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This work presents airborne observations of sub-3 nm particles in the lower troposphere and investigates new particle formation (NPF) within an evolving boundary layer (BL). We studied particle concentrations together with supporting gas and meteorological data inside the planetary BL over a boreal forest site in Hyytiälä, southern Finland. The analysed data were collected during three flight measurement campaigns: May–June 2015, August 2015 and April–May 2017, including 27 morning and 26 afternoon vertical profiles. As a platform for the instrumentation, we used a Cessna 172 aircraft. The analysed flight data were collected horizontally within a 30 km distance from SMEAR II in Hyytiälä and vertically from 100 m above ground level up to 2700 m. The number concentration of 1.5–3 nm particles was observed to be, on average, the highest near the forest canopy top and to decrease with increasing altitude during the mornings of NPF event days. This indicates that the precursor vapours emitted by the forest play a key role in NPF in Hyytiälä. During daytime, newly formed particles were observed to grow in size and the particle population became more homogenous within the well-mixed BL in the afternoon. During undefined days with respect to NPF, we also detected an increase in concentration of 1.5–3 nm particles in the morning but not their growth in size, which indicates an interrupted NPF process during these undefined days. Vertical mixing was typically stronger during the NPF event days than during the undefined or non-event days. The results shed light on the connection between boundary layer dynamics and NPF.

When the supersonic solar wind encounters the Earth's magnetosphere a shock, called bow shock, is formed and the plasma is decelerated and thermalized in the magnetosheath downstream from the shock. Sometimes, however, due to discontinuities in the solar wind, bow shock ripples or ionized dust clouds carried by the solar wind, high speed jets (HSJs) are observed in the magnetosheath. These HSJs have typically a Vx component larger than 200 km s−1 and their dynamic pressure can be a few times the solar wind dynamic pressure. They are typically observed downstream from the quasi-parallel bow shock and have a typical size around one Earth radius (RE) in XGSE. We use a conjunction of Cluster and MMS, crossing simultaneously the magnetopause, to study the characteristics of these HSJs and their impact on the magnetopause. Over 1 h 15 min interval in the magnetosheath, Cluster observed 21 HSJs. During the same period, MMS observed 12 HSJs and entered the magnetosphere several times. A jet was observed simultaneously by both MMS and Cluster and it is very likely that they were two distinct HSJs. This shows that HSJs are not localized into small regions but could span a region larger than 10 RE, especially when the quasi-parallel shock is covering the entire dayside magnetosphere under radial IMF. During this period, two and six magnetopause crossings were observed, respectively, on Cluster and MMS with a significant angle between the observation and the expected normal deduced from models. The angles observed range between from 11° up to 114°. One inbound magnetopause crossing observed by Cluster (magnetopause moving out at 142 km s−1) was observed simultaneous to an outbound magnetopause crossing observed by MMS (magnetopause moving in at −83 km s−1), showing that the magnetopause can have multiple local indentation places, most likely independent from each other. Under the continuous impacts of HSJs, the magnetopause is deformed significantly and can even move in opposite directions at different places. It can therefore not be considered as a smooth surface anymore but more as surface full of local indents. Four dust impacts were observed on MMS, although not at the time when HSJs are observed, showing that dust clouds would have been present during the observations. No dust cloud in the form of Interplanetary Field Enhancements was however observed in the solar wind which may exclude large clouds of dust as a cause of HSJs. Radial IMF and Alfvén Mach number above 10 would fulfill the criteria for the creation of bow shock ripples and the subsequent crossing of HSJs in the magnetosheath.

The Cluster mission has been operated successfully for 14 years. During this time period, the evolution of the orbit has enabled Cluster to sample many more magnetospheric regions than was initially anticipated. So far, the separation of the Cluster spacecraft has been changed more than 30 times and has ranged from a few kilometres up to 36 000 km. These orbital changes have enabled the science team to address a wide variety of scientific objectives in key regions of Earth's geospace environment: the solar wind and bow shock, the magnetopause, polar cusps, magnetotail, plasmasphere and the auroral acceleration region. Recent results have shed new light on solar wind turbulence. They showed that the magnetosheath can be asymmetric under low Mach number and that it can contain density enhancement that may affect the magnetosphere. The magnetopause was found to be thinner and to have a higher current density on the duskside than on the dawnside. New methods have been used to obtain characteristic of the magnetotail current sheet and high-temporal-resolution measurements of electron pitch angle within flux transfer events (FTEs). Plasmaspheric wind has been discovered, and the refilling of the plasmasphere was observed for the first time over a very wide range of L shells. New models of global electric and magnetic fields of the magnetosphere have been obtained where Cluster, due to its polar orbit, has been essential. Finally, magnetic reconnection was viewed for the first time with high-resolution wave and electron measurements and acceleration of plasma was observed during times of varying rate of magnetic reconnection. The analysis of Cluster data was facilitated by the creation of the Cluster Science Data System (CSDS) and the Cluster Science Archive (CSA). Those systems were implemented to provide, for the first time for a plasma physics mission, a long-term public archive of all calibrated high-resolution data from all instruments.

Aromatic hydrocarbons are associated with direct adverse human health effects and can have negative impacts on ecosystems due to their toxicity, as well as indirect negative effects through the formation of tropospheric ozone and secondary organic aerosol, which affect human health, crop production and regional climate. Measurements of aromatic hydrocarbons were conducted at the Welgegund measurement station (South Africa), which is considered to be a regionally representative background site. However, the site is occasionally impacted by plumes from major anthropogenic source regions in the interior of South Africa, which include the western Bushveld Igneous Complex (e.g. platinum, base metal and ferrochrome smelters), the eastern Bushveld Igneous Complex (platinum and ferrochrome smelters), the Johannesburg–Pretoria metropolitan conurbation (> 10 million people), the Vaal Triangle (e.g. petrochemical and pyrometallurgical industries), the Mpumalanga Highveld (e.g. coal-fired power plants and petrochemical industry) and also a region of anticyclonic recirculation of air mass over the interior of South Africa. The aromatic hydrocarbon measurements were conducted with an automated sampler on Tenax-TA and Carbopack-B adsorbent tubes with heated inlet for 1 year. Samples were collected twice a week for 2 h during daytime and 2 h during night-time. A thermal desorption unit, connected to a gas chromatograph and a mass selective detector was used for sample preparation and analysis. Results indicated that the monthly median (mean) total aromatic hydrocarbon concentrations ranged between 0.01 (0.011) and 3.1 (3.2) ppb. Benzene levels did not exceed the local air quality standard limit, i.e. annual mean of 1.6 ppb. Toluene was the most abundant compound, with an annual median (mean) concentration of 0.63 (0.89) ppb. No statistically significant differences in the concentrations measured during daytime and night-time were found, and no distinct seasonal patterns were observed. Air mass back trajectory analysis indicated that the lack of seasonal cycles could be attributed to patterns determining the origin of the air masses sampled. Aromatic hydrocarbon concentrations were in general significantly higher in air masses that passed over anthropogenically impacted regions. Inter-compound correlations and ratios gave some indications of the possible sources of the different aromatic hydrocarbons in the source regions defined in the paper. The highest contribution of aromatic hydrocarbon concentrations to ozone formation potential was also observed in plumes passing over anthropogenically impacted regions.

After 12 years of operations, the Cluster mission continues to successfully fulfil its scientific objectives. The main goal of the Cluster mission, comprised of four identical spacecraft, is to study in three dimensions small-scale plasma structures in key plasma regions of the Earth's environment: solar wind and bow shock, magnetopause, polar cusps, magnetotail, plasmasphere and auroral zone. During the course of the mission, the relative distance between the four spacecraft has been varied from 20 km to 36 000 km to study the scientific regions of interest at different scales. Since summer 2005, new multi-scale constellations have been implemented, wherein three spacecraft (C1, C2, C3) are separated by 10 000 km, while the fourth one (C4) is at a variable distance ranging between 20 km and 10 000 km from C3. Recent observations were conducted in the auroral acceleration region with the spacecraft separated by 1000s km. We present highlights of the results obtained during the last 12 years on collisionless shocks, magnetopause waves, magnetotail dynamics, plasmaspheric structures, and the auroral acceleration region. In addition, we highlight Cluster results on understanding the impact of Coronal Mass Ejections (CME) on the Earth environment. We will also present Cluster data accessibility through the Cluster Science Data System (CSDS), and the Cluster Active Archive (CAA), which was implemented to provide a permanent and public archive of high resolution Cluster data from all instruments.

