Atypical connectivity in autistic spectrum disorders

Autism is a developmental disorder that is currently defined in terms of a triad of impairments in social interaction, communication, and behavioural flexibility. Psychological models have focussed on deficits in high level social and cognitive processes, such as ‘weak central coherence’ and deficits in ‘theory of mind’. Converging evidence from different fields of neuroscience research indicates that the underlying neural dysfunction is associated with atypical patterns of cortical connectivity (Rippon et al., 2007). This arises very early in development and results in sensory, perceptual and cognitive deficits at a much earlier and more fundamental level than previously suggested, but with cascading effects on higher level psychological and social processes. Earlier research in this sphere has focussed mainly on patterns of underconnectivity in distributed cortical networks underpinning process such as language and executive function. (Just et al., 2007). Such research mainly utilises imaging techniques with high spatial resolution. This paper focuses on evidence associated with local over-connectivity, evident in more low level and transitory processes and hence more easily measurable with techniques with high temporal resolution, such as MEG and EEG. Results are described which provide evidence of such local over-connectivity, characterised by atypical results in the gamma frequency range (Brown et al., 2005) together with discussions about the future directions of such research and its implications for remediation.

Multiple Dipole Source Models for Scalp-Recorded Event-Related Potentials: Example from Complex Visual Processing in the Human Brain

2000 Mathematics Subject Classification: 62P10, 92C20

Magnetoencephalography in epilepsy

Magnetoencephalographic (MEG) signals, like electroencephalographic (EEG) measures, are the direct extracranial manifestations of neuronal activation. The two techniques can detect time-varying changes in electromagnetic activity with a sub-millisecond time resolution. Extra-cranial electromagnetic measures are the cornerstone of the non-invasive diagnostic armamentarium in patients with epilepsy. Their extremely high temporal resolution – comparable to intracranial recordings – is the basis for a precise definition of onset and propagation of ictal and interictal abnormalities. Given the cost of the infrastructure and equipment, MEG has yet to develop into a routinely applicable diagnostic tool in clinical settings. However, in recent years, an increasing number of patients with epilepsy have been investigated – usually in the context of presurgical evaluation of refractory epilepsies – and initial encouraging results have been reported. We will briefly review the principles and the technology behind MEG and its contribution in the diagnostic work-up of patients with epilepsy.

(Data D1) Annual climate proxy data from the NGRIP ice core, Greenland

The last two abrupt warmings at the onset of our present warm interglacial period, interrupted by the Younger Dryas cooling event, were investigated at high temporal resolution from the North Greenland Ice Core Project ice core. The deuterium excess, a proxy of Greenland precipitation moisture source, switched mode within 1 to 3 years over these transitions and initiated a more gradual change (over 50 years) of the Greenland air temperature, as recorded by stable water isotopes. The onsets of both abrupt Greenland warmings were slightly preceded by decreasing Greenland dust deposition, reflecting the wetting of Asian deserts. A northern shift of the Intertropical Convergence Zone could be the trigger of these abrupt shifts of Northern Hemisphere atmospheric circulation, resulting in changes of 2 to 4 kelvin in Greenland moisture source temperature from one year to the next.

Dinocyst-derived sea-surface characteristics, palynomorph abundances, ice-rafted debris, and planktonic foraminifera abundances and d18O of the 35-41 ka BP interval of core MD99-2285

The last glacial millennial climatic events (i.e. Dansgaard-Oeschger and Heinrich events) constitute outstanding case studies of coupled atmosphere-ocean-cryosphere interactions. Here, we investigate the evolution of sea-surface and subsurface conditions, in terms of temperature, salinity and sea ice cover, at very high-resolution (mean resolution between 55 and 155 years depending on proxies) during the 35-41 ka cal BP interval covering three Dansgaard-Oeschger cycles and including Heinrich event 4, in a new unpublished marine record, i.e. the MD99-2285 core (62.69°N; -3.57s°E). We use a large panel of complementary tools, which notably includes dinocyst-derived sea-ice cover duration quantifications. The high temporal resolution and multiproxy approach of this work allows us to identify the sequence of processes and to assess ocean-cryosphere interactions occurring during these periodic ice-sheet collapse events. Our results evidence a paradoxical hydrological scheme where (i) Greenland interstadials are marked by a homogeneous and cold upper water column, with intensive winter sea ice formation and summer sea ice melting, and (ii) Greenland and Heinrich stadials are characterized by a very warm and low saline surface layer with iceberg calving and reduced sea ice formation, separated by a strong halocline from a less warm and saltier subsurface layer. Our work also suggests that this stadial surface/subsurface warming started before massive iceberg release, in relation with warm Atlantic water advection. These findings thus support the theory that upper ocean warming might have triggered European ice-sheet destabilization. Besides, previous paleoceanographic studies conducted along the Atlantic inflow pathways close to the edge of European ice-sheets suggest that such a feature might have occurred in this whole area. Nonetheless, additional high resolution paleoreconstructions are required to confirm such a regional scheme.

