Mechanisms of chemical and physical transdermal penetration enhancement

The underlying theme of this thesis is one of exploring the processes involved in the enhancement of percutaneous absorption. The development of an attenuated total reflectance Fourier-Transform infrared (ATR-FTIR) spectroscopic method to analyse diffusion of suitable topically applied compounds in membrane is described. Diffusion coefficients (D/h2) and membrane solubility (AO) for topically applied compounds were determined using a solution to Fick's second law of diffusion. This method was employed to determine the diffusional characteristics of a model permeant, 4-cyanophenol (CP), across silicone membrane as a function of formulation applied and permeant physicochemical properties. The formulations applied were able to either affect CP diffusivity and/or its membrane solubility in the membrane; such parameters partially correlated with permeant physicochemical properties in each formulation. The interplay during the diffusion process between drug, enhancer and vehicle in stratum corneum (SC) was examined. When enhancers were added to the applied formulations, CP diffusivity and solubility were significantly enhanced when compared to the neat propylene glycol (PG) application. Enhancers did not affect PG diffusivity in SC but enhancers did affect PG solubility in SC. PG diffusion closely resembled that of CP, implying that the respective transport processes were inter-related. Additionally, a synergistic effect, which increases CP diffusivity and membrane solubility in SC, was found to occur between PG and water. Using 12-azidooleic acid (AOA) as an IR active probe for oleic acid, the simultaneous penetration of CP, AOA and PG into human stratum corneum was determined. It was found that the diffusion profiles for all three permeants were similar. This indicated that the diffusion of each species through SC was closely related and most likely occurred via the same route or SC microenvironment.

Investigations of the site and mechanisms of drug-induced reductions in the reabsorption of divalent cations by the kidney

Disturbances in electrolyte homeostasis are a frequent adverse side-effect of the administration of aminoglycoside antibiotics such as gentamicin, and the antineoplastic agent cis-platinum. The aims of this work were to further elucidate the site(s) and mechanism(s) by which these drugs may produce disturbances in the renal reabsorption of calcium and magnesium. These investigations were undertaken using a range of in vivo and in vitro techniques and models. Initially, a series of in vivo studies was conducted to delineate aspects of the acute and chronic effects of both drugs on renal electrolyte handling and to select and evaluate an appropriate animal model: subsequent investigations were focused on gentamicin. In a study of the acute and chronic effects of cis-platinum administration, there were pronounced acute changes in a variety of indices of nephrotoxic injury, including electrolyte excretion. Most effects resolved but there were chronic increases in the urinary excretion of calcium and magnesium. The renal response of three strains of rat (Fischer 344, Sprague-Dawley (SD), and Wistar) to a ranges of doses of gentamicin was also investigated. Drug administration produced substantially different responses between strains, in particular marked differences in calcium and magnesium excretion. The results suggested that the SD rat was an appropriately sensitive strain for use in further investigations. Acute infusion of gentamicin in the anaesthetised SD rat produced rapid, substantial increases in the fractional excretion of calcium and magnesium, while sodium and potassium output were unaffected, confirming previous results of similar experiments using F344 rats. Studies using lithium clearance measurements in the anaesthetised SD rat were undertaken to investigate the effects of gentamicin on proximal tubular calcium reabsorption. Lithium clearance was unaffected by acute gentamicin infusion, suggesting that the site of acute gentamicin-induced hypercalciuria may not be located in the proximal tubule. Inhibition of Ca2+ ATPase activity was investigated as a potential mechanism by which calcium reabsorption could be affected after aminoglycoside administration. In vitro, both Ca2+ ATPase and Na+/K+ ATPase activity could be similarly inhibited by the presence of aminoglycosides, in a dose-related manner. Whilst inhibition of Na+/K+ ATPase could be demonstrated biochemically after in vivo administration of gentamicin, there were no concurrent effects on Ca2+ ATPase activity, suggesting that inhibition of Ca2+ ATPase activity is unlikely to be a primary mechanism of aminoglycoside-induced reductions of calcium reabsorption. Histochemical studies could not discern inhibition of either Na+/K+ ATPase or Ca2+ ATPase activity after in vivo administration of gentamicin. Selection of renal cell lines for further investigative in vitro studies on the mechanisms of altered cation reabsorption was considered using MTT (3-(4,5,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Neutral Red cytotoxicity assays. The ability of LLC-PK1 and LLC-RK1 cell lines to correctly rank a series of nephrotoxic compounds with their known nephrotoxic potency in vivo was studied. Using these cell lines grown on semi-permeable inserts, alterations in the paracellular transport of 45Ca was investigated as a possible mechanism by which gentamicin could alter calcium reabsorption in vivo. Short term exposure (I h) of LLC-RK1 cells to gentamicin, via both cell surfaces, resulted in a reduction in paracellular permeability to both transepithelial 3H-mannitol and 45Ca fluxes. When LLC-RK1 cells were exposed via the apical surface only, similar dose-related reductions were seen to those observed when cells were exposed to the drug from both sides. Short-term basal exposure to gentamicin appeared to contribute less to the observed reductions in 3H-mannitol and 45Ca fluxes. Experiments investigating transepithelial movement of 45Ca and 3H-mannitol on LLC-PK1 cells after acute gentamicin exposure were inconclusive. Longer exposure (48 h) to gentamicin caused an increase in the permeability of the monolayer and a consequent increase in transepithelial 45Ca flux in the LLC-RK1 cell line; increases in permeability of LLC-PK1 cells to 45Ca and 3H-mannitol were not apparent under the same conditions. The site and mechanism at which gentamicin, in particular, alters calcium reabsorption cannot be definitively described from these studies. However, indirect evidence from lithium clearance studies suggests that the site of the lesion is unlikely to be located in the proximal tubule. The mechanism by which gentamicin exposure alters calcium reabsorption may be by reducing paracellular permeability to calcium rather than by altering active calcium transport processes.

