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Using membership of 85 open clusters from previous studies (Pang et al. 2021a,b, 2022b; Li et al. 2021) based on Gaia DR3 data, we identify binary candidates in the color-magnitude diagram, for systems with mass ratio q > 0.4. The binary fraction is corrected for incompleteness at different distances due to the Gaia angular resolution limit. We find a decreasing binary fraction with increasing cluster age, with substantial scatter. For clusters with a total mass > 200$M_\odot$, the binary fraction is independent of cluster mass. The binary fraction depends strongly on stellar density. Among four types of cluster environments, the lowest-density filamentary and fractal stellar groups have the highest mean binary fraction: 23.6% and 23.2%, respectively. The mean binary fraction in tidal-tail clusters is 20.8%, and is lowest in the densest halo-type clusters: 14.8%. We find clear evidence of early disruptions of binary stars in the cluster sample. The radial binary fraction depends strongly on the cluster-centric distance across all four types of environments, with the smallest binary fraction within the half-mass radius $r_h$, and increasing towards a few $r_h$. Only hints of mass segregation is found in the target clusters. The observed amount of mass segregation is not significant to generate a global effect inside the target clusters. We evaluate the bias of unresolved binary systems (assuming a primary mass of 1$M_\odot$) in 1D tangential velocity, which is 0.1-1$\,\rm km\,s^{-1}$. Further studies are required to characterize the internal star cluster kinematics using Gaia proper motions.

Although debris disks may be common in exoplanet systems, only a few systems are known in which debris disks and planets coexist. Planets and the surrounding stellar population can have a significant impact on debris disk evolution. Here we study the dynamical evolution of debris structures around stars embedded in star clusters, aiming to determine how the presence of a planet affects the evolution of such structures. We combine NBODY6++GPU and REBOUND to carry out N-body simulations of planetary systems in star clusters (N=8000; Rh=0.78 pc) for a period of 100 Myr, in which 100 solar-type stars are assigned 200 test particles. Simulations are carried out with and without a Jupiter-mass planet at 50 au. We find that the planet destabilizes test particles and speeds up their evolution. The planet expels most particles in nearby and resonant orbits. Remaining test particles tend to retain small inclinations when the planet is present, and fewer test particles obtain retrograde orbits. Most escaping test particles with speeds smaller than the star cluster's escape speed originate from cold regions of the planetary system or from regions near the planet. We identify three regions within planetary systems in star clusters: (i) the private region of the planet, where few debris particles remain (40 - 60 au), (ii) the reach of the planet, in which particles are affected by the planet (0 - 400 au), and (iii) the territory of the planetary system, most particles outside which will eventually escape (0 - 700 au)., 17 pages, 20 figures, and 3 tables. Accepted for publication in MNRAS

Purpose\ud \ud To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE).\ud \ud \ud \ud Methods\ud \ud Three 3T MRI experiments were performed comparing 4DEPI to 4DGRE: steady flow through straight tubes, pulsatile flow in a left-ventricle phantom, and intracardiac flow in 10 healthy volunteers. For each experiment, 4DEPI was repeated with readout and blip phase-encoding gradient in different orientations, parallel or perpendicular to the flow direction. In vitro flow rates were compared with timed volumetric collection. In the left-ventricle phantom and in vivo, voxel-based speed and spatio-temporal median speed were compared between sequences, as well as mitral and aortic transvalvular net forward volume.\ud \ud \ud \ud Results\ud \ud In steady-flow phantoms, the flow rate error was largest (12%) for high velocity (>2 m/s) with 4DEPI readout gradient parallel to the flow. Voxel-based speed and median speed in the left-ventricle phantom were ≤5.5% different between sequences. In vivo, mean net forward volume inconsistency was largest (6.4 ± 8.5%) for 4DEPI with nonblip phase-encoding gradient parallel to the main flow. The difference in median speed for 4DEPI versus 4DGRE was largest (9%) when the 4DEPI readout gradient was parallel to the flow.\ud \ud \ud \ud Conclusions\ud \ud Velocity and flow rate are inaccurate for 4DEPI with EPI factor 5 when flow is parallel to the readout or blip phase-encoding gradient. However, mean differences in flow rate, voxel-based speed, and spatio-temporal median speed were acceptable (≤10%) when comparing 4DEPI to 4DGRE for intracardiac flow in healthy volunteers.