Modelling plasma entry in the polar cusp has been successful in reproducing ion dispersions observed in the cusp at low and mid-altitudes. The use of a realistic convection pattern, when the IMF-By is large and stable, allowed Wing et al. (2001) to predict double cusp signatures that were subsequently observed by the DMSP spacecraft. In this paper we present a cusp crossing where two cusp populations are observed, separated by a gap around 1° Invariant Latitude (ILAT) wide. Cluster 1 (C1) and Cluster 2 (C2) observed these two cusp populations with a time delay of 3 min, and about 15 and 42 min later Cluster 4 (C4) and Cluster 3 (C3) observed, respectively, a single cusp population. A peculiarity of this event is the fact that the second cusp population seen on C1 and C2 was observed at the same time as the first cusp population on C4. This would tend to suggest that the two cusp populations had spatial features similar to the double cusp. Due to the nested crossing of C1 and C2 through the gap between the two cusp populations, C2 being first to leave the cusp and last to re-enter it, these observations are difficult to be explained by two distinct cusps with a gap in between. However, since we observe the cusp in a narrow area of local time post-noon, a second cusp may have been present in the pre-noon sector but could not be observed. On the other hand, these observations are in agreement with a motion of the cusp first dawnward and then back duskward due to the effect of the IMF-By component.

The South African savannah region is a complex environment of air pollution and natural emissions influenced by a strong seasonal cycle in biomass burning and strong precipitation. However, the scarcity of long-term observations means that the knowledge of controlling aerosol processes in this environment is limited. Here we use a recent dataset of 18 months of aerosol size distribution observations trying to understand the annual cycle of cloud condensation nuclei (CCN). Our observations show that the concentration of CCN-sized particles remains, in line with previous studies, high throughout the year with the highest concentrations during the dry winter and the lowest during the wet summer. During the wet season with reduced anthropogenic and biomass burning primary emissions, this pool of CCN is partly filled by boundary layer nucleation with subsequent growth. The enhanced importance of formation and growth during the wet season is addressed to increased biogenic activity together with enhanced free tropospheric removal decreasing the concentration of pre-existing CCN. During the dry season, while frequent new particle formation takes place, particle growth is reduced due to reduced condensing vapour concentrations. Thus in the dry season particles are not able to grow to sizes where they may act as CCN nearly as efficiently as during the wet season. The observations are compared to simulations by a global aerosol model GLOMAP. To our surprise, the global aerosol model utilized to explain the observations was not capable of re-producing the characteristics of particle formation and the annual CCN cycle, despite earlier good performance in predicting the particle concentrations in a number of diverse environments, including the South African savannah region. While the average yearly CCN concentrations of modelled CCN is close to observed concentrations, the characteristics of nucleation bursts and subsequent growth are not captured satisfactory by the model. Our sensitivity tests using different nucleation parameterizations and condensing organic vapour production rates show that neither of these is likely to explain the differences between observed and modelled nucleation and growth rates. A sensitivity study varying 28 modelling parameters indicates that the main uncertainties in the result are due to uncertainties in biomass burning emissions during the dry season, and anthropogenic sulphur emissions during the wet season, both in terms or emitted mass and particle sizes. The uncertainties appear to be mostly related to uncertainties in primary particle emissions, including the emissions variability not captured by monthly emission inventories. The results of this paper also highlights the fact that deficiencies in emissions estimates may result in deficiencies in particle production fluxes, while the end product such as modelled CCN concentration may be in line with observations.

This study presents a total of four years of sub-micron aerosol particle size distribution measurements in the southern African savannah, an environment with few previous observations covering a full seasonal cycle and the size range below 100 nm. During the first 19 months, July 2006–January 2008, the measurements were carried out at Botsalano, a semi-clean location, whereas during the latter part, February 2008–May 2010, the measurements were carried out at Marikana (approximately 150 km east of Botsalano), which is a more polluted location with both pyrometallurgical industries and informal settlements nearby. The median total concentration of aerosol particles was more than four times as high at Marikana than at Botsalano. In the size ranges of 12–840 nm, 50–840 nm and 100–840 nm the median concentrations were 1856, 1278 and 698 particles cm−3 at Botsalano and 7805, 3843 and 1634 particles cm−3 at Marikana, respectively. The diurnal variation of the size distribution for Botsalano arose as a result of frequent regional new particle formation. However, for Marikana the diurnal variation was dominated by the morning and evening household burning in the informal settlements, although regional new particle formation was even more frequent than at Botsalano. The effect of the industrial emissions was not discernible in the size distribution at Marikana although it was clear in the sulphur dioxide diurnal pattern, indicating the emissions to be mostly gaseous. Seasonal variation was strongest in the concentration of particles larger than 100 nm, which was clearly elevated at both locations during the dry season from May to September. In the absence of wet removal during the dry season, the concentration of particles larger than 100 nm had a correlation above 0.7 with CO for both locations, which implies incomplete burning to be an important source of aerosol particles during the dry season. However, the sources of burning differ: at Botsalano the rise in concentration originates from regional wild fires, while at Marikana domestic heating in the informal settlements is the main source. Air mass history analysis for Botsalano identified four regional scale source areas in southern Africa and enabled the differentiation between fresh and aged rural background aerosol originating from the clean sector, i.e., western sector with very few large anthropogenic sources. Comparison to size distributions published for other comparable environments in Northern Hemisphere shows southern African savannah to have a unique combination of sources and meteorological parameters. The observed strong link between combustion and seasonal variation is comparable only to the Amazon basin; however, the lack of long-term observations in the Amazonas does not allow a quantitative comparison. All the data presented in the figures, as well as the time series of monthly mean and median size distributions are included in numeric form as a Supplement to provide a reference point for the aerosol modelling community.

The Kelvin-Helmholtz Instability (KHI) can drive waves at the magnetopause. These waves can grow to form rolled-up vortices and facilitate transfer of plasma into the magnetosphere. To investigate the persistence and frequency of such waves at the magnetopause we have carried out a survey of all Double Star 1 magnetopause crossings, using a combination of ion and magnetic field measurements. Using criteria originally used in a Geotail study made by Hasegawa et al. (2006) (forthwith referred to as H2006), 17 candidate events were identified from the entire TC-1 mission (covering ~623 orbits where the magnetopause was sampled), a majority of which were on the dayside of the terminator. The relationship between density and shear velocity was then investigated, to identify the predicted signature of a rolled up vortex from H2006 and all 17 events exhibited some level of rolled up behavior. The location of the events had a clear dawn-dusk asymmetry, with 12 (71%) on the post noon, dusk flank suggesting preferential growth in this region.

South Africa holds significant mineral resources, with a substantial fraction of these reserves occurring and being processed in a large geological structure termed the Bushveld Igneous Complex (BIC). The area is also highly populated by informal, semi-formal and formal residential developments. However, knowledge of air quality and research related to the atmosphere is still very limited in the area. In order to investigate the characteristics and processes affecting sub-micron particle number concentrations and formation events, air ion and aerosol particle size distributions and number concentrations, together with meteorological parameters, trace gases and particulate matter (PM) were measured for over two years at Marikana in the heart of the western BIC. The observations showed that trace gas (i.e. SO2, NOx, CO) and black carbon concentrations were relatively high, but in general within the limits of local air quality standards. The area was characterised by very high condensation sink due to background aerosol particles, PM10 and O3 concentration. The results indicated that high amounts of Aitken and accumulation mode particles originated from domestic burning for heating and cooking in the morning and evening, while during daytime SO2-based nucleation followed by the growth by condensation of vapours from industrial, residential and natural sources was the most probable source for large number concentrations of nucleation and Aitken mode particles. Nucleation event day frequency was extremely high, i.e. 86% of the analysed days, which to the knowledge of the authors is the highest frequency ever reported. The air mass back trajectory and wind direction analyses showed that the secondary particle formation was influenced both by local and regional pollution and vapour sources. Therefore, our observation of the annual cycle and magnitude of the particle formation and growth rates during nucleation events were similar to results previously published for a semi-clean savannah site in South Africa.