A Modeling Approach to Determine the Impacts of Land Use and Climate Change Scenarios on the Water Flux of the Upper Mara River

With the flow of the Mara River becoming increasingly erratic especially in the upper reaches, attention has been directed to land use change as the major cause of this problem. The semi-distributed hydrological model Soil and Water Assessment Tool 5 (SWAT) and Landsat imagery were utilized in the upper Mara River Basin in order to 1) map existing field scale land use practices in order to determine their impact 2) determine the impacts of land use change on water flux; and 3) determine the impacts of rainfall (0%, ±10% and ±20%) and air temperature variations (0% and +5%) based on the Intergovernmental Panel on Climate Change projections on the water flux of the 10 upper Mara River. This study found that the different scenarios impacted on the water balance components differently. Land use changes resulted in a slightly more erratic discharge while rainfall and air temperature changes had a more predictable impact on the discharge and water balance components. These findings demonstrate that the model results 15 show the flow was more sensitive to the rainfall changes than land use changes. It was also shown that land use changes can reduce dry season flow which is the most important problem in the basin. The model shows also deforestation in the Mau Forest increased the peak flows which can also lead to high sediment loading in the Mara River. The effect of the land use and climate change scenarios on the sediment and 20 water quality of the river needs a thorough understanding of the sediment transport processes in addition to observed sediment and water quality data for validation of modeling results.

Age determination of sediment cores of the Golf of Lions

Siliciclastic turbidites represent huge volumes of sediments, which are of particular significance for (1) petroleum researchers, interested in their potential as oil reservoirs and (2) sedimentologists, who aim at understanding sediment transport processes from continent to deep-basins. An important challenge when studying marine turbidites has been to establish a reliable chronology for the deposits. Indeed, conventional marine proxies applied to hemipelagic sediments are often unreliable in detrital clays. In siliciclastic turbidites, those proxies can be used only in hemipelagic intervals, providing a poor constraint on their chronology. In this study, we have used sediments from the Rhône Neofan (NW Mediterranean Sea) to demonstrate that pollen grains can provide a high-resolution chronostratigraphical framework for detrital clays in turbidites. Vegetation changes occurring from the end of Marine Isotopic Stage 3 to the end of Marine Isotopic Stage 2 (from ~30 to ~18 ka cal. BP) are clearly recorded where other proxies have failed previously, mainly because the scarcity of foraminifers in these sediments prevented any continuous Sea Surface Temperature (SST) record and radiocarbon dating to be obtained. We show also that the use of palynology in turbidite deposits is able to contribute to oceanographical and sedimentological purposes: (1) Pinus pollen grains can document the timing of sea-level rise, (2) the ratio between pollen grains transported from the continent via rivers and dinoflagellate cysts (elutriating) allows us to distinguish clearly detrital sediments from pelagic clays. Finally, taken together, all these tools show evidence that the Rhône River disconnected from the canyon during the sea-level rise and thus evidence the subsequent rapid starvation of the neofan at 18.5 ka cal. BP. Younger sediments are hemipelagic: the frequency of foraminifers allowed to date sediments with radiocarbon. First results of Sea Surface Temperature obtained on foraminifers are in good agreement with the dinoflagellate cysts climatic signal. Both provide information on the end of the deglaciation and the Holocene.

