Latest developments in the microarray analysis of human brain mRNA

Microarrays are used to monitor the expression of thousands of gene transcripts. This technique requires high-quality RNA, which can be extracted from a variety sources, including autopsy brain tissue. Most nucleic acids and proteins are reasonably stable post mortem. However, their abundance and integrity can exhibit marked intraand inter-subject variability, so care must be taken when comparisons between case-groups are made. We will review issues associated with the sampling of RNA from autopsy brain tissue in relation to various ante- and post-mortem factors.

Spectroscopic analysis of terrestrial analogues for the interpretation of surface composition of rocky bodies in the solar system. Effects of mineral mixing and particle size. Applications to moon, mars and implications for mercury.

Among the Solar System’s bodies, Moon, Mercury and Mars are at present, or have been in the recent years, object of space missions aimed, among other topics, also at improving our knowledge about surface composition. Between the techniques to detect planet’s mineralogical composition, both from remote and close range platforms, visible and near-infrared reflectance (VNIR) spectroscopy is a powerful tool, because crystal field absorption bands are related to particular transitional metals in well-defined crystal structures, e.g., Fe2+ in M1 and M2 sites of olivine or pyroxene (Burns, 1993). Thanks to the improvements in the spectrometers onboard the recent missions, a more detailed interpretation of the planetary surfaces can now be delineated. However, quantitative interpretation of planetary surface mineralogy could not always be a simple task. In fact, several factors such as the mineral chemistry, the presence of different minerals that absorb in a narrow spectral range, the regolith with a variable particle size range, the space weathering, the atmosphere composition etc., act in unpredictable ways on the reflectance spectra on a planetary surface (Serventi et al., 2014). One method for the interpretation of reflectance spectra of unknown materials involves the study of a number of spectra acquired in the laboratory under different conditions, such as different mineral abundances or different particle sizes, in order to derive empirical trends. This is the methodology that has been followed in this PhD thesis: the single factors previously listed have been analyzed, creating, in the laboratory, a set of terrestrial analogues with well-defined composition and size. The aim of this work is to provide new tools and criteria to improve the knowledge of the composition of planetary surfaces. In particular, mixtures composed with different content and chemistry of plagioclase and mafic minerals have been spectroscopically analyzed at different particle sizes and with different mineral relative percentages. The reflectance spectra of each mixture have been analyzed both qualitatively (using the software ORIGIN®) and quantitatively applying the Modified Gaussian Model (MGM, Sunshine et al., 1990) algorithm. In particular, the spectral parameter variations of each absorption band have been evaluated versus the volumetric FeO% content in the PL phase and versus the PL modal abundance. This delineated calibration curves of composition vs. spectral parameters and allow implementation of spectral libraries. Furthermore, the trends derived from terrestrial analogues here analyzed and from analogues in the literature have been applied for the interpretation of hyperspectral images of both plagioclase-rich (Moon) and plagioclase-poor (Mars) bodies.

Quantitative microscopic analysis of histological sections of brain tissue

This article reviews methods for quantifying the abundance of histological features in thin tissue sections of brain such as neurons, glia, blood vessels, and pathological lesions. The sampling methods by which quantitative measures can be obtained are described. In addition, methods are described for determining the spatial pattern of an object and for measuring the degree of spatial correlation between two or more histological features.

Quantifying the pathology of neurodegenerative disorders:Quantitative measurements, sampling strategies and data analysis

The use of quantitative methods has become increasingly important in the study of neurodegenerative disease. Disorders such as Alzheimer's disease (AD) are characterized by the formation of discrete, microscopic, pathological lesions which play an important role in pathological diagnosis. This article reviews the advantages and limitations of the different methods of quantifying the abundance of pathological lesions in histological sections, including estimates of density, frequency, coverage, and the use of semiquantitative scores. The major sampling methods by which these quantitative measures can be obtained from histological sections, including plot or quadrat sampling, transect sampling, and point-quarter sampling, are also described. In addition, the data analysis methods commonly used to analyse quantitative data in neuropathology, including analyses of variance (ANOVA) and principal components analysis (PCA), are discussed. These methods are illustrated with reference to particular problems in the pathological diagnosis of AD and dementia with Lewy bodies (DLB).