In this paper we introduce new in situ observations of atmospheric aerosols, especially chemical composition, physical and optical properties, on the eastern brink of the heavily polluted Highveld area in South Africa. During the observation period between 11 February 2009 and 31 January 2011, the mean particle number concentration (size range 10–840 nm) was 6310 cm3 and the estimated volume of sub-10 μm particles 9.3 μm3 m−3. The aerosol absorption and scattering coefficients at 637 nm were 8.3 Mm−1 and 49.5 Mm−1, respectively. The mean single-scattering albedo at 637 nm was 0.84 and the Ångström exponent of scattering was 1.5 over the wavelength range 450–635 nm. The mean O3, SO2, NOx and H2S-concentrations were 37.1, 11.5, 15.1 and 3.2 ppb, respectively. The observed range of concentrations was large and attributed to the seasonal variation of sources and regional meteorological effects, especially the anticyclonic re-circulation and strong winter-time inversions. In a global context, the levels of gases and particulates were typical for continental sites with strong anthropogenic influence, but clearly lower than the most polluted areas of south-eastern Asia. Of all pollutants observed at the site, ozone is the most likely to have adverse environmental effects, as the concentrations were high also during the growing season. The measurements presented here will help to close existing gaps in the ground-based global atmosphere observation system, since very little long-term data of this nature is available for southern Africa.

This study is based on 18 months (20 July 2006–5 February 2008) of continuous measurements of aerosol particle size distributions, air ion size distributions, trace gas concentrations and basic meteorology in a semi-clean savannah environment in Republic of South Africa. New particle formation and growth was observed on 69% of the days and bursts of non-growing ions/sub-10 nm particles on additional 14% of the days. This new particle formation frequency is the highest reported from boundary layer so far. Also the new particle formation and growth rates were among the highest reported in the literature for continental boundary layer locations; median 10 nm formation rate was 2.2 cm−3 s−1 and median 10–30 nm growth rate 8.9 nm h−1. The median 2 nm ion formation rate was 0.5 cm−3 s−1 and the median ion growth rates were 6.2, 8.0 and 8.1 nm h−1 for size ranges 1.5–3 nm, 3–7 nm and 7–20 nm, respectively. The growth rates had a clear seasonal dependency with minimum during winter and maxima in spring and late summer. The relative contribution of estimated sulphuric acid to the growth rate was decreasing with increasing particle size and could explain more than 20% of the observed growth rate only for the 1.5–3 nm size range. Also the air mass history analysis indicated the highest formation and growth rates to be associated with the area of highest VOC (Volatile Organic Compounds) emissions following from biological activity rather than the highest estimated sulphuric acid concentrations. The frequency of new particle formation, however, increased nearly monotonously with the estimated sulphuric acid reaching 100% at H2SO4 concentration of 6 · 107 cm−3, which suggests the formation and growth to be independent of each other.

We have analyzed one year (July 2006–July 2007) of measurement data from a relatively clean background site located in dry savannah in South Africa. The annual-median trace gas concentrations were equal to 0.7 ppb for SO2, 1.4 ppb for NOx, 36 ppb for O3 and 105 ppb for CO. The corresponding PM1, PM2.5 and PM10 concentrations were 9.0, 10.5 and 18.8 μg m−3, and the annual median total particle number concentration in the size range 10–840 nm was 2340 cm−3. During Easterly winds, influence of industrial sources approximately 150 km away from the measurement site was clearly visible, especially in SO2 and NOx concentrations. Of gases, NOx and CO had a clear annual, and SO2, NOx and O3 clear diurnal cycle. Atmospheric new-particle formation was observed to take place in more than 90% of the analyzed days. The days with no new particle formation were cloudy or rainy days. The formation rate of 10 nm particles varied in the range of 0.1–28 cm−3 s−1 (median 1.9 cm−3 s−1) and nucleation mode particle growth rates were in the range 3–21 nm h−1 (median 8.5 nm h−1). Due to high formation and growth rates, observed new particle formation gives a significant contribute to the number of cloud condensation nuclei budget, having a potential to affect the regional climate forcing patterns.

During the last 30 years, several magnetospheric missions have recorded the presence of narrow proton structures in the ring current region. These structures have been referred as "nose-like" structures, due to their appearance when represented in energy-time spectrograms, characterized by a flux value increase for a narrow energy range. Cluster's polar orbit, with a 4 RE perigee, samples the ring current region. The ion distribution functions obtained in-situ by the CIS experiment (for energies of ~5 eV/q to 40 keV/q) reveal the simultaneous presence of several (up to 3) narrow nose-like structures. A statistical study (over one year and a half of CIS data) reveals that double nose structures are preferentially observed in the post-midnight sector. Also, the characteristic energy of the nose (the one observed at the lower energy range when several noses occur simultaneously) reveals a clear MLT dependence during quiet events (Kp Numerical simulations of particles trajectories, using large-scale electric and magnetic field models are also presented. Most of the features have been accurately reproduced (namely the single and double noses), but the triple noses cannot be produced under these conditions and require to consider a more complex electric field model.

The four Cluster satellites each carry two instruments designed for measuring the electric field: a double-probe instrument (EFW) and an electron drift instrument (EDI). We compare data from the two instruments in a representative sample of plasma regions. The complementary merits and weaknesses of the two techniques are illustrated. EDI operations are confined to regions of magnetic fields above 30 nT and where wave activity and keV electron fluxes are not too high, while EFW can provide data everywhere, and can go far higher in sampling frequency than EDI. On the other hand, the EDI technique is immune to variations in the low energy plasma, while EFW sometimes detects significant nongeophysical electric fields, particularly in regions with drifting plasma, with ion energy (in eV) below the spacecraft potential (in volts). We show that the polar cap is a particularly intricate region for the double-probe technique, where large nongeophysical fields regularly contaminate EFW measurments of the DC electric field. We present a model explaining this in terms of enhanced cold plasma wake effects appearing when the ion flow energy is higher than the thermal energy but below the spacecraft potential multiplied by the ion charge. We suggest that these conditions, which are typical of the polar wind and occur sporadically in other regions containing a significant low energy ion population, cause a large cold plasma wake behind the spacecraft, resulting in spurious electric fields in EFW data. This interpretation is supported by an analysis of the direction of the spurious electric field, and by showing that use of active potential control alleviates the situation.

The Double Star Programme (DSP) was first proposed by China in March, 1997 at the Fragrant Hill Workshop on Space Science, Beijing, organized by the Chinese Academy of Science. It is the first mission in collaboration between China and ESA. The mission is made of two spacecraft to investigate the magnetospheric global processes and their response to the interplanetary disturbances in conjunction with the Cluster mission. The first spacecraft, TC-1 (Tan Ce means "Explorer"), was launched on 29 December 2003, and the second one, TC-2, on 25 July 2004 on board two Chinese Long March 2C rockets. TC-1 was injected in an equatorial orbit of 570x79000 km altitude with a 28° inclination and TC-2 in a polar orbit of 560x38000 km altitude. The orbits have been designed to complement the Cluster mission by maximizing the time when both Cluster and Double Star are in the same scientific regions. The two missions allow simultaneous observations of the Earth magnetosphere from six points in space. To facilitate the comparison of data, half of the Double Star payload is made of spare or duplicates of the Cluster instruments; the other half is made of Chinese instruments. The science operations are coordinated by the Chinese DSP Scientific Operations Centre (DSOC) in Beijing and the European Payload Operations Service (EPOS) at RAL, UK. The spacecraft and ground segment operations are performed by the DSP Operations and Management Centre (DOMC) and DSOC in China, using three ground station, in Beijing, Shanghai and Villafranca.