Heavy mineral investigations from surface sediments of the East Greenland continental margin

During the expeditions ARK-VII/1, ARK-VII/3 and ARK-Xl2 sediment cores were taken by "RV Polarstern" from the shelf and the fjords of East Greenland and the Greenland Sea. The magnetic susceptibility and heavy mineral were determined at 48 surface sediment samples from undisturbed box cores. The main objective of this study was the identification of source areas and transport processes of terrigenous sediments at the East Greenland continental margin. The results can be summarized as lollows: 1a) Magnetic susceptibility in the North Atlantic is useful to detect delivery regions of the material transported by currents. b) The magnetic susceptibility is controlled by the ferromagnetic particles of the silt fraction. c) There are four important source areas: . The ferromagnetic particles of the box core PS2644-2 are transported from the Iceland Archipelago. . The material from the Geiki-Plateau effects the magnetic susceptibility in the Scoresby Sund Basin. . The magnetic susceptibility in the shelf regions in the North are produced by material from the fjords. . The ferromagnetic particles in the Greenland Sea are derived from the Mid Atlantic Ridges in the east. d) It is possible to determine the rock type, which delivers the ferromagnetic material because of differences in magnetic susceptibility of different intensity. . The erosion of the basalts of the Geiki-Plateau and the basalts of the Mid Atlantic ridges produce the high magnetic susceptibility in the south. . The magnetic susceptibility on the shelf in the north are probably produced by erosionproducts of the gneises of East Greenland. (2a) Heavy mineral assemblages show a significant difference between material transported by the Transpolar Drift from the Eurasian shelf regions (amphiboles, clinopyroxene, orthopyroxene) and material derived from East Greenland (garnets and opaque minerals). Transport via ice is dominant. b) lt is also possible to show different petrographic provenances (volcanic and metamorphic provenances). These associations verify the source areas. c) The information of heavy mineral composition gives no more detailed hint on the rock type or rock formation in the source area, due to mixing processes, large area of investigation and the sample quantity.

Lithofacies distribution in the western Bay of Plenty, New Zealand

Sediment dynamics on a storm-dominated shelf (western Bay of Plenty, New Zealand) were mapped and analyzed using the newly developed multi-sensor benthic profiler MARUM NERIDIS III. An area of 60 km × 7 km between 2 and 35 m water depth was surveyed with this bottom-towed sled equipped with a high-resolution camera for continuous close-up seafloor photography and a CTD with connected turbidity sensor. Here we introduce our approach of using this multi-parameter dataset combined with sidescan sonography and sedimentological analyses to create detailed lithofacies and bedform distribution maps and to derive regional sediment transport patterns. For the assessment of sediment distribution, photographs were classified and their spatial distribution mapped out according to associated acoustic backscatter from a sidescan sonar. This provisional map was used to choose target locations for surficial sediment sampling and subsequent laboratory analysis of grain size distribution and mineralogical composition. Finally, photographic, granulometric and mineralogical facies were combined into a unified lithofacies map and corresponding stratigraphic model. Eight distinct types of lithofacies with seawards increasing grain size were discriminated and interpreted as reworked relict deposits overlain by post-transgressional fluvial sediments. The dominant transport processes in different water depths were identified based on type and orientation of bedforms, as well as bottom water turbidity and lithofacies distribution. Observed bedforms include subaquatic dunes, coarse sand ribbons and sorted bedforms of varying dimensions, which were interpreted as being initially formed by erosion. Under fair weather conditions, sediment is transported from the northwest towards the southeast by littoral drift. During storm events, a current from the southeast to the northweast is induced which is transporting sediment along the shore in up to 35 m water depth. Shorewards oriented cross-shore transport is taking place in up to 60 m water depth and is likewise initiated by storm events. Our study demonstrates how benthic photographic profiling delivers comprehensive compositional, structural and environmental information, which compares well with results obtained by traditional probing methods, but offers much higher spatial resolution while covering larger areas. Multi-sensor benthic profiling enhances the interpretability of acoustic seafloor mapping techniques and is a rapid and economic approach to seabed and habitat mapping especially in muddy to sandy facies.

