The Application of Dental Anthropology to Population Dynamics, Economy and Health in the Prehispanic Canary Islands

This is a dental anthropology study of prehispanic (pre. 1400 AD) societies in the Canary Islands, comprising the analysis of morphology (ASUDAS dental scoring system) and pathology (dental caries and hypoplasia; cranial trauma) to examine population biology, diet, behaviour and health. The study was configured temporo-spatially, employed demographic variables, and was contextualised using archaeological, ecological and historical data. An MNI of 896 individuals was examined. Biologically, the Canarians appear to have been temporo-spatially homogenous; except for minor fluctuations probably caused by influxes from the mainland, the island populations were probably always socially interlinked and were not therefore a series of isolates as previously believed. The marked cultural diversity in the archipelago is therefore more likely to be the result of promulgating socio-political autonomy (at certain points at least) rather than involuntary socio-cultural isolation. Dental pathology suggested a diet intermediate between agriculture and foraging, with a relatively low caries rate that was probably linked to the consumption of dairy produce. There were minor differences between the sexes (the exact significance of this is unclear) and little evidence for temporal trends. While there was considerable variability in economic signatures, probably partially dictated by ecology and environment, there appears to have been considerable leeway in the manner that Native Canarians configured their lives. Populations were generally healthy, with the highest prevalence of hypoplasia being found in densely-populated islands that may have been vulnerable to economic stress linked to the islands erratic climatic regime. All islands show a hypoplasia peak in late childhood and early adolescence, possibly reflecting social maturation/independence. Health did not differ conspicuously between the sexes, and there was no significant temporal trend in hypoplasia prevalence. Cranial trauma was very common and spatially variable in the Canarian archipelago, with higher overall prevalence in densely populated islands. Males possessed higher prevalence of trauma than females; there was no temporal trend. Judging from the appearance and distribution of the lesions, much of the trauma seems to have been caused by inter-personal conflict. This study provides an array of information concerning Native Canarian lifestyle and behaviour, and has implications for the development of Canarian archaeology, general island archaeology and also the study of how ecology and sociality can determine pattern and process in human adaptation

Cognitive Neuroscience of Schizophrenia: Stochastic Modelling of Cognitive-Process Latencies and Nonlinear Dynamics of Neuro-signals

We study known and potential numerical earmarks of schizophrenia through mathematical methods. One known numerical characteristic of schizophrenia is that of prolonged encoding latencies in response to cognitive stimuli. Motivated by the need to explain interaction patterns in 2 x 2 factorial data where one factor is encoding load and the other is diagnostic status, we define a class of general serial mixture models based on the number of encoding subprocesses executed and the speed at which they are executed. Mathematical derivations performed on these models yield closed form expressions for the mean encoding latency and average intertrial variance, which in turn yield expressions for the mean interaction contrast and variance interaction contrast. Different interaction signatures correspond to different members of the model class. A wealth of examples are provided linking various potential physical and neurophysiological encoding mechanisms to members of the model class. We also derive results for a specific subset of the general model class where only the number of subprocesses is allowed to vary over factorial cells. Our development includes a numerical test (verified by theory and simulation methods) to determine if the number of encoding subprocesses varies over trials. Theoretical results are then developed for the case where the speed of encoding subprocesses is allowed to vary. Secondly, by means of an exhaustive literature search and application of contingency tables, we investigate whether a collection of numerical indices, called nonlinear indices or complexity indices, can be utilized to support or refute a conjecture in the literature which states that complexity in EEG recordings tends to be higher in schizophrenia patients than controls with this tendency being dampened (and even inverted) by medication, increasing age, and decreasing symptomatology. Our analysis indicates only weak effects due to age and medication, and suggests that symptomatology may play a greater role. Moreover, we observe a strong ``study effect\u27\u27 which suggests that laboratory procedures may also play a role. Our systematic review of nonlinear indices does, however, indicate that heart rate variability is reduced in schizophrenia and bipolar disorder

Recent Developments in Smart Healthcare

Medicine is undergoing a sector-wide transformation thanks to the advances in computing and networking technologies. Healthcare is changing from reactive and hospital-centered to preventive and personalized, from disease focused to well-being centered. In essence, the healthcare systems, as well as fundamental medicine research, are becoming smarter. We anticipate significant improvements in areas ranging from molecular genomics and proteomics to decision support for healthcare professionals through big data analytics, to support behavior changes through technology-enabled self-management, and social and motivational support. Furthermore, with smart technologies, healthcare delivery could also be made more efficient, higher quality, and lower cost. In this special issue, we received a total 45 submissions and accepted 19 outstanding papers that roughly span across several interesting topics on smart healthcare, including public health, health information technology (Health IT), and smart medicine

