Showing papers by "Stockholm University published in 1992"

Linguistic experience alters phonetic perception in infants by 6 months of age

Abstract: Linguistic experience affects phonetic perception. However, the critical period during which experience affects perception and the mechanism responsible for these effects are unknown. This study of 6-month-old infants from two countries, the United States and Sweden, shows that exposure to a specific language in the first half year of life alters infants' phonetic perception.

Emotional stress and eyewitness memory: a critical review.

Abstract: The eyewitness literature often claims that emotional stress leads to an impairment in memory and, hence, that details of unpleasant emotional events are remembered less accurately than details of neutral or everyday events. A common assumption behind this view is that a decrease in available processing capacity occurs at states of high emotional arousal, which, therefore, leads to less efficient memory processing. The research reviewed here shows that this belief is overly simplistic. Current studies demonstrate striking interactions between type of event, type of detail information, time of test, and type of retrieval information. This article also reviews the literature on memory for stressful events with respect to two major theories: the Yerkes-Dodson law and Easter-brook's cue-utilization hypothesis. To account for the findings from real-life studies and laboratory studies, this article discusses the possibility that emotional events receive some preferential processing mediated by factors related to early perceptual processing and late conceptual processing.

Seed and microsite limitation of recruitment in plant populations.

Abstract: Availability of seed and microsites, respectively, are two factors that potentially may limit recruitment in plant populations. Microsites are small-scale sites suitable for germination and survival of seedlings. We discuss this dichotomy of recruitment limitation both from a theoretical and empirical point of view. Investigations of recruitment in 14 woodland species showed that 3 species were seed limited, 6 species were limited by a combination of seed and microsite availability, and 5 species were found not to be seed limited, but the limiting factor was not identified. A “combination of seed and microsite limitation” implies that recruitment is promoted by increasing both seed and microsite availability. We suggest that the importance of seed limitation in plant populations has been underestimated, and that the operating limiting factors may be dependent on spatial and temporal scale. We expect that many species, if adequately studied, will turn out to be both seed and microsite limited. Experimental field studies that incorporate a range of seed and microsite “densities” in various spatial and temporal scales are needed to examine the extent to which plant populations are seed and microsite limited.

Fennoscandian summers from ad 500: temperature changes on short and long timescales

Abstract: Quantitative estimates of 1480 years of summer temperatures in northern Fennoscandia have previously been derived from continuous treering records from northern Sweden. Here we show the results of spectral analyses of these data. Only a few peaks in the spectra are consistently significant when the data are analyzed over a number of sub-periods. Relatively timestable peaks are apparent at periods of 2.1, 2.5, 3.1, 3.6, 4.8, ∼ 32–33 and for a range between ∼ 55–100 years. These results offer no strong evidence for solar-related forcing of summer temperatures in these regions. Our previously published reconstruction was limited in its ability to represent long-timescale temperature change because of the method used to standardize the original tree-ring data. Here we employ an alternative standardization technique which enables us to capture temperature change on longer timescales. Considerable variance is now reconstructed on timescales of several centuries. In comparison with modern normals (1951–70) generally extended periods when cool conditions prevailed, prior to the start of the instrumental record, include 500–700, 790–870, 1110–1150, 1190–1360, 1570–1750 (A.D.) with the most significant cold troughs centred on about 660, 800, 1140, 1580–1620 and 1640. Predominantly warm conditions occurred in 720–790, 870–1110 and 1360–1570 with peaks of warmth around 750, 930, 990, 1060, 1090, 1160, 1410, 1430, 1760 and 1820.

Tumour and normal tissue responses to fractionated non-uniform dose delivery.

Abstract: The dose–volume response of tumours and normal tissues is discussed in terms of ‘parallelity’ and ‘seriality’. The volume dependence of the radiation response of a tumour depends primarily on the eradication of all its clonogenic cells and the tumour has a parallel organization. The response of heterogeneous tumours is examined, and it is shown that a small resistant clonogen population may cause a low dose–response gradient, γ. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of stem cells or differentiated cells that in addition may have a complex structural and functional organization. The volume dependence of the dose–response relation of normal tissues is therefore described here by a new parameter, the ‘relative seriality’, s, of the infrastructure of the organ. The model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose–response relat...