Radiotherapy Treatment Assessment using DCE-MRI

Abstract

The goal of modern radiotherapy is to precisely deliver a prescribed radiation dose to delineated target volumes that contain a significant amount of tumor cells while sparing the surrounding healthy tissues/organs. Precise delineation of treatment and avoidance volumes is the key for the precision radiation therapy. In recent years, considerable clinical and research efforts have been devoted to integrate MRI into radiotherapy workflow motivated by the superior soft tissue contrast and functional imaging possibility. Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive technique that measures properties of tissue microvasculature. Its sensitivity to radiation-induced vascular pharmacokinetic (PK) changes has been preliminary demonstrated. In spite of its great potential, two major challenges have limited DCE-MRI’s clinical application in radiotherapy assessment: the technical limitations of accurate DCE-MRI imaging implementation and the need of novel DCE-MRI data analysis methods for richer functional heterogeneity information.

This study aims at improving current DCE-MRI techniques and developing new DCE-MRI analysis methods for particular radiotherapy assessment. Thus, the study is naturally divided into two parts. The first part focuses on DCE-MRI temporal resolution as one of the key DCE-MRI technical factors, and some improvements regarding DCE-MRI temporal resolution are proposed; the second part explores the potential value of image heterogeneity analysis and multiple PK model combination for therapeutic response assessment, and several novel DCE-MRI data analysis methods are developed.

I. Improvement of DCE-MRI temporal resolution. First, the feasibility of improving DCE-MRI temporal resolution via image undersampling was studied. Specifically, a novel MR image iterative reconstruction algorithm was studied for DCE-MRI reconstruction. This algorithm was built on the recently developed compress sensing (CS) theory. By utilizing a limited k-space acquisition with shorter imaging time, images can be reconstructed in an iterative fashion under the regularization of a newly proposed total generalized variation (TGV) penalty term. In the retrospective study of brain radiosurgery patient DCE-MRI scans under IRB-approval, the clinically obtained image data was selected as reference data, and the simulated accelerated k-space acquisition was generated via undersampling the reference image full k-space with designed sampling grids. Two undersampling strategies were proposed: 1) a radial multi-ray grid with a special angular distribution was adopted to sample each slice of the full k-space; 2) a Cartesian random sampling grid series with spatiotemporal constraints from adjacent frames was adopted to sample the dynamic k-space series at a slice location. Two sets of PK parameters’ maps were generated from the undersampled data and from the fully-sampled data, respectively. Multiple quantitative measurements and statistical studies were performed to evaluate the accuracy of PK maps generated from the undersampled data in reference to the PK maps generated from the fully-sampled data. Results showed that at a simulated acceleration factor of four, PK maps could be faithfully calculated from the DCE images that were reconstructed using undersampled data, and no statistically significant differences were found between the regional PK mean values from undersampled and fully-sampled data sets. DCE-MRI acceleration using the investigated image reconstruction method has been suggested as feasible and promising.

Second, for high temporal resolution DCE-MRI, a new PK model fitting method was developed to solve PK parameters for better calculation accuracy and efficiency. This method is based on a derivative-based deformation of the commonly used Tofts PK model, which is presented as an integrative expression. This method also includes an advanced Kolmogorov-Zurbenko (KZ) filter to remove the potential noise effect in data and solve the PK parameter as a linear problem in matrix format. In the computer simulation study, PK parameters representing typical intracranial values were selected as references to simulated DCE-MRI data for different temporal resolution and different data noise level. Results showed that at both high temporal resolutions (<1s) and clinically feasible temporal resolution (~5s), this new method was able to calculate PK parameters more accurate than the current calculation methods at clinically relevant noise levels; at high temporal resolutions, the calculation efficiency of this new method was superior to current methods in an order of 102. In a retrospective of clinical brain DCE-MRI scans, the PK maps derived from the proposed method were comparable with the results from current methods. Based on these results, it can be concluded that this new method can be used for accurate and efficient PK model fitting for high temporal resolution DCE-MRI.

