Enzyme Immobilisation on Mesoporous Silica, Inspired by Chaperonins

In nature, chaperonins stabilise enzymes and protect them from high temperature and unfavourable solution conditions. We are inspired by some of chaperonins’ fundamental properties when investigating materials for enzyme immobilisation. In this project, mesoporous silica SBA-15 is used as a synthetic chaperonin analogue because of its controlled mesopore diameter and its negatively charged surface. Mesoporous silica SBA-15 have been synthesised by an acidic sol-gel method. The morphologies and textural parameters of the SBA-15 have been characterised using electron microscopy, gas physisorption, and small-angle Xray scattering. The synthesised SBA-15 samples are used to immobilise several model proteins: myoglobin, lysozyme, trypsin, and pepsin. At equilibrium, protein immobilisation can be described by the Langmuir model of physical adsorption. The maximum amount of protein that can be adsorbed onto SBA-15 increases with increasing pore diameter. The kinetics of adsorption of the protein myoglobin is found to be affected by the pore size of the SBA-15, with the protein diffusing faster through a larger pore. Immobilising enzymes to SBA-15 is shown to increase their biocatalytic activity under some solution conditions. For myoglobin and lysozyme, the protective effects were strongest in solutions where the enzyme is strongly electrostatically attracted to the silica surface. Immobilised myoglobin is also found to be protected from digestion by the protease pepsin. For trypsin, the relationship between electrostatic attraction and improved activity was inconclusive. SBA-15 pore size was shown to affect the activity of the smallest enzyme, lysozyme. In summary, this thesis recommends the following prioritisations for enzyme immobilisation: strong electrostatic attraction between enzyme and material, followed by pore size just exceeding the diameter of the enzyme. By determining the relative importance of these parameters, this thesis increases the fundamental understanding of enzyme immobilisation by physical adsorption onto porous materials

In Vitro Evaluation of the Reciprocating Disposable Prophylaxis Angle Versus the Rotating Disposable Prophylaxis Angle in Extrinsic Stain Removal Effectiveness

This study determined the extrinsic tooth stain removing effectiveness of a 90° counter-rotational disposable prophylaxis angle (DPA) with rubber cup compared to the traditional 360° unirotational DPA with rubber cup. Four randomly-assigned groups of cleaned, sterilized, extracted human teeth, artificially stained with coffee, tea, tobacco, and red wine, were polished on the buccal and lingual surfaces using one of the 2 DPAs. Each dependent variable (4 different stain types) was tested 4 times with each prophylaxis angle, using 4 prophylaxis paste conditions, and 3 different rpm; therefore, 2 trials x 2 angles x 3 speeds x 4 stains x 4 grits = 192 trials on 96 teeth. For each trial, a DPA attached to a handpiece controlled by an eStylus™ was mounted on a testing apparatus that together controlled handpiece rpm and rubber cup pressure against the tooth. Stain removal effectiveness was measured with a Bioform Color Ordered Shade Guide both before and after the DPA was used with one of three different grits of prophylaxis pastes and a trial using no paste at 1500, 2000, and 3000 rpm. The evaluator was blind to the treatment status. Data were analyzed using a 3-way analysis of variance at p= .05 level. Results revealed no statistically significant difference between the two DPAs in extrinsic tooth stain removal. There was a statistically significant interaction among rpm (3000) of the DPA and the grit abrasivity of the prophylaxis paste suggesting that additional study may be indicated since coarse prophylaxis pastes remove stain more rapidly, but in doing so, can scratch and roughen the tooth enamel. Extrinsic stain removal effectiveness of the 2 DPAs were comparable when using different abrasivity prophylaxis paste and different rpm. [ABSTRACT FROM AUTHOR

Vital Tooth Whitening Effects on Oral Health-Related Quality of Life in Older Adults

Purpose: The purpose of this study was to determine if vital tooth whitening affects oral health-related quality of life (OHRQOL) in adults age 50 years and older, and if tooth whitening causes increased participation in social activities. Methods: Using a 2 group, single blind, randomized, pre-test, multiple post-test design, 62 participants were enrolled. The experimental group used a whitening product twice daily for 3 weeks. The control group used no whitening products. The Oral Health Impact Profile (OHIP) served as the pre- and post-test measure. The OHIP measures OHRQOL on 7 subscales: functional factors, psychological disabilities, psychological discomforts, physical disabilities, social disabilities, handicaps and physical pain. Additional questions measured the subjects\u27 social activities at baseline, 3 weeks and 3 months. Data from 53 participants, who completed the study, were analyzed using paired t-tests and ANOVA at p=0.05. Results: Statistical significance was observed for the OHIP physical pain subscale (p=0.0029) and the handicap subscale (p=0.05). Pre- to post-test means of the physical pain subscale increased in the experimental group (4.84 to 7.10), suggesting a lower OHRQOL, most likely related to tooth sensitivity experienced by the experimental group. Means from pre- to post-test of the handicap subscale (1.96 to 1.19) reveal that the experimental group reported an improved OHRQOL and felt they were more willing to work. Repeated measures ANOVA and Tukey\u27s post-hoc tests revealed that the experimental group reported significantly less (p=0.04) social activities at the 3 month post-test (3.92 to 3.45). No statistically significant between-group differences were observed in the overall OHIP score for functional factors, psychological disabilities, psychological discomforts, physical disabilities and social disabilities. Conclusion: Results indicate that vital tooth whitening does not improve overall OHRQOL in older adults

