Star clusters across the ages: internal kinematics from stellar nurseries to ancient globulars

This thesis comprises the dynamical study of star clusters in the Milky Way and Magellanic Clouds from early to ancient times. Much is unknown about the formation of high-mass stars and clusters — our understanding is deeply hindered by the obscuration of stars by thick columns of dust and gas. One can infer the motions of stars in star-forming regions, however, via radio observations of ionised gas. By way of example, I examine a young, bipolar H II region in the Galactic disc which lies at the centre of a massive (∼ 10^3 M⊙) infrared-dark cloud filament. Intriguingly, the region known as G316.81– 0.06, displays a large velocity gradient (47.81 ± 3.21 km s−1 pc−1) along the same direction as the filament — a phenomenon scarcely observed at this stage of evolution. Based on a qualitative comparison between G316.81–0.06 and simulations of young star-forming regions, the velocity gradient can be explained by rotation, inferred to be a direct result of the initial angular momentum of the natal molecular cloud. If true, this kinematic signature should be common in other young (bipolar) H II regions and may help to discern the scenario by which star clusters form and evolve. Star clusters at ancient times (i.e. globulars) appear in an entirely different form. Rid of their natal gaseous cocoons, globulars visibly contain 10^5 − 10^6 stars, held together by their mutual gravity. One particular conundrum appeared in recent decades: observed mass-to-light ratios (M/L) of metal-rich globular clusters (GCs) disagree with theoretical predictions. This discrepancy is of fundamental importance since stellar population models provide the stellar masses that underpin most of extragalactic astronomy, near and far. Using integral-field unit data from the WAGGS project, I have extracted radial velocities for 1,622 stars located in the centres of 59 Milky Way GCs — twelve of which have no previous kinematic information — in order to calculate dynamical masses and M/L_V ratios via N-body modelling. Most importantly, the sample includes NGC 6528 and NGC 6553, which extend the metallicity range of GCs with measured M/L up to [Fe/H] ∼ −0.1 dex. The results confirm that metal-rich clusters have M/L_V more than two times lower than what is predicted by simple stellar population models, and thus the discrepant M/L– [Fe/H] relation remains a serious concern. I have explored the potential origin of the divergence, and it appears that dynamical effects are the most likely explanation. With great technological advances in recent years, the internal kinematics of more distant star clusters can also be probed, such as massive star clusters in the Magellanic Clouds. These clusters are as young as ∼ 1 Myr and are thought to be the progenitors of ancient globulars. Thus, this provides a unique opportunity for the study of globular formation at a relatively unexplored snapshot in time. I have carried out a preliminary study of eleven (young, intermediate-age and old) massive clusters in the Clouds as an extension of the M/L–[Fe/H] study of GCs. With this, I can then test stellar population models and improve constraints on theories of dynamical evolution at early times. Newly discovered Gaia star clusters present another avenue for novel research. Home to a new area of parameter space, these clusters appear to be old and compact, yet they are faint (V-band magnitude < −2.5 mag). This is an exciting opportunity to advance our knowledge of (heavily dissolved) star clusters which seem to be approaching the end of their lifetime

Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin α3 in human pancreatic cancer.

Monoclonal antibody (mAb) technology is an excellent tool for the discovery of overexpressed cell surface tumour antigens and the development of targeting agents. Here, we report the development of two novel mAbs against CFPAC-1 human pancreatic cancer cells. Using ELISA, flow cytometry, immunoprecipitation, mass spectrometry, Western blot and immunohistochemistry, we found that the target antigens recognised by the two novel mAbs KU44.22B and KU44.13A, are integrin α3 and CD26 respectively, with high levels of expression in human pancreatic and other cancer cell lines and human pancreatic cancer tissue microarrays. Treatment with naked anti-CD26 mAb KU44.13A did not have any effect on the growth and migration of cancer cells nor did it induce receptor downregulation. In contrast, treatment with anti-integrin α3 mAb KU44.22B inhibited growth in vitro of Capan-2 cells, increased migration of BxPC-3 and CFPAC-1 cells and induced antibody internalisation. Both novel mAbs are capable of detecting their target antigens by immunohistochemistry but not by Western blot. These antibodies are excellent tools for studying the role of integrin α3 and CD26 in the complex biology of pancreatic cancer, their prognostic and predictive values and the therapeutic potential of their humanised and/or conjugated versions in patients whose tumours overexpress integrin α3 or CD26