II. Development of DCE-MRI analysis methods for therapeutic response assessment. This part aims at methodology developments in two approaches. The first one is to develop model-free analysis method for DCE-MRI functional heterogeneity evaluation. This approach is inspired by the rationale that radiotherapy-induced functional change could be heterogeneous across the treatment area. The first effort was spent on a translational investigation of classic fractal dimension theory for DCE-MRI therapeutic response assessment. In a small-animal anti-angiogenesis drug therapy experiment, the randomly assigned treatment/control groups received multiple fraction treatments with one pre-treatment and multiple post-treatment high spatiotemporal DCE-MRI scans. In the post-treatment scan two weeks after the start, the investigated Rényi dimensions of the classic PK rate constant map demonstrated significant differences between the treatment and the control groups; when Rényi dimensions were adopted for treatment/control group classification, the achieved accuracy was higher than the accuracy from using conventional PK parameter statistics. Following this pilot work, two novel texture analysis methods were proposed. First, a new technique called Gray Level Local Power Matrix (GLLPM) was developed. It intends to solve the lack of temporal information and poor calculation efficiency of the commonly used Gray Level Co-Occurrence Matrix (GLCOM) techniques. In the same small animal experiment, the dynamic curves of Haralick texture features derived from the GLLPM had an overall better performance than the corresponding curves derived from current GLCOM techniques in treatment/control separation and classification. The second developed method is dynamic Fractal Signature Dissimilarity (FSD) analysis. Inspired by the classic fractal dimension theory, this method measures the dynamics of tumor heterogeneity during the contrast agent uptake in a quantitative fashion on DCE images. In the small animal experiment mentioned before, the selected parameters from dynamic FSD analysis showed significant differences between treatment/control groups as early as after 1 treatment fraction; in contrast, metrics from conventional PK analysis showed significant differences only after 3 treatment fractions. When using dynamic FSD parameters, the treatment/control group classification after 1st treatment fraction was improved than using conventional PK statistics. These results suggest the promising application of this novel method for capturing early therapeutic response.

The second approach of developing novel DCE-MRI methods is to combine PK information from multiple PK models. Currently, the classic Tofts model or its alternative version has been widely adopted for DCE-MRI analysis as a gold-standard approach for therapeutic response assessment. Previously, a shutter-speed (SS) model was proposed to incorporate transcytolemmal water exchange effect into contrast agent concentration quantification. In spite of richer biological assumption, its application in therapeutic response assessment is limited. It might be intriguing to combine the information from the SS model and from the classic Tofts model to explore potential new biological information for treatment assessment. The feasibility of this idea was investigated in the same small animal experiment. The SS model was compared against the Tofts model for therapeutic response assessment using PK parameter regional mean value comparison. Based on the modeled transcytolemmal water exchange rate, a biological subvolume was proposed and was automatically identified using histogram analysis. Within the biological subvolume, the PK rate constant derived from the SS model were proved to be superior to the one from Tofts model in treatment/control separation and classification. Furthermore, novel biomarkers were designed to integrate PK rate constants from these two models. When being evaluated in the biological subvolume, this biomarker was able to reflect significant treatment/control difference in both post-treatment evaluation. These results confirm the potential value of SS model as well as its combination with Tofts model for therapeutic response assessment.

In summary, this study addressed two problems of DCE-MRI application in radiotherapy assessment. In the first part, a method of accelerating DCE-MRI acquisition for better temporal resolution was investigated, and a novel PK model fitting algorithm was proposed for high temporal resolution DCE-MRI. In the second part, two model-free texture analysis methods and a multiple-model analysis method were developed for DCE-MRI therapeutic response assessment. The presented works could benefit the future DCE-MRI routine clinical application in radiotherapy assessment.

