Atmospheric deposition and soil water chemistry in Swedish forests since 1985 - Effects of reduced emissions of sulphur and nitrogen.

Trends for the atmospheric deposition of sulphur (S) and inorganic nitrogen (inorg-N) to forests and changes in the forest soil water chemistry in Sweden have been assessed since 1985, with special focus on the last 25 years, based on measurements within the Swedish Throughfall Monitoring Network (SWETHRO). The reductions in the deposition of S and inorg-N in the southern part of Sweden corresponded relatively well with the pollutant emission reductions for S and inorg-N from both EU27 + UK and Sweden during 1996/97-2021/22. For northern Sweden the deposition of S and inorg-N decreased to a lesser extent than both European and Swedish emissions. The bulk deposition of NO3-N has decreased more than the deposition of NH4-N over the last 25-year period, which is consistent with the much larger emission reductions for NOx compared to NH3 from EU27 + UK and Sweden. The S concentrations in the soil water, at 50 cm below soil surface, have decreased during the last 25 years, however somewhat less than the S deposition. At sites with low ANC and pH in the beginning of the period, the increase in ANC was generally greater and the increase in pH was smaller, but at sites with high pH and ANC above zero, the increase in pH was dominant, in line with the nonlinear relationship between pH and ANC in the soil water. The incidence of elevated concentrations of NO3-N in the soil water was highest in southwest Sweden, ranging between 4 and 19 % of all measuring occasions since 1985/86. The reduced deposition of N over the 35-year period was not reflected in the incidence of elevated concentrations of NO3-N in the soil water over time.

Twenty years of nitrogen deposition to Norway spruce forests in Sweden.

The yearly, total (dry+wet) deposition of inorganic nitrogen (inorg-N) to Norway spruce forests was estimated with a full spatial coverage over Sweden for a twenty-year period, 2001-2020, based on combined measurements with Teflon string samplers, throughfall deposition and bulk deposition to the open field. The results were based on a novel method to apply estimates of the dry deposition based on measurements at a limited number of sites, to a larger number of sites with only bulk deposition measurements, in turn based on the existence of a strong geographical gradient in the dry deposition of inorg-N from southwest to northeast Sweden. The method should be applicable for other geographical regions where gaseous NH3, NO2 and HNO3 are not main drivers of N dry deposition and where geographical gradients in dry deposition could be defined. It was shown that Norway spruce forests in south Sweden receive more N from deposition than has been previously estimated, based on modelling. Clear time trends were demonstrated for decreased deposition of inorg-N to Norway spruce forests in all parts of Sweden. The decreases were somewhat larger than what could be expected from the decrease in the reported emissions of inorg-N from Europe. The results emphasize that estimates of the total deposition are necessary in order to map levels and follow the development of N deposition in forests.

Optimization of droplet digital PCR assays for the type-specific detection and quantification of five HPV genotypes, including additional data on viral loads of nine different HPV genotypes in cervical carcinomas.

The droplet digital PCR (ddPCR) system enables high-sensitivity detection of nucleic acids and direct absolute quantification of the targets. The aim of this research was to evaluate this system for viral load (VL) analysis of the human papillomavirus (HPV) genotypes HPV31, 35, 39, 51 and 56 measured in number of viral particles per cell. The sample types used for the optimization of the ddPCR assay were formalin-fixed paraffin-embedded (FFPE) tissues and cervical liquid cytology samples. The presently optimized ddPCR assays, together with assays optimized previously for HPV16, 18, 33 and 45, with the same ddPCR method, were used for the VL analysis of cervical tumor samples. Results published previously on the present study cohort showed that women with a cervical tumor containing multiple high-risk HPV genotypes had a worse prognosis compared to women with single-genotype-infected tumors. The VL was therefore analyzed in this study for the same cohort, as a possible explanatory factor to the prognostic differences. The results of the optimization part of the study, with analysis of VL using ddPCR in DNA from varying sample types (FFPE and liquid cytology samples), showed that each of the five assays demonstrated good inter- and intra-assay means with a coefficient of variation (CV) under 8% and 6% respectably. The cohort results showed no difference in VL between tumors with multiple and single HPV infections, and therefore did most likely not constitute a contributing factor for prognostic differences observed previously. However, tumors from women aged 60 years or older or containing certain HPV genotypes and genotype genera were associated with a higher VL.

Heavy metal and nitrogen concentrations in mosses are declining across Europe whilst some "hotspots" remain in 2010.

