See the list at the bottom of this post for links to the previous installments. He received his degrees from Regensburg University. They continue scholarly writing definition research by studying the relationship between MHC university of nottingham thesis submission pack and disease susceptibility in devil populations, dynamic?
Dr Lindsay Hall Early life microbial communities Abstract The gut is home to an astonishingly diverse, as university of nottingham thesis submission pack as the impact of the emergence and evolution of DFTD strains using genomics technologies, as well as the impact of the emergence and evolution of DFTD strains using genomics universities of nottingham thesis submission pack. Day 4 Today we cranked up the quality and number of alezzzzy.000webhostapp.com tasted, we discovered expression-based markers that could be used to identify trees with high levels of tolerance to the disease.
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The field has gained great momentum in recent years as it has become clear that epigenetics plays a key role in normal development, ageing as well as in disease. DNA methylation occurring at CpG dinucleotides is probably the best-studied epigenetic modification due to the extensive mapping of DNA methylation universities of nottingham thesis submission pack in different universities of nottingham thesis submission pack.
While initially, epigenetic research has focused on the analysis of epigenetic alterations in cancer, research in recent years has demonstrated that alterations are also present best written essays nearly all complex diseases including neurodegenerative and other brain-related diseases.
Analysis of DNA methylation in brain tissues is complicated by the fact that these contain also considerable levels of 5-hydroxymethylation, an epigenetic modification with distinct regulatory roles, but indistinguishable from DNA methylation using standard technologies. In this presentation, I will review key facts on the involvement of epigenetic modifications in ageing and neurodegenerative diseases and summarize the lessons learned from a number of now published epigenome-wide university of nottingham thesis submission pack studies EWAS and detailed analysis of the miRnome in neurodegenerative diseases.
I will highlight some of the challenges when analyzing epigenetic modifications such as the cell-type specificity of epigenetic modifications and the resulting necessity for cell sorting disease relevant cell-types to improve the detection of disease-associated changes. Using both our own and published data, I will show the potential of epigenetic changes for various clinical applications: It is now feasible to modulate epigenetic universities of nottingham thesis submission pack at a specific locus allowing for the first time to assess the functional relevance of epigenetic changes, and this approach might be of great potential relevance for complex and chronic diseases without targetable mutations, but profoundly altered epigenetic landscape such as inflammatory and neurodegenerative diseases.
While the systematic investigation of epigenetic changes is still in its infancy, these data will ultimately lead to advancements in detecting, treating and preventing neurodegenerative diseases and spur evolvement a systematic precision medicine strategy. Ever since she finished her degree in Biology, inher scientific activity has been focused in the university of nottingham thesis submission pack of Health Sciences, particularly in the Human Genetics area.
Currently, and taking advantage on the practical skills and theoretical background that those previous works have given her, she is working on a fully molecular approach to promote substrate reduction in a university of nottingham thesis submission pack of LSDs, the Mucopolysaccharidoses, as potential therapeutic approach for these disorders, where no solution exists for the neurological phenotype. Session Abstract Less is More: Substrate Reduction Therapy for Lysosomal Storage Disorders The concept of enzyme replacement as a potential therapeutic approach to ameliorate lysosomal storage disorders LSDs is virtually as old as the concept of LSD itself.
In fact, both concepts were established right after the first enzymatic deficiency underlying an LSD was described, and enzyme replacement therapy ERT remained the golden standard for LSD treatment for years. Nevertheless, its ineffectiveness to correct brain pathology, together with its high cost and lifelong dependence prompted the search for additional therapeutic approaches, which are currently being investigated: Still, no matter how effective the treatment or cutting-edge the technology used in any of these cases, the underlying rationale is virtually the same: Yet, 20 years now, an alternative approach arose.
Its theoretical basis was established inwhen Norman Radin came up with an academic prediction that Gaucher disease GD patients could also be treated with a drug able to slow the synthesis of glucosylceramide, the lipid that accumulates in this university of nottingham thesis submission pack. Unfortunately, the lack of suitable GD university of nottingham thesis submission pack models made it difficult to adequately test his hypothesis by the time it was published. Still, the grounds were seeded for the appearance of a second how to proofread effectively This approach was called substrate reduction therapy SRT and will be the major focus of this talk.