The recent launch of the equatorial spacecraft of the Double Star mission, TC-1, has provided an unprecedented opportunity to monitor the southern hemisphere dayside magnetopause boundary layer in conjunction with northern hemisphere observations by the quartet of Cluster spacecraft. We present first results of one such situation where, on 6 April 2004, both Cluster and the Double Star TC-1 spacecraft were on outbound transits through the dawnside magnetosphere. The observations are consistent with ongoing reconnection on the dayside magnetopause, resulting in a series of flux transfer events (FTEs) seen both at Cluster and TC-1, which appear to lie north and south of the reconnection line, respectively. In fact, the observed polarity and motion of each FTE signature advocates the existence of an active reconnection region consistently located between the positions of Cluster and TC-1, with Cluster observing northward moving FTEs with +/- polarity, whereas TC-1 sees -/+ polarity FTEs. This assertion is further supported by the application of a model designed to track flux tube motion for the prevailing interplanetary conditions. The results from this model show, in addition, that the low-latitude FTE dynamics are sensitive to changes in convected upstream conditions. In particular, changing the interplanetary magnetic field (IMF) clock angle in the model suggests that TC-1 should miss the resulting FTEs more often than Cluster and this is borne out by the observations.

We study the wave-related (AC) and static (DC) parallel Poynting vector (Poynting energy flux) as a function of altitude in auroral field lines using Polar EFI and MFE data. The study is statistical and contains 5 years of data in the altitude range 5000–30000 km. We verify the low altitude part of the results by comparison with earlier Astrid-2 EMMA Poynting vector statistics at 1000 km altitude. The EMMA data are also used to statistically compensate the Polar results for the missing zonal electric field component. We compare the Poynting vector with previous statistical DMSP satellite data concerning the electron precipitation power. We find that the AC Poynting vector (Alfvén-wave related Poynting vector) is statistically not sufficient to power auroral electron precipitation, although it may, for Kp>2, power 25–50% of it. The statistical AC Poynting vector also has a stepwise transition at R=4 RE, so that its amplitude increases with increasing altitude. We suggest that this corresponds to Alfvén waves being in Landau resonance with electrons, so that wave-induced electron acceleration takes place at this altitude range, which was earlier named the Alfvén Resonosphere (ARS). The DC Poynting vector is ~3 times larger than electron precipitation and corresponds mainly to ionospheric Joule heating. In the morning sector (02:00–06:00 MLT) we find that the DC Poynting vector has a nontrivial altitude profile such that it decreases by a factor of ~2 when moving upward from 3 to 4 RE radial distance. In other nightside MLT sectors the altitude profile is more uniform. The morning sector nontrivial altitude profile may be due to divergence of the perpendicular Poynting vector field at R=3–4 RE. Keywords. Magnetospheric physics (Auroral phenomena; Magnetosphere-ionosphere interactions) – Space plasma physics (Wave-particle interactions)

An isolated plasma sheet flow burst took place at 22:02 UT, 1 September 2002, when the Cluster footpoint was located within the area covered by the Magnetometers-Ionospheric Radars-All-sky Cameras Large Experiment (MIRACLE). The event was associated with a clear but weak ionospheric disturbance and took place during a steady southward IMF interval, about 1h preceding a major substorm onset. Multipoint observations, both in space and from the ground, allow us to discuss the temporal and spatial scale of the disturbance both in the magnetosphere and ionosphere. Based on measurements from four Cluster spacecraft it is inferred that Cluster observed the dusk side part of a localized flow channel in the plasma sheet with a flow shear at the front, suggesting a field-aligned current out from the ionosphere. In the ionosphere the equivalent current pattern and possible field-aligned current location show a pattern similar to the auroral streamers previously obtained during an active period, except for its spatial scale and amplitude. It is inferred that the footpoint of Cluster was located in the region of an upward field-aligned current, consistent with the magnetospheric observations. The entire disturbance in the ionosphere lasted about 10min, consistent with the time scale of the current sheet disturbance in the magnetosphere. The plasma sheet bulk flow, on the other hand, had a time scale of about 2min, corresponding to the time scale of an equatorward excursion of the enhanced electrojet. These observations confirm that localized enhanced convection in the magnetosphere and associated changes in the current sheet structure produce a signature with consistent temporal and spatial scale at the conjugate ionosphere.

In the vicinity of the plasmapause, around the geomagnetic equator, the four Cluster satellites often observe banded hiss-like electromagnetic emissions (BHE); below the electron gyrofrequency but above the lower hybrid resonance, from 2kHz to 10kHz. We show that below 4kHz, these waves propagate in the whistler mode. Using the first year of scientific operations of WHISPER, STAFF and WBD wave experiments on Cluster, we have identified the following properties of the BHE waves: (i) their location is strongly correlated with the position of the plasmapause, (ii) no MLT dependence has been found, (iii) their spectral width is generally 1 to 2kHz, and (iv) the central frequency of their emission band varies from 2kHz to 10kHz. All these features suggest that BHE are in fact mid-latitude hiss emissions (MLH). Moreover, the central frequency was found to be correlated with the Kp index. This suggests either that these banded emissions are generated in a given f/fce range, or that there is a Kp dependent Doppler shift between the satellites and a possible moving source of the MLH.

Recent statistical studies show the existence of an island of cavities and enhanced electric field structures at 4-5RE radial distance in the evening and midnight magnetic local time (MLT) sectors in the auroral region during disturbed conditions, as well as ion beam occurrence frequency changes at the same altitude. We study the possibility that the mechanism involved is electron Landau resonance with incoming Alfvén waves and study the feasibility of the idea further with Polar electric field, magnetic field, spacecraft potential and electron data in an event where Polar maps to a substorm over the CANOPUS magnetometer array. Recently, a new type of auroral kilometric radiation (AKR) emission originating from ~2-3RE radial distance, the so-called dot-AKR emission, has been reported to occur during substorm onsets and suggested to also be an effect of Alfvénic wave acceleration in a pre-existing auroral cavity. We improve the analysis of the dot-AKR, giving it a unified theoretical handling with the high-altitude Landau resonance phenomena. The purpose of the paper is to study the two types of Alfvénic electron acceleration, acknowledging that they have different physical mechanisms, altitudes and roles in substorm-related auroral processes.

The aim of the paper is to study how auroral potential structures close at high altitude. We analyse all electric field data collected by Polar on auroral field lines in 1996–2001 by integrating the electric field along the spacecraft orbit to obtain the plasma potential, from which we identify potential minima by an automatic method. From these we estimate the associated effective mapped-down electric field Ei, defined as the depth of the potential minimum divided by its half-width in the ionosphere. Notice that although we use the ionosphere as a reference altitude, the field Ei does not actually exist in the ionosphere but is just a convenient computational quantity. We obtain the statistical distribution of Ei as a function of altitude, magnetic local time (MLT), Kp index and the footpoint solar illumination condition. Surprisingly, we find two classes of electric field structures. The first class consists of the low-altitude potential structures that are presumably associated with inverted-V regions and discrete auroral arcs and their set of associated phenomena. We show that the first class exists only below ~3RE radial distance, and it occurs in all nightside MLT sectors (RE=Earth radius). The second class exists only above radial distance R=4RE and almost only in the midnight MLT sector, with a preference for high Kp values. Interestingly, in the middle altitudes (R=3–4RE) the number of potential minima is small, suggesting that the low and high altitude classes are not simple field-aligned extensions of each other. This is also underlined by the fact that statistically the high altitude structures seem to be substorm-related, while the low altitude structures seem to correspond to stable auroral arcs. The new finding of the existence of the two classes is important for theories of auroral acceleration, since it supports a closed potential structure model for stable arcs, while during substorms, different superposed processes take place that are associated with the disconnected high-altitude electric field structures. Key words. Magnetospheric physics (electric fields; auroral phenomena) – Space plasma physics (electrostatic structures)