In recent decades, naturally growing mosses have been used successfully as biomonitors of atmospheric deposition of heavy metals and nitrogen. Since 1990, the European moss survey has been repeated at five-yearly intervals. In 2010, the lowest concentrations of metals and nitrogen in mosses were generally found in northern Europe, whereas the highest concentrations were observed in (south-)eastern Europe for metals and the central belt for nitrogen. Averaged across Europe, since 1990, the median concentration in mosses has declined the most for lead (77%), followed by vanadium (55%), cadmium (51%), chromium (43%), zinc (34%), nickel (33%), iron (27%), arsenic (21%, since 1995), mercury (14%, since 1995) and copper (11%). Between 2005 and 2010, the decline ranged from 6% for copper to 36% for lead; for nitrogen the decline was 5%. Despite the Europe-wide decline, no changes or increases have been observed between 2005 and 2010 in some (regions of) countries.

Protonation behavior and solution properties of amine oxide surfactants containing a pyridyl group.

Hydrogen bonding between surfactant molecules plays an important role in self-assembly formation. For long alkyl chain amine oxide surfactants, the specific protonation degree dependence of some solution properties has been considered to be due to hydrogen bonding between protonated and deprotonated species. In addition to this type of hydrogen bonding, we introduced a pyridyl group into an alkylamine oxide molecule as a new hydrogen-bonding site. The pyridyl group has three different structural isomers based on the position of the substituent. An amine oxide group in pyridylamine oxides was preferentially protonated. In addition, protonation of the pyridyl group revealed a pronounced substituent position effect on the critical micelle concentration, micellar size, and solubilization of oil-soluble dye into micelles. The intermolecular or intramolecular hydrogen bond formation could be controlled by altering the substituent position.

Disease patterns and immune responses in the offspring to sows with high or low antibody levels to Actinobacillus pleuropneumoniae serotype 2.

The serum antibody responses to Actinobacillus pleuropneumoniae and the secondary invader Pasteurella multocida were monitored from birth until slaughter in the offspring to sows with high or low levels of serum antibodies to A. pleuropneumoniae. Serum antibody concentrations to A. pleuropneumoniae were higher from birth to the age of 9 weeks in piglets delivered by high responding sows. In contrast, antibody levels to P. multocida were similar in both groups during this period. From the age of 20 and 15 weeks, antibody levels to A. pleuropneumoniae and P. multocida, respectively, were higher in the offspring to high responding sows. This implies that the offspring to sows with high levels of antibodies may be better protected during the first period of life because of a higher level of passively derived immunity. These piglets will also mount a higher antibody response when later infected, indicating a heritability of the humoral immune response.

High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.

Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results.

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7-36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15-24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88-89%) or new T2 lesions (70-78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20-0.21, and 68-73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3-5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme.

Estimates of AOT ozone indices from time-integrated ozone data and hourly air temperature measurements in southwest Sweden.

Surface ozone concentration and surface air temperature was measured hourly at three coastal sites, four low elevation inland sites and two high elevation inland sites in southwestern Sweden. Diurnal ozone concentration range (DOR) and diurnal temperature range (DTR) were strongly correlated, both spatially and temporally, most likely because both depended on atmospheric stability. Accumulated ozone exposure above a threshold concentration of x nmol mol(-1) (AOTx) was estimated from time-integrated ozone concentration (as from diffusive sampling) and measures of ozone concentration variability. Two methods both estimated 24-h AOTx with high accuracy (modelling efficiencies >90% for x

Anosognosia versus unilateral neglect. Coexistence and their relations to age, stroke severity, lesion site and cognition.

The aim of this study was to examine the association between anosognosia and unilateral neglect (UN), with special focus on age, stroke severity, lesion location and pre-stroke dementia. The basis of this investigation was a population-based stroke incidence study. Anosognosia was assessed using a questionnaire, and UN using a three-item version of the Behaviour Inattention Test, the Baking Tray Task and a test of personal neglect. Stroke severity was assessed using the NIH stroke scale. Patients with anosognosia were older, and they more often had pre-stroke dementia than patients having UN only. No particular lesion localization was associated with anosognosia, while UN was strongly associated with previously defined lesion sites, often in the parietal lobe. There was a borderline significance regarding stroke severity in patients having anosognosia compared with those with UN only. Patients with anosognosia had higher mortality than patients without, but when controlled for age and stroke severity, this effect was not independent. While UN is closely associated with 'classical' lesion sites, anosognosia is a condition that more often occurs in a previously impaired brain. For anosognosia, lesion location appears to be less important. Anosognosia also tends to occur with larger strokes.

Effects of human plasma proteins on maturation of monocyte-derived dendritic cells.

