2,133 research outputs found

    Ethnic identity, political identity and ethnic conflict: simulating the effect of congruence between the two identities on ethnic violence and conflict

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    This thesis outlines and presents an alternative hypothetical process to the emergence of ethnic conflict. Ethnic conflicts, rather than being dependent upon pre-existing 'ancient hatreds', are instead the result of a congruence between ethnic and political identity which grants individuals the ability to use ethnicity to identify and eliminate political threats. This hypothesis is formed by the examination of three case studies of ethnic conflict: Lebanon, Northern Ireland and Croatia. This hypothesis is then formalised and tested using an agent based simulation in which agent interactions are dependent upon ethnic and political identity and the congruence between the two. As predicted there was a strong positive correlation between how accurately ethnic identity reflected political identity and the level of ethnically motivated violence in the simulation, although the relationship was not linear. Furthermore the effect of a shift in congruence was found to be roughly comparable to the effect of initialising agents with a moderate level of pre-existing ethnic antagonism

    Exposure to extremely low frequency electromagnetic fields alters the behaviour, physiology and stress protein levels of desert locusts

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    Electromagnetic fields (EMFs) are present throughout the modern world and are derived from many man-made sources including overhead transmission lines. The risks of extremely-low frequency (ELF) electromagnetic fields are particularly poorly understood especially at high field strengths as they are rarely encountered at ground level. Flying insects, however, can approach close to high field strength transmission lines prompting the question as to how these high levels of exposure affect behaviour and physiology. Here we utilise the accessible nervous system of the locust to ask how exposure to high levels of ELF EMF impact at multiple levels. We show that exposure to ELF EMFs above 4 mT leads to reduced walking. Moreover, intracellular recordings from an identified motor neuron, the fast extensor tibiae motor neuron, show increased spike latency and a broadening of its spike in exposed animals. In addition, hind leg kick force, produced by stimulating the extensor tibiae muscle, was reduced following exposure, while stress-protein levels (Hsp70) increased. Together these results suggest that ELF EMF exposure has the capacity to cause dramatic effects from behaviour to physiology and protein expression, and this study lays the foundation to explore the ecological significance of these effects in other flying insects

    On multi-path longitudinal spin relaxation in brain tissue

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    The purpose of this paper is to confirm previous reports that identified magnetization transfer (MT) as an inherent driver of longitudinal relaxation in brain tissue by asserting a substantial difference between the T1T_1 relaxation times of the free and the semi-solid spin pools. Further, we aim to identify an avenue towards the quantification of these relaxation processes on a voxel-by-voxel basis in a clinical imaging setting, i.e. with a nominal resolution of 1mm isotropic and full brain coverage in 12min. To this end, we optimized a hybrid-state pulse sequence for mapping the parameters of an unconstrained MT model. We scanned 4 people with relapsing-remitting multiple sclerosis (MS) and 4 healthy controls with this pulse sequence and estimated T1f1.90T_1^f \approx 1.90s and T1s0.327T_1^s \approx 0.327s for the free and semi-solid spin pool of healthy WM, respectively, confirming previous reports and questioning the commonly used assumptions T1s=T1fT_1^s = T_1^f or T1s=1T_1^s = 1s. Further, we estimated a fractional size of the semi-solid spin pool of m0s0.202m_0^s \approx 0.202, which is larger than previously assumed. An analysis of T1fT_1^f in normal appearing white matter revealed statistically significant differences between individuals with MS and controls. In conclusion, we confirm that longitudinal spin relaxation in brain tissue is dominated by MT and that the hybrid state facilitates a voxel-wise fit of the unconstrained MT model, which enables the analysis of subtle neurodegeneration

    Behavioral and Other Phenotypes in a Cytoplasmic Dynein Light Intermediate Chain 1 Mutant Mouse

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    The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system

    Rapid quantitative magnetization transfer imaging: utilizing the hybrid state and the generalized Bloch model

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    Purpose: To improve spatial resolution and scan time of quantitative magnetization transfer (qMT) imaging without constraints on model parameters. Theory and Methods: We combine two recently-proposed models in a Bloch-McConnell equation: the dynamics of the free spin pool is confined to the hybrid state and the dynamics of the semi-solid spin pool is described by the generalized Bloch model. We numerically optimize the flip angles and durations of a train of radio frequency pulses to enhance the encoding of three marked qMT parameters while accounting for an 8-parameter model. We sparsely sample each time frame along this spin dynamics with a 3D radial koosh-ball trajectory, reconstruct the data with sub-space modeling, and fit the qMT model with a neural network for computational efficiency. Results: We were able to extract qMT parameter maps of the whole brain with a nominal resolution of 1mm isotropic and high SNR from a 12.6 minute scan. In lesions of multiple sclerosis subjects, we observe a decreased size of the semi-solid spin pool and slower relaxation, consistent with previous reports. Conclusion: The encoding power of the hybrid state, combined with regularized image reconstruction, and the accuracy of the generalized Bloch model provide an excellent basis for highly efficient quantitative magnetization transfer imaging

    From Farmer Participation to Pro?poor Seed Markets: The Political Economy of Commercial Cereal Seed Networks in Ghana

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    The current agricultural policy discourse in Ghana emphasises ‘pro?poor market’ approaches to seeds and input delivery systems by creating public?private partnerships and an enabling environment for agri?business. This has resulted in a particular configuration of actors and interests that define the country's emerging Green Revolution agenda, of which certified seed is a critical component. This article draws on the results of a political economic analysis of Ghana's cereal seed system to examine how influential alliances of public and private actors have constructed a particular vision of the future of agriculture in the country which serves a narrow set of political interests and constrains local innovation and opportunity in the seed sector. It highlights how this universalising ‘consensus’ is acting to close down efforts to establish more pluralistic, participatory approaches in favour of a single, dominant, commercially oriented model of agricultural development

    Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis.

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    In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis.Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum-pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points.A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum-pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum-pemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67-1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5-31.5) versus 22.5 months (95% CI 20.2-28.8) for osimertinib and platinum-pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18-1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16-0.28; P0.001). At DCO, 99/136 (73%) patients in the platinum-pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥3, 1%) and rash (grouped term; 32%; grade ≥3,1%) in the osimertinib arm, versus nausea (47%; grade ≥3, 3%) in the platinum-pemetrexed arm.In patients with T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum-pemetrexed, which possibly reflects the high crossover rate of patients from platinum-pemetrexed to osimertinib.ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981

    The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

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    Objective: Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands. Methods: Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry. Results: Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell. Conclusions: Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus
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