Detection of T cell cytokine production as a tool for monitoring immunotherapy

There are many complex relationships between tu- mour cells and effector cells in the immune system. These interactions are controlled predominantly by cy- tokines, either within the tumour environment, or sys- temically where the effector cells may be stimulated as a response to the presence of the tumour. Favourable clinical responses in cancer patients have been shown to be associated with enhanced cell-mediated immunity as well as T cell infiltration in tumours. This status is controlled in part by a predominantly Th1 cytokine profile e.g. IFN γ , TNF α and IL-12. Conversely, pa- tients with advancing cancer may have impaired cell- mediated immunity as a result of an imbalance of Th1 and Th2 cytokines e.g. IL-4 and IL-10 [6,9,15]. Whilst cytokines have long been known to orchestrate the im- mune system by allowing communication between reg- ulatory and effector cells, the pleiotropic nature of these molecules results in a very complex environment in which to study any single molecule’s properties. Several in vitro protocols have been developed,which aim to closely reflect cytokine production and T cell function in vivo. However, these assays have been developed in artificial settings and as such only allow conclusions to be drawn within a defined context [11]. The aim of this report is to outline the basic proto-cols and applications for the detection of intracellular cytokines by flow cytometry, in the context of disease monitoring

Use of Nest Web Cameras and Citizen Science to Quantify Osprey Prey Delivery Rate and Nest Success

Ospreys (Pandion haliaetus) are obligate piscivores and their nesting success depends on sufficient amounts of fish delivered to the nests during the breeding season. Nests are considered successful when pairs raise a minimum of one young to fledging or near-fledging age. Through web cameras and online broadcasts of Osprey nests, citizen scientists quantified daily number of fish deliveries, nest survival, and nest success. We received and analyzed curated data (one to seven seasons, 2014–2020) from citizen scientist groups representing 19 Osprey web cameras from four countries in North America and Europe. We compared the average and the coefficient of variation of the number of fish delivered per day within the early breeding season between the failed and successful nests using a Wilcoxon rank-sum test. We also analyzed the effects of the average and the coefficient of variation of the number of fish delivered per day on the number of days of nest survival and whether a nest was successful or not using generalized linear mixed models. Successful and failed nests had significant differences in the average number of fish delivered per day and the failed nests had a higher variation in the number of fish deliveries. Moreover, the variation and average number of fish delivered per day had strong associations with whether a nest would fail or succeed. The global effort and manner in which these data were collected are novel and can further our understanding of this charismatic species. The combination of citizen science and technology is a powerful modern tool that can provide insights and has the potential to advance raptor research worldwide

Inverse Magnetoresistance of Molecular Junctions

We present calculations of spin-dependent electron transport through single organic molecules bridging pairs of iron nanocontacts. We predict the magnetoresistance of these systems to switch from positive to negative with increasing applied bias for both conducting and insulating molecules. This novel inverse magnetoresistance phenomenon is robust, does not depend on the presence of impurities, and is unique to molecular and atomic nanoscale magnetic junctions. Its physical origin is identified and its relevance to experiment and to potential technological applications is discussed.Comment: 5 pages, 3 figures; published version Phys. Rev.

Inter-specific variation in bud banks and flowering effort among semi-arid African savanna grasses

Population viability and productivity of grasses in southern African savannas are dependent upon both successful seed production and tiller recruitment from the belowground bud bank. Relative recruitment rates from buds versus seeds influence population dynamics, genetic diversity, and patterns of vegetation productivity. We assessed patterns in bud bank size and flowering effort in fourteen semi-arid savanna grass species in the Kalahari region of Botswana. There was high inter-specific variability and between-year variability in flowering effort (percentage of tillers flowering). Bud production (number of buds per tiller) exhibited high inter-specific variability, but was more consistent between-years than flowering effort. Relative allocation to flowering versus bud production varied with life history, with longer-lived perennial grasses showing higher bud production and lower flowering effort relative to shorter-lived grasses. Several species showed higher bud production and lower flowering effort in a wet year compared to a dry year, and grass species that are regularly grazed maintained significantly larger bud banks than non-grazed species. These differential demographic responses among co-occurring species suggest that environmental change in semi-arid savannas may alter the composition, relative abundances and diversity of grasses, and that the maintenance of a belowground bud bank is an important factor influencing their resiliency, their capacity to recover from grazing and/or drought, and their persistence and sustainability under changing environmental conditions. Meristem-limitation in species that maintain few viable buds may constrain their population viability under changing conditions in semi-arid savannas. (C) 2012 SAAB. Published by Elsevier B.V. All rights reserved

