A new approach to detect similar proteins from 2D Gel Electrophoresis Images.

This paper addressed the problem of identification errors due to protein mobility, common in earlier methods. A generalised shape matching algorithm is described that achieved and accuracy of greater than 90% on the test samples. The algorithm was also highly selective in defining the search space, thereby offering a significant computational speed advantage. The output from this work later formed part of an image object keying database, that offered significant benefits to other researchers

High yield fusion in a Staged Z-pinch

We simulate fusion in a Z-pinch; where the load is a xenon-plasma liner imploding onto a deuterium-tritium plasma target and the driver is a 2 MJ, 17 MA, 95 ns risetime pulser. The implosion system is modeled using the dynamic, 2-1/2 D, radiation-MHD code, MACH2. During implosion a shock forms in the Xe liner, transporting current and energy radially inward. After collision with the DT, a secondary shock forms pre-heating the DT to several hundred eV. Adiabatic compression leads subsequently to a fusion burn, as the target is surrounded by a flux-compressed, intense, azimuthal-magnetic field. The intense-magnetic field confines fusion $\alpha$-particles, providing an additional source of ion heating that leads to target ignition. The target remains stable up to the time of ignition. Predictions are for a neutron yield of $3.0\times 10^{19}$ and a thermonuclear energy of 84 MJ, that is, 42 times greater than the initial, capacitor-stored energy

A framework for molecular biology databases integration using context graph keying.

This paper proposed a novel framework for integrating public domain molecular biology databases with the aid of a context graph. A context graph is used to map data in order to establish an integration domain for the participating multi-resource database federation. Data are presented in a consolidated form upon retrieval from the multiple databases. The approach presented in this paper is novel in the sense that, it can be implemented within a component database and can initiate data consolidation collected from multiple sources without users' intervention. The approach has received considerable interest from the research community

Prediction of Type II MODY3 diabetes using backpercolation.

This paper examined the use of the backpercolation neural network algorithm to identify mutated MODY3 gene sequence data that is responsible for type II (maturity onset) diabetes. It was then demonstrated that a supervised feed forward method gave more accurate results in predicting point mutation in genes than the neural network backpropagation method. This paper brought the technique to the attention of other researchers as to how the method can be used for this and for the prediction of other diseases. The technique had been widely used in analysing environmental data is now commonly used in Bioinformatics

Integration of biological data resources using image object keying.

This paper proposes a novel concept of ‘image object keying'. The work builds on earlier research in this area and shows how the 3D structure of a protein can be retrieved interactively from a gel electrophoresis protein spot. It uses intelligent image matching operations like the Hough Transform and Edge Detection techniques. Unique aspects are that searches may be initiated from multiple biological resources but with the results being integrated into a single page. A significant outcome of this work is that it enables researchers to search the database without the need to write and complex script

Natural history of mitochondrial disorders: a systematic review

The natural history of a disease defines the age of onset, presenting features, clinical phenotype, morbidity and mortality outcomes of disease that is unmodified by treatments. A clear understanding of the natural history of mitochondrial disorders is essential for establishing genotype-phenotype-prognosis correlations. We performed a systematic review of the reported natural history of mitochondrial disease by searching the literature for all published natural history studies containing at least 20 individuals. We defined a phenotype as 'common' if it was observed in ≥30% of cases in a study, thereby highlighting common and uncommon phenotypes for each disorder. Thirty-seven natural history studies were identified encompassing 29 mitochondrial disease entities. Fifty-nine percent of disorders had an onset before 18 months and 81% before 18 years. Most disorders had multisystemic involvement and most often affected were the central nervous system, eyes, gastrointestinal system, skeletal muscle, auditory system and the heart. Less frequent involvement was seen for respiratory, renal, endocrine, hepatic, haematological and genitourinary systems. Elevated lactate was the most frequent biochemical abnormality, seen in 72% of disorders. Age of death was <1 y in 13% of disorders, <5 y in 57% and <10 y in 74%. Disorders with high mortality rates were generally associated with earlier deaths. The most robust indicators of poor prognosis were early presentation of disease and truncating mutations. A thorough knowledge of natural history has helped to redefine diagnostic criteria for classical clinical syndromes and to establish a clinical baseline for comparison in single-arm clinical trials of novel therapies

Moving Towards Clinical Trials for Mitochondrial Diseases

Primary mitochondrial diseases represent some of the most common and severe inherited metabolic disorders, affecting approximately 1 in 4300 live births. The clinical and molecular diversity typified by mitochondrial diseases has contributed to the lack of licensed disease‐modifying therapies available. Management for the majority of patients is primarily supportive. The failure of clinical trials in mitochondrial disease partly relates to the inefficacy of compounds studied. However, it is also likely to be a consequence of the significant challenges faced by clinicians and researchers when designing trials for mitochondrial diseases, which have historically been hampered by a lack of natural history data, biomarkers and outcome measures to detect a treatment effect. Encouragingly, over the past decade there have been significant advances in therapy development for mitochondrial diseases, with many small molecules now transitioning from preclinical to early phase human interventional studies. In this review, we present the treatments and management strategies currently available to people with mitochondrial disease. We evaluate the challenges and potential solutions to trial design and highlight the emerging pharmacological and genetic strategies that are moving from the laboratory to clinical trials for this group of disorders