Neuropathological heterogeneity in Alzheimer's disease:A study of 80 cases using principal components analysis

Three hypotheses have been proposed to explain neuropathological heterogeneity in Alzheimer's disease (AD): the presence of distinct subtypes ('subtype hypothesis'), variation in the stage of the disease ('phase hypothesis') and variation in the origin and progression of the disease ('compensation hypothesis'). To test these hypotheses, variation in the distribution and severity of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in 80 cases of AD using principal components analysis (PCA). Principal components analysis using the cases as variables (Q-type analysis) suggested that individual differences between patients were continuously distributed rather than the cases being clustered into distinct subtypes. In addition, PCA using the abundances of SP and NFT as variables (R-type analysis) suggested that variations in the presence and abundance of lesions in the frontal and occipital lobes, the cingulate gyrus and the posterior parahippocampal gyrus were the most important sources of heterogeneity consistent with the presence of different stages of the disease. In addition, in a subgroup of patients, individual differences were related to apolipoprotein E (ApoE) genotype, the presence and severity of SP in the frontal and occipital cortex being significantly increased in patients expressing apolipoprotein (Apo)E allele ε4. It was concluded that some of the neuropathological heterogeneity in our AD cases may be consistent with the 'phase hypothesis'. A major factor determining this variation in late-onset cases was ApoE genotype with accelerated rates of spread of the pathology in patients expressing allele ε4.

The use of multivariate methods in the identification of subtypes of Alzheimer's disease: a comparison of principal components and cluster analysis

Two contrasting multivariate statistical methods, viz., principal components analysis (PCA) and cluster analysis were applied to the study of neuropathological variations between cases of Alzheimer's disease (AD). To compare the two methods, 78 cases of AD were analyzed, each characterised by measurements of 47 neuropathological variables. Both methods of analysis revealed significant variations between AD cases. These variations were related primarily to differences in the distribution and abundance of senile plaques (SP) and neurofibrillary tangles (NFT) in the brain. Cluster analysis classified the majority of AD cases into five groups which could represent subtypes of AD. However, PCA suggested that variation between cases was more continuous with no distinct subtypes. Hence, PCA may be a more appropriate method than cluster analysis in the study of neuropathological variations between AD cases.

A simulation analysis of spoke-terminals operating in LTL Hub-and-Spoke freight distribution systems

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT The research presented in this thesis is concerned with Discrete-Event Simulation (DES) modelling as a method to facilitate logistical policy development within the UK Less-than-Truckload (LTL) freight distribution sector which has been typified by “Pallet Networks” operating on a hub-and-spoke philosophy. Current literature relating to LTL hub-and-spoke and cross-dock freight distribution systems traditionally examines a variety of network and hub design configurations. Each is consistent with classical notions of creating process efficiency, improving productivity, reducing costs and generally creating economies of scale through notions of bulk optimisation. Whilst there is a growing abundance of papers discussing both the network design and hub operational components mentioned above, there is a shortcoming in the overall analysis when it comes to discussing the “spoke-terminal” of hub-and-spoke freight distribution systems and their capabilities for handling the diverse and discrete customer profiles of freight that multi-user LTL hub-and-spoke networks typically handle over the “last-mile” of the delivery, in particular, a mix of retail and non-retail customers. A simulation study is undertaken to investigate the impact on operational performance when the current combined spoke-terminal delivery tours are separated by ‘profile-type’ (i.e. retail or nonretail). The results indicate that a potential improvement in delivery performance can be made by separating retail and non-retail delivery runs at the spoke-terminal and that dedicated retail and non-retail delivery tours could be adopted in order to improve customer delivery requirements and adapt hub-deployed policies. The study also leverages key operator experiences to highlight the main practical implementation challenges when integrating the observed simulation results into the real-world. The study concludes that DES be harnessed as an enabling device to develop a ‘guide policy’. This policy needs to be flexible and should be applied in stages, taking into account the growing retail-exposure.

Analysis of climate change scenarios based on modelling of the seasonal dynamics of a Danubian copepod species

Climate change is one of the most crucial ecological problems of our age with great influence. Seasonal dynamics of aquatic communities are — among others — regulated by the climate, especially by temperature. In this case study we attempted the simulation modelling of the seasonal dynamics of a copepod species, Cyclops vicinus, which ranks among the zooplankton community, based on a quantitative database containing ten years of data from the Danube’s Göd area. We set up a simulation model predicting the abundance of Cyclops vicinus by considering only temperature as it affects the abundance of population. The model was adapted to eight years of daily temperature data observed between 1981 and 1994 and was tested successfully with the additional data of two further years. The model was run with the data series of climate change scenarios specified for the period around 2070- 2100. On the other hand we looked for the geographically analogous areas with the Göd region which are mostly similar to the future climate of the Göd area. By means of the above-mentioned points we can get a view how the climate of the region will change by the end of the 21st century, and the way the seasonal dynamics of a chosen planktonic crustacean species may follow this change. According to our results the area of Göd will be similar to the northern region of Greece. The maximum abundance of the examined species occurs a month to one and a half months earlier, moreover larger variances are expected between years in respect of the abundance. The deviations are expected in the direction of smaller or significantly larger abundance not observed earlier.