Bridging the Scale Gap from Leaf to Canopy in Biosphere-Atmosphere Gas and Particle Exchanges

Terrestrial ecosystems, occupying more than 25% of the Earth's surface, can serve as

`biological valves' in regulating the anthropogenic emissions of atmospheric aerosol

particles and greenhouse gases (GHGs) as responses to their surrounding environments.

While the signicance of quantifying the exchange rates of GHGs and atmospheric

aerosol particles between the terrestrial biosphere and the atmosphere is

hardly questioned in many scientic elds, the progress in improving model predictability,

data interpretation or the combination of the two remains impeded by

the lack of precise framework elucidating their dynamic transport processes over a

wide range of spatiotemporal scales. The diculty in developing prognostic modeling

tools to quantify the source or sink strength of these atmospheric substances

can be further magnied by the fact that the climate system is also sensitive to the

feedback from terrestrial ecosystems forming the so-called `feedback cycle'. Hence,

the emergent need is to reduce uncertainties when assessing this complex and dynamic

feedback cycle that is necessary to support the decisions of mitigation and

adaptation policies associated with human activities (e.g., anthropogenic emission

controls and land use managements) under current and future climate regimes.

With the goal to improve the predictions for the biosphere-atmosphere exchange

of biologically active gases and atmospheric aerosol particles, the main focus of this

dissertation is on revising and up-scaling the biotic and abiotic transport processes

from leaf to canopy scales. The validity of previous modeling studies in determining

iv

the exchange rate of gases and particles is evaluated with detailed descriptions of their

limitations. Mechanistic-based modeling approaches along with empirical studies

across dierent scales are employed to rene the mathematical descriptions of surface

conductance responsible for gas and particle exchanges as commonly adopted by all

operational models. Specically, how variation in horizontal leaf area density within

the vegetated medium, leaf size and leaf microroughness impact the aerodynamic attributes

and thereby the ultrane particle collection eciency at the leaf/branch scale

is explored using wind tunnel experiments with interpretations by a porous media

model and a scaling analysis. A multi-layered and size-resolved second-order closure

model combined with particle

uxes and concentration measurements within and

above a forest is used to explore the particle transport processes within the canopy

sub-layer and the partitioning of particle deposition onto canopy medium and forest

oor. For gases, a modeling framework accounting for the leaf-level boundary layer

eects on the stomatal pathway for gas exchange is proposed and combined with sap

ux measurements in a wind tunnel to assess how leaf-level transpiration varies with

increasing wind speed. How exogenous environmental conditions and endogenous

soil-root-stem-leaf hydraulic and eco-physiological properties impact the above- and

below-ground water dynamics in the soil-plant system and shape plant responses

to droughts is assessed by a porous media model that accommodates the transient

water

ow within the plant vascular system and is coupled with the aforementioned

leaf-level gas exchange model and soil-root interaction model. It should be noted

that tackling all aspects of potential issues causing uncertainties in forecasting the

feedback cycle between terrestrial ecosystem and the climate is unrealistic in a single

dissertation but further research questions and opportunities based on the foundation

derived from this dissertation are also brie

y discussed.

Sedimentology on surface samples from the White Sea

In this study, the grain-size and clay-mineral compositions of 73 surface sediment samples collected in a variety of environmental settings in the White Sea are presented to characterize recent sedimentation processes, reconstruct transport pathways, and identify potential source areas of the terrigenous components. Areas >100 m deep are invariably characterized by silty clay, whereas areas <100 m deep exhibit more heterogeneous grain-size compositions plausibly explained by coastal erosion and (re-)distribution mechanisms, particularly tidal currents. The dominance of sand in the estuarine areas of the Onega and Dvina rivers as well as toward Gorlo Strait connecting the White Sea with the Barents Sea, is attributed to increased current speeds. Illite and smectite are the dominant clay minerals in recent sediments of the southwestern and eastern White Sea sectors, respectively. Their distribution patterns largely depend on the geology of the source areas and mirror surface circulation patterns, especially in Dvina Bay. Smectite is a key clay mineral in White Sea surface sediments as it reveals the dominating influence of the Northern Dvina's runoff on sedimentation and water circulation throughout the basin of the sea. In comparison to other Eurasian shelf seas, the White Sea is characterized by a greater diversity of clay-mineral assemblages, which range from illite- to smectite-dominated sectors containing variable amounts of chlorite and kaolinite.