Consistency Algorithms and Protocols for Distributed Interactive Applications

The Internet has a major impact not only on how people retrieve information but also on how they communicate. Distributed interactive applications support the communication and collaboration of people through the sharing and manipulation of rich multimedia content via the Internet. Aside from shared text editors, meeting support systems, and distributed virtual environments, shared whiteboards are a prominent example of distributed interactive applications. They allow the presentation and joint editing of documents in video conferencing scenarios. The design of such a shared whiteboard application, the multimedia lecture board (mlb), is a main contribution of this thesis. Like many other distributed interactive applications, the mlb has a replicated architecture where each user runs an instance of the application. This has the distinct advantage that the application can be deployed in a lightweight fashion, without relying on a supporting server infrastructure. But at the same time, this peer-to-peer architecture raises a number of challenging problems: First, application data needs to be distributed among all instances. For this purpose, we present the network protocol RTP/I for the standardized communication of distributed interactive applications, and a novel application-level multicast protocol that realizes efficient group communication while taking application-level knowledge into account. Second, consistency control mechanisms are required to keep the replicated application data synchronized. We present the consistency control algorithms “local lag”, “Timewarp”, and “state request”, show how they can be combined, and discuss how to provide visual feedback so that the session members are able to handle conflicting actions. Finally, late-joining participants need to be initialized with the current application state before they are able to participate in a collaborative session. We propose a novel late-join algorithm, which is both flexible and scalable. All algorithms and protocols presented in this dissertation solve the aforementioned problems in a generic way. We demonstrate how they can be employed for the mlb as well as for other distributed interactive applications

Information Processing under Physiological Pulsatile Stimulation in a G-protein Coupled Signaling Pathway

The cellular microenvironment is often dynamic, and several physiological ligands are released in pulsatile bursts. The main hypothesis driving this study is that cells are able to discern these time-varying dynamic inputs and must have evolved to exploit the temporal information available in their microenvironment to their advantage. Taking Muscarinic M3 (a G-protein coupled receptor)-mediated signaling as an example, this thesis explores how information is processed under pulsatile stimulation. Several experimental and computational approaches techniques including microfluidics, real-time multi-color fluorescence imaging of single cells, reaction kinetics modeling and information and noise analysis are implemented to gain mechanistic insights into the signaling circuit architecture. A major finding of this thesis is that receptor-mediated signaling forms a low pass filter while downstream calcium-induced NFAT (Nuclear Factor of Activated T-Lymphocytes, a transcription factor) nuclear translocation forms a high pass filter. The combination acts as a band-pass filter optimized for intermediate frequencies of stimulation. Sensitivity analysis shows that receptor and downstream kinetics determine critical features of the band-pass and that the band-pass may be shifted for different receptors or NFAT dynamics. Another important finding in this thesis is that for weak physiological inputs, cells exhibit apparent stochastic responses that can be explained within a deterministic framework. Computational analysis suggests that cells may utilize apparent stochasticity to enhance selectivity in downstream responses. This thesis also demonstrates that pulsatile inputs enhance information transfer downstream in noisy biochemical pathways. Finally, a microfluidic experimental method is developed to measure two microfluidic observables in the same cell, similar to a ‘two-reporter’ system, to estimate biochemical noise. Analysis with this method suggests that effect of drug action increases with increasing biochemical noise. Although this thesis focuses on one particular receptor and ligand, the conclusions from this work may be applied to several signaling systems. Investigation of band-pass processing may lead to gaining mechanistic insights into hidden or unknown regulatory motifs in several signaling pathways that are poorly understood. Using pulsatility to modulate selectivity and sensitivity of signaling response amidst biochemical noise provides tools to synthetic biologists and pharmacologists for developing enhanced lab-on-chip devices and pharmaceutical interventions.PHDBiophysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135745/1/msumit_1.pd

Metabolism in haematological cancer cells

Cancer cells exhibit a rewired metabolism to meet their specific energy needs for cell proliferation. Despite remarkable efforts to unravel how cancer cells reprogram their metabolism, characterization of the metabolic differences between the different subtypes of cancer has not been well performed. Haematological cancers can be divided into subtypes with significant implications for diagnosis and treatment. The metabolic profiles of a panel of 18 haematological cancer cell lines representing acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), multiple myeloma (MM), Burkitt’s lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) were characterised using an NMR approach. I found a notable widespread metabolic heterogeneity between haematological cancer subtypes, even though all haematological cancer cells showed a typical Warburg effect with lactate production. Intriguingly, MM cells were observed with a large amount of leucine uptake. The exploration of leucine metabolism using stable isotope tracer revealed that leucine is fully metabolised in MM cells and feeds the TCA cycle as well as sialic acid formation. Moreover, metabolic differences between BL and DLBCL were scrutinised, as these diseases tend to share similar morphological, immunophenotypic and genetic characteristics. Exogenous asparagine was found to regulate serine metabolism in BL cells. Furthermore, the combination of asparaginase (ASNase), a clinically used agent that depletes exogenous asparagine, with a PHGDH inhibitor (NCT503) had a synergistic effect on the viability in BL cells, exhibiting more decrease in cell viability as compared to those obtained from treatment of ASNase alone. Conversely, the combination of ASNase with NCT503 showed no synergistic effect on the viability of DLBCL cells, suggesting that the combination of ASNase with NCT503 is solely synergistic for BL. Hence, NMR-based metabolite profiling has revealed how metabolism alters in haematological cancers. This thesis has highlighted and investigated metabolic dependencies and vulnerabilities in different haematological cancer which can be utilised for diagnostic and therapeutic purposes in future