Background Protocols for assessment of (neuro)psychological outcomes in lower-grade glioma patients vary between hospitals. This potentially complicates generalization of these outcomes. We compared standardized scores on tests of two frequently impaired cognitive domains (attention and executive functioning (EF)), and two relevant patient-reported outcomes (PROs; depression and fatigue) of two neuro-oncological hospitals that use different measurement instruments. Material and Methods Data were used from preoperative assessments of patients with (IDH-mut) WHO grade II/III glioma tested between 2007 and 2021 at Amsterdam UMC (AMS) or at Elisabeth-Tweesteden Hospital Tilburg (ETZ). AMS patients were referred for (neuro)psychological assessment based on physician and patient preference (paper and pencil tests), whereas all ETZ patients routinely undergo screening (computerized tests). To compare scores of the different attention and EF tests we converted patients’ performances to z-scores based on normative data. For cognitive performance, we compared scores of different cognitive flexibility tests (CST vs SAT), processing speed tests (SDC vs LDMT), and Stroop tests (Stroop I and Stroop III). PROs included the CES-D vs HADS-D and the CIS-fatigue vs MVI-general fatigue (AMS vs ETZ, resp.). Differences were tested using Fisher's, χ 2, and Mann-Whitney U tests. Results Assessments were done median 4 weeks (AMS, n=97, range 19-0 weeks) and 1 day (ETZ, n=106; range 14-0 days) preoperatively. Age, sex, tumor location and histology were comparable between cohorts (p>0.05), but the AMS cohort showed significantly more grade III tumors (36% vs 16%) and more awake surgeries (84% vs 46%). Z-scores measuring attention and EF (n=94 and n=95, AMS vs ETZ) were not significantly different (CST vs SAT, percentage with a disorder (z

In order to study the stellar population and possible substructures in the outskirts of Double Cluster $h$ and $\chi$ Persei, we investigate using the GAIA DR2 data a sky area of about 7.5 degrees in radius around the Double Cluster cores. We identify member stars using various criteria, including their kinematics (viz, proper motion), individual parallaxes, as well as photometric properties. A total of 2186 member stars in the parameter space were identified as members. Based on the spatial distribution of the member stars, we find an extended halo structure of $h$ and $\chi$ Persei, about 6 - 8 times larger than their core radii. We report the discovery of filamentary substructures extending to about 200 pc away from the Double Cluster. The tangential velocities of these distant substructures suggest that they are more likely to be the remnants of primordial structures, instead of a tidally disrupted stream from the cluster cores. Moreover, the internal kinematic analysis indicates that halo stars seems to be experiencing a dynamic stretching in the RA direction, while the impact of the core components is relatively negligible. This work also suggests that the physical scale and internal motions of young massive star clusters may be more complex than previously thought., Comment: 9 pagges, 9 figures, Accecpted to A&A

As of August 2019, among the more than 4000 confirmed exoplanets, only one has been detected in a globular cluster (GC) M4. The scarce of exoplanet detections motivates us to employ direct $N$-body simulations to investigate the dynamical stability of planets in young massive clusters (YMCs), which are potentially the progenitors of GCs. In an $N=128{\rm k}$ cluster of virial radius 1.7 pc (comparable to Westerlund-1), our simulations show that most wide-orbit planets ($a\geq 20$~au) will be ejected within a timescale of 10 Myr. Interestingly, more than $70\%$ of planets with $a, 12 pages, 11 figures, 1 table, accepted by MNRAS

