Production of liquid transportation fuels from biomass-derived syngas via Fischer-Tropsch synthesis

In this thesis the use of foamed iron (III) oxide catalysts for the production of liquid fuels from a carbon dioxide rich bio syngas via the Fischer Tropsch process is evaluated. Unsupported Fe2O3 catalysts promoted with Cu and K are generated using both a co precipitation and a foaming sol gel process before being characterised to study the effect of synthesis conditions on physical properties. Experiments were then performed in a purpose-built fixed bed reactor to assess the catalyst performance under industrial Fischer Tropsch conditions. The co precipitated catalysts, both unpromoted and promoted, were shown to have activity in the Fisher Tropsch reaction. Promotion increased the rate of conversion of syngas to hydrocarbons and increased production of longer chain lengths. In contrast, the unpromoted foamed catalysts exhibited little Fischer Tropsch activity. However, high levels of inherent activity are achieved once promoted. All the promoted foamed catalysts produced a comparable product range, with similar Anderson Schulz Flory distributions being seen. However overall rates of conversion CO and H2 to hydrocarbons varied within the promoted foamed catalyst group. Higher calcination temperatures resulted in a dramatic loss of microporous surface area and hence lower overall hydrocarbon production rates as active surface sites were lost. Production rates over foamed catalyst pellets in excess of 300μm diameter suffered from the introduction of mass transfer limitations, thus reducing the rate. In addition, a new dynamic model of the Fischer Tropsch reaction was developed, accounting for variable temperature dependant gas density and the reduction in gas velocity as the reaction proceeds. This was used to investigate the dynamic thermal response of the reactor to changes in inlet conditions, demonstrating the exaggeration of thermal responses generated when reaction contraction is accounted for. The phenomenon of wrong way behaviour over a fixed bed is also reviewed for loss of feed heating and reduced feed flow cases.Open Acces

Lithological and sequence stratigraphic examination of the Madison Group marker beds, eastern Williston Basin margin, North Dakota

The Frobisher-Alida interval consists of eight log-defined subintervals or “beds” within the Mississippian upper Mission Canyon and lower Charles Formations of the Madison Group in the Williston Basin. The subintervals are composed of predominantly evaporite and carbonate lithologies, and include in descending order: 1) Midale, 2) Rival, 3) Bluell, 4) Sherwood, 5) Mohall, 6) Glenburn, 7) Wayne, and 8) Landa. The top of the lower six subintervals are separated by thin but areal extensive log-defined markers of contrasting lithologies and include in descending order: 1) State A, 2) Sherwood Argillaceous Marker (S.A.M.), 3) K-1, 4) K-2, 5) K-3, and 6) Landa Marker. An additional localized marker, State A2, is identified defining the lower boundary of an Upper Bluell subinterval. This study focuses on the lithologic and sequence stratigraphic significance of markers with the exception of the Landa Marker. The area studied covers Burke, Mountrail, Renville, Ward, western Bottineau and northwestern McHenry Counties in North Dakota. Geologically, the region is situated on the eastern flank of the Williston Basin; characterized by a shallow dipping (between 0.25 and 0.5 degrees) carbonate platform of an epicontinental sea on the western flank of the North American craton. Seventy-three marker descriptions were completed on the six markers from fifty-eight different cores throughout the study area. Six lithotypes reflecting unique depositional conditions were identified within the markers and include: 1) anhydrite, 2) dolomudstone, 3) dolomitic sandstone, 4) calc-mud/wackestone, 5) grain-supported, and 6) skeletal wackestone. Of these, the dolomudstone and dolomitic sandstone lithotypes are considered characteristic marker bed lithotypes, while the remaining are present as interbeds. The lithotypes reflect deposition in a variety of environments from a supralittoral, salina-like embayment to the east, through shallow sublittoral settings and into an open marine environment to the west. The section studied lies within the first-order Kaskaskian megasequence and second-order Madison sequence which includes part of the upper Bakken shale and extends to the basinwide Madison unconformity. The Frobisher-Alida interval represents a single third-order sequence spanning 2-3 million years and the compositional subintervals are considered fourth-order sequences. The subintervals are progradational and become increasingly restrictive up section and therefore represent individual fourth-order regressive systems tracts. Markers dominated by the dolomudstone lithotype (State A, State A2, S.A.M.) reflect deposition during a highstand systems tract where the basal contact represents a fourth-order maximum flooding surface. Dolomitic sandstone markers reflect initial deposition during a lowstand systems tract with unconsolidated sediments reworked and further cemented with the subsequent transgressive tract. Contrasting sediment input and consolidating mechanisms obscure definitive sequence surfaces; therefore, a sequence stratigraphic model is defined that places the maximum regressive surface at the lower contact and maximum flooding surface at the upper contact of the sandstone dominated markers

A feasibility investigation of mindfulness-based cognitive therapy for people with Huntington's disease

Background Huntington’s disease (HD) is an inherited neurodegenerative condition which affects movement, coordination and cognitive functioning. Psychological difficulties are commonly experienced; however, psychological interventions have been little researched with this population. We investigated the feasibility of conducting a randomised controlled trial (RCT) of mindfulness-based cognitive therapy (MBCT) with people with the HD genetic mutation, either pre-manifest (before onset of movement symptoms) or at an early disease stage. Specifically, we evaluated the willingness of participants to be recruited into and complete the intervention; the acceptability of the study measures in relation to completion; the feasibility of offering the standard MBCT course to people with HD; the acceptability of the intervention and the estimated effect sizes. Methods Participants were recruited from two UK HD centres and took part in an 8-week course of MBCT, with three reunions throughout the following year. Stress, depression, anxiety, and mindfulness were measured pre-, mid-, and post-course, at 3 months and at 1 year. Sleep, quality of life, positive affect and coping were measured pre- and post-course, at 3 months and at 1 year. Descriptive data and approximate effect sizes were calculated. Interviews were conducted post-course and at 1 year and data pertaining to the acceptability of the course were extracted. Results Twelve participants took part in two groups; all were pre-manifest. Levels of depression and anxiety were low pre-course leaving little room for improvement. Changes in stress and in some aspects of mindfulness were medium to large. The qualitative data suggested participants rated the course highly and found it helpful and no changes to the standard course were needed. Recruitment levels were below those anticipated. Most measures were found to be acceptable. Conclusions Although the course was acceptable to those who took part, given the difficulties in recruiting and the rarity of HD, conducting an RCT of MBCT teaching groups in person does not seem feasible. However, alternative modes of course delivery (e.g. online) would allow the recruitment of people from a greater geographical area and may make an RCT feasible; this revised focus would be suitable for future feasibility studies