Annual Report 2016 Institute of Resource Ecology

The Institute of Resource Ecology (IRE) is one of the eight institutes of the Helmholtz-Zentrum Dresden – Rossendorf (HZDR). The research activities are mainly integrated into the program “Nuclear Waste Management, Safety and Radiation Research (NUSAFE)” of the Helmholtz Association (HGF) and focused on the topics “Safety of Nuclear Waste Disposal” and “Safety Research for Nuclear Reactors”..

Light-activateable apoptosis via genetic code expansion as an in-vivo single-cell ablation tool in Caenorhabditis elegans

Natural proteins are biopolymers built from a limited variety of canonical amino acids that are encoded by corresponding triplet codons. Genetic code expansion via amber suppression enables me to install (incorporate) in a target protein a “designer” amino acid beyond canonical amino acids, at the site of a pre-introduced amber stop codon. This is through expression in the host cell of an orthogonal pair, consisting of an aminoacyl-tRNA synthetase and an amber-suppressing tRNA (tRNACUA) evolved for the non-canonical amino acids (NCAA). Site-specific incorporation of NCAA endows target proteins with new properties, enabling protein measurement and/or manipulation in ways that are otherwise impossible. Photo-caged cysteine (PCCys) as a useful NCAA has not been used in any animal before. By using a PCCRS/tRNAPylCUA pair evolved from a PylRS/tRNAPylCUA pair, I introduced (PCCys) into protein synthesis of multicellular model species Caenorhabditis elegans (C. elegans). I demonstrated this incorporation of PCCys by expressing a fluorescent reporter either throughout the nematode or in two different neuronal classes. I used site-specific PCCys incorporation to develop a light-activatable caspase for precisely ablating cells (especially neurons) in living worms. Cell ablation has been widely adopted in studies on C. elegans cell lineage and cell functions. Common ablation methods include high-powered laser ablation, genetic ablation and optogenetic ablation. However, they are unable to ablate single cells in fully developed worms. Caspase is a core executor of apoptosis of both C. elegans and human cells. I designed and engineered a photo-caged caspase from human Caspase-3 by replacing its catalytic cysteine with PCCys. 365-nm UVA illumination removes the caging group of PCCys in the caged caspase, thereby activating the caspase to induce apoptosis of the cell(s) targeted. I succeeded in using global UV illumination to activate respective apoptosis events of oxygen-sensing neurons, touch receptor neurons and muscular cells in adult worms. Also, I demonstrate that individual adult neurons can be selectively targeted and efficiently killed with the use of a microscope-mounted 365-nm laser. With this better spatiotemporal control than other ablation methods, our approach is likely to facilitate future C. elegans studies with unprecedented specificity and precision

Performance Comparison of Dual Connectivity and Hard Handover for LTE-5G Tight Integration in mmWave Cellular Networks

This Thesis will propose an LTE-5G tight integration architecture, based on mobile terminals' dual connectivity to LTE and 5G radio access networks, and will evaluate which are the new network procedures that will be needed to support it. Moreover, this new architecture will be implemented in the ns-3 simulator, and a thorough simulation campaign will be conducted in order to evaluate its performance, with respect to the baseline of handover between LTE and 5

Human Rights Treaty Commitment and Compliance: A Machine Learning-based Causal Inference Approach

Why do states ratify international human rights treaties? How much do human rights treaties influence state behaviors directly and indirectly? Why are some human rights treaty monitoring procedures more effective than others? What are the most predictively and causally important factors that can reduce and prevent state repression and human rights violations? This dissertation provide answers to these keys causal questions in political science research, using a novel approach that combines machine learning and the structural causal model framework. The four research questions are arranged in a chronological order that refects the causal process relating to international human rights treaties, going from (a) the causal determinants of treaty ratification to (b) the causal mechanisms of human rights treaties to (c) the causal effects of human rights treaty monitoring procedures to (d) other factors that causally influence human rights violations. Chapter 1 identifies the research traditions within which this dissertation is located, offers an overview of the methodological advances that enable this research, specifies the research questions, and previews the findings. Chapters 2, 3, 4, and 5 present in chronological order four empirical studies that answer these four research questions. Finally, Chapter 6 summarizes the substantive findings, suggests some other research questions that could be similarly investigated, and recaps the methodological approach and the contributions of the dissertation