Rheological characterisation of biofilms in both linear and nonlinear viscoelastic regimes

Ph. D. ThesisBiofilms are a ubiquitous mode of bacteria proliferation found within aqueous environments. The structure and architecture that a biofilm self assembles into confers mechanical resistance against shear forces. A characteristic trait of biofilm is the production of extra cellular materials which act as the “glue” in the ECM/bacteria composite. The myriad physical properties of biofilm systems result in highly variable mechanical properties, which are studied using rheology. Previous studies about biofilm mechanics were mainly focused on linear viscoelastic regions. However the linear region is unable to provide information regarding the dynamics of deformation and structural rearrangement. Probing the biofilm nonlinear viscoelastic regime and yielding dynamics opens a window to access how the rearrangement behaviour of the EPS network and bacterium network are impacted by EPS composition and bacterial network topology. In addition, to determine the rheological properties of biofilms within the linear viscoelastic regime using the rotational rheometer, this thesis sheds light on utilising high fidelity non-linear rheological techniques and advanced imaging techniques to produce a framework explaining the emergence of characteristic biofilm mechanical behaviours across an array of species, chemical environments and genetic mutations. I have demonstrated the applicability of three types of large amplitude oscillatory shear (LAOS) analysis methodologies to Pseudomonas fluorescens biofilms and the rheological effects of divalent cations and a chaotropic compound. It was shown that by increasing ionic concentration the characteristic behaviour changes from a repulsive glass to an attractive glass. To understand the rheological and architectural effects of capsular polysaccharide secretion in biofilms, I selected the bacterium Pantoea sp. I revealed how the secretion of amylovoren and stewartin causes a characteristic rheological change from viscoelastic liquid to glass and how this is primarily driven by changes in EPS polymer concentration and packing fraction. Finally, I investigated the yielding behaviours across a range of bacteria with different geometries (rods/cocci) and EPS compositions. I identified four different types of yielding behaviour across the tested bacterial strains and used a range of rheological and microscopy data to identify the extent of short- and long-range polymer networks which determine the viscoelastic response of bacterial biofilms. Biofilms are a ubiquitous mode of bacteria proliferation found within aqueous environments. The structure and architecture that a biofilm self assembles into confers mechanical resistance against shear forces. A characteristic trait of biofilm is the production of extra cellular materials which act as the “glue” in the ECM/bacteria composite. The myriad physical properties of biofilm systems result in highly variable mechanical properties, which are studied using rheology. Previous studies about biofilm mechanics were mainly focused on linear viscoelastic regions. However the linear region is unable to provide information regarding the dynamics of deformation and structural rearrangement. Probing the biofilm nonlinear viscoelastic regime and yielding dynamics opens a window to access how the rearrangement behaviour of the EPS network and bacterium network are impacted by EPS composition and bacterial network topology. In addition, to determine the rheological properties of biofilms within the linear viscoelastic regime using the rotational rheometer, this thesis sheds light on utilising high fidelity non-linear rheological techniques and advanced imaging techniques to produce a framework explaining the emergence of characteristic biofilm mechanical behaviours across an array of species, chemical environments and genetic mutations. I have demonstrated the applicability of three types of large amplitude oscillatory shear (LAOS) analysis methodologies to Pseudomonas fluorescens biofilms and the rheological effects of divalent cations and a chaotropic compound. It was shown that by increasing ionic concentration the characteristic behaviour changes from a repulsive glass to an attractive glass. To understand the rheological and architectural effects of capsular polysaccharide secretion in biofilms, I selected the bacterium Pantoea sp. I revealed how the secretion of amylovoren and stewartin causes a characteristic rheological change from viscoelastic liquid to glass and how this is primarily driven by changes in EPS polymer concentration and packing fraction. Finally, I investigated the yielding behaviours across a range of bacteria with different geometries (rods/cocci) and EPS compositions. I identified four different types of yielding behaviour across the tested bacterial strains and used a range of rheological and microscopy data to identify the extent of short- and long-range polymer networks which determine the viscoelastic response of bacterial biofilms. In summary, this thesis demonstrates how contemporary rheological methods and soft matter physics can be used in a reductive approach towards linking biofilm mechanics, microstructure and phenomenology.EPSRC DT

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurement of the t¯tZ and t¯tW cross sections in proton-proton collisions at √s=13 TeV with the ATLAS detector

A measurement of the associated production of a top-quark pair (t¯t) with a vector boson (W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV is presented, using 36.1  fb−1 of integrated luminosity collected by the ATLAS detector at the Large Hadron Collider. Events are selected in channels with two same- or opposite-sign leptons (electrons or muons), three leptons or four leptons, and each channel is further divided into multiple regions to maximize the sensitivity of the measurement. The t¯tZ and t¯tW production cross sections are simultaneously measured using a combined fit to all regions. The best-fit values of the production cross sections are σt¯tZ=0.95±0.08stat±0.10syst pb and σt¯tW=0.87±0.13stat±0.14syst pb in agreement with the Standard Model predictions. The measurement of the t¯tZ cross section is used to set constraints on effective field theory operators which modify the t¯tZ vertex

Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Biogel scavenging slows the sinking of organic particles to the ocean depths

peer reviewedOne of Earth’s largest carbon fluxes is driven by particles made from photosynthetically fixed matter, which aggregate and sink into the deep ocean. While biodegradation is known to reduce this vertical flux, the biophysical processes that control particle sinking speed are not well understood. Here, we use a vertical millifluidic column to video-track single particles and find that biogels scavenged by particles during sinking significantly reduce the particles’ sinking speed, slowing them by up to 45% within one day. Combining observations with a mathematical model, we determine that the mechanism for this slowdown is a combination of increased drag due to the formation of biogel tendrils and increased buoyancy due to the biogel’s low density. Because biogels are pervasive in the ocean, we propose that by slowing the sinking of organic particles they attenuate the vertical carbon flux in the ocean.R-AGR-3401 - A17/MS/11572821/MBRACE - part UL - SENGUPTA Anupam6. Clean water and sanitation14. Life below water13. Climate actio

Innovation in Diabetes - Ideas and Initiatives

A collection of multiple reports on MyDiabetesMyWay (MDMW). Included reports are: MyDiabetesMyWay Patient Portal; MyDiabetesMyWay e-learning hub (Moodle) ; SCI-diabetes/ MDMW Communication Portal- Tools for Remote Communication/ Consultation; Risk Modelling for Care Planning- integration into Informatics Dashboard for Clinical Use; Access to Chronic Medication Service (CMS) and Pharmaceutical Care Planning Medication and Lifestyle Coaching; Multi-media Diabetes Resources; Promoting Diabetes Education; Tele-Pharmacy; Understanding my diabetes medication; Pharmaceutical Industry and Medical Technology (PIMTs); An on-line and interactive education system for young people with type 1 diabetes to understand self-management for their lifestyle; Proof of Concept study to deliver personalised use of information to support diabetes management and behaviour change; right information; right time; right way; Virtual promotion of physical activity for people with type 2 diabetes; Remote foot ulcer management: RAPID (Reducing Amputation in People with Diabetes); Diabetic foot screening – development of technology; Portable capillary HbA1c testing for diagnosis and self-monitoring of diabetes; Possibility of mobile phone adaption for testing; Web app for decision support for patients with type 1 diabetes undertaking sport or exercise; Online level 3 structured education for type 1 diabetes; My Diabetes My Way electronic personal health record – uptake at scale; TeleClinics for diabetes; Develop a diabetes sim / game in which the main character has diabetes. Young people need to keep the sim / character alive as they face the various challenges of life or the game; Development of meaningful automated glucose data to in-patient clinical areas; In-patient Care: Integrated eHealth solutions to improve patient care, safety and outcomes; Innovative model of care to address the 'process of care' in managing people with long term conditions; Young Persons Remote Clinic Consultation; Maximise use of the data to support self-management of patients with co-morbidities; Virtual practice outreach and education in primary care

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections

Search for excited electrons singly produced in proton–proton collisions at \sqrt{s} = 13 TeV with the ALAS experiment at the LHC

A search for excited electrons produced in pp collisions at s√ = 13 TeV via a contact interaction qq¯→ee∗ is presented. The search uses 36.1 fb −1 of data collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider. Decays of the excited electron into an electron and a pair of quarks ( eqq¯ ) are targeted in final states with two electrons and two hadronic jets, and decays via a gauge interaction into a neutrino and a W boson ( νW ) are probed in final states with an electron, missing transverse momentum, and a large-radius jet consistent with a hadronically decaying W boson. No significant excess is observed over the expected backgrounds. Upper limits are calculated for the pp→ee∗→eeqq¯ and pp→ee∗→eνW production cross sections as a function of the excited electron mass me∗ at 95% confidence level. The limits are translated into lower bounds on the compositeness scale parameter Λ of the model as a function of me∗ . For me∗<0.5 TeV , the lower bound for Λ is 11 TeV . In the special case of me∗=Λ , the values of me∗<4.8 TeV are excluded. The presented limits on Λ are more stringent than those obtained in previous searches

Medium-Induced Modification of Z-Tagged Charged Particle Yields in Pb+Pb Collisions at 5.02 TeV with the ATLAS Detector

The yield of charged particles opposite to a Z boson with large transverse momentum ( p T ) is measured in 260     pb − 1 of p p and 1.7     nb − 1 of Pb + Pb collision data at 5.02 TeV per nucleon pair recorded with the ATLAS detector at the Large Hadron Collider. The Z boson tag is used to select hard-scattered partons with specific kinematics, and to observe how their showers are modified as they propagate through the quark-gluon plasma created in Pb + Pb collisions. Compared with p p collisions, charged-particle yields in Pb + Pb collisions show significant modifications as a function of charged-particle p T in a way that depends on event centrality and Z boson p T . The data are compared with a variety of theoretical calculations and provide new information about the medium-induced energy loss of partons in a p T regime difficult to measure through other channels