Conjunctions in the cusp between the four Cluster spacecraft and SuperDARN ground-based radars offer unique opportunities to compare the signatures of transient plasma injections simultaneously in the high-altitude dayside magnetosphere and in the ionosphere. We report here on such observations on 17 March 2001, when the IMF initially northward and duskward, turns southward and dawnward for a short period. The changes in the convection direction at Cluster are well correlated with the interplanetary magnetic field (IMF) By variations. Moreover, the changes in the ionosphere follow those in the magnetosphere, with a 2–3min delay. When mapped into the ionosphere, the convection velocity at Cluster is about 1.5 times larger than measured by SuperDARN. In the high-altitude cusp, field and particle observations by Cluster display the characteristic signatures of plasma injections into the magnetosphere suggestive of Flux Transfer Events (FTEs). Simultaneous impulsive and localized convection plasma flows are observed in the ionospheric cusp by the HF radars. A clear one-to-one correlation is observed for three successive injections, with a 2–3min delay between the magnetospheric and ionospheric observations. For each event, the drift velocity of reconnected flux tubes (phase velocity) has been compared in the magnetosphere and in the ionosphere. The drift velocity measured at Cluster is of the order of 400–600ms–1 when mapped into the ionosphere, in qualitative agreement with SuperDARN observations. Finally, the reconnected flux tubes are elongated in the north-south direction, with an east-west dimension of 30–60km in the ionosphere from mapped Cluster observations, which is consistent with SuperDARN observations, although slightly smaller. Key words. Ionosphere (plasma convection) – Magnetospheric physics (magnetopause, cusp, and boundary layers; magnetosphere-ionosphere interactions)

Field-aligned anisotropic electron distribution functions of T∥ > T⊥ type are observed on auroral field lines at both low and high altitudes. We show that typically the anisotropy is limited to a certain range of energies, often below 1keV, although sometimes extending to slightly higher energies as well. Almost always there is simultaneously an isotropic electron distribution at higher energies. Often the anisotropies are up/down symmetrical, although cases with net upward or downward electron flow also occur. For a statistical analysis of the anisotropies we divide the energy range into low (below 100eV), middle (100eV–1keV) and high (above 1keV) energies and develop a measure of anisotropy expressed in density units. The statistical magnetic local time and invariant latitude distribution of the middle-energy anisotropies obeys that of the average auroral oval, whereas the distributions of the low and high energy anisotropies are more irregular. This suggests that it is specifically the middle-energy anisotropies that have something to do with auroral processes. The anisotropy magnitude decreases monotonically with altitude, as one would expect, because electrons have high mobility along the magnetic field and thus, the anisotropy properties spread rapidly to different altitudes. Key words. Magnetospheric physics (auroral phenomena). Space plasma physics (wave-particle interactions; changed particle motion and acceleration)

Using spacecraft potential measurements of the Polar electric field experiment, we investigate electron density variations of key plasma regions within the magnetosphere, including the polar cap, cusp, trough, plasmapause, and auroral zone. The statistical results were presented in the first part of this study, and the present paper reports detailed structures revealed by individual satellite passes. The high-altitude (> 3 RE) polar cap is generally one of the most tenuous regions in the magnetosphere, but surprisingly, the polar cap boundary does not appear as a steep density decline. At low altitudes (1 RE) in summer, the polar densities are very high, several 100 cm-3 , and interestingly, the density peaks at the central polar cap. On the noonside of the polar cap, the cusp appears as a dense, 1–3° wide region. A typical cusp density above 4 RE distance is between several 10 cm-3 and a few 100 cm-3 . On some occasions the cusp is crossed multiple times in a single pass, simultaneously with the occurrence of IMF excursions, as the cusp can instantly shift its position under varying solar wind conditions, similar to the magnetopause. On the nightside, the auroral zone is not always detected as a simple density cavity. Cavities are observed but their locations, strengths, and sizes vary. Also, the electric field perturbations do not necessarily overlap with the cavities: there are cavities with no field disturbances, as well as electric field disturbances observed with no clear cavitation. In the inner magnetosphere, the density distributions clearly show that the plasmapause and trough densities are well correlated with geomagnetic activity. Data from individual orbits near noon and midnight demonstrate that at the beginning of geomagnetic disturbances, the retreat speed of the plasmapause can be one L-shell per hour, while during quiet intervals the plasmapause can expand anti-earthward at the same speed. For the trough region, it is found that the density tends to be an order of magnitude higher on the day-side (~1 cm-3) than on the nightside (~0.1–1 cm-3), particularly during low Kp.Key words. Magnetospheric physics (auroral phenomena; plasmasphere; polar cap phenomena)

We study the altitude dependence of plasma depletions above the auroral region in the 5000–30 000 km altitude range using five years of Polar spacecraft potential data. We find that besides a general decrease of plasma density with altitude, there frequently exist additional density depletions at 2–4 RE radial distance, where RE is the Earth radius. The position of the depletions tends to move to higher altitude when the ionospheric footpoint is sunlit as compared to darkness. Apart from these cavities at 2–4 RE radial distance, separate cavities above 4 RE occur in the midnight sector for all Kp and also in the morning sector for high Kp. In the evening sector our data remain inconclusive in this respect. This holds for the ILAT range 68–74. These additional depletions may be substorm-related. Our study shows that auroral phenomena modify the plasma density in the auroral region in such a way that a nontrivial and interesting altitude variation results, which reflects the nature of the auroral acceleration processes.Key words. Magnetospheric physics (auroral phenomena; magnetosphere–ionosphere interactions)

Forty-five months of continuous spacecraft potential measurements from the Polar satellite are used to study the average electron density in the magnetosphere and its dependence on geomagnetic activity and season. These measurements offer a straightforward, passive method for monitoring the total electron density in the magnetosphere, with high time resolution and a density range that covers many orders of magnitude. Within its polar orbit with geocentric perigee and apogee of 1.8 and 9.0 RE, respectively, Polar encounters a number of key plasma regions of the magnetosphere, such as the polar cap, cusp, plasmapause, and auroral zone that are clearly identified in the statistical averages presented here. The polar cap density behaves quite systematically with season. At low distance (~2 RE), the density is an order of magnitude higher in summer than in winter; at high distance (>4 RE), the variation is somewhat smaller. Along a magnetic field line the density declines between these two altitudes by a factor of 10–20 in winter and by a factor of 200–1000 in summer. A likely explanation for the large gradient in the summer is a high density of heavy ions that are gravitationally bound in the low-altitude polar cap. The geomagnetic effects are also significant in the polar cap, with the average density being an order of magnitude larger for high Kp; for an individual case, the polar cap density may increase even more dramatically. The plasma density in the cusp is controlled primarily by the solar wind variables, but nevertheless, they can be characterized to some extent in terms of the Kp index. We also investigate the local time variation of the average density at the geosynchronous distance that appears to be in accordance with previous geostationary observations. The average density decreases with increasing Kp at all MLT sectors, except at 14–17 MLT, where the average density remains constant. At all MLT sectors the range of the density varies by more than 3 orders of magnitude, since the geostationary orbit may cut through different plasma regions, such as the plasma sheet, trough, and plasmasphere.Key words. Magnetospheric physics (magnetospheric configuration and dynamics; plasmasphere; polar cap phenomena)

We investigate plasma and wave disturbances generated by nitrogen (N2) gas releases from the cooling system of an IR-camera on board the Vega 1 and Vega 2 spacecraft, during their flybys of comet Halley in March 1986. N2 molecules are ionized by solar UV radiation at a rate of ~ 7 · 10-7 s-1 and give rise to a plasma cloud expanding around the spacecraft. Strong disturbances due to the interaction of the solar wind with the N+2 ion cloud are observed with a plasma and wave experiment (APV-V instrument). Three gas releases are accompanied by increases in cold electron density and simultaneous decreases of the spacecraft potential; this study shows that the spacecraft potential can be monitored with a reference sensor mounted on a short boom. The comparison between the model and observations suggests that the gas expands as an exhaust plume, and approximately only 1% of the ions can escape the beam within the first meters. The releases are also associated with significant increases in wave electric field emission (8 Hz–300 kHz); this phenomenon lasts for more than one hour after the end of the release, which is most likely due to the temporary contamination of the spacecraft surface by nitrogen gas. DC electric fields associated with the events are complex but interesting. No magnetic field perturbations are detected, suggesting that no significant diamagnetic effect (i.e. magnetic cavity) is associated with these events.Key words. Ionosphere (planetary ionosphere) – Space plasma physics (active perturbation experiments; instruments and techniques)