Benchmarking a decade of holistic agro-environmental studies within the Agricultural Catchments Programme

peer-reviewedMeeting sustainable food production challenges requires efficient ways to manage nutrients and mitigate the losses of nitrogen (N) and phosphorus (P) to water. Future nutrient management therefore requires a clearer understanding of the relative influence of soils, geology, farm practice, landscape and weather on the propensity for nutrients to be lost to water. Within the Agricultural Catchments Programme (ACP), environmental, agronomic and socioeconomic data have been gathered since 2009, using the same experimental methodology in five meso-scale river catchments, and one karst spring zone, covering a range of soils, landscapes and farming systems. The ACP has contributed to a better understanding of nutrient mobilisation and transfer pathways and highlighted the influence of the physical and chemical environment as well as agricultural and meteorological drivers on diffuse nutrient loss to ground and surface waters. The environmental quality standards were breached for N and/or P in some of the catchments, but for different reasons and not always clearly linked to the source pressures within the catchment. There are clearly no one-size-fits-all solutions for mitigation of nutrient losses to water. A better understanding of the underlying processes is required to identify critical source areas, to select mitigation strategies, when to implement them and to build realistic expectations of their impact. Sustainability in an agricultural setting is not confined to environmental issues, but also includes social, economic and innovative aspects. To maximise farmers’ uptake of environmental measures, the actions should encompass all these aspects of sustainability. Integrated knowledge transfer is key

W=0 pairing in Hubbard and related models of low-dimensional superconductors

Lattice Hamiltonians with on-site interaction $W$ have W=0 solutions, that is, many-body {\em singlet} eigenstates without double occupation. In particular, W=0 pairs give a clue to understand the pairing force in repulsive Hubbard models. These eigenstates are found in systems with high enough symmetry, like the square, hexagonal or triangular lattices. By a general theorem, we propose a systematic way to construct all the W=0 pairs of a given Hamiltonian. We also introduce a canonical transformation to calculate the effective interaction between the particles of such pairs. In geometries appropriate for the CuO$_{2}$ planes of cuprate superconductors, armchair Carbon nanotubes or Cobalt Oxides planes, the dressed pair becomes a bound state in a physically relevant range of parameters. We also show that W=0 pairs quantize the magnetic flux like superconducting pairs do. The pairing mechanism breaks down in the presence of strong distortions. The W=0 pairs are also the building blocks for the antiferromagnetic ground state of the half-filled Hubbard model at weak coupling. Our analytical results for the $4\times 4$ Hubbard square lattice, compared to available numerical data, demonstrate that the method, besides providing intuitive grasp on pairing, also has quantitative predictive power. We also consider including phonon effects in this scenario. Preliminary calculations with small clusters indicate that vector phonons hinder pairing while half-breathing modes are synergic with the W=0 pairing mechanism both at weak coupling and in the polaronic regime.Comment: 42 pages, Topical Review to appear in Journal of Physics C: Condensed Matte

A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation

Nanoparticles introduced in living cells are capable of strongly promoting the aggregation of peptides and proteins. We use here molecular dynamics simulations to characterise in detail the process by which nanoparticle surfaces catalyse the self- assembly of peptides into fibrillar structures. The simulation of a system of hundreds of peptides over the millisecond timescale enables us to show that the mechanism of aggregation involves a first phase in which small structurally disordered oligomers assemble onto the nanoparticle and a second phase in which they evolve into highly ordered beta-sheets as their size increases

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Recruitment and follow-up of adolescent and young adult cancer survivors: the AYA HOPE Study

IntroductionCancer is rare in adolescents and young adults (AYA), but these patients have seen little improvement in survival in contrast to most other age groups. Furthermore, participation in research by AYAs is typically low. We conducted a study to examine the feasibility of recruiting a population-based sample of AYA survivors to examine issues of treatment and health outcomes.MethodsIndividuals diagnosed in 2007-08 and age 15-39 at the time of diagnosis with acute lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell cancer or sarcoma were identified by 7 Surveillance, Epidemiology, and End-Results (SEER) cancer registries, mailed surveys within 14 months after diagnosis and again a year later, and had medical records reviewed.Results525 (43%) of the eligible patients responded, 39% refused and 17% were lost to follow-up. Extensive efforts were required for most potential respondents (87%). 76% of respondents completed the paper rather than online survey version. In a multivariate model, age, cancer site, education and months from diagnosis to the first mailing of the survey were not associated with participation, although males (p  <  0.01), Hispanics and non-Hispanic blacks (p  <  0.001) were less likely to participate. 91% of survivors completing the initial survey completed the subsequent survey.DiscussionDespite the response rate, those who participated adequately reflected the population of AYA cancer survivors. The study demonstrates that cancer registries are valuable foundations for conducting observational, longitudinal population-based research on AYA cancer survivors.Implications for cancer survivorsAchieving a reasonable response rate in this population is possible, but requires extensive resources

Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

<p>Abstract</p> <p>Background</p> <p>Several studies demonstrated that epidermal growth factor receptor (EGFR) gene copy number (GCN) correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC) and to anti-EGFR monoclonal antibodies (MoAbs) in metastatic colorectal cancer (CRC). In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic <it>in situ </it>hybridization (CISH) is an alternative technique to fluorescence <it>in situ </it>hybridization (FISH), but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC) of lung nodules has not yet been established.</p> <p>Methods</p> <p>We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas) and 13 lung metastases from CRC.</p> <p>Results</p> <p>Of the 33 FNAC analyzed by CISH, 27 (82%) presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30%) showed a low polysomy, 15 (45%) a high polysomy and 2 (6%) NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p < 0.0001). Two cases were amplified with both assays, whereas 1 case of NSCLC was amplified by FISH only. CISH sensitivity was 67%, the specificity and positive predictive value (PPV) was 100%, and the negative predictive value (NPV) was 97%.</p> <p>Conclusions</p> <p>Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.</p