Reversible and irreversible intermediates during photoinhibition of photosystem II: stable reduced QA species promote chlorophyll triplet formation

Abstract: Photoinhibition of photosynthesis was studied in isolated photosystem II membranes by using chlorophyll fluorescence and electron paramagnetic resonance (EPR) spectroscopy combined with protein analysis. Under anaerobic conditions four sequentially intermediate steps in the photoinhibitory process were identified and characterized. These intermediates show high dark chlorophyll fluorescence (Foi) with typical decay kinetics (fast, semistable, stable, and nondecaying). The fast-decaying state has no bound QB but possesses a single reduced QA species with a 30-s decay half-time in the dark (QB, second quinone acceptor; QA, first quinone acceptor). In the semistable state, Q-A is stabilized for 2-3 min, most likely by protonation, and gives rise to the Q-A Fe2+ EPR signal in the dark. In the stable state, QA has become double reduced and is stabilized for 0.5-2 hr by protonation and a protein conformational change. The final, nondecaying state is likely to represent centers where QA H2 has left its binding site. The first three photoinhibitory states are reversible in the dark through reestablishment of QA to QB electron transfer. Significantly, illumination at 4 K of anaerobically photoinhibited centers trapped in all but the fast state gives rise to a spinpolarized triplet EPR signal from chlorophyll P680 (primary electron donor). When oxygen is introduced during anaerobic illumination, the light-inducible chlorophyll triplet is lost concomitant with induction of D1 protein degradation. The results are integrated into a model for the photoinhibitory process involving initial loss of bound QB followed by stable reduction and subsequent loss of QA facilitating chlorophyll P680 triplet formation. This in turn mediates light-induced formation of highly reactive and damaging singlet oxygen.

Anthropogenic influence on the distribution of tropospheric sulphate aerosol

Abstract: HUMAN activities have increased global emissions of sulphur gases by about a factor of three during the past century, leading to increased sulphate aerosol concentrations, mainly in the Northern Hemisphere. Sulphate aerosols can affect the climate directly, by increasing the backscattering of solar radiation in cloud-free air, and indirectly, by providing additional cloud condensation nuclei1–4. Here we use a global transport–chemistry model to estimate the changes in the distribution of tropospheric sulphate aerosol and deposition of non-seasalt sulphur that have occurred since pre-industrial times. The increase in sulphate aerosol concentration is small over the Southern Hemisphere oceans, but reaches a factor of 100 over northern Europe in winter. Our calculations indicate, however, that at most 6% of the anthropogenic sulphur emissions is available for the formation of new aerosol particles. This is because about one-half of the sulphur dioxide is deposited on the Earth's surface, and most of the remainder is oxidized in cloud droplets so that the sulphate becomes associated with pre-existing particles. Even so, the rate of formation of new sulphate particles may have doubled since pre-industrial times.

On The Bayesian Bootstrap

Abstract: A method to compare the Bayesian bootstrap with a parametric analysis is derived. The method is applied to the mean of a Poisson distribution.

Initialization of the HIRLAM Model Using a Digital Filter

Abstract: Spurious high-frequency oscillations occur in forecasts made with the primitive equations if the initial fields of mass and wind are not in an appropriate state of balance with each other. These oscillations are due to gravity-inertia waves of unrealistically large amplitude; the primary purpose of initialization is the removal or reduction of this high-frequency noise by a delicate adjustment of the analyzed data. In this paper a simple method of eliminating spurious oscillations is presented. The method uses a digital filter applied to time series of the model variables generated by short-range forward and backward integrations from the initial time. The digital filtering technique is applied to initialize data for the High-Resolution Limited-Area Model (HIRLAM). The method is shown to have the three characteristics essential to any satisfactory initialization scheme: (i) high-frequency noise is effectively removed from the forecast; (ii) changes made to the analyzed fields are acceptably small...

Aminergic neurons in the brain of blowflies and Drosophila: dopamine- and tyrosine hydroxylase-immunoreactive neurons and their relationship with putative histaminergic neurons.

