Search for the standard model production of a single top quark in association with a Z0 boson using machine learning techniques

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London.This thesis presents a search for the production of a single top quark in association with a Z0 boson in the dileptonic decay channel as predicted by the Standard Model. The search uses 77.8 fb−1 of data from √ = 13 TeV proton– proton collisions collected by the Compact Muon Solenoid experiment at the Large Hadron Collider during the 2016–2017 data-taking period. The search identified events containing a Z0 boson decay by requiring two opposite-sign same-flavour electrons or muons in the final state with invariant mass compatible with the nominal Z0 boson mass. Products of the top quark decay were identified using techniques developed to identify jets originating from bottom quarks and searching for a jet pair with invariant mass compatible with the W± boson mass. Machine learning techniques were used to further discriminate the signal process from background events. A study was carried out, comparing the performance of boosted decision trees with hyperparameters optimised using a Gaussian process and multi-layer perceptrons on this problem. The boosted decision trees were found to outperform the multi-layer perceptrons. A signal strength of ̂ = 6.52+2.30 −2.05 was observed, where ̂ = 1.0 corresponds to the Standard Model expectation. The corresponding observed (expected) significance is 3.12 (0.48).Science and Technologies Facilities Counci

Structural Characterization of Porcine Adeno-Associated Virus Capsid Protein with Nuclear Trafficking Protein Importin Alpha Reveals a Bipartite Nuclear Localization Signal

Adeno-associated viruses (AAV) are important vectors for gene therapy, and accordingly, many aspects of their cell transduction pathway have been well characterized. However, the specific mechanisms that AAV virions use to enter the host nucleus remain largely unresolved. We therefore aimed to reveal the interactions between the AAV Cap protein and the nuclear transport protein importin alpha (IMPα) at an atomic resolution. Herein we expanded upon our earlier research into the Cap nuclear localization signal (NLS) of a porcine AAV isolate, by examining the influence of upstream basic regions (BRs) towards IMPα binding. Using a high-resolution crystal structure, we identified that the IMPα binding determinants of the porcine AAV Cap comprise a bipartite NLS with an N-terminal BR binding at the minor site of IMPα, and the previously identified NLS motif binding at the major site. Quantitative assays showed a vast difference in binding affinity between the previously determined monopartite NLS, and bipartite NLS described in this study. Our results provide a detailed molecular view of the interaction between AAV capsids and the nuclear import receptor, and support the findings that AAV capsids enter the nucleus by binding the nuclear import adapter IMPα using the classical nuclear localization pathway

Delayed gastric emptying and reduced postprandial small bowel water content of equicaloric whole meal bread versus rice meals in healthy subjects: novel MRI insights

BACKGROUND/OBJECTIVES: Postprandial bloating is a common symptom in patients with functional gastrointestinal (GI) diseases. Whole meal bread (WMB) often aggravates such symptoms though the mechanisms are unclear. We used magnetic resonance imaging (MRI) to monitor the intragastric fate of a WMB meal (11% bran) compared to a rice pudding (RP) meal. SUBJECTS/METHODS: 12 healthy volunteers completed this randomised crossover study. They fasted overnight and after an initial MRI scan consumed a glass of orange juice with a 2267 kJ WMB or an equicaloric RP meal. Subjects underwent serial MRI scans every 45 min up to 270 min to assess gastric volumes and small bowel water content and completed a GI symptom questionnaire. RESULTS: The MRI intragastric appearance of the two meals was markedly different. The WMB meal formed a homogeneous dark bolus with brighter liquid signal surrounding it. The RP meal separated into an upper, liquid layer and a lower particulate layer allowing more rapid emptying of the liquid compared to solid phase (sieving). The WMB meal had longer gastric half emptying times (132±8 min) compared to the RP meal (104±7 min), P<0.008. The WMB meal was associated with markedly reduced MRI-visible small bowel free mobile water content compared to the RP meal, P<0.0001. CONCLUSIONS: WMB bread forms a homogeneous bolus in the stomach which inhibits gastric sieving and hence empties slower than the equicaloric rice meal. These properties may explain why wheat causes postprandial bloating and could be exploited to design foods which prolong satiation

Analysis of model rotor blade pressures during parallel interaction with twin vortices