Dendritic cells (DC) are a promising tool for vaccine therapy due to their unique properties as antigen presenting cells and their ability to prime naïve T cells. Increasing evidence suggests that maturation stage of DC critically influences the fate of the immune response. Generation of monocyte-derived DC for clinically applicable immunotherapy requires the use of well-defined components and stringent culture conditions. An alternative strategy is to use human autologous serum. However, its constituents are not stable and reflect the inflammatory condition of the donor. In order to investigate whether DC properties are influenced by proteins present in the plasma, we matured human monocyte-derived DC with four main plasma components: fibrinogen, fibronectin, plasminogen or C-reactive protein. These purified proteins were added at various concentrations on day 6 after the initial differentiation induced by IL-4 and GM-CSF. The maturation was assessed by phenotyping of maturation-associated marker (CD83) and co-stimulatory molecule CD86 as well as IL-12 production. Functional properties of DC were assessed by endocytic activity and mixed leukocyte culture. Our results indicate that fibrinogen had DC-maturation effect comparable to poly-I:C, TNF-alpha and PGE(2) as a positive control, but it failed to induce IL-12 production. The other plasma proteins had no effect on DC maturation. CRP at high concentration had rather inhibitory effect on DC induced lymphocyte function. We conclude that none of the tested plasma components and acute phase proteins sufficiently induce fully competent mature DC. This finding is important for the preparation of human DC-based vaccines supplemented by autologous sera.

On the logarithmic relationship between NO2 concentration and the distance from a highroad.

Measurements of nitrogen dioxide (NO2) concentrations, performed with passive diffusion samplers in gradients from a highway in South-west Sweden, were used to test the assumption that the NO2 concentration contributed by the highway varies with the logarithm of the distance from the highway. The five data sets used corroborated the hypothesis, and it was shown that all data could be accommodated to a common relationship with high correlation (R2=0.95) using the concentration of 10 m away from the highroad as the reference. The data were also well in accordance with a recently published study from Canada, although the slope of the relationship between the NO2 concentration contributed by a highway and the logarithm of the distance was somewhat stronger for the Swedish data compared to the Canadian. The regression slope is likely to be sensitive to wind speed, atmospheric stability, surface roughness and the background ozone concentrations of the area.

Activation of p53 by scaffold-stabilised expression of Mdm2-binding peptides: visualisation of reporter gene induction at the single-cell level.

Small peptides that perturb intracellular signalling pathways are useful tools in the identification and validation of new drug targets. To facilitate the analysis of biologically active peptides, we have developed retroviral vectors expressing an intracellular scaffold protein that significantly enhances the stability of small peptides in mammalian cells. This approach was chosen because retroviral transduction results in efficient and controlled delivery of the gene encoding the effector peptide, while the scaffold protein not only stabilises the peptide but also facilitates the analysis and potential isolation of the target protein. Here, we have adapted a p53-responsive reporter assay to flow cytometry to demonstrate the versatility of this approach by using peptides with known Mdm2-binding activities inserted into a stable scaffold protein that is suitable for intracellular expression in multiple compartments of mammalian cells. This strategy should be generally applicable to the study of small biologically active peptides in diverse functional assays.

Recovery from unilateral neglect after right-hemisphere stroke.

PURPOSE: To show the recovery process for different forms of unilateral neglect (UN)--including personal neglect and neglect of far space--in relationship to impairment, disability, cognition and mood. METHOD: Patients were tested at 2-4 weeks, at 6 months and at 1 year. We used the Behaviour Inattention Test and a test for personal neglect. We also used the NIH Stroke Scale, the Functional Independence Measure (FIM), the Mini-Mental State Evaluation and the Geriatric Depression Scale. RESULTS: Peripersonal neglect diminishes within 6 months, but complete recovery occurred in only 13%. The prognosis for personal neglect and neglect of far space is better, with a recovery ratio at 6 months of 52% and 46%, respective. The correlations between UN and FIM are high. A few patients deteriorate in the absence of recurrent stroke. CONCLUSIONS: For clinical purposes, it is practical to postpone UN evaluation until a couple of weeks after a stroke. Many of the patients who then have UN are likely to retain their UN, although many will improve. Patients with UN should receive special attention in the rehabilitation phase, as well as at discharge. One explanation of the worsening of UN seen in some patients, may be continuing cerebral atherosclerosis.

Clinical mass spectrometry in neuroscience. Proteomics and peptidomics.

In this review we discuss the merits and drawbacks with the use of proteomic and peptidomic strategies for identification of proteins and peptides in their multidimensional interactions in complex biological processes. The progress in proteomics and peptidomics during the last years offer us new challenges to study changes in the protein and peptide synthesis. These strategies also offer new tools to follow post-translational modifications and other disturbed chemical processes that may be indicative of pathophysiological alteration(s). Furthermore these techniques can contribute to improvements in the diagnosis and therapy of neurodegenerative diseases, such as Alzheimer's disease, and psychiatric diseases, as depression and post traumatic stress disorders. We also consider different practical aspects of the applications of mass spectrometry in clinical neuroscience, illustrated by example from our laboratories. The new proteomic and peptidomic strategies will further enable the progress for clinical neuroscience research.

Assessing unilateral neglect: shortcomings of standard test methods.