Abstract: The distribution and morphology of neurons reacting with antisera against dopamine (DA), tyrosine hydroxylase (TH) and histamine (HA) were analyzed in the blowflies Calliphora erythrocephala and Phormia terraenovae. TH-immunoreactive (THIR) and HA-immunoreactive (HAIR) neurons were also mapped in the fruitfly Drosophila melanogaster. The antisera against DA and TH specifically labeled the same neurons in the blowflies. About 300 neurons displayed DA immunoreactivity (DAIR) and THIR in the brain and subesophageal ganglion of the blowflies. Most of these neurons were located in bilateral clusters; some were distributed as bilateral pairs, and two ventral unpaired median (VUM) neurons were seen in the subesophageal ganglion. Immunoreactive processes were found in all compartments of the mushroom bodies except the calyces, in all divisions of the central body complex, in the medulla, lobula and lobula plate of the optic lobe, and in non-glomerular neuropil of protocerebrum, tritocerebrum and the subesophageal ganglion. No DA or TH immunoreactivity was seen in the antennal lobes. In Drosophila, neurons homologous to the blowfly neurons were detected with the TH antiserum. In Phormia and Drosophila, 18 HA-immunoreactive neurons were located in the protocerebrum and 2 in the subesophageal ganglion. The HAIR neurons arborized extensively, but except for processes in the lobula, all HAIR processes were seen in non-glomerular neuropil. The deuto- and tritocerebrum was devoid of HAIR processes. Double labeling experiments demonstrated that TH and HA immunoreactivity was not colocalized in any neuron. In some regions there wasm however, substantial superposition between the two systems. The morphology of the extensively arborizing aminergic neurons described suggests that they have modulatory functions in the brain and subesophageal ganglion.

Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin-like interactions.

Abstract: Herein we describe an assay that was developed to quantitate the binding of normal red blood cells (RBC), labeled with carboxy fluorescein diacetate (C-FDA), to rosetting Plasmodium falciparum-infected RBC. The binding of RBC obtained from various animal species or humans to different strains or clones of rosetting P. falciparum-infected RBC was studied. A strain-specific preference of rosetting was observed for either blood group A/AB or B/AB RBC for all parasites tested. The higher affinity of rosette binding of blood group A, B, or AB vs. O RBC was reflected in larger rosettes when a given parasite was grown in RBC of the preferred blood group. The small size of the rosettes formed when P. falciparum was grown in blood group O RBC may be the in vitro correlate of the relative protection against cerebral malaria afforded by belonging to blood group O rather than to blood group A or B. Rosettes of a blood group A-preferring parasite could be completely disrupted by heparin only when grown in blood group O or B RBC, but not when grown in blood group A RBC. Similarly, the rosettes of a blood group B-preferring parasite could be more easily disrupted by heparin when grown in blood group O or A RBC than when grown in blood group B RBC. Several different saccharides inhibited rosetting of group O RBC, including two monosaccharides that are basic components of heparin. The rosetting of the same parasites grown in blood group A or B RBC was less sensitive to heparin and was specifically inhibited only by the terminal mono- and trisaccharides of the A and the B blood group antigens, the H disaccharide, and fucose. Our results suggest that rosetting is mediated by multiple lectin-like interactions, the usage of which rely on the parasite phenotype and whether the receptors are present on the host cell or not.

Cytokine Regulation of Neuronal Survival

Abstract: Interleukin-1 is a cytokine involved in the immune response to infection and inflammation as well as a growth promotor for several cell types. Interleukin-1-like immunoreactive material has been found in the nervous system. We now show that antisera, which blocked the T-cell proliferative effects of interleukin-1 alpha, decreased neuronal cell counts (to 40% of control) in dissociated spinal cord cultures derived from fetal mice. This neuronal loss was prevented by addition of interleukin-1 alpha, and to a lesser extent by interleukin-1 beta. Exogenous interleukin-1 alpha increased the survival of neurons when added to cultures in which the electrical activity was blocked with tetrodotoxin, whereas no such cytokine-related increase in neuronal survival was observed in electrically active cultures. The antiserum-induced death could also be prevented by cotreatment of the cultures with 0.1 nM vasoactive intestinal peptide, a substance that induces the secretion of neuronal trophic factors from nonneuronal spinal cord cells and thereby increases neuronal survival in electrically inactive cultures. These studies indicate that the cytokine interleukin-1, or an immunologically cross-reactive protein, can increase neuronal survival.