This paper presents and provides analysis of unsteady surface pressures measured on a model rotor blade as the blade experienced near parallel blade vortex interaction with a twin vortex system. To provide a basis for analysis, the vortex system was characterized by hot-wire measurements made in the interaction plane but in the absence of the rotor. The unsteady pressure response resulting from a single vortex interaction is then presented to provide a frame of reference for the twin vortex results. A series of twin vortex interaction cases are then presented and analyzed. It is shown that the unsteady blade pressures and forces are very sensitive to the inclination angle and separation distance of the vortex pair. When the vortex cores lie almost parallel to the blade chord, the interaction is characterized by a two-stage response associated with the sequential passage of the two cores. Conversely, when the cores lie on a plane that is almost perpendicular to the blade chord, the response is similar to that of a single vortex interaction. In all cases, the normal force response is consistent with the distribution of vertical velocity in the flow field of the vortex system. The pitching moment response, on the other hand, depends on the localized suction associated with the vortex cores as they traverse the blade chord

Genomic and phenotypic characterization of finger millet indicates a complex diversification history

Advances in sequencing technologies mean that insights into crop diversification can now be explored in crops beyond major staples. We use a genome assembly of finger millet, an allotetraploid orphan crop, to analyze DArTseq single nucleotide polymorphisms (SNPs) at the whole and sub‐genome level. A set of 8778 SNPs and 13 agronomic traits was used to characterize a diverse panel of 423 landraces from Africa and Asia. Through principal component analysis (PCA) and discriminant analysis of principal components, four distinct groups of accessions were identified that coincided with the primary geographic regions of finger millet cultivation. Notably, East Africa, presumed to be the crop's origin, exhibited the lowest genetic diversity. The PCA of phenotypic data also revealed geographic differentiation, albeit with differing relationships among geographic areas than indicated with genomic data. Further exploration of the sub‐genomes A and B using neighbor‐joining trees revealed distinct features that provide supporting evidence for the complex evolutionary history of finger millet. Although genome‐wide association study found only a limited number of significant marker‐trait associations, a clustering approach based on the distribution of marker effects obtained from a ridge regression genomic model was employed to investigate trait complexity. This analysis uncovered two distinct clusters. Overall, the findings suggest that finger millet has undergone complex and context‐specific diversification, indicative of a lengthy domestication history. These analyses provide insights for the future development of finger millet

Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI : comparison of split vs single dose

Peer reviewe

Psyllium reduces inulin-induced colonic gas production in IBS:MRI and in vitro fermentation studies

Objective Health-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production. Design A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. Results Colonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC(0-360 min) 3145 (848-6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62-2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0-360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC(0-360 min) from 7230 (3255-17910) ppm·hour to 1035 (360-4320) ppm·hour, p=0.007. Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. Conclusions Psyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study.</p

Stroke-Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications Following Intracerebral Haemorrhage

Introduction: Newly diagnosed cardiovascular complications following an ischaemic stroke, termed stroke-heart syndrome, are common and associated with worse outcomes. Little is known regarding stroke-heart syndrome in relation to intracerebral haemorrhage (ICH). This study aimed to investigate the incidence and 5-year major adverse cardiovascular events (MACE; acute myocardial infarction, ischaemic stroke, all-cause mortality and recurrent ICH) of newly diagnosed cardiovascular complications following incident ICH, using a global federated database. Methods: A retrospective cohort study was conducted using anonymised electronic medical records. Patients aged ≥18 years with non-traumatic ICH and 5-year follow-up were included. Patients with newly diagnosed cardiovascular complications within 4 weeks following the initial ICH were 1:1 propensity score-matched with patients without new-onset cardiovascular complications. Each cardiovascular complications were investigated as a composite stroke-heart syndrome cohort and separately for associated MACE. Cox hazard regression models were used to determine the 5-year incidence of MACE. Results: Before propensity score matching, 171,489 patients with nontraumatic ICH, 15% experienced ≥1 newly diagnosed cardiovascular complication within 4 weeks. After matching, patients with ICH and cardiovascular complications were associated with a significantly higher risk of 5-year MACE (HR 1.35 [95% CI 1.32-1.38]), and in each composite compared to matched controls. There was no significant risk of rehospitalisation over 5-year follow-up [HR 0.90 [0.73-1.13]). The risk of MACE was significantly higher in patients with newly diagnosed cardiovascular complications (separately). Conclusions: Newly diagnosed cardiovascular complications following ICH (i.e., stroke-heart syndrome) were common and associated with a significantly worsened 5-year prognosis