Global surface net-radiation at 5 km from MODIS Terra

Reliable and fine resolution estimates of surface net-radiation are required for estimating latent and sensible heat fluxes between the land surface and the atmosphere. However, currently, fine resolution estimates of net-radiation are not available and consequently it is challenging to develop multi-year estimates of evapotranspiration at scales that can capture land surface heterogeneity and are relevant for policy and decision-making. We developed and evaluated a global net-radiation product at 5 km and 8-day resolution by combining mutually consistent atmosphere and land data from the Moderate Resolution Imaging Spectroradiometer (MODIS) on board Terra. Comparison with net-radiation measurements from 154 globally distributed sites (414 site-years) from the FLUXNET and Surface Radiation budget network (SURFRAD) showed that the net-radiation product agreed well with measurements across seasons and climate types in the extratropics (Wilmott’s index ranged from 0.74 for boreal to 0.63 for Mediterranean sites). Mean absolute deviation between the MODIS and measured net-radiation ranged from 38.0 ± 1.8 W∙m−2 in boreal to 72.0 ± 4.1 W∙m−2 in the tropical climates. The mean bias was small and constituted only 11%, 0.7%, 8.4%, 4.2%, 13.3%, and 5.4% of the mean absolute error in daytime net-radiation in boreal, Mediterranean, temperate-continental, temperate, semi-arid, and tropical climate, respectively. To assess the accuracy of the broader spatiotemporal patterns, we upscaled error-quantified MODIS net-radiation and compared it with the net-radiation estimates from the coarse spatial (1° × 1°) but high temporal resolution gridded net-radiation product from the Clouds and Earth’s Radiant Energy System (CERES). Our estimates agreed closely with the net-radiation estimates from the CERES. Difference between the two was less than 10 W•m−2 in 94% of the total land area. MODIS net-radiation product will be a valuable resource for the science community studying turbulent fluxes and energy budget at the Earth’s surface.

Benthic foraminiferal record from Santa Barbara basin

The oxygen minimum zone (OMZ) of the late Quaternary California margin experienced abrupt and dramatic changes in strength and depth in response to changes in intermediate water ventilation, ocean productivity, and climate at orbital through millennial time scales. Expansion and contraction of the OMZ is exhibited at high temporal resolution (107-126 year) by quantitative benthic foraminiferal assemblage changes in two piston cores forming a vertical profile in Santa Barbara Basin (569 m, basin floor; 481 m, near sill depth) to 34 and 24 ka, respectively. Variation in the OMZ is quantified by new benthic foraminiferal groupings and new dissolved oxygen index based on documented relations between species and water-mass oxygen concentrations. Foraminiferal-based paleoenvironmental assessments are integrated with principal component analysis, bioturbation, grain size, CaCO3, total organic carbon, and d13C to reconstruct basin oxygenation history. Fauna responded similarly between the two sites, although with somewhat different magnitude and taxonomic expression. During cool episodes (Younger Dryas and stadials), the water column was well oxygenated, most strongly near the end of the glacial episode (17-16 ka; Heinrich 1). In contrast, the OMZ was strong during warm episodes (Bølling/Allerød, interstadials, and Pre-Boreal). During the Bølling/Allerød, the OMZ shoaled to <360 m of contemporaneous sea level, its greatest vertical expansion of the last glacial cycle. Assemblages were then dominated by Bolivina tumida, reflecting high concentrations of dissolved methane in bottom waters. Short decadal intervals were so severely oxygen-depleted that no benthic foraminifera were present. The middle to late Holocene (6-0 ka) was less dysoxic than the early Holocene.

Hydrological and meteorological investigations in a lake near Kangerlussuaq, west Greenland

Few hydrological studies have been made in Greenland, other than on glacial hydrology associated with the ice sheet. Understanding permafrost hydrology and hydroclimatic change and variability, however, provides key information for understanding climate change effects and feedbacks in the Arctic landscape. This paper presents a new extensive and detailed hydrological and meteorological open access dataset, with high temporal resolution from a 1.56 km**2 permafrost catchment with a lake underlain by a through talik close to the ice sheet in the Kangerlussuaq region, western Greenland. The paper describes the hydrological site investigations and utilized equipment, as well as the data collection and processing. The investigations were performed between 2010 and 2013. The high spatial resolution, within the investigated area, of the dataset makes it highly suitable for various detailed hydrological and ecological studies on catchment scale.

