An investigation into the potential impacts of ocean acidification and ocean fertilisation on the genetic diversity of marine bacterial assemblages

Based on the increase of 16S rRNA gene sequences in databases it is possible to design improved oligonucleotide primers for this gene. Primers were designed in silico to specifically amplify fragments of the gene from the Alpha, Beta and Gamma subgroups of the Proteobacteria, as well as from Bacteroidetes, Firmicutes, Cyanobacteria and Planctomycetes and tested in silico and in vitro. The aim was to investigate bacterioplankton diversity and reveal greater fingerprint diversity within these groups than is possible using primers specific for the entire domain Bacteria, and also to reduce clone library redundancy. It was then aimed to investigate the potential impacts of increased pCO2 and ocean fertilisation with iron (Fe) and phosphorus (P), on bacterioplankton diversity. Group-specific clone libraries representing contrasting marine regions were analysed, and the usefulness and specificity of the primers validated. The clone libraries showed members of the oligotrophic marine group (OMG) to be present in an in situ coastal mesocosm supplemented with nutrients. The newly-developed group-specific primers were used in combination with an improved method of denaturing gradient gel electrophoresis (DGGE) to profile in detail bacterial communities in mesocosms, which were maintained at 750 ppm of pCO2, the level projected for the global surface ocean in the year 3000, and 380 ppm of CO2, the present level. Increased pCO2 correlated with a decrease in abundance of some members of the Gammaproteobacteria. Otherwise there was little impact on diversity due to raised pCO2. The same DGGE protocol was applied to samples from an ocean Fe and P fertilisation experiment. Diversity change due to Fe was not evident. However in seawater amended with P there was an explosive growth of some cells with 16S rRNA genes similar to those of the SAR86 clade, and others with similarity to Gammaproteobacteria with large genomes such as Oceanospirillum sp. and Psychromonas sp

The mechanisms of antibody generation in the llama

The llama is able to generate a unique class of antibody. The heavy chain immunoglobulins consist only of two heavy chain polypeptides and bind antigen specifically through single protein domains. Although the mechanisms by which such an antibody interacts with antigen has been studied at some length the manner in which the heavy chain antibody is generated within the llama is unknown. In this study a number of components of the llama immune system have been characterised. The isolation of genes encoding the variable domain of the heavy chain antibody indicates that specific genetic elements within the llama genome are responsible for the generation of the heavy chain antibody. The discovery of constant region genes that encode the heavy chain antibody provides an explanation for the absence of a major immunoglobulin domain from the final, secreted gene product. The lack of this domain within the expressed antibody is believed to be the result of a single nucleotide splice site mutation. In order to investigate the process of llama antibody generation further additional components of the llama immune system, the recombination activating genes (rag) were isolated. One such llama rag gene (rag-i) was cloned, expressed and utilised in an in vitro assay system to investigate recombination events taking place during antibody generation. This assay involved the use of specific signal sequences derived from variable domain gene sequence data and represents, to our knowledge, the first examination of non-murine RAG activity. Through the use of this system distinct differences between llama and mouse recombination signal sequences (RSSs) were uncovered. These differences, located within a specific region of the RSS known as the coding flank, may play an important role in llama antibody generation. These results have led to the proposal of a number of models for the mechanisms involved in llama antibody generation

An investigation into the potential impacts of ocean acidification and ocean fertilisation on the genetic diversity of marine bacterial assemblages

Based on the increase of 16S rRNA gene sequences in databases it is possible to design improved oligonucleotide primers for this gene. Primers were designed in silico to specifically amplify fragments of the gene from the Alpha, Beta and Gamma subgroups of the Proteobacteria, as well as from Bacteroidetes, Firmicutes, Cyanobacteria and Planctomycetes and tested in silico and in vitro. The aim was to investigate bacterioplankton diversity and reveal greater fingerprint diversity within these groups than is possible using primers specific for the entire domain Bacteria, and also to reduce clone library redundancy. It was then aimed to investigate the potential impacts of increased pCO2 and ocean fertilisation with iron (Fe) and phosphorus (P), on bacterioplankton diversity. Group-specific clone libraries representing contrasting marine regions were analysed, and the usefulness and specificity of the primers validated. The clone libraries showed members of the oligotrophic marine group (OMG) to be present in an in situ coastal mesocosm supplemented with nutrients. The newly-developed group-specific primers were used in combination with an improved method of denaturing gradient gel electrophoresis (DGGE) to profile in detail bacterial communities in mesocosms, which were maintained at 750 ppm of pCO2, the level projected for the global surface ocean in the year 3000, and 380 ppm of CO2, the present level. Increased pCO2 correlated with a decrease in abundance of some members of the Gammaproteobacteria. Otherwise there was little impact on diversity due to raised pCO2. The same DGGE protocol was applied to samples from an ocean Fe and P fertilisation experiment. Diversity change due to Fe was not evident. However in seawater amended with P there was an explosive growth of some cells with 16S rRNA genes similar to those of the SAR86 clade, and others with similarity to Gammaproteobacteria with large genomes such as Oceanospirillum sp. and Psychromonas sp.EThOS - Electronic Theses Online ServiceNatural Environment Research Council (Great Britain) (NERC)GBUnited Kingdo

Trialling the Cambridge Personal Styles Questionnaire: Measuring and profiling values of BSc nursing students.

Collaborative project between Bucks New University and Cambridge Assessment (University of Cambridge Examinations). We are one of the institutions (including City University) trialling the CPSQ (Cambridge Personal Styles Questionnaire)

Structure-based design of a bromodomain and extraterminal domain (BET) inhibitor selective for the N-terminal bromodomains that retains an anti-inflammatory and antiproliferative phenotype

The bromodomain and extraterminal domain (BET) family of epigenetic regulators comprises four proteins (BRD2, BRD3, BRD4, BRDT), each containing tandem bromodomains. To date, small molecule inhibitors of these proteins typically bind all eight bromodomains of the family with similar affinity, resulting in a diverse range of biological effects. To enable further understanding of the broad phenotype characteristic of pan-BET inhibition, the development of inhibitors selective for individual, or sets of, bromodomains within the family is required. In this regard, we report the discovery of a potent probe molecule possessing up to 150-fold selectivity for the N-terminal bromodomains (BD1s) over the C-terminal bromodomains (BD2s) of the BETs. Guided by structural information, a specific amino acid difference between BD1 and BD2 domains was targeted for selective interaction with chemical functionality appended to the previously developed I-BET151 scaffold. Data presented herein demonstrate that selective inhibition of BD1 domains is sufficient to drive anti-inflammatory and antiproliferative effects

Implementing, monitoring and measuring a programme of relationship marketing

This single, embedded case study examined the marketing activities of Flensted Catering A/S, a Danish food company. The case is the first one in a series of case studies constituting a larger research project with the overall objective of understanding how to implement relationship marketing, how to monitor the outputs and how to measure the returns. In 1996, the company embarked on a three-phase programme directed at building relations with customers. As a prelude to the implementation, Flensted Catering A/S conducted focus groups and issued questionnaires to determine customer perceptions of how the company could meliorate its performance. Subsequently, the Danish firm established project teams, instituted customer-focused staff training and sought to improve communications with customers. Following the implementation, the monitoring revealed that Flensted Catering A/S was rated as a better supplier by 43 per cent of its customers and that customer retention had risen to 94 per cen

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

Pratical geometry for technical drawing

256 p.; 25 cm