Abiotic synthesis of amino acids under hydrothermal conditions and the origin of life: a perpetual phenomenon?

Abstract: Today, subaqueous hydrothermal activity is a very dynamic process. For example, the entire volume of water in the ocean is circulated in approximately 10 million years through the more than 70000 km length of global ridge systems scarring the bottom of the Earth's oceans [1]. Hydrothermal circulation also takes place off-ridges in the oceanic crust and the covering sediments [2, 3]. Early in the Earth's history (4 × 10 9 years ago or so) hydrothermal activity was even more intensive, mostly because of the lack of thick continental masses and higher heat fluxes cooling the planet. As soon as water was able to condense at the surface of the Earth, all processes associated with subaqueous hydrothermal activity began, and probably continued uninterrupted until the present. The physical and chemical conditions within submarine hydrothermal systems can vary greatly. Aqueous hydrothermal fluid temperature can range from cold (temperature of bottom seawater) in the recharge areas, to hot (e.g., 650-700°C, closest approach of aqueous fluid to magma [2]) closer to magmatic heat sources, deeper in the Earth's crust. Redox conditions (E h, which are of extreme importance in determining the direction of chemical reactions and the stability of chemical species, also vary, from relatively oxidizing in the hotter zones to more reducing in the colder zones of the system. For the redox couple CO2/CH4, the conditions are oxidizing (stability field of CO2) at higher temperatures (above 300 or 400 °C), and reducing (stability field of CH4) at lower temperatures in a typical oceanic crust environment [4]. Many other parameters show variations, for example, mineral assemblages, chemical species activities, and pH, to name only a few [2]. Hydrothermal conditions are ubiquitous in the Earth's crust. Direct, observable expression of hydrothermal activity at the seafloor is in the form of hot aqueous fluids (at temperatures of up to 400°C or more) emanating directly from vents or seeps [5, 6]. However, hydrothermal fluids at the temperature conditions measured in vents and seeps represent only a very small portion of the entire mass of aqueous fluid perpetually circulating in the oceanic crust. An estimated 96 °7o of the mass of hydrothermal water circulating in the oceanic crust is at a temperature of around 150°C [3, 7, 8]. The E h of aqueous fluids circulating in the hydrothermally altered oceanic crust is reducing, and is generally controlled by the mineral assemblage pyrite/pyrrhotite/magnetite [9, 10]. The pH is close to neutral around 150°C, becoming more acidic as temperature increases towards 250°C, and then less acidic again at higher temperatures [t 1]. Chemical reactions take place in response to changes in chemical and physical conditions. For example, at 150°C, dissolved CO 2 introduced in a system consisting of an aqueous phase in contact with the pyrite/pyrrhotite/ magnetite mineral assemblage should be reduced to C H 4 as the system responds to reach equilibrium [4]. However, stable chemical equilibrium be-

Using ratios of stable nitrogen isotopes to estimate bioaccumulation and flux of polychlorinated dibenzo‐p‐dioxins (PCDDs) and dibenzofurans (PCDFs) in two food chains from the Northern Baltic

Abstract: Presented in this study is a new method to quantitatively estimate in situ biomagnification of organic contaminants that uses ratios of naturally occurring stable isotopes of nitrogen to classify trophic levels of organisms from one littoral and one pelagic food chain in the northern Baltic proper. Results indicated a biomagnification of the three most toxic 2378-substituted polychlorinated dibenzo-p-dioxins and -dibenzofurans (PCDD/Fs), whereas the total concentration of 2378- substituted PCDD/Fs, and particularly octachlorodibenzo-p-dioxin and -dibenzofuran (OCDD/F), decreased with increasing trophic level in the food chains. A calculated flux estimate of PCDD/Fs in juvenile eider ducks was supported by results from the biomagnification study; that is, the most toxic 2378-substituted isomers tended to accumulate in the tissue of the eider duck. Out of the total PCDD/Fs consumed by the eider ducks, only 10% were recovered in the body and approximately 10% were recovered in feces, whereas 80% were not recovered, that is, were excreted or remained as unidentified metabolites. Of the most toxic 2378-substituted isomers, 57% were recovered in the tissue, 30% were recovered in the feces, and only 13% were not recovered (i.e., metabolized and/or excreted).