Sediment budget and geomorphic process units of the Swedish Kärkevagge, link to ArcInfo E00 files

Geomorphic process units have been derived in order to allow quantification via GIS techniques at a catchment scale. Mass movement rates based on existing field measurements are employed in the budget calculations. In the Kärkevagge catchment, Northern Sweden, 80% of the area can be identified either as a source area for sediments or as a zone where sediments are deposited. The overall budget for the slopes beneath the rockwalls in the Kärkevagge is approximately 680 t/a whilst about 150 t a-1 are transported into the fluvial system.

Grain-size analysis of surface sediments, continental margin off NW Africa

The terrigenous fraction of seabed sediments recovered along the north-west African continental margin illustrates spatial variability in grain size attributed to different transport mechanisms. Three subpopulations are determined from the grain-size analyses (n = 78) of the carbonate-free silt fraction applying an end-member modelling algorithm (G. J. Weltje, 1997). The two coarsest end-members are interpreted as representing aeolian dust, and the fine-grained end-member is related to fluvial supply. The end-member model thus allows aeolian fallout to be distinguished from fluvial-sourced mud in this area. The relative contributions of the end-members show distinct regional variations that can be related to different transport processes and pathways. Understanding present-day sediment dispersal and mixing is important for a better understanding of older sedimentary records and palaeoclimate reconstructions in the region.

Seawater carbonate chemistry, Mg/Ca, Sr/Ca, oxygen production and calcification rate during experiments with coral Pocillopora damicornis, 2011

The Sr/Ca of aragonitic coral skeletons is a commonly used palaeothermometer. However skeletal Sr/Ca is typically dominated by weekly-monthly oscillations which do not reflect temperature or seawater composition and the origins of which are currently unknown. To test the impact of transcellular Ca2+ transport processes on skeletal Sr/Ca, colonies of the branching coral, Pocillopora damicornis, were cultured in the presence of inhibitors of Ca-ATPase (ruthenium red) and Ca channels (verapamil hydrochloride). The photosynthesis, respiration and calcification rates of the colonies were monitored throughout the experiment. The skeleton deposited in the presence of the inhibitors was identified (by 42Ca spike) and analysed for Sr/Ca and Mg/Ca by secondary ion mass spectrometry. The Sr/Ca of the aragonite deposited in the presence of either of the inhibitors was not significantly different from that of the solvent (dimethyl sulfoxide) control, although the coral calcification rate was reduced by up to 66% and 73% in the ruthenium red and verapamil treatments, respectively. The typical precision (95% confidence limits) of mean Sr/Ca determinations within any treatment was <±1% and differences in skeletal Sr/Ca between treatments were correspondingly small. Either Ca-ATPase and Ca channels transport Sr2+ and Ca2+ in virtually the same ratio in which they are present in seawater or transcellular processes contribute little Ca2+ to the skeleton and most Ca is derived from seawater transported directly to the calcification site. Variations in the activities of Ca-ATPase and Ca-channels are not responsible for the weekly-monthly Sr/Ca oscillations observed in skeletal chronologies, assuming that the specificities of Ca transcellular transport processes are similar between coral genera.

Coccolithophore biomineralization: New questions, new answers.

Coccolithophores are unicellular phytoplankton that are characterized by the presence intricately formed calcite scales (coccoliths) on their surfaces. In most cases coccolith formation is an entirely intracellular process - crystal growth is confined within a Golgi-derived vesicle. A wide range of coccolith morphologies can be found amongst the different coccolithophore groups. This review discusses the cellular factors that regulate coccolith production, from the roles of organic components, endomembrane organization and cytoskeleton to the mechanisms of delivery of substrates to the calcifying compartment. New findings are also providing important information on how the delivery of substrates to the calcification site is co-ordinated with the removal of H(+) that are a bi-product of the calcification reaction. While there appear to be a number of species-specific features of the structural and biochemical components underlying coccolith formation, the fluxes of Ca(2+) and a HCO3(-) required to support coccolith formation appear to involve spatially organized recruitment of conserved transport processes.

Coccolithophore biomineralization: New questions, new answers.