INTRODUCTION: When investigating the incidence of unilateral neglect in a first-ever stroke population, we found that some patients showed clinical signs of neglect, but managed to pass our tests. The purpose of this paper is to describe the nature of such signs, and analyse why test instruments were insufficiently corresponding to those signs. METHOD: One hundred and thirty-one consecutive patients with first-ever stroke in a community-based sample were evaluated for the presence of unilateral neglect. We used a test battery consisting of tests for visuo-spatial neglect, personal neglect, and anosognosia. Twenty cases of neglect were discovered by standard methods. We asked our collaborators at the wards to report any behavioural abnormality reminiscent of neglect present in patients who had normal test results. Such patients were evaluated clinically. RESULTS: Nine cases with neglect-like symptoms were discovered. Our clinical evaluation of the nine patients indicated several possible explanations for their behavioural abnormalities, including motor neglect, neglect for far extrapersonal space, disturbances of proprioception, and spatial disturbances other than neglect. CONCLUSION: Standard neglect tests do not cover all clinical forms of neglect. It is therefore important not to rely completely on test instruments when diagnosing neglect. More versatile test instruments are desired.

High-peak power nanosecond optical parametric amplifier with periodically poled KTP.

A two-stage optical parametric amplifier generating 5 ns 208 kW peak power pulses in the spectral region at 1.535 microm in a diffraction-limited beam was realized in a single periodically poled KTP crystal. The maximum small-signal gain for the two stages reached 75dB and the total conversion efficiency was 30%. An analysis of the small-signal gain dependence on the M2 of the pump beam is presented for the collinear and noncollinear OPA. Efficient spectral broadening of the signal was demonstrated in short pieces of single-mode telecommunication fiber.

Increased nasal mucosal swelling in subjects with asthma.

OBJECTIVE: The objective of this study was to evaluate nasal mucosal swelling with acoustic rhinometry in subjects with asthma and in healthy controls. METHODS: We examined 184 individuals with asthma and compared with 156 randomly selected controls outside the pollen season, where 144 subjects in the asthma group and 80 controls had a previous history of non-infectious rhinitis (NIR). Nasal mucosal swelling was assessed with acoustic rhinometry before and after nasal decongestion with oxymetazoline and was analysed for the crosssectional area (4cm from the nostril) and the volume between 3.3 and 4cm from the nostril. Symptom scores for nasal blockage, secretion, itching and sneezing were assessed on a 0-10 visual analogue scale as well as peak nasal inspiratory flow and spirometry. RESULTS: Before decongestion there was a decrease in the cross-sectional area at 4 cm (1.32 cm2 vs. 1.59 cm2, mean left + right P = 0.04) and in the volume (1.70 vs. 1.91 cm3 P = 0.03) in the asthma group compared with healthy controls. After decongestion there were no significant differences in cross-sectional area at 4cm (1.66 vs. 1.73cm2 P=0.32) or volume (2.12 vs. 2.24cm3 P=0.32). Combined nasal symptom scores were higher in the asthma group (1.8 vs. 0.8, P=0.0001) and peak nasal inspiratory flow was lower (119 vs. 124 L/min, P = 0.38) than the healthy controls. FEV1 (% predicted) was also lower in asthma group (84 vs. 93% P < 0.0001). CONCLUSION: We have been able to demonstrate an increased nasal mucosal swelling in a population sample of persons with asthma compared to healthy controls. These data support previous reports of a generalized airway inflammation in patients with asthma and suggest that acoustic rhinometry can be used to monitor the nasal mucosal swelling in these patients.

Longitudinal study of interleukin-10, tumor necrosis factor-alpha, anti-U1-snRNP antibody levels and disease activity in patients with mixed connective tissue disease.

OBJECTIVE: To investigate the levels and relationship between IL-10, TNF-alpha, anti-U1snRNP antibodies and disease activity in longitudinally collected serum samples from patients with mixed connective tissue disease (MCTD). METHODS: Six patients followed for 17-138 months were investigated with ELISA for estimation of cytokine levels and antibodies to the different epitopes of the U1snRNP. Disease activity was assessed by systemic lupus activity measure (SLAM). RESULTS: IL-10 and TNF-alpha levels fluctuated with time in at least half of the patients. Three patients had increased IL-10 levels and two had increased TNF-alpha in all samples. There was no correlation between cytokine levels and disease activity or clinical manifestations. All patients had increased levels of antibodies to the main components of the U1snRNP. Both antibody levels and disease activity decreased with time. A correlation between TNF-alpha and U1snRNP antibody levels were observed in five patients. CONCLUSIONS: Increased and fluctuating levels of IL-10 or TNF-alpha without correlation to disease activity were observed in MCTD patients. In some patients increased cytokine levels were observed over several years irrespective of disease activity indicating that they could be constitutively increased in these individuals.