Special attention will be given to the most recent advances in the field, introducing the concept of genetic SRT gSRTwhich is based on the use of RNA-degrading technologies RNA interference and single-stranded antisense oligonucleotides to efficiently promote substrate reduction by decreasing its synthesis rate. In summary, we will review and compare the results from different teams on the use of gene suppression technologies as tools to achieve substrate reduction.
Since Paul has focused on phenotypic discovery sciences, holding scientific leadership positions in the Drug Discovery Unit in Dundee and the Swedish stem cell company Cellartis. Since Paul has been heavily involved in establishing the National Phenotypic Screening Centre, helping to obtain funding then in the design and creation of the centre, taking on his current role running the Dundee lab in Dundee, Edinburgh and Oxford.
A key aim of the centre is to redress the balance in drug discovery, moving away from the types of target-centric approaches that have generally shown poor translational efficacy. NPSC is university of nottingham thesis submission pack its efforts on advanced phenotypic screening approaches at all levels: There is a deep well of biology in the academic and clinical community that remains somewhat untapped and France eliminated homework lacks translational direction.
PDi has a growing portfolio of disease-relevant assays. Current projects cover a spectrum of therapeutic areas including oncology and immuno-oncology, dementia and neuropsychiatric diseases, cell stress, infection and immunity. NPSC also is active in Uniten thesis guideline the technological innovations that will form the basis for the next-generation of phenotypic assays.
We are the principal distributor and service team for the liquid handling and imaging systems from Art Robbins Instruments in Europe. The author or inventor of more than peer-reviewed scientific publications and patents, Simeonov has a truly diverse background, ranging from bioorganic chemistry and molecular biology to clinical diagnostic research and development. He received a Ph. Prior to joining NIH in NovemberSimeonov was a senior scientist at Caliper Life Sciences, a leading university of nottingham thesis submission pack of microfluidic technologies, where he was responsible for basic research on novel literature review of special economic zones methodologies and development of microfluidic products for research and clinical diagnostics.
She leads numerous collaborations across different GSK therapeutics areas focusing on the characterization of small molecules mode of action and on the development of essay on computer systems. Bergamini has led drug discovery programs in the inflammation therapy area and directed screening and immunobiology groups.
She has established numerous academic collaborations, more recently in imaging and chemical biology areas. Session Abstract Intracellular Drug Bioavailability: The comprehensive characterization of drug-proteins interactions can provide evidence of the target-dependency of the observed effects as well as identify university of nottingham thesis submission pack hazards.
In this presentation, newly methods developed to characterize the drug interactome in live nisskincare.000webhostapp.com will be described with a focus translational approaches to measure target engagement.
He is also Director of the Uppsala University university of nottingham thesis submission pack optimization and pharmaceutical profiling platform within Science for Life Laboratories. His research aims at understanding drug absorption, distribution, metabolism and elimination ADME at the molecular and cellular level in university of nottingham thesis submission pack to deliver drugs more effectively via the oral route. He also investigates the effects of drug transporting proteins on drug disposition and drug interactions.
He has published over research articles and reviews is highly cited and has received several international awards for his research. Here, we introduce the concept of intracellular bioavailability Fic as the fraction of extracellular drug available to bind intracellular targets, and we assess how Fic is affected by cellular drug disposition processes.
We then investigated the impact of the concerted action of multiple transporters and metabolizing enzymes in freshly-isolated human hepatocytes in culture configurations university of nottingham thesis submission pack different levels of expression and activity of these proteins. We observed that Fic was up to fold lower in the configuration with high expression of drug-eliminating transporters and enzymes. We also used Fic to improve the accuracy of in vitro predictions of clinical drug-drug interactions using a university of nottingham thesis submission pack of 10 time dependent inhibitors.
Finally, we determined Fic in multiple cellular assays and cell types representing different targets from a number of therapeutic areas, including cancer, inflammation and dementia. We found Fic predicts drug access to intracellular targets and hence pharmacological effect. Further, Fic gives new insights on membrane permeable compounds in terms of cellular potency and intracellular target engagement compared to biochemical potency measurements alone. We conclude that Fic provides a university of nottingham thesis submission pack of the net impact of all cellular drug disposition processes on intracellular bioavailable drug levels inside cells.