An exergy based engineering and economic analysis of sustainable building

To achieve the goal of sustainable development, the building energy system was evaluated from both the first and second law of thermodynamics point of view. The relationship between exergy destruction and sustainable development were discussed at first, followed by the description of the resource abundance model, the life cycle analysis model and the economic investment effectiveness model. By combining the forgoing models, a new sustainable index was proposed. Several green building case studies in U.S. and China were presented. The influences of building function, geographic location, climate pattern, the regional energy structure, and the technology improvement potential of renewable energy in the future were discussed. The building’s envelope, HVAC system, on-site renewable energy system life cycle analysis from energy, exergy, environmental and economic perspective were compared. It was found that climate pattern had a dramatic influence on the life cycle investment effectiveness of the building envelope. The building HVAC system energy performance was much better than its exergy performance. To further increase the exergy efficiency, renewable energy rather than fossil fuel should be used as the primary energy. A building life cycle cost and exergy consumption regression model was set up. The optimal building insulation level could be affected by either cost minimization or exergy consumption minimization approach. The exergy approach would cause better insulation than cost approach. The influence of energy price on the system selection strategy was discussed. Two photovoltaics (PV) systems—stand alone and grid tied system were compared by the life cycle assessment method. The superiority of the latter one was quite obvious. The analysis also showed that during its life span PV technology was less attractive economically because the electricity price in U.S. and China did not fully reflect the environmental burden associated with it. However if future energy price surges and PV system cost reductions were considered, the technology could be very promising for sustainable buildings in the future.

The development of optimized high performance liquid chromatography systems for the analysis of improvised explosives

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.

The Allelic Abundance of Afghanistan, a Pool for West and South Eurasian Genes and a Blockade against Eastern Admixture

In this study, I divided samples from individuals within Afghanistan based upon geography (i.e., north versus south). I determined allelic frequencies and other statistical parameters for 15 STR loci (i.e., D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, Dl3S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA). I conducted pairwise comparisons with 19 neighboring Eurasian populations to assign Gstatistics and p-values. Categorizing the populations into five groups (i.e., Central Asia, East Asia, South Asia, the Middle East, and the Caucasus/Anatolia), I derived values for intra-population, inter-population, and total variance. Admixture analyses determined the highest allelic contributions to be from the Caucasus/ Anatolia, while negligible contributions were made by Central Asia and East Asia. A Correspondence Analysis revealed clustering of both northern and southern Afghanistan with Georgia, Turkey, northern Iran, and southern Iran of the Caucasus/ Anatolia and the Middle East. A Neighbor-Joining phylogenetic tree was constructed to generate bootstrap values over 1, 000 reiterations.

An Exergy Based Engineering and Economic Analysis of Sustainable Building

To achieve the goal of sustainable development, the building energy system was evaluated from both the first and second law of thermodynamics point of view. The relationship between exergy destruction and sustainable development were discussed at first, followed by the description of the resource abundance model, the life cycle analysis model and the economic investment effectiveness model. By combining the forgoing models, a new sustainable index was proposed. Several green building case studies in U.S. and China were presented. The influences of building function, geographic location, climate pattern, the regional energy structure, and the technology improvement potential of renewable energy in the future were discussed. The building’s envelope, HVAC system, on-site renewable energy system life cycle analysis from energy, exergy, environmental and economic perspective were compared. It was found that climate pattern had a dramatic influence on the life cycle investment effectiveness of the building envelope. The building HVAC system energy performance was much better than its exergy performance. To further increase the exergy efficiency, renewable energy rather than fossil fuel should be used as the primary energy. A building life cycle cost and exergy consumption regression model was set up. The optimal building insulation level could be affected by either cost minimization or exergy consumption minimization approach. The exergy approach would cause better insulation than cost approach. The influence of energy price on the system selection strategy was discussed. Two photovoltaics (PV) systems – stand alone and grid tied system were compared by the life cycle assessment method. The superiority of the latter one was quite obvious. The analysis also showed that during its life span PV technology was less attractive economically because the electricity price in U.S. and China did not fully reflect the environmental burden associated with it. However if future energy price surges and PV system cost reductions were considered, the technology could be very promising for sustainable buildings in the future.