In order to study the stellar population and possible substructures in the outskirts of Double Cluster $h$ and $��$ Persei, we investigate using the GAIA DR2 data a sky area of about 7.5 degrees in radius around the Double Cluster cores. We identify member stars using various criteria, including their kinematics (viz, proper motion), individual parallaxes, as well as photometric properties. A total of 2186 member stars in the parameter space were identified as members. Based on the spatial distribution of the member stars, we find an extended halo structure of $h$ and $��$ Persei, about 6 - 8 times larger than their core radii. We report the discovery of filamentary substructures extending to about 200 pc away from the Double Cluster. The tangential velocities of these distant substructures suggest that they are more likely to be the remnants of primordial structures, instead of a tidally disrupted stream from the cluster cores. Moreover, the internal kinematic analysis indicates that halo stars seems to be experiencing a dynamic stretching in the RA direction, while the impact of the core components is relatively negligible. This work also suggests that the physical scale and internal motions of young massive star clusters may be more complex than previously thought., 9 pagges, 9 figures, Accecpted to A&A

This paper describes the results of a research project that aimed to establish passenger values of crowding on public transport services in the Paris region. Qualitative research, stated preference (SP) experiments, and passenger counts and surveys were conducted to obtain such values. A simple method was developed to quantify the passenger benefits of specific public transport projects aiming to reduce crowding on existing lines. This method was applied in a case study to the regional rail (RER) RER Line E extension project. With regard to the value of crowding, the research indicated that the perceived disutility of crowding could be more accurately described as a constant disutility per trip than as a travel time multiplier. However, for ease of application often the multiplier formulation was preferred. When the value of crowding was expressed as a travel time multiplier, values were obtained ranging from 1.0 when all passengers could be seated to 1.7 for standing bus passengers when the vehicles reached their maximum capacity. Also for seated passengers, multipliers well above 1.0 were observed for (highly) congested vehicles (maximum value = 1.5 for bus passengers). These values were applied in a case study that estimated the effects of an extension of the regional rail line RER E in the western direction, partially running parallel to the existing RER Line A. This extension would reduce the current (very) high crowding levels on the RER A and B lines to more moderate levels and generate benefits of about €23 million per year.

Background.Region-specific types of neglect (peripersonal and extrapersonal) have been dissociated, yet, differential behavioural consequences are unknown.Objective.The aim of the current study was to investigate behavioural consequences at the level of basic activities of daily living of region-specific neglect, using the Catherine Bergego Scale (CBS).Methods.118 stroke patients were screened within the first two weeks after admission to the rehabilitation center for inpatient rehabilitation.Results.Patients with peripersonal neglect and patients with neglect for both regions had significantly higher total score on the CBS compared to nonneglect patients. Total scores for patients with extrapersonal neglect were comparable to non-neglect patients. ADL impairments were found across activities (e.g., looking towards one side, forgetting body parts, colliding) for both patients with peripersonal neglect and patients with neglect for both regions. Patients with extrapersonal neglect were only impaired on the item on way finding.Conclusions.When diagnosing neglect, it is relevant to distinguish the type of region-specific neglect and, where needed, to adjust the rehabilitation program accordingly. As the CBS isnotdeveloped to typically measure ADL in extrapersonal neglect, it would be of importance to add other (instrumental) activities that heavily rely on processing information in farther space.

U Scorpii (U Sco) is a recurrent nova which has been observed in outburst on 10 occasions, most recently in 2010. We present near-infrared (near-IR) and optical spectroscopy of the 2010 outburst of U Sco. The reddening of U Sco is found to be E(B − V) = 0.14 ± 0.12, consistent with previous determinations, from simultaneous optical and near-IR observations. The spectra show the evolution of the linewidths and profiles to be consistent with previous outbursts. Velocities are found to be up to 14 000 km s−1 in broad components and up to 1800 km s−1 in narrow-line components, which become visible around day 8 due to changes in the optical depth. From the spectra we derive a helium abundance of N(He)/N(H) = 0.073 ± 0.031 from the most reliable lines available; this is lower than most other estimates and indicates that the secondary is not helium-rich, as previous studies have suggested.

