Showing papers by "University of Vienna published in 1990"

Supercompilers for parallel and vector computers

Abstract: Table of Contents * Supercomputer and Supercompilers * Supercomputer Architectures * Scalar Analysis * Data Dependence * Standard Transformations * Vectorization * Parallelization * Supercompilers and their Environments * Appendices

Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light.

Abstract: Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte-derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF-alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation.

Influence of the modulation method on the conduction and switching losses of a PWM converter system

Abstract: The authors explore the dependency of the conduction losses of a bridge leg of a pulsewidth modulation (PWM) power converter system with a high pulse rate on the shape of the phase modulation functions. This is done for modulation methods that are optimized with respect to minimum harmonic current RMS values. The results are compared to the results gained for simple sinusoidal modulation. Besides conduction losses, the switching losses of the electric valves are calculated. The main topic is the determination of those power loss components of a PWM converter system that can be (besides the harmonic losses) influenced by the modulation method selected. As the calculations show, these modulation methods allow a significant increase of the effective switching frequency. The optimal modulation as calculated leads to a reduction of the harmonic power loss in the upper modulation region. Furthermore, due to the frequency modulation the spectrum is spread out to a wider frequency band as compared to operation with constant pulse frequency. >

Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats.

Abstract: Apoptosis is a form of cell death involved in the regulation of cell number in various organs and tumors. Quantitative determination of cell loss through apoptosis in histological sections requires, in addition to counts of apoptotic cells, information on the duration of the histologically visible stages of apoptosis. Here we describe a method to determine the duration of apoptosis in (i) normal and (ii) putative preneoplastic tissue of the liver. (i) Female rats were treated with high doses of the hepatomitogen cyproterone acetate (CPA) to induce liver hyperplasia. After stopping CPA treatment, the hyperplasia partially regressed and excessive hepatocytes were eliminated by apoptosis. CPA was given to block the initiation of apoptosis, and thereafter the time course of elimination of apoptotic cell residues (apoptotic bodies, ABs) from the liver was studied. The mean duration of the histological stages of apoptosis was found to be approximately 3 h. (ii) Phenotypically altered cell foci in rat liver were produced by a single dose of N-nitrosomorpholine and subsequent promotion for 39 weeks with phenobarbital (PB). PB was withdrawn to stop foci growth and to stimulate apoptosis. Then rats were retreated with PB to block initiation of apoptosis in foci. The results indicate that the majority of apoptotic bodies in foci disappeared within 4 h after PB, suggesting that the stages of apoptosis are as short in foci as in normal liver. Finally a simple formula is given to calculate the cell loss rate by apoptosis. The method presented may provide data for quantitative cancer risk assessment from mathematical models of carcinogenesis.

Brain iron and ferritin in Parkinson's and Alzheimer's diseases.

Abstract: Semiquantitative histological evaluation of brain iron and ferritin in Parkinson's (PD) and Alzheimer's disease (DAT) have been performed in paraffin sections of brain regions which included frontal cortex, hippocampus, basal ganglia and brain stem. The results indicate a significant selective increase of Fe3+ and ferritin in substantia nigra zona compacta but not in zona reticulata of Parkinsonian brains, confirming the biochemical estimation of iron. No such changes were observed in the same regions of DAT brains. The increase of iron is evident in astrocytes, macrophages, reactive microglia and non-pigmented neurons, and in damaged areas devoid of pigmented neurons. In substantia nigra of PD and PD/DAT, strong ferritin reactivity was also associated with proliferated microglia. A faint iron staining was seen occasionally in peripheral halo of Lewy bodies. By contrast, in DAT and PD/DAT, strong ferritin immunoreactivity was observed in and around senile plaques and neurofibrillary tangles. The interrelationship between selective increase of iron and ferritin in PD requires further investigation, because both changes could participate in the induction of oxidative stress and neuronal death, due to their ability to promote formation of oxygen radicals.

Erythropoietin treatment of anemia associated with multiple myeloma.

Abstract: Anemia is a common complication of multiple myeloma. It resolves early in the disease if chemotherapy induces a complete remission, but persists if the disease progresses, causing disabling symptoms and often requiring blood transfusions. We treated 13 patients with myeloma-associated anemia by administering recombinant human erythropoietin three times a week for six months. Eleven patients (85 percent) had steady increases in hemoglobin levels and eventual correction of the anemia. Their symptoms of anemia subsided, and they reported a heightened sense of well-being. No patient had any adverse side effects, particularly episodes of hypertension. Monitoring of the serum M component showed a predominantly stable tumor load without apparent interaction between the underlying disease and the response to erythropoietin therapy. The number of erythroid burst-forming units in the bone marrow and peripheral blood and the level of erythropoiesis in bone marrow smears increased significantly during therapy. Pretreatment serum levels of erythropoietin were higher in the patients who did not respond and in those who required more than two months of treatment before they responded. Serum iron, ferritin, and transferrin concentrations reflected responses to treatment. We conclude that recombinant human erythropoietin is a promising therapeutic tool for treating myeloma-associated anemia.

Test of gamma-ray strength functions in nuclear reaction model calculations

Abstract: The impact of models for E1 and M1 gamma-ray strength functions on the results of nuclear model calculations of total average radiation widths, radiative capture cross sections, and gamma-ray spectra has been studied. We considered strength functions that reproduce photoabsorption and/or average resonance data but significantly differ from each other at low gamma-ray energies. As the calculated quantities critically depend on the strength functions in this energy region, model calculations can be used to test the low-energy behavior of strength functions. By analyzing the $^{197}\mathrm{Au}$, $^{143}\mathrm{Nd}$, $^{105}\mathrm{Pd}$, and $^{93}\mathrm{Nd}$ neutron capture reactions we found strong evidence for a model of the E1 strength function, which is characterized by the following properties: (i) an energy dependent spreading width of the underlying Lorentzian for the photoabsorption cross section and (ii) a nonzero, temperature dependent, limit as the transition energy tends to zero. This model is founded in theoretical work by Zaretskij, Sirotkin, and Kadmenskij and represents a partial breakdown of Brink's hypothesis.

Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy.

Abstract: The beneficial effects of physiologic dual-chamber (DDD) pacing in the treatment of end-stage idiopathic dilated cardiomyopathy were evaluated in 16 patients in whom conventional drug therapy had failed. Candidates for cardiac transplantation as well as patients not accepted for transplantation participated. During DDD pacing at an atrioventricular delay of 100 ms, left ventricular ejection fraction increased from 16.0 ± 8.4 to 25.6 ± 8.6% (p

Loss of neurons in the frontal cortex in AIDS brains.

Abstract: Neurons of Area 11 in the fronto-orbital cortex of 18 unselected AIDS brains are analyzed by means of stereology. Neurological abnormalities including dementing symptoms were described in eight patients. Neuropathology diagnosed human immunodeficiency virus (HIV)-specific changes in four, and diffuse poliodystrophy in eight brains. The majority (71.4%) of these brains was immunoreactive for HIV antigens when tested by immunocytochemistry. A significant loss of neurons is found as compared to normal controls. Neuronal density in AIDS brains is reduced by 18%, and the perikaryon volume fractions is reduced by 31%. Although only speculation on pathogenesis of this neuronal loss is possible at present, it may represent a part of