For accurate measurements of electric fields, spherical double probes are electronically controlled to be at a positive potential of approximately 1 V relative to the ambient magnetospheric plasma. The spacecraft will acquire a potential which balances the photoelectrons escaping to the plasma and the electron flux collected from the plasma. The probe-to-plasma potential difference can be measured with a time resolution of a fraction of a second, and provides information on the electron density over a wide range of electron densities from the lobes (~ 0.01 cm-3) to the magnetosheath (>10 cm-3) and the plasmasphere (>100 cm-3). This technique has been perfected and calibrated against other density measurements on GEOS, ISEE-1, CRRES, GEOTAIL and POLAR. The Cluster spacecraft potential measurements opens the way for new approaches, particularly near boundaries and gradients where four-point measurements will provide information never obtained before. Another interesting point is that onboard data storage of this simple parameter can be done for complete orbits and thereby will provide background information for the shorter full data collection periods on Cluster. Preliminary calibrations against other density measurements on Cluster will be reported.Key words. Magnetospheric physics (magnetopause, cusp, and boundary layers) Space plasma physics (spacecraft sheaths, wakes, charging; instruments and techniques)

Highlights are presented from studies of the electric field data from various regions along the Cluster orbit. They all point towards a very high coherence for phenomena recorded on four spacecraft that are separated by a few hundred kilometers for structures over the whole range of apparent frequencies from 1 mHz to 9 kHz. This presents completely new opportunities to study spatial-temporal plasma phenomena from the magnetosphere out to the solar wind. A new probe environment was constructed for the CLUSTER electric field experiment that now produces data of unprecedented quality. Determination of plasma flow in the solar wind is an example of the capability of the instrument.Key words. Magnetospheric physics (electric fields) – Space plasma physics (electrostatic structures; turbulence)

We present a statistical study of Polar electric field observations using auroral oval passes over Scandinavia above the acceleration region. We are especially interested in seeing whether we can find large perpendicular electric fields associated with an upward extended classical U-shaped potential drop for these passes, during which Polar is in the northern hemisphere usually at about 4 RE altitude. We also use Polar magnetic field data to infer the existence of a field-aligned current (FAC) and conjugate ground-based magnetometers (the IMAGE magnetometer network) to check whether the event is substorm-related or not. We find several events with a FAC but only weak perpendicular electric fields at Polar. In those rare cases where the Polar electric field was large, its direction was mostly found to be incompatible with the U-shaped potential model, or it was associated with disturbed conditions (substorms), where one cannot easily distinguish between inductive and static perpendicular electric fields. We found only two cases which are compatible with the upward extended U-shaped potential picture, and even in those cases the potential value is quite small (1-2 kV). To check the validity of the analysis method we also estimate the perpendicular electric field on the southern hemisphere, where Polar flies within or below the acceleration region, and we found a large number of inverted-V-type signatures as expected from previous studies. To explain the lack of perpendicular electric fields at high altitudes we suggest an O-shaped potential model instead of the U-shaped one.Key words. Ionosphere (particle acceleration) · Magnetospheric physics (auroral phenomena; magnetosphere · ionosphere interactions)

The effects on double-probe electric field measurements induced by electron density and temperature gradients are investigated. We show that on some occasions such gradients may lead to marked spurious electric fields if the probes are assumed to lie at the same probe potential with respect to the plasma. The use of a proper bias current will decrease the magnitude of such an error. When the probes are near the plasma potential, the magnitude of these error signals, ∆E, can vary as ∆E ~ Te(∆ne/ne)+0.5∆Te, where Te is the electron temperature, ∆ne/ne the relative electron density variation between the two sensors, and ∆Te the electron temperature difference between the two sensors. This not only implies that the error signals will increase linearly with the density variations but also that such signatures grow with Te, i.e., such effects are 10 times larger in a 10-eV plasma than in a 1-eV plasma. This type of error is independent of the probe separation distance provided the gradient scale length is much larger than this distance. The largest errors occur when the probes are near to the plasma potential. At larger positive probe potentials with respect to the plasma potential, the error becomes smaller if the probes are biased, as is usually the case with spherical double-probe experiments in the tenuous magnetospheric plasmas. The crossing of a plasma boundary (like the plasmapause or magnetopause) yields an error signal of a single peak. During the crossing of a small structure (e.g., a double layer) the error signal appears as a bipolar signature. Our analysis shows that errors in double-probe measurements caused by plasma gradients are not significant at large scale (»1 km) plasma boundaries, and may only be important in cases where small-scale (

The effects on double-probe electric field measurements induced by electron density and temperature gradients are investigated. We show that on some occasions such gradients may lead to marked spurious electric fields if the probes are assumed to lie at the same probe potential with respect to the plasma. The use of a proper bias current will decrease the magnitude of such an error. When the probes are near the plasma potential, the magnitude of these error signals, ∆E, can vary as ∆E ~ Te(∆ne/ne)+0.5∆Te, where Te is the electron temperature, ∆ne/ne the relative electron density variation between the two sensors, and ∆Te the electron temperature difference between the two sensors. This not only implies that the error signals will increase linearly with the density variations but also that such signatures grow with Te, i.e., such effects are 10 times larger in a 10-eV plasma than in a 1-eV plasma. This type of error is independent of the probe separation distance provided the gradient scale length is much larger than this distance. The largest errors occur when the probes are near to the plasma potential. At larger positive probe potentials with respect to the plasma potential, the error becomes smaller if the probes are biased, as is usually the case with spherical double-probe experiments in the tenuous magnetospheric plasmas. The crossing of a plasma boundary (like the plasmapause or magnetopause) yields an error signal of a single peak. During the crossing of a small structure (e.g., a double layer) the error signal appears as a bipolar signature. Our analysis shows that errors in double-probe measurements caused by plasma gradients are not significant at large scale (»1 km) plasma boundaries, and may only be important in cases where small-scale (

Abstract This paper reviews Cluster observations of the high altitude and exterior (outer) cusp, and adjacent regions in terms of new multi-spacecraft analysis and the geometry of the surrounding boundary layers. Several crossings are described in terms of the regions sampled, the boundary dynamics and the electric current signatures observed. A companion paper in this issue focuses on the detailed plasma distributions of the boundary layers. The polar Cluster orbits take the four spacecraft in a changing formation out of the magnetosphere, on the northern leg, and into the magnetosphere, on the southern leg, of the orbits. During February to April the orbits are centred on a few hours of local noon and, on the northern leg, generally pass consecutively through the northern lobe and the cusp at mid- to high-altitudes. Depending upon conditions, the spacecraft often sample the outer cusp region, near the magnetopause, and the dayside and tail boundary layer regions adjacent to the central cusp. On the southern, inbound leg the sequence is reversed. Cluster has therefore sampled the boundaries around the high altitude cusp and nearby magnetopause under a variety of conditions. The instruments onboard provide unprecedented resolution of the plasma and field properties of the region, and the simultaneous, four-spacecraft coverage achieved by Cluster is unique. The spacecraft array forms a nearly regular tetrahedral configuration in the cusp and already the mission has covered this region on multiple spatial scales (100–2000 km). This multi-spacecraft coverage allows spatial and temporal features to be distinguished to a large degree and, in particular, enables the macroscopic properties of the boundary layers to be identified: the orientation, motion and thickness, and the associated current layers. We review the results of this analysis for a number of selected crossings from both the North and South cusp regions. Several key results have been found or have confirmed earlier work: (1) evidence for magnetically defined boundaries at both the outer cusp/magnetosheath interface and the␣inner cusp/lobe or cusp/dayside magnetosphere interface, as would support the existence of a distinct exterior cusp region; (2) evidence for an associated indentation region on the magnetopause across the outer cusp; (3) well defined plasma boundaries at the edges of the mid- to high-altitude cusp “throat”, and well defined magnetic boundaries in the high-altitude “throat”, consistent with a funnel geometry; (4) direct control of the cusp position, and its extent, by the IMF, both in the dawn/dusk and North/South directions. The exterior cusp, in particular, is highly dependent on the external conditions prevailing. The magnetic field geometry is sometimes complex, but often the current layer has a well defined thickness ranging from a few hundred (for the inner cusp boundaries) to 1000 km. Motion of the inner cusp boundaries can occur at speeds up to 60 km/s, but typically 10–20 km/s. These speeds appear to represent global motion of the cusp in some cases, but also could arise from expansion or narrowing in others. The mid- to high-altitude cusp usually contains enhanced ULF wave activity, and the exterior cusp usually is associated with a substantial reduction in field magnitude. [ABSTRACT FROM AUTHOR]