Stochastic trends and economic fluctuations in a small open economy

Abstract: In this paper we describe how restricted vector autoregressions can be employed to examine the sources of macroeconomic fluctuations. We show how cointegration restrictions can be used to identify a VAR system with common stochastic trends subject to transitory and permanent changes in average growth, and how we may investigate the system's responses to permanent shocks, i.e. to innovations to the trends. Theoretical cointegration vectors are derived from a small open economy growth model for terms of trade, real GDP, real consumption, and real investments. Applying these methods to Swedish annual data (1875–1986) we find that permanent real (supply) shocks account for most of the fluctuations in GDP, even in the short run.

Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria

Abstract: The ability of Plasmodium falciparum-infected red blood cells (RBC) to form spontaneous erythrocyte rosettes was studied in 130 fresh isolates from Gambian children with cerebral or uncomplicated malaria from August to November 1990. All isolates (24 of 24) from patients with cerebral malaria formed rosettes, but only 61 of 106 isolates from children with uncomplicated malaria formed rosettes. The mean rate of rosette formation in isolates from children with cerebral malaria (28.3%) was significantly greater than that in isolates from children with uncomplicated malaria (8.5%). Giant rosettes were more frequently formed in isolates from patients with cerebral malaria than in those from patients with uncomplicated malaria. Sera of children with cerebral disease generally lacked anti-rosette activity, while many sera from children with uncomplicated malaria showed strong anti-rosette activity when tested against the patients' ow parasites. Some sera that were devoid of autologous rosette-disrupting activity were able to disrupt rosettes formed in other isolates, indicating the presence of different rosette formation mechanisms. Forty percent (6 of 15) of the sera from patients with cerebral malaria caused microagglutination of the patients' own uninfected and infected RBC, while only 10% (3 of 31) of sera from children with uncomplicated disease caused microagglutination. The ability of infected RBC to bind to melanoma cells grown in vitro did not differ between patients with cerebral or uncomplicated malaria. The results of this study, taken in conjunction with our previous findings, establish a strong association between rosette formation in P. falciparum-infected RBC and cerebral malaria.

Pollination systems, dispersal modes, life forms, and diversification rates in angiosperm families.

Abstract: An important aspect of evolution in higher order taxa, such as mammals, molluscs, and plants, is the rate of diversification (R), i.e., the rate at which the number of species increases over evolutionary time (Darwin, 1859; Simpson, 1944; Mayr, 1963; Pieiou, 1979; Stanley, 1979, 1989). Stanley (1979) presented an extensive summary and analysis of data pertaining to this issue, and he advocated two tentative causal mechanisms behind variation in R among taxa. First, R should increase in association with increased \"adaptive complexity.\" The occurrence of complex behavior, of any kind, increases the rate of speciation because it fosters reproductive isolation. On the other hand, adaptive complexity also promotes extinction risk due to ecological specialization. This implies increased species turnover, which is characteristic for lineages with high R (Stanley, 1979). A similar idea was mentioned by Darwin (1859) as an explanation for the difference in evolutionary rate he perceived between terrestrial and marine organisms, the former ones exhibiting higher rates than the latter ones. Second, increased dispersal ability should decrease R. There are two rationales for this mechanism. Speciation rate is expected to decrease with increased dispersal ability because geographic isolation is not easily maintained ifspecies disperse widely (Mayr, 1963). Furthermore, dispersal ability correlates positively with species longevity (Mayr, 1963; Jackson, 1974), and species longevity is in turn inversely related to R (Stanley, 1979). In comparison with some animal taxa, the diversification rates exhibited by angiosperms are poorly known. They were not included in Stanley (1979), and only a few attempts have been made to estimate R values for higher plants (Niklas et aI., 1985). Despite the scarcity ofconclusive evidence, several authors have suggested reproductive and life form features associated with high diversification rates among angiosperms. Grant (1949) argued that pollination by animals is a prevalent isolating mechanism between plant species. Occurrence of\"faithful pollinators\" would thus promote species diversification (Stebbins, 1981; Crepet, 1984). In the fossil record, insect pollination is associated with angiosperm diversification during Late Cretaceous and Early Tertiary (Friis and Crepet, 1987; Crepet and Friis, 1987). The \"insect (animal) pollination hypothesis\" was considered by Stanley (1979) as the \"plant analogue\" to the hypothesis that R increases in association with increased adaptive complexity. Under the assumption that pollination by animals is more efficient than wind pollination in sparse populations, Raven (1977) argued that animal pollinated plants would experience reduced extinction risks under conditions when population density becomes reduced. Regal (1977), Burger (1981), and Crepet (1984) further proposed that the combined effect of pollination by animals, and dispersal by animals, promotes species diversification because dispersal by animals would create a population structure in which animal pollination is advantageous. However, this proposal has some weaknesses. If local populations become isolated by distances exceeding the flight distances of pollinators, it is not obvious that animal pollination is advantageous compared with wind pollination. Furthermore, ifcross pollination does occur between widely scattered individuals, it might hinder rather than promote speciation (Stebbins, 1981). Apart from the suggested \"animal pollination/animal dispersal\" mechanism, the possession ofanimal dispersed seed, in itself, has been viewed as increasing species diversification rates. If dispersal by animals increases long distance dispersal, this would promote establishment of isolated populations in which speciation may take place (Snow, 1981; Tiffney, 1984, 1986). There is evidence that fruit dispersal by birds enhances long distance dispersal. Ridley (1930) described prevalence of fleshy fruited species on oceanic island. Moreover, in the family Rubiaceae, genera possessing drupes are over-represented both on oceanic islands and among genera with transoceanic distributions (Bremer and Eriksson, in press). In addition to reproductive features, the life form of plants might influence diversification rate. Short-lived plants, especially herbs, are expected to exhibit a high rate ofdiversification due to their comparatively short generation time (Tiffney, 1986). Furthermore, populations of short lived plants are often semi-isolated, occupy transient habitats, and experience unpredictable fluctuations, conditions that all may promote R (Levin, 1984; Niklas et aI., 1985). The empirical basis for scrutinizing the hypotheses