Rate of Belowground Carbon Allocation Differs with Successional Habit of Two Afromontane Trees

Background: Anthropogenic disturbance of old-growth tropical forests increases the abundance of early successional tree species at the cost of late successional ones. Quantifying differences in terms of carbon allocation and the proportion of recently fixed carbon in soil CO2 efflux is crucial for addressing the carbon footprint of creeping degradation. Methodology: We compared the carbon allocation pattern of the late successional gymnosperm Podocarpus falcatus (Thunb.) Mirb. and the early successional (gap filling) angiosperm Croton macrostachyus Hochst. es Del. in an Ethiopian Afromontane forest by whole tree (CO2)-C-13 pulse labeling. Over a one-year period we monitored the temporal resolution of the label in the foliage, the phloem sap, the arbuscular mycorrhiza, and in soil-derived CO2. Further, we quantified the overall losses of assimilated C-13 with soil CO2 efflux. Principal Findings: C-13 in leaves of C. macrostachyus declined more rapidly with a larger size of a fast pool (64% vs. 50% of the assimilated carbon), having a shorter mean residence time (14 h vs. 55 h) as in leaves of P. falcatus. Phloem sap velocity was about 4 times higher for C. macrostachyus. Likewise, the label appeared earlier in the arbuscular mycorrhiza of C. macrostachyus and in the soil CO2 efflux as in case of P. falcatus (24 h vs. 72 h). Within one year soil CO2 efflux amounted to a loss of 32% of assimilated carbon for the gap filling tree and to 15% for the late successional one. Conclusions: Our results showed clear differences in carbon allocation patterns between tree species, although we caution that this experiment was unreplicated. A shift in tree species composition of tropical montane forests (e. g., by degradation) accelerates carbon allocation belowground and increases respiratory carbon losses by the autotrophic community. If ongoing disturbance keeps early successional species in dominance, the larger allocation to fast cycling compartments may deplete soil organic carbon in the long run.

Transcriptional dynamics of the developing sweet cherry (Prunus avium L.) fruit: sequencing, annotation and expression profiling of exocarp-associated genes

The exocarp, or skin, of fleshy fruit is a specialized tissue that protects the fruit, attracts seed dispersing fruit eaters, and has large economical relevance for fruit quality. Development of the exocarp involves regulated activities of many genes. This research analyzed global gene expression in the exocarp of developing sweet cherry (Prunus avium L., 'Regina'), a fruit crop species with little public genomic resources. A catalog of transcript models (contigs) representing expressed genes was constructed from de novo assembled short complementary DNA (cDNA) sequences generated from developing fruit between flowering and maturity at 14 time points. Expression levels in each sample were estimated for 34 695 contigs from numbers of reads mapping to each contig. Contigs were annotated functionally based on BLAST, gene ontology and InterProScan analyses. Coregulated genes were detected using partitional clustering of expression patterns. The results are discussed with emphasis on genes putatively involved in cuticle deposition, cell wall metabolism and sugar transport. The high temporal resolution of the expression patterns presented here reveals finely tuned developmental specialization of individual members of gene families. Moreover, the de novo assembled sweet cherry fruit transcriptome with 7760 full-length protein coding sequences and over 20 000 other, annotated cDNA sequences together with their developmental expression patterns is expected to accelerate molecular research on this important tree fruit crop.

A space-time hybrid hourly rainfall model for derived flood frequency analysis

For derived flood frequency analysis based on hydrological modelling long continuous precipitation time series with high temporal resolution are needed. Often, the observation network with recording rainfall gauges is poor, especially regarding the limited length of the available rainfall time series. Stochastic precipitation synthesis is a good alternative either to extend or to regionalise rainfall series to provide adequate input for long-term rainfall-runoff modelling with subsequent estimation of design floods. Here, a new two step procedure for stochastic synthesis of continuous hourly space-time rainfall is proposed and tested for the extension of short observed precipitation time series. First, a single-site alternating renewal model is presented to simulate independent hourly precipitation time series for several locations. The alternating renewal model describes wet spell durations, dry spell durations and wet spell intensities using univariate frequency distributions separately for two seasons. The dependence between wet spell intensity and duration is accounted for by 2-copulas. For disaggregation of the wet spells into hourly intensities a predefined profile is used. In the second step a multi-site resampling procedure is applied on the synthetic point rainfall event series to reproduce the spatial dependence structure of rainfall. Resampling is carried out successively on all synthetic event series using simulated annealing with an objective function considering three bivariate spatial rainfall characteristics. In a case study synthetic precipitation is generated for some locations with short observation records in two mesoscale catchments of the Bode river basin located in northern Germany. The synthetic rainfall data are then applied for derived flood frequency analysis using the hydrological model HEC-HMS. The results show good performance in reproducing average and extreme rainfall characteristics as well as in reproducing observed flood frequencies. The presented model has the potential to be used for ungauged locations through regionalisation of the model parameters.