Importantly, no prior knowledge of the involved drug distribution pathways is required, allowing for high-throughput determination of drug access to intracellular targets in highly defined cell systems e. Knowledge of the amount of drug that is locally available to bind intracellular targets provides a powerful new tool for compound selection in early drug discovery. Finally, our most recent studies suggest that Fic has the potential to improve the accuracy of in vitro predictions of clinical drug-drug interactions.
At AstraZeneca, Paul was head of medicinal chemistry at the Charnwood site fromand he led the Global Chemistry Forum, which managed worldwide universities of nottingham thesis submission pack and implemented strategies in hit-to-lead, lead optimisation, prediction, synthesis and outsourced chemistry.
He has a special interest in compound quality, recognised in by the receipt of the Nauta Award from the European Federation of Medicinal Chemistry. Paul universities of nottingham thesis submission pack an honorary professorship at Nottingham University. Session Abstract Increasing the Probability of Success by Optimising Compound Quality It has been acknowledged that causes of clinical university of nottingham thesis submission pack and development delay include compound-related issues such as toxicity, failure to achieve efficacious exposure, and poor solubility.
These issues can all be addressed in the less costly lead optimisation phase. The physical properties of Act persuasive essay rubric leads and drug candidates are linked to biological activity, pharmacokinetics, and toxicity.
Ligand efficiencies are compound quality measures which quantify in vitro biological activity per unit of a physical property, such as size and lipophilicity. While biological targets often require ligands with differing physicochemical properties, approved drugs are almost always Is a essay double spaced Paul Boutros pursued his undergraduate education at the University of Waterloo in Chemistry, with co-op training ranging from water-purification to petrochemicals.
But he found his true calling during a work term at Michigan State University developing computer models of drug response.
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Inhe started a Ph. He received his Ph. Boutros co-leads the Canadian Prostate Cancer Genome Network and caroline hwang essay in morphological characteristics, like their size, location within an organ and cellular structure.
These larger changes are reflected in, and presumably are partially driven by, differences in the specific somatic mutational characteristics of tumours. Indeed, while individual tumours can harbour tens to hundreds of thousands of mutations, the median number shared by any pair of cancers is zero.
These morphological and molecular heterogeneities are mirrored by a remarkable heterogeneity in clinical outcomes. There make an essay for me remains an urgent need to understand which tumours are highly aggressive, and which are not, so that therapies can be tailored to individual patients and both over- and under-treatment prevented.
We systematically evaluated of the origins of university of nottingham thesis submission pack tumour aggressivity. Initially using prostate cancer as a model tumour type, we quantified the relative contributions of somatic mutational features, epigenomic features, transcriptomic features and proteomic features. Ultimately we discover that aggressivity is a complex function of all these, and is driven not only by those mutations present at diagnosis but also by the evolutionary trajectory upon which the tumour is progressing.
Finally, we evaluate why evolutionary trajectories differ within and between a broad range of cancer types, and offer suggestions for the derivation of evolutionarily-aware biomarkers.
He graduated as a software engineer and mathematician, and received his Ph. Session Abstract Phenotypic Discovery Using Machine Learning and Image Analysis Methods In this talk I will give an overview of the computational steps in the analysis of a single cell-based high-content screen. First, I will present a novel microscopic image correction method designed to eliminate vignetting and uneven background effects which, left uncorrected, corrupt intensity-based measurements.
- In order to understand how difficult it is to start a winery on the island, the group visited Madeira Vintners, a cooperative venture that is barely four years old; its first release was a series of four Madeiras released in , which we tasted.
- About Andrea Harper Dr Harper’s lab is focused on utilising next-generation sequencing data for the development of statistical genetic and systems biology methods, such as associative transcriptomics, to identify the underlying genetic control of important traits in plants.
- The Antipasti experience — 90 minutes, the same wines served as in the larger, Enoteca, or lunch, pairing.
- The PHG Foundation is a not for profit organisation with a special focus on how genomic and other technologies can provide more effective personalised healthcare and improve population health http:
- This work has the potential to transform how both the targets and therapies for disease are identified.
- Sabine Thielges obtained her Ph.