A large population of fragile, wide (> 1000 AU) binary systems exists in the Galactic field and halo. These wide binary stars cannot be primordial because of the high stellar density in star forming regions, while formation by capture in the Galactic field is highly improbable. We propose that these binary systems were formed during the dissolution phase of star clusters (see Kouwenhoven et al. 2010, for details). Stars escaping from a dissolving star cluster can have very similar velocities, which can lead to the formation of a wide binary systems. We carry out N-body simulations to test this hypothesis. The results indicate that this mechanism explains the origin of wide binary systems in the Galaxy. The resulting wide binary fraction and semi-major axis distribution depend on the initial conditions of the dissolving star cluster, while the distributions in eccentricity and mass ratio are universal. Finally, since most stars are formed in (relatively tight) primordial binaries, we predict that a large fraction of the wide "binary stars" are in fact higher-order multiple systems., 5 pages, 3 figures, to be published in the proceedings of the 9th Pacific-Rim Conference on Stellar Astrophysics

Over the last decades, numerous wide (>1000 AU) binaries have been discovered in the Galactic field and halo. The origin of these wide binaries cannot be explained by star formation or by dynamical interactions in the Galactic field. We explain their existence by wide binary formation during the dissolution phase of young star clusters. In this scenario, two single stars that leave the dissolving cluster at the same time, in the same direction, and with similar velocities, form a new, very wide binary. Using N-body simulations we study how frequently this occurs, and how the orbital parameters of such binaries depend on the properties of the cluster from which they originate. The resulting wide binary fraction for individual star clusters is 1-30%, depending on the initial conditions. As most stars form as part of a binary or multiple system, we predict that a large fraction of these wide binaries are in fact wide triple and quadruple systems., 4 pages, to appear in the proceedings of "BINKEY: Binaries - a Key to Comprehension of the Universe", held 8-12 June 2009 in Brno, Czech Republic

In The Netherlands, major infrastructure projects are assessed using cost-benefit analysis, following official guidelines. Until recently, the reliability of travel times could not be included in the cost-benefit analysis, because the corresponding monetary valuation was unknown. In recent years, the literature on valuing reliability of travel times was reviewed for the Dutch transport ministry. The outcomes of this were discussed at an expert workshop, which led to an agreement on preliminary monetary values for passenger transport. A key concept is that of the reliability ratio. This is defined as the value of reliability (measured as the standard deviation of travel time) divided by the value of travel time itself. For freight transport a follow-up study was carried out, which transforms the results of earlier stated preference research into a reliability ratio. The paper presents and explains the preliminary values, focussing on the derivation of reliability values for freight transport. It also describes how these values can be used in practical project evaluations., European Journal of Transport and Infrastructure Research, Vol 9 No 2 (2009)

We show that the same initial mass function (IMF) can result from very different modes of star formation from very similar underlying core and/or system mass functions. In particular, we show that the canonical IMF can be recovered from very similar system mass functions, but with very different mass ratio distributions within those systems. This is a consequence of the basically log-normal shapes of all of the distributions. We also show that the relationships between the shapes of the core, system, and stellar mass functions may not be trivial. Therefore, different star formation in different regions could still result in the same IMF., Comment: 6 pages, 4 figures. MNRAS, in press

Observations over the last decade have indicated that a large fraction of the stars are part of a binary or multiple system. For our understanding of star formation it is therefore of crucial importance to characterise the outcome of the star forming process in terms of binary parameters. This thesis describes the recovery of the primordial binary population in the nearby OB association Sco OB2. The current binary population in Sco OB2 is first recovered using two adaptive optics surveys (ADONIS, NAOS-CONICA), a literature study, and a detailed analysis of the selection effects of visual, spectroscopic, and astrometric binary surveys. Our results indicate a binary fraction close to 100%. The mass ratio distribution (among A/B primaries) has the form f(q) = q^-0.4, while random pairing is excluded. The semi-major axis distribution has the form f(log a) = constant. Due to its youth and low stellar density, the current binary population of Sco OB2 is very similar to its primordial binary population. Our study further indicates a small brown dwarf companion frequency and a small substellar-to-stellar companion frequency among A and B type stars. These properties, often referred to as the brown dwarf desert, are a natural result of the mass ratio distribution in Sco OB2. The embryo ejection scenario is not necessary to explain observations. The brown dwarf desert may be ascribed to an excess of planetary companions, rather than by a lack of brown dwarf companions., PhD thesis, University of Amsterdam, 2006 (very low resolution). Full-resolution PDF available at http://dare.uva.nl/en/record/195643