In vivo microvascular oximetry using multispectral imaging

This thesis describes the application of multispectral imaging to several novel oximetry applications. Chapter 1 motivates optical microvascular oximetry, outlines oxygen transport in the body, describes the theory of oximetry, and describes the challenges associated with in vivo oximetry, in particular imaging through tissue. Chapter 2 reviews various imaging techniques for quantitative in vivo oximetry of the microvasculature, including multispectral and hyperspectral imaging, photoacoustic imaging, optical coherence tomography, and laser speckle techniques. Chapter 3 describes a two-wavelength oximetry study of two microvascular beds in the anterior segment of the eye: the bulbar conjunctival and episcleral microvasculature. This study reveals previously unseen oxygen diffusion from ambient air into the bulbar conjunctival microvasculature, altering the oxygen saturation of the bulbar conjunctiva. The response of the bulbar conjunctival and episcleral microvascular beds to acute mild hypoxia is quantified and the rate at which oxygen diffuses into bulbar conjunctival vessels is measured. Chapter 4 describes the development and application of a highly novel non-invasive retinal angiography technique: Oximetric Ratio Contrast Angiography (ORCA). ORCA requires only multispectral imaging and a small perturbation of blood oxygen saturation to produce angiographic sequences. A pilot study of ORCA in human subjects was conducted. This study demonstrates that ORCA can produce angiographic sequences with features such as sequential vessel filling and laminar flow. The application and challenges of ORCA are discussed, with emphasis on comparison with other angiography techniques, such as fluorescein angiography. Chapter 5 describes the development of a multispectral microscope for oximetry in the spinal cord dorsal vein of rats. Measurements of blood oxygen saturation are made in the dorsal vein of both healthy rats, and in rats with the Experimental autoimmune encephalomyelitis (EAE) disease model of multiple sclerosis. The venous blood oxygen saturation of EAE disease model rats was found to be significantly lower than that of healthy controls, indicating increased oxygen uptake from blood in the EAE disease model of multiple sclerosis. Chapter 6 describes the development of video-rate red eye oximetry; a technique which could enable stand-off oximetry of the blood-supply of the eye with high temporal resolution. The various challenges associated with video-rate red eye oximetry are investigated and their influence quantified. The eventual aim of this research is to track circulating deoxygenation perturbations as they arrive in both eyes, which could provide a screening method for carotid artery stenosis, which is major risk-factor for stroke. However, due to time constraints, it was not possible to thoroughly investigate if video-rate red eye can detect such perturbations. Directions and recommendations for future research are outlined.

Radiogenic isotopes in the Mediterranean Sea: water mass exchange and precessional variability during the Messinian

During the late Miocene, exchange between the Mediterranean Sea and Atlantic Ocean changed dramatically, culminating in the Messinian Salinity Crisis (MSC). Understanding Mediterranean-Atlantic exchange at that time could answer the enigmatic question of how so much salt built up within the Mediterranean, while furthering the development of a framework for future studies attempting to understand how changes may have impacted global thermohaline circulation. Due to their association with specific water masses at different scales, radiogenic Sr, Pb, and Nd isotope records were generated from various archives contained within marine deposits to endeavour to understand better late Miocene Mediterranean-Atlantic exchange. The archives used include foraminiferal calcite (Sr), fish teeth and bone (Nd), dispersed authigenic ferromanganese oxyhydroxides (Nd, Pb), and a ferromanganese crust (Pb). The primary focus is on sediments preserved at one end of the Betic corridor, a gateway that once connected the Mediterranean to the Atlantic through southern Spain, although other locations are investigated. The Betic gateway terminated within several marginal sub-basins before entering the Western Mediterranean; one of these is the Sorbas Basin, a well-studied location whose sediments have been astronomically tuned at high temporal resolution, providing the necessary age control for sub-precessional resolution records. Since the climatic history of the Mediterranean is strongly controlled by precessional changes in regional climate, the aim was to produce records at high (sub-precessional) temporal resolution, to be able to observe clearly any precessional cyclicity driven by regional climate which could be superimposed over longer trends. This goal was achieved for all records except the ferromanganese crust record. The 87Sr/86Sr isotope record (Ch. 3) shows precessional frequency excursions away from the global seawater curve. As precessional frequency oscillations are unexpected for this setting, a numerical box model was used to determine the mechanisms causing the excursions. To enable parameterisation of model variables, regional Sr characteristics, data from general circulation model HadCM3L, and new benthic foraminiferal assemblage data are employed. The model results imply that the Sorbas Basin likely had a positive hydrologic budget in the late Miocene, very different to that of today. Moreover, the model indicates that the mechanism controlling the Sr isotope ratio of Sorbas Basin seawater was not restriction, but a lack of density-driven exchange with the Mediterranean. Beyond improving our understanding of how marginal Mediterranean sub-basins may evolve different isotope signatures, these results have implications for astronomical tuning and stratigraphy in the region, findings which are crucial considering the geological and climatic history of the late Miocene Mediterranean is based entirely on marginal deposits. An improved estimate for the Nd isotope signature of late Miocene Mediterranean Outflow (MO) was determined by comparing Nd isotope signatures preserved in the deeper Alborán Sea at ODP Site 978 with literature data as well as the signature preserved in the Sorbas Basin (Ch. 4; -9.34 to -9.92 ± 0.37 εNd(t)). It was also inferred that it is unlikely that Nd isotopes can be used reliably to track changes in circulation within the shallow settings characteristic of the Mediterranean-Atlantic connections; this is significant in light of a recent publication documenting corridor closure using Nd isotopes. Both conclusions will prove useful for future studies attempting to understand changes in Mediterranean-Atlantic exchange. Excursions to high values, with precessional frequency, are also observed in the radiogenic Pb isotope record for the Sorbas Basin (Ch. 5). Widening the scope to include locations further away from the gateways, records were produced for late Miocene sections on Sicily and Northern Italy, and similar precessional frequency cyclicity was observed in the Pb isotope records for these sites as well. Comparing these records to proxies for Saharan dust and available whole rock data indicates that, while further analysis is necessary to draw strong conclusions, enhanced dust production during insolation minima may be driving the observed signal. These records also have implications for astronomical tuning; peaks in Pb isotope records driven by Saharan dust may be easier to connect directly to the insolation cycle, providing improved astronomical tuning points. Finally, a Pb isotope record derived using in-situ laser ablation performed on ferromanganese crust 3514-6 from the Lion Seamount, located west of Gibraltar within the MO plume, has provided evidence that plume depth shifted during the Pliocene. The record also suggests that Pb isotopes may not be a suitable proxy for changes in late Miocene Mediterranean-Atlantic exchange, since the Pb isotope signatures of regional water masses are too similar. To develop this record, the first published instance of laser ablation derived 230Thexcess measurements are combined with 10Be dating.

Ocean-Atmosphere Interactions: Linking Oceanic Biological Activity to Marine Aerosol Physico-Chemical and Cloud Properties

In this work, in-situ measurements of aerosol chemical composition, particle number size distribution, cloud-relevant properties and ground-based cloud observations were combined with high-resolution satellite sea surface chlorophyll-a concentration and air mass back-trajectory data to investigate the impact of the marine biota on aerosol physico-chemical and cloud properties. Studies were performed over the North-Eastern Atlantic Ocean, the central Mediterranean Sea, and the Arctic Ocean, by deploying both multi-year datasets and short-time scale observations. All the data were chosen to be representative of the marine atmosphere, reducing to a minimum any anthropogenic input. A relationship between the patterns of marine biological activity and the time evolution of marine aerosol properties was observed, under a variety of aspects, from chemical composition to number concentration and size distribution, up to the most cloud‐relevant properties. At short-time scales (1-2 months), the aerosol properties tend to respond to biological activity variations with a delay of about one to three weeks. This delay should be considered in model applications that make use of Chlorophyll-a to predict marine aerosol properties at high temporal resolution. The impact of oceanic biological activity on the microphysical properties of marine stratiform clouds is also evidenced by our analysis, over the Eastern North Atlantic Ocean. Such clouds tend to have a higher number of smaller cloud droplets in periods of high biological activity with respect to quiescent periods. This confirms the possibility of feedback interactions within the biota-aerosol-cloud climate system. Achieving a better characterization of the time and space relationships linking oceanic biological activity to marine aerosol composition and properties may significantly impact our future capability of predicting the chemical composition of the marine atmosphere, potentially contributing to reducing the uncertainty of future climate predictions, through a better understanding of the natural climate system.