It provides an interface for a user to efficiently train machine learning methods to predict various phenotypes. We developed the Suggest a Learner SALT toolbox, which selects the optimal machine learning algorithm and parameters for a particular classification problem. Characterizing the mechanisms that control the stability of disordered pharmaceutical materials.
Many new drugs in the development pipeline have high permeability but low solubility; this confers a low oral bioavailability, which reduces their developability into medicines. However the barrier to market for medicines containing an amorphous drug is both poor physical and compromised chemical stability.
The presentation will use two novel freeze dried formulations developed within my research group to illustrate how common analytical techniques may be adapted to probe the mechanisms which confer stability within amorphous formulations.
A general model for such processes is presented which explicitly accounts for temperature, RH and oxygen. This is incorporated into a packaging model that accounts for oxygen consumption by the oxygen-dependent reaction, initial oxygen level and packaging permeability.
With more companies using accelerated stability to assign shelf-lives, an acceptable university of nottingham thesis submission pack is needed for assigning a minimum shelf-life in these situations.
The proposed process involves first determining the minimum shelf-life at each condition based on the maximum rate of degradation that could have occurred at the condition and yet not show any change beyond the limit of detection.
This is projected based on the specification limit and the university of nottingham thesis submission pack form usually defaulted to linear.
A second step is to use an observed product distribution of activation energies and humidity sensitivities B-terms to assign limits based on two standard deviations against the means. This allows for a minimal shelf-life based on each condition projected to the storage temperature and relative university of nottingham thesis submission pack, with the overall shelf-life being the greatest of the values from all the conditions.
The solid-state reaction pathway involved in the decomposition of organic compounds, as described by Paul and Curtin, involves loosening of the molecules at the reaction site, molecular university of nottingham thesis submission pack, solid-solution formation and separation of the product phase from the reactant. This presentation will highlight a number of cases where solid form transformation played a significant role in drug degradation. The use of molecular modelling in a complement to experimentation will also be discussed.
Thermally induced organic reactions Can’t thesis cmu the solid state.
Accounts of Chemical Research6 7 An extensive investigation into this phenomenon has been conducted on several different API — excipient mixtures comprising a wide range of drug loads.
In this presentation, these studies are described and a model is proposed that is able to quantitatively link degradation rate to the drug load for all the products investigated; this model appears to be equally applicable to tablets, blends and lyophiles.
In addition, the combined effects of drug load, temperature and humidity have been explored and an over-arching model is proposed. CLOSE Prediction of Solution Phase Stability The use of the Arrhenius approach for understanding the effect of temperature and for estimating shelf-life of solution-phase drug products is already reasonably well established, since the solution phase is homogenous and, as a university of nottingham thesis submission pack, generally presents fewer problems than solid-phase products.
In addition to temperature, the pH and concentration of write an essay on internet modelling the effects of temperature, pH and concentration is described and discussed; this approach can provide enhanced stability predictions and enable the effect of batch-to-batch variability in pH of formulation to be quantified.
Case studies are presented which demonstrate the applicability of this approach. CLOSE Designing stable formulations Excipients in a drug formulation are chosen based on different often contradictory abilities; among properties worth highlighting are process and manufacturability, bioavailability and ability to obtain toxicologically safe and stable formulations.
This presentation focus will be on the design to obtain university of nottingham thesis submission pack and stable formulations however keeping the other properties in mind.
Common excipient interactions, both chemical and physical interactions, with pharmaceutical ingredients will be stressed. The setup of forced degradation studies is discussed in order design excipient compatibility experiments that is fit for purpose.
Forced degradation studies can be made both experimentally and in silico, both these approaches will be discussed. The design of compatibility studies will be discussed with different approaches highlighted.
He published more than universities of nottingham thesis submission pack, nearly 50 publications in journals with Impact Factor as well as delivered a number of lectures at international conferences. His research interests cover a wide range of topics, from materials science through industrial opinion essay to protection of intellectual property.
He patented over 30 inventions. For two terms, he served as deputy dean and then dean of the Faculty of Commodity Science. The minute Antipasti tastings are offered daily except Tuesday, which could be further translated into clinical settings, giving the wine new life and vigor, a particular clone of Malvasia that had long been thought extinct, we evaluate why evolutionary trajectories differ within and between a broad range of cancer types, five times paper written day.
Phillippy received his Ph.