The Development of High Performance Liquid Chromatography Systems for the Analysis of Improvised Explosives

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.

Land-cover detection and landscape structure analysis in the Pachitea Basin, Peruvian Amazon

Classification procedures, including atmospheric correction satellite images as well as classification performance utilizing calibration and validation at different levels, have been investigated in the context of a coarse land-cover classification scheme for the Pachitea Basin. Two different correction methods were tested against no correction in terms of reflectance correction towards a common response for pseudo-invariant features (PIF). The accuracy of classifications derived from each of the three methods was then assessed in a discriminant analysis using crossvalidation at pixel, polygon, region, and image levels. Results indicate that only regression adjusted images using PIFs show no significant difference between images in any of the bands. A comparison of classifications at different levels suggests though that at pixel, polygon, and region levels the accuracy of the classifications do not significantly differ between corrected and uncorrected images. Spatial patterns of land-cover were analyzed in terms of colonization history, infrastructure, suitability of the land, and landownership. The actual use of the land is driven mainly by the ability to access the land and markets as is obvious in the distribution of land cover as a function of distance to rivers and roads. When considering all rivers and roads a threshold distance at which disproportional agro-pastoral land cover switches from over represented to under represented is at about 1km. Best land use suggestions seem not to affect the choice of land use. Differences in abundance of land cover between watersheds are more prevailing than differences between colonist and indigenous groups.

The mosses of Terra Nova National Park, Eastern Newfoundland, a bryofloristic analysis and interpretation

The known moss flora of Terra Nova National Park, eastern Newfoundland, comp~ises 210 species. Eighty-two percent of the moss species occurring in Terra Nova are widespread or widespread-sporadic in Newfoundland. Other Newfoundland distributional elements present in the Terra Nova moss flora are the northwestern, southern, southeastern, and disjunct elements, but four of the mosses occurring in Terra Nova appear to belong to a previously unrecognized northeastern element of the Newfoundland flora. The majority (70.9%) of Terra Nova's mosses are of boreal affinity and are widely distributed in the North American coniferous forest belt. An additional 10.5 percent of the Terra Nova mosses are cosmopolitan while 9.5 percent are temperate and 4.8 percent are arctic-montane species. The remaining 4.3 percent of the mosses are of montane affinity, and disjunct between eastern and western North America. In Terra Nova, temperate species at their northern limit are concentrated in balsam fir stands, while arctic-montane species are restricted to exposed cliffs, scree slopes, and coastal exposures. Montane species are largely confined to exposed or freshwater habitats. Inability to tolerate high summer temperatures limits the distributions of both arctic-montane and montane species. In Terra Nova, species of differing phytogeographic affinities co-occur on cliffs and scree slopes. The microhabitat relationships of five selected species from such habitats were evaluated by Discriminant Functions Analysis and Multiple Regression Analysis. The five mosses have distinct and different microhabitats on cliffs and scree slopes in Terra Nova, and abundance of all but one is associated with variation in at least one microhabitat variable. Micro-distribution of Grimmia torquata, an arctic-montane species at its southern limit, appears to be deterJ]lined by sensitivity to high summer temperatures. Both southern mosses at their northern limit (Aulacomnium androgynum, Isothecium myosuroides) appear to be limited by water availability and, possibly, by low winter temperatures. The two species whose distributions extend both north and south or the study area (Encalypta procera, Eurhynchium pulchellum) show no clear relationship with microclimate. Dispersal factors have played a significant role in the development of the Terra Nova moss flora. Compared to the most likely colonizing source (i .e. the rest of the island of Newfoundland), species with small diaspores have colonized the study area to a proportionately much greater extent than have species with large diaspores. Hierarchical log-linear analysis indicates that this is so for all affinity groups present in Terra Nova. The apparent dispersal effects emphasize the comparatively recent glaciation of the area, and may also have been enhanced by anthropogenic influences. The restriction of some species to specific habitats, or to narrowly defined microhabitats, appears to strengthen selection for easily dispersed taxa.