Coccolithophores are unicellular phytoplankton that are characterized by the presence intricately formed calcite scales (coccoliths) on their surfaces. In most cases coccolith formation is an entirely intracellular process - crystal growth is confined within a Golgi-derived vesicle. A wide range of coccolith morphologies can be found amongst the different coccolithophore groups. This review discusses the cellular factors that regulate coccolith production, from the roles of organic components, endomembrane organization and cytoskeleton to the mechanisms of delivery of substrates to the calcifying compartment. New findings are also providing important information on how the delivery of substrates to the calcification site is co-ordinated with the removal of H(+) that are a bi-product of the calcification reaction. While there appear to be a number of species-specific features of the structural and biochemical components underlying coccolith formation, the fluxes of Ca(2+) and a HCO3(-) required to support coccolith formation appear to involve spatially organized recruitment of conserved transport processes.

Développement de procédés technologiques pour une intégration 3D monolithique de dispositifs nanoélectroniques sur CMOS

Résumé : Le transistor monoélectronique (SET) est un dispositif nanoélectronique très attractif à cause de son ultra-basse consommation d’énergie et sa forte densité d’intégration, mais il n’a pas les capacités suffisantes pour pouvoir remplacer complètement la technologie CMOS. Cependant, la combinaison de la technologie SET avec celle du CMOS est une voie intéressante puisqu’elle permet de profiter des forces de chacune, afin d’obtenir des circuits avec des fonctionnalités additionnelles et uniques. Cette thèse porte sur l’intégration 3D monolithique de nanodispositifs dans le back-end-of-line (BEOL) d’une puce CMOS. Cette approche permet d’obtenir des circuits hybrides et de donner une valeur ajoutée aux puces CMOS actuelles sans altérer le procédé de fabrication du niveau des transistors MOS. L’étude se base sur le procédé nanodamascène classique développé à l’UdeS qui a permis la fabrication de dispositifs nanoélectroniques sur un substrat de SiO2. Ce document présente les travaux réalisés sur l’optimisation du procédé de fabrication nanodamascène, afin de le rendre compatible avec le BEOL de circuits CMOS. Des procédés de gravure plasma adaptés à la fabrication de nanostructures métalliques et diélectriques sont ainsi développés. Le nouveau procédé nanodamascène inverse a permis de fabriquer des jonctions MIM et des SET métalliques sur une couche de SiO2. Les caractérisations électriques de MIM et de SET formés avec des jonctions TiN/Al2O3 ont permis de démontrer la présence de pièges dans les jonctions et la fonctionnalité d’un SET à basse température (1,5 K). Le transfert de ce procédé sur CMOS et le procédé d’interconnexions verticales sont aussi développés par la suite. Finalement, un circuit 3D composé d’un nanofil de titane connecté verticalement à un transistor MOS est réalisé et caractérisé avec succès. Les résultats obtenus lors de cette thèse permettent de valider la possibilité de co-intégrer verticalement des dispositifs nanoélectroniques avec une technologie CMOS, en utilisant un procédé de fabrication compatible.

Nocturnal surface ozone enhancement over Portugal during winter: Influence of different atmospheric conditions

our distinct nocturnal surface ozone (NSO) enhancement events were observed, with NSO concentration exceeding 80μg/m3, at multiple ozone (O3) monitoring stations (32 sites) in January, November and December between year 2000–2010, in Portugal. The reasonable explanation for the observed bimodal pattern of surface ozone with enhanced NSO concentration during nighttime has to be transport processes, as the surface ozone production ceases at nighttime. Simultaneous measurements of O3 at multiple stations during the study period in Portugal suggest that horizontal advection alone cannot explain the observed NSO enhancement. Thus, detailed analysis of the atmospheric conditions, simulated with the Weather Research and Forecasting (WRF) model, were performed to evaluate the atmospheric mechanisms responsible for NSO enhancement in the region. Simulations revealed that each event occurred as a result of one or the combination of different atmospheric processes such as, passage of a cold front followed by a subsidence zone; passage of a moving surface trough, with associated strong horizontal wind speed and vertical shear; combination of vertical and horizontal transport at the synoptic scale; formation of a low level jet with associated vertical mixing below the jet stream. The study confirmed that large-scale flow pattern resulting in enhanced vertical mixing in the nocturnal boundary layer, plays a key role in the NSO enhancement events, which frequently occur over Portugal during winter months.