Introduction: Deep brain stimulation (DBS) is a rapidly developing therapeutic intervention with constantly expanding neurological and psychiatric indications. A major challenge for the approach is the precise targeting and limitation of the effect on the desired neural pathways. We have introduced a new approach, orientation selective stimulation (OSS) that allows free rotation of the induced electric field on a plane when using a probe with three parallel electrodes forming an equilateral triangle at the tip. Here, we expand the technique by introducing a tetrahedral stimulation probe that enables adjustment of the primary electric field direction freely at any angle in a 3D space around the stimulating probe. OSS in 3D will enable better targeting of the electric field according to the local brain anatomy. We tested its utility in a rat model of DBS for treatment-resistant depression. The stimulation directed to the subgenual anterior cingulate cortex (sgACC) has yielded dramatic improvement in individual patients suffering from therapy resistant depression, but no consistent benefit in larger series. This failure has been ascribed to the challenging anatomy of sgACC with several crossing neural tracts and individual differences in the local anatomy., Methods: We stimulated infralimbic cortex (IL), the rat analog of sgACC, and recorded local electrical responses in amygdala (AMG) that is monosynaptically connected to IL and plays a central role in emotional states. We further traced AMG-IL connections using a viral vector and tractography using diffusion magnetic resonance imaging (MRI). Finally, we mimicked the clinical situation by delivering sustained 130 Hz stimulation at IL at the most effective field orientation and followed changes in resting-state functional connectivity with IL using functional MRI. To help interpretation of responses in functional connectivity, we stimulated only the left IL, which we did not expect to evoke measurable changes in the rat behavior., Results: The AMG evoked responses depended systematically on the IL stimulation field orientation and yielded the maximum response in near vertical field orientation in accordance with tractography. Sustained 130 Hz stimulation at a field orientation yielding the strongest AMG evoked responses increased functional connectivity between IL and AMG on the stimulation side., Conclusion: These findings suggest that OSS in 3D provides a new approach to optimize the DBS for every individual patient with a single stimulation probe implantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gureviciene, Laakso, Narvaez, Paasonen, Lehto, Gurevicius, Mangia, Michaeli, Gröhn, Sierra and Tanila.)

Background: The usefulness of neurofilament light (NfL) as a biomarker for small vessel disease has not been established. We examined the relationship between NfL, neuroimaging changes, and clinical findings in subjects with varying degrees of white matter hyperintensity (WMH)., Methods: A subgroup of participants (n = 35) in the Helsinki Small Vessel Disease Study underwent an analysis of NfL in cerebrospinal fluid (CSF) as well as brain magnetic resonance imaging (MRI) and neuropsychological and motor performance assessments. WMH and structural brain volumes were obtained with automatic segmentation., Results: CSF NfL did not correlate significantly with total WMH volume (r = 0.278, p = 0.105). However, strong correlations were observed between CSF NfL and volumes of cerebral grey matter (r = -0.569, p < 0.001), cerebral cortex (r = -0.563, p < 0.001), and hippocampi (r = -0.492, p = 0.003). CSF NfL also correlated with composite measures of global cognition (r = -0.403, p = 0.016), executive functions (r = -0.402, p = 0.017), memory (r = -0.463, p = 0.005), and processing speed (r = -0.386, p = 0.022). Regarding motor performance, CSF NfL was correlated with Timed Up and Go (TUG) test (r = 0.531, p = 0.001), and gait speed (r = -0.450, p = 0.007), but not with single-leg stance. After adjusting for age, associations with volumes in MRI, functional mobility (TUG), and gait speed remained significant, whereas associations with cognitive performance attenuated below the significance level despite medium to large effect sizes., Conclusion: NfL was strongly related to global gray matter and hippocampal atrophy, but not to WMH severity. NfL was also associated with motor performance. Our results suggest that NfL is independently associated with brain atrophy and functional mobility, but is not a reliable marker for cerebral small vessel disease., Competing Interests: JKo and JLö are employed by Combinostics Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kartau, Melkas, Kartau, Arola, Laakso, Pitkänen, Lempiäinen, Koikkalainen, Lötjönen, Korvenoja, Ahlström, Herukka, Erkinjuntti and Jokinen.)

Background: Vascular endothelial growth factors (VEGFs) are major regulators of intratumoral angiogenesis in ovarian cancer (OVCA). Overexpression of VEGFs is associated with increased tumor growth and metastatic tendency and VEGF-targeting therapies are thus considered as potential treatments for OVCA. Here, we examined the antiangiogenic and antitumoral effects on OVCA of adeno-associated virus 8 (AAV8)-mediated expression of soluble VEGF receptors (sVEGFRs) sVEGFR2 and sVEGFR3 together with paclitaxel and carboplatin chemotherapy., Materials and Methods: Immunodeficient mice were inoculated with human OVCA cell line SKOV-3m. Development of tumors was confirmed with magnetic resonance imaging (MRI) and mice were treated with gene therapy and paclitaxel and carboplatin chemotherapy. The study groups included (I) non-treated control group, (II) blank control vector AAV8-CMV, (III) AAV8-CMV with chemotherapy, (IV) AAV8-sVEGFR2, (V) AAV8-sVEGFR3, (VI) AAV8-sVEGFR2 and AAV8-sVEGFR3, and (VII) AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy. Antiangiogenic and antitumoral effects were evaluated with immunohistochemical stainings and serial MRI., Results: Reduced intratumoral angiogenesis was observed in all antiangiogenic gene therapy groups. The combined use of AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy suppressed ascites fluid formation and tumor growth, thus improving the overall survival of mice. Antitumoral effect was mainly caused by AAV8-sVEGFR2 while the benefits of AAV8-sVEGFR3 and chemotherapy were less prominent., Conclusion: Combined use of the AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy reduces intratumoral angiogenesis and tumor growth in OVCA mouse model. Results provide preclinical proof-of-concept for the use of soluble decoy VEGFRs and especially the AAV8-sVEGFR2 in the treatment of OVCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kujala, Valkonen, Sallinen, Tuppurainen, Laakso, Ylä-Herttuala, Liimatainen, Kujala, Jokelainen, Sironen, Anttila and Ylä-Herttuala.)

Purpose: To develop a high temporal resolution functional MRI method for tracking repeating events in the brain., Methods: We developed a novel functional MRI method using multiband sweep imaging with Fourier transformation (SWIFT), termed event-recurring SWIFT (EVER-SWIFT). The method is able to image similar repeating events with subsecond temporal resolution. Here, we demonstrate the use of EVER-SWIFT for detecting functional MRI responses during deep brain stimulation of the medial septal nucleus and during spontaneous isoflurane-induced burst suppression in the rat brain at 9.4 T with 200-ms temporal resolution., Results: The EVER-SWIFT approach showed that the shapes and time-to-peak values of the response curves to deep brain stimulation significantly differed between downstream brain regions connected to the medial septal nucleus, resembling findings obtained with traditional 2-second temporal resolution. In contrast, EVER-SWIFT allowed for detailed temporal measurement of a spontaneous isoflurane-induced bursting activity pattern, which was not achieved with traditional temporal resolution., Conclusion: The EVER-SWIFT technique enables subsecond 3D imaging of both stimulated and spontaneously recurring brain activities, and thus holds great potential for studying the mechanisms of neuromodulation and spontaneous brain activity., (© 2022 International Society for Magnetic Resonance in Medicine.)