Stroke is a common cause of death and disability in our society. Stroke is associated with changes in immune responses within the central nervous system as well as systemically. The cells contributing to such changes as well as the factors contributing to formation of the inflammatory infiltrate observed in stroke remain to be clarified. In this study, blood monocytes and corresponding mononuclear cells (MNC) were separated and examined in parallel within 4 days and 1-3 months after onset of ischemic stroke. Numbers of TNF-alpha-, IL-12-, IL-6-, and IL-10-secreting cells and of cells expressing mRNA for matrix metalloproteinase (MMP)-1, -2, -7, -9 and tissue inhibitor of MMP (TIMP)-1 were studied. The TNF-alpha-, IL-12-, and IL-6-secreting monocytes and MNC were elevated during the acute phase compared to healthy controls. Such differences were not observed when stroke patients were examined during convalescence. The IL-10-secreting monocytes did not change over the course of stroke. Levels of monocytes expressing MMP-1, MMP-7 and TIMP-1 mRNA were elevated in the acute phase of stroke patients compared to convalescence and healthy controls, as were levels of MMP-1, -2, -7, -9 and TIMP-1 mRNA expressing blood MNC. The MMP-2 and -9 activity as measured by zymography also was higher in MNC supernatants in the acute phase of stroke compared to convalescence. The high levels of proinflammatory cytokines and MMPs in blood monocytes and MNC further demonstrate the presence of systemic aberrations in the acute phase of stroke. Such changes may contribute to the influx of blood-borne cells into the ischemic lesions during the acute phase of stroke.

The human sufferings and socioeconomic burden due to whip-lash-associated disorders (WAD) are obvious but the pathogenesis of WAD is obscure. The possible involvement of the immune system during the disease process in WAD is not known. Effector molecules including chemokines and their receptors could play a role in WAD. In a prospective study using flow cytometry, we examined percentages of blood mononuclear cells (MNC) expressing the chemokines RANTES, MCP-1, MIP-1alpha, MIP-1beta, and IL-8, the chemokine receptor CCR-5, the T cell activation marker CD25, and the T cell chemoattractant IL-16 in patients with WAD and, for reference, in healthy controls. Higher percentages of RANTES-expressing blood MNC and T cells were observed in patients with WAD examined within 3 days compared to 14 days after the whiplash injury and, likewise, compared with healthy controls. The patients with WAD examined within 3 days after the accident also had higher percentages of CCR-5-expressing blood MNC, T cells, and CD45RO+ T cells compared to healthy controls. In contrast, there were no differences for any of these variables between patients with WAD examined 14 days after injury and healthy controls. In conclusion, WAD is associated with a systemic but transient dysregulation in percentages of RANTES and CCR-5 expressing MNC and T cells.

