length and membrane-anchored GTPases in vitro. Lipid modified protein was produced, which showed a weak affinity for liposomes, and so structural studies of membrane anchored protein are within reach. Further method development is now required to achieve stable membrane anchoring of lipid modified GTPases for detailed NMR studies.

O presente trabalho apresenta a modelagem do escoamento de ar sobre um terreno complexo empregando, e comparando os resultados, três programas comerciais de previsão de potencial eólico, WaSP, Meteodyn WT e WindSim. Por se tratar de um modelo simplificado, o programa WaSP nem sempre é adequado para previsão de energia em terrenos muito complexos pois não é capaz de prever turbulência, separação de escoamento e efeitos de estabilidade existentes neste tipo de terreno. Para que se consiga modelar a turbulência existente de maneira mais coerente, utilizam-se programas de mecânica dos fluidos computacional como o Meteodyn WT e o WindSim que modelam o escoamento através das equações médias de Reynolds. A finalidade do estudo é identificar a capacidade de previsão das velocidades de vento por meio de cada um dos programas em um parque eólico localizado na Chapada da Diamantina, tendo em vista que a correta previsão da produção de energia depende de um entendimento correto e detalhado dos recursos disponíveis. Avaliando apenas condição atmosférica neutra e comparando os resultados obtidos, conclui-se que o programa WindSim obteve o menor erro na estimativa da velocidade do vento, -3,7% quando comparado aos outros programas WaSP e Meteodyn, -5,1% e -6,5% respectivamente. O maior erro de aproximação foi obtido pelo programa WaSP, +11% quando comparado aos outros programas Meteodyn e WindSim, +10,6% e +7,9% respectivamente. Para o programa Meteodyn foram avaliados casos com diferentes condições de estabilidade, o erro máximo e mínimo foi de +10,6% e -6,5%, respectivamente em atmosfera estável, mantendo-se elevado. O programa WindSim permite a alteração de variáveis que são fixas no Meteodyn e também a simulação dos efeitos de estabilidade através da inclusão da equação de energia inicializada através do comprimento de Monin-Obukhov o que, implicou em uma melhora significativa nos resultados obtidos e em um maior tempo computacional. O erro, menor e maior, apresentado pelo programa WindSim foi reduzido a, -1,8% e +4,4% respectivamente. Destaca-se que as conclusões obtidas se aplicam ao caso estudado. / This work studies the air flow modeling over a complex terrain using and comparing the results of three commercial programs that estimates the wind field in a site: WaSP, Meteodyn WT and WindSim. Being WAsP a simplified model, it is not always suitable to estimate the flow in complex terrain because it is not able to predict the turbulence, flow separations and stability effects present in these kind of terrains. To model the existing turbulence two computational fluid mechanics programs i.e. Meteodyn WT and WindSim, which models the flow through the Reynolds Averaged Navier-Stokes equations have been used. This study aims to identify the wind speed predictive capacity of each program in a windfarm located on Chapada da Diamantina, as a correct production prediction depends on a correct estimation of the wind field. Evaluating only neutral atmospheric setup and comparing it with the measures, WindSim had the lowest wind speed estimation error, -3.7% compared with WaSP and Meteodyn programs, that provided -5.1% and -6.5% respectively. The greatest error was obtained by WaSP program, +11%, followed by Meteodyn, +10.6% and WindSim, +7.9%. WindSim enables changes in some variables that are fixed in Meteodyn and enables also the simulation of stability effects through the introduction of the energy equation with a Monin-Obukhov length initialization. For Meteodyn program different stabilities were evaluated, but the results obtained were not satisfactory. The maximum and minimum error were reduced to +10.6% and -6.5%, respectively, in stable atmosphere. Due to the specific site studied conditions the simulation of stability effects resulted in a significant improvement in the results even though a larger computational time. Enabling the energy equations setting up stable atmospheric stability, both WindSim errors are reduced to -1.8% and +4.4% respectively. It is noteworthy that the conclusions apply to the case studied.

This diploma thesis analyses pupils' knowledge of invertebrate animals. Knowledge was tested through pupils' drawings and an educational test. An analysis was also made on the textbooks the students were taught from. The research took place on a total of 186 pupils in first-stage elementary education at two elementary schools. The research results show what knowledge the pupils have of invertebrate animals.