Understanding the link between the brain activity and behavior is a key challenge in modern neuroscience. Behavioral neuroscience, however, lacks tools to record whole-brain activity in complex behavioral settings. Here we demonstrate that a novel Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) functional magnetic resonance imaging (fMRI) approach enables whole-brain studies in spontaneously behaving head-fixed rats. First, we show anatomically relevant functional parcellation. Second, we show sensory, motor, exploration, and stress-related brain activity in relevant networks during corresponding spontaneous behavior. Third, we show odor-induced activation of olfactory system with high correlation between the fMRI and behavioral responses. We conclude that the applied methodology enables novel behavioral study designs in rodents focusing on tasks, cognition, emotions, physical exercise, and social interaction. Importantly, novel zero echo time and large bandwidth approaches, such as MB-SWIFT, can be applied for human behavioral studies, allowing more freedom as body movement is dramatically less restricting factor., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. The animals affected by TLE-induced white matter abnormalities exhibited increased functional connectivity between the thalamus and medial prefrontal and somatosensory cortex in adulthood. Furthermore, histological analyses of additional animal groups at P15 and P18 showed only mild changes in white matter integrity, suggesting a gradual age-dependent impact of TLE progression. Taken together, TLE progression in the immature brain distorts white matter development with a peak around postnatal day 28, followed by substantial recovery in adulthood. This developmental delay might give rise to cognitive and behavioural comorbidities typical for early-onset TLE., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Electrical epidural spinal cord stimulation (SCS) is used as a treatment for chronic pain as well as to partially restore motor function after a spinal cord injury. Monitoring the spinal cord activity during SCS with fMRI could provide important and objective measures of integrative responses to treatment. Unfortunately, spinal cord fMRI is severely challenged by motion and susceptibility artifacts induced by the implanted electrode and bones. This pilot study introduces multi-band sweep imaging with Fourier transformation (MB-SWIFT) technique for spinal cord fMRI during SCS in rats. Given the close to zero acquisition delay and high bandwidth in 3 dimensions, MB-SWIFT is demonstrated to be highly tolerant to motion and susceptibility-induced artifacts and thus holds promise for fMRI during SCS., Methods: MB-SWIFT with 0.78 × 0.78 × 1.50 mm 3 spatial resolution and 3-s temporal resolution was used at 9.4 Tesla in rats undergoing epidural SCS at different frequencies. Its performance was compared with spin echo EPI. The origin of the functional contrast was also explored using suppression bands., Results: MB-SWIFT was tolerant to electrode-induced artifacts and respiratory motion, leading to substantially higher fMRI sensitivity than spin echo fMRI. Clear stimulation frequency-dependent responses to SCS were detected in the rat spinal cord close to the stimulation site. The origin of MB-SWIFT fMRI signals was consistent with dominant inflow effects., Conclusion: fMRI of the rat spinal cord during SCS can be consistently achieved with MB-SWIFT, thus providing a valuable experimental framework for assessing the effects of SCS on the central nervous system., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In this study, the effects of LDR on the development and progression of mammary cancer in FVB/N-Tg(MMTVneu)202Mul/J mice were investigated. Animals were chronically exposed to total doses of 10, 100, and 2000 mGy via tritiated drinking water, and were assessed at 3.5, 6, and 8 months of age. Results indicated an increased proportion of NK cells in various organs of LDR exposed mice. LDR significantly influenced NK and T cell function and activation, despite diminishing cell proliferation. Notably, the expression of NKG2D receptor on NK cells was dramatically reduced at 3.5 months but was upregulated at later time-points, while the expression of NKG2D ligand followed the opposite trend, with an increase at 3.5 months and a decrease thereafter. No noticeable impact was observed on mammary cancer development, as measured by tumor load. Our results demonstrated that LDR significantly influenced the proportion, proliferation, activation, and function of immune cells. Importantly, to the best of our knowledge, this is the first report demonstrating that LDR modulates the cross-talk between the NKG2D receptor and its ligands.

Treatment of prostate cancer confronts resistance to androgen receptor (AR)-targeted therapies. AR-associated coregulators and chromatin proteins hold a great potential for novel therapy targets. Here, we employed a powerful chromatin-directed proteomics approach termed ChIP-SICAP to uncover the composition of chromatin protein network, the chromatome, around endogenous AR in castration resistant prostate cancer (CRPC) cells. In addition to several expected AR coregulators, the chromatome contained many nuclear proteins not previously associated with the AR. In the context of androgen signaling in CRPC cells, we further investigated the role of a known AR-associated protein, a chromatin remodeler SMARCA4 and that of SIM2, a transcription factor without a previous association with AR. To understand their role in chromatin accessibility and AR target gene expression, we integrated data from ChIP-seq, RNA-seq, ATAC-seq and functional experiments. Despite the wide co-occurrence of SMARCA4 and AR on chromatin, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, especially those involved in cell morphogenetic changes in epithelial-mesenchymal transition. The depletion also inhibited the CRPC cell growth, validating SMARCA4's functional role in CRPC cells. Although silencing of SIM2 reduced chromatin accessibility similarly, it affected the expression of a much larger group of androgen-regulated genes, including those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of CRPC cells and tumor size in chick embryo chorioallantoic membrane assay, further emphasizing the importance of SIM2 in CRPC cells and pointing to the functional relevance of this potential prostate cancer biomarker in CRPC cells. Overall, the chromatome of AR identified in this work is an important resource for the field focusing on this important drug target.

Purpose: To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer., Methods: Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm 2 , respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential)., Results: Significant changes were observed in DWI data during the tumor growth, indicated by ADC m , ADC s , and ADC k . Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1-4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model., Conclusion: Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Merisaari, Laakso, Liljenbäck, Virtanen, Aronen, Minn, Poutanen, Roivainen, Liimatainen and Jambor.)

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation times T RAFF2 and T RAFF4 than with the continuous wave T 1ρ , adiabatic T 1ρ , adiabatic T 2ρ , T 1 , T 2 or water ADC. Human PC3 prostate cancer cells expressing a red fluorescent protein were implanted in 21 male mice. Docetaxel chemotherapy was given once a week starting 1 week after cell implantation for 10 randomly selected mice, while the rest served as a control group (n = 11). The MRI consisted of relaxation along a fictitious field (RAFF) in the second (RAFF2) and fourth (RAFF4) rotating frames, T 1 and T 2 , continuous wave T 1ρ , adiabatic T 1ρ and adiabatic T 2ρ relaxation time measurements and water ADC. MRI was conducted at 7 T, once a week up to 4 weeks from cell implantation. The tumor volume was monitored using T 2 -weighted MRI and optical imaging. The histology was evaluated after the last imaging time point. Significantly reduced RAFFn, T 1ρ, T 2ρ and conventional relaxation times 4 weeks after tumor implantation were observed in the treated tumors compared with the controls. The clearest short- and long-term responses were obtained with T 1 , while no clear improvement in response to treatment was detected with novel methods compared with conventional methods or with RAFFn compared with all others. The tumor volume decreased after a two-week time point for the treated group and increased significantly in the control group, which was supported by increasing red fluorescent light emission in the control tumors. Decreased relaxation times were associated with successful chemotherapy outcomes. The results indicate altered relaxation mechanisms compared with higher dose chemotherapies previously published., (© 2021 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Epidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.

Remyelination is a naturally occurring response to demyelination and has a central role in the pathophysiology of multiple sclerosis and traumatic brain injury. Recently we demonstrated that a novel MRI technique entitled Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) achieved exceptional sensitivity in detecting the demyelination processes induced by lysophosphatidylcholine (LPC) in rat brain. In the present work, our aim was to test whether RAFF4, along with magnetization transfer (MT) and diffusion tensor imaging (DTI), would be capable of detecting the changes in the myelin content and microstructure caused by modifications of myelin sheets around axons or by gliosis during the remyelination phase after LPC-induced demyelination in the corpus callosum of rats. We collected MRI data with RAFF4, MT and DTI at 3 days after injection (demyelination stage) and at 38 days after injection (remyelination stage) of LPC ( n = 12) or vehicle ( n = 9). Cell density and myelin content were assessed by histology. All MRI metrics detected differences between LPC-injected and control groups of animals in the demyelination stage, on day 3. In the remyelination phase (day 38), RAFF4, MT parameters, fractional anisotropy, and axial diffusivity detected signs of a partial recovery consistent with the remyelination evident in histology. Radial diffusivity had undergone a further increase from day 3 to 38 and mean diffusivity revealed a complete recovery correlating with the histological assessment of cell density attributed to gliosis. The combination of RAFF4, MT and DTI has the potential to differentiate between normal, demyelinated and remyelinated axons and gliosis and thus it may be able to provide a more detailed assessment of white matter pathologies in several neurological diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Holikova, Laakso, Salo, Shatillo, Nurmi, Bares, Vanicek, Michaeli, Mangia, Sierra and Gröhn.)