The human sufferings and socioeconomic burden due to whip-lash-associated disorders (WAD) are obvious but the pathogenesis of WAD is obscure. The possible involvement of the immune system during the disease process in WAD is not known. Effector molecules including chemokines and their receptors could play a role in WAD. In a prospective study using flow cytometry, we examined percentages of blood mononuclear cells (MNC) expressing the chemokines RANTES, MCP-1, MIP-1alpha, MIP-1beta, and IL-8, the chemokine receptor CCR-5, the T cell activation marker CD25, and the T cell chemoattractant IL-16 in patients with WAD and, for reference, in healthy controls. Higher percentages of RANTES-expressing blood MNC and T cells were observed in patients with WAD examined within 3 days compared to 14 days after the whiplash injury and, likewise, compared with healthy controls. The patients with WAD examined within 3 days after the accident also had higher percentages of CCR-5-expressing blood MNC, T cells, and CD45RO+ T cells compared to healthy controls. In contrast, there were no differences for any of these variables between patients with WAD examined 14 days after injury and healthy controls. In conclusion, WAD is associated with a systemic but transient dysregulation in percentages of RANTES and CCR-5 expressing MNC and T cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease characterised by immune abnormalities in the central nervous system (CNS) as well as systemically. Activated, blood-borne monocytes are abundant in MS lesions, the properties of circulating monocytes are incompletely known. To delineate phenotype and levels of cytokine secreting monocytes in MS patients' blood, ELISPOT assays were used for detection and enumeration of monocytes secreting the cytokines IL-6, IL-12, TNF-alpha and IL-10. In parallel, the expression by monocytes of co-stimulatory molecules (CD40, CD80, CD86), major histocompatibility complex molecules (HLA-ABC, HLA-DR) and Fcgamma receptors (CD16, CD64) was examined by flow cytometry. Levels of blood monocytes secreting IL-6 and IL-12 were higher in patients with untreated MS and other neurological diseases (OND) compared to healthy controls, while levels of monocytes secreting TNF-alpha and IL-10 did not differ between groups. MS patients' blood monocytes also displayed elevated mean fluorescence intensity for the co-stimulatory molecule CD86, and MS patients with longer disease duration (>10 years) and higher disease severity (EDSS >3) had higher percentages of CD80 expressing monocytes compared to patients with short duration or lower severity. In conclusion, monocyte aberrations occur in MS and may change over the disease course.

Interferon-beta (IFN-beta) has a beneficial influence on the course of multiple sclerosis (MS) and has become standard treatment of this disease, though its mechanisms of action are incompletely understood. This study examines the effect of IFN-beta treatment on the cytokines IL-6, TNF-alpha, IFN-gamma and IL-10; the metalloproteinases MMP-3, -7 and -9 and the tissue inhibitor of metalloproteinase-1 (TIMP-1). IFN-beta treatment resulted in decreased numbers of mononuclear cells (MNC) secreting IL-6 and TNF-alpha and expressing mRNA of MMP-3 and MMP-9 compared to pretreatment levels. On the contrary, numbers of IL-10 secreting MNC and TIMP-1 mRNA expressing were augmented during IFN-beta therapy. Whether the down-regulatory effects on pro-inflammatory and upregulatory effects on anti-inflammatory molecules are a direct result of IFN-beta on the immune system or secondary to clinical stabilization of MS pathology induced by IFN-beta remains to be evaluated.

Interferon-beta (IFN-beta) has a beneficial influence on the course of multiple sclerosis (MS) and has become standard treatment of this disease, though its mechanisms of action are incompletely understood. This study examines the effect of IFN-beta treatment on the cytokines IL-6, TNF-alpha, IFN-gamma and IL-10; the metalloproteinases MMP-3, -7 and -9 and the tissue inhibitor of metalloproteinase-1 (TIMP-1). IFN-beta treatment resulted in decreased numbers of mononuclear cells (MNC) secreting IL-6 and TNF-alpha and expressing mRNA of MMP-3 and MMP-9 compared to pretreatment levels. On the contrary, numbers of IL-10 secreting MNC and TIMP-1 mRNA expressing were augmented during IFN-beta therapy. Whether the down-regulatory effects on pro-inflammatory and upregulatory effects on anti-inflammatory molecules are a direct result of IFN-beta on the immune system or secondary to clinical stabilization of MS pathology induced by IFN-beta remains to be evaluated.