Sulfate Cooling Effect on Climate Through In-Cloud Oxidation of Anthropogenic SO2.

Abstract: Anthropogenic SO(2) emissions may exert a significant cooling effect on climate in the Northern Hemisphere through backscattering of solar radiation by sulfate particles. Earlier estimates of the sulfate climate forcing were based on a limited number of sulfate-scattering correlation measurements from which a high sulfate-scattering efficiency was derived. Model results suggest that cloud processing of air is the underlying mechanism. Aqueous phase oxidation of SO(2) into sulfate and the subsequent release of the dry aerosol by cloud evaporation render sulfate a much more efficient scatterer than through gas-phase SO(2) oxidation.

Bacterial toxin-induced cytokine production studied at the single-cell level.

Abstract: Bacterial toxins constitute one group of many virulence factors by which bacteria cause disease. Advances in our knowledge of bacterial toxins concern their interaction with the host's immune system, in particular by inducing release of cytokines. The latter effect has been studied both in vitro and in vivo particularly in regard to the actions of endotoxin, the lipopolysaccharide (LPS) component of Gramnegative bacteria. It is capable of inducing fever, shock and the acute-phase response in human patients {Peavy et al. 1970, Berry 1977). Many of these effects are caused by the capacity of endotoxin to induce cytokines with pyrogenic activity {Dinarello 1984, Lasfargues et al. 1987, Beutler & Cerami 1989, Cannon et al. 1990). Structurally, LPS consists of three regions: Hpid A, core oligosaccharide and 0-polysaccharide (Luderitz et al. 1984, Warner et al. 1985). LPS is a potent activator of macrophages in their production of monokines (Hamilton & Adams 1987, Prpic et al. 1987). Though there are many candidates for LPS ligands on the cellular surface, the mechanism of endotoxicity remains unclear One receptor for LPS complexted with its binding protein is the CD14 structure (Wright et al. 1990). Exotoxins produced by Gram-positive bacteria have long been recognized as human pathogens, but plausible mechanisms of toxicity have only recently been revealed. The toxins comprise a large group of proteins produced by several different types of bacteria including staphylococci, streptococci and mycoplasma and are involved in different clinical manifestations. A group of toxins produced by various strains of Staphylococcus aureus, staphyloccocal enterotoxin A, B, C]_3, D, E (SEA-E), exfoliating toxins A + B and TSST-1, caused food poisoning,