Astronomy outreach in Namibia: H.E.S.S. and beyond

Astronomy plays a major role in the scientific landscape of Namibia. Becauseof its excellent sky conditions, Namibia is home to ground-based observatorieslike the High Energy Spectroscopic System (H.E.S.S.), in operation since 2002.Located near the Gamsberg mountain, H.E.S.S. performs groundbreaking science bydetecting very-high-energy gamma rays from astronomical objects. Thefascinating stories behind many of them are featured regularly in the ``Sourceof the Month'', a blog-like format intended for the general public with morethan 170 features to date. In addition to other online communication via socialmedia, H.E.S.S. outreach activities have been covered locally, e.g. through`open days' and guided tours on the H.E.S.S. site itself. An overview of theH.E.S.S. outreach activities are presented in this contribution, along withdiscussions relating to the current landscape of astronomy outreach andeducation in Namibia. There has also been significant activity in the countryin recent months, whereby astronomy is being used to further sustainabledevelopment via human capacity-building. Finally, as we take into account thefuture prospects of radio astronomy in the country, momentum for a wider rangeof astrophysics research is clearly building -- this presents a greatopportunity for the astronomy community to come together to capitalise on thismovement and support astronomy outreach, with the overarching aim to advancesustainable development in Namibia.<br

Suite2p: beyond 10,000 neurons with standard two-photon microscopy

Two-photon microscopy of calcium-dependent sensors has enabled unprecedented recordings from vast populations of neurons. While the sensors and microscopes have matured over several generations of development, computational methods to process the resulting movies remain inefficient and can give results that are hard to interpret. Here we introduce Suite2p: a fast, accurate and complete pipeline that registers raw movies, detects active cells, extracts their calcium traces and infers their spike times. Suite2p runs on standard workstations, operates faster than real time, and recovers ~2 times more cells than the previous state-of-the-art method. Its low computational load allows routine detection of ~10,000 cells simultaneously with standard two-photon resonant-scanning microscopes. Recordings at this scale promise to reveal the fine structure of activity in large populations of neurons or large populations of subcellular structures such as synaptic boutons

Assessing the influence of one astronomy camp over 50 years

The International Astronomical Youth Camp has benefited thousands of lives during its 50-year history. We explore the pedagogy behind this success, review a survey taken by more than 300 previous participants, and discuss some of the challenges the camp faces in the future.Comment: 10 pages, 4 figure

Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects

The anti-tumour effects of thalidomide have been associated with its anti-angiogenic properties. Second generation thalidomide analogues are distinct compounds with enhanced therapeutic potential. Although these compounds are beginning to enter trials for the treatment of cancer there is very little information regarding the anti-angiogenic activity of these clinically relevant compounds. Furthermore, it is not known how the various immunomodulatory activities of these compounds relate to anti-angiogenic activity. In this study we assessed the anti-angiogenic activity of compounds from both IMiD™ and SelCID™ classes of analogues using a novel in vitro multicellular human assay system and the established rat aorta assay. Our results show that both the IMiDs and SelCIDs tested are significantly more potent than thalidomide. The anti-angiogenic potency of the analogues was not related to inhibition of endothelial cell proliferation, nor their TNF-α/PDE type 4 inhibitory properties. However, anti-migratory effects in vitro and inhibition of tumour growth in vivo was observed with the analogue IMiD-1 (clinically known as REVIMID™). Our results show that anti-angiogenic activity spans both currently defined classes of thalidomide analogue and is not related to their previously described immunomodulatory properties. Identification of the differential effects of these compounds will enable targeting of such compounds into the appropriate clinical setting