The up-regulated B cell responses detectable in cerebrospinal fluid (CSF) and the augmented myelin antigen-specific T cell responses observed in the CSF as well as systematically in patients with multiple sclerosis (MS) suggest the involvement of cytokines in disease development and perpetuation. Here we report on the parallel involvement of TNF-alpha, IL-6, IFN-gamma and IL-10 in MS and controls, using enzyme-linked immunospot (ELISPOT) assays to detect and enumerate cytokine-secreting mononuclear cells (MNC) prepared from blood and, for IL-6 and IL-10, from CSF without in vitro stimulation. MS is associated with elevated levels of TNF-alpha-secreting blood MNC when compared with levels in groups of control patients with myasthenia gravis (MG) and other neurological diseases (OND) or healthy subjects. This elevation was confined to patients with untreated MS and not present in those examined during ongoing treatment with IFN-beta. Untreated patients with MS had lower numbers of IL-10-secreting blood MNC compared with the three control groups. In patients undergoing treatment with IFN-beta, numbers of IL-10-secreting cells were in the same range as in controls. Normalization of TNF-alpha from elevated, and of IL-10 from decreased levels could be one reason for the beneficial effects of IFN-beta in MS, although it remains to be shown whether these changes reflect phenomena primarily involved in MS pathogenesis or secondary changes. In CSF, levels of IL-10-secreting cells were higher than in blood in both MS and OND, with no difference between these groups. Systemic aberrations of IL-6 and IFN-gamma and of IL-6 in CSF in MS versus controls were only minor, irrespective of treatment with IFN-beta.

The cytokine interleukin (IL)-10 has immune response down-regulatory properties, which include suppression of the synthesis of pro-inflammatory cytokines such as interferon (IFN)-gamma and of major histocompatibility complex (MHC) class II expression on monocytes. To further elucidate the involvement of IL-10 in multiple sclerosis (MS), an enzyme-linked immunospot assay was adopted to enumerate IL-10-secreting mononuclear cells (MNC) in peripheral blood. IFN-gamma secreting MNC were detected in parallel. Levels of IL-10-secreting cells were lower in patients with MS compared with other neurological diseases (OND) and healthy subjects. This difference was seen only in patients with untreated MS, and not in those undergoing treatment with IFN-beta-1b. No differences were observed when subgrouping the patients with MS regarding clinical phase (exacerbation, remission, secondary progression), duration of MS or disability status. Levels of IFN-gamma-secreting blood MNC did not differ in patients with MS, irrespective of treatment with IFN-beta-1b, compared with OND and healthy subjects. Patients with MS, but not the two groups of controls, had elevated numbers of IL-10- and IFN-gamma-secreting cells upon stimulation with MBP compared with culture in the absence of antigen. The data suggest that IL-10 is decreased in MS and that treatment resulting in its up-regulation beneficially influence the disease.

The T(H)1 vs non-T(H)1 cytokine balance in Guillain-Barré syndrome (GBS) is unknown. Using enzyme-linked immunospot (ELISPOT) assays, we observed elevated numbers of interleukin (IL)-6 and IL-10-secreting blood mononuclear cells (BMNC) during the acute phase in untreated patients, and low levels of tumor necrosis factor alpha-secreting BMNC in the recovery phase of GBS. Numbers of IL-12p70-secreting BMNC were not affected over the course of GBS. The non-T(H)1 cytokine profile observed early in GBS may explain the self-limited clinical course associated with GBS.

Superconductors and semiconductors are crucial platforms in the field of quantum computing. They can be combined to hybrids, bringing together physical properties that enable the discovery of new emergent phenomena and provide novel strategies for quantum control. The involved semiconductor materials, however, suffer from disorder, hyperfine interactions or lack of planar technology. Here we realise an approach that overcomes these issues altogether and integrate gate-defined quantum dots and superconductivity into a material system with strong spin-orbit coupling. In our germanium heterostructures, heavy holes with mobilities exceeding 500,000 cm$^2$/Vs are confined in shallow quantum wells that are directly contacted by annealed aluminium leads. We demonstrate gate-tunable superconductivity and find a characteristic voltage $I_cR_n$ that exceeds 10 $\mu$V. Germanium therefore has great promise for fast and coherent quantum hardware and, being compatible with standard manufacturing, could become a leading material in the quantum revolution., Comment: 7 pages, 5 figures