A pilot evaluation of mindfulness based cognitive therapy for Huntington's disease

Background Many people with the Huntington’s disease (HD) gene, both pre-manifest and manifest, experience low mood, anxiety and other psychological difficulties. Medication can alleviate these difficulties to some extent, but it is not effective for everyone, and is not always the preferred option. Psychological interventions may provide an alternative or additional way of alleviating distress. Aims To see if a particular type of psychological therapy, mindfulness-based cognitive therapy (MBCT), is an acceptable and useful way of alleviating psychological distress for people with the HD gene who are pre-manifest or at an early disease stage. Methods To date 10 pre-manifest HD gene carriers have completed an 8 week course of MBCT led by an experienced mindfulness teacher. The course consisted of weekly 2 hour sessions and up to an hour of home practice every day. Quantitative measures of anxiety, depression, stress and mindfulness were administered pre- and post-course. Qualitative data about participants’ experiences were gathered via semi-structured interview. We are currently recruiting for a second course and aim to run this in Autumn 2016. Results Mean depression levels were low pre-course and thus, unsurprisingly, little change was observed in mean depression post course. However, large effect sizes were seen for mean changes in anxiety and stress and in five aspects of mindfulness (describing, non-judging, non-reacting, observing and acting with awareness). The interview data (and participants’ regular attendance) also suggested that participants found the course acceptable. Furthermore they reported that they thought it beneficial for their wellbeing now and also that the skills they had learnt would be useful in the future. Conclusions MBCT appears to be an acceptable psychological approach for some pre-manifest individuals with the HD gene. Early results indicate that learning mindfulness is possible and can be beneficial. Further research is needed with larger samples to show if it can significantly reduce psychological distress and would benefit from including more individuals with raised depression at baseline to enable changes in depression to be detected. Some recruitment difficulties were encountered and these and the possible implications for future courses will be presented

Experiences of mindfulness-based cognitive therapy for premanifest Huntington’s disease

Background:Psychological difficulties such as anxiety, depression, and irritability are common in Huntington’s disease, even for premanifest individuals. However, very little evidence exists of psychological approaches to manage this distress. We have conducted a feasibility study with an embedded qualitative component to investigate the possibility of using mindfulness-based cognitive therapy (MBCT) and present here the findings from the qualitative data. Objective:To investigate the experience of premanifest individuals learning and practising mindfulness through completing a course of MBCT. Methods:Twelve premanifest individuals completed a course of MBCT and attended three follow up reunion meetings over the following year. Eleven participants agreed to be interviewed post-course and ten participants one year post-course about their experience of the course and any impact on their lives. Seven participants nominated a friend or relative (supporter) to be involved in the research, of whom six agreed to be interviewed post-course and two at one year about the impact of the course on the participants. Data were analysed using reflexive thematic analysis. Results:Four themes were constructed from the data: 1) A meeting of minds: the group facilitating learning and support; 2) Mindfulness is hard, but enables more effective emotional management; 3) Mindfulness can change the relationship with self and others; and 4) Benefiting from mindfulness: the importance of persistence. Conclusion:The participants who completed the course found it beneficial. Some participants reported reductions in psychological distress, a greater sense of calm and better emotion regulation, with some of these positive changes also noticed by supporters. MBCT is worthy of further investigation for this population

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands

Bi-allelic loss-of-function CACNA1B mutations in progressive epilepsy-dyskinesia

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment

Prevalence, phenotype and architecture of developmental disorders caused by de novo mutation: The Deciphering Developmental Disorders Study

Individuals with severe, undiagnosed developmental disorders (DDs) are enriched for damaging de novo mutations (DNMs) in developmentally important genes. We exome sequenced 4,293 families with individuals with DDs, and meta-analysed these data with published data on 3,287 individuals with similar disorders. We show that the most significant factors influencing the diagnostic yield of de novo mutations are the sex of the affected individual, the relatedness of their parents and the age of both father and mother. We identified 94 genes enriched for damaging de novo mutation at genome-wide significance (P < 7 × 10−7), including 14 genes for which compelling data for causation was previously lacking. We have characterised the phenotypic diversity among these genetic disorders. We demonstrate that, at current cost differentials, exome sequencing has much greater power than genome sequencing for novel gene discovery in genetically heterogeneous disorders. We estimate that 42% of our cohort carry pathogenic DNMs (single nucleotide variants and indels) in coding sequences, with approximately half operating by a loss-of-function mechanism, and the remainder resulting in altered-function (e.g. activating, dominant negative). We established that most haplo insufficient developmental disorders have already been identified, but that many altered-function disorders remain to be discovered. Extrapolating from the DDD cohort to the general population, we estimate that developmental disorders caused by DNMs have an average birth prevalence of 1 in 213 to 1 in 448 (0.22-0.47% of live births), depending on parental age

Prevalence and architecture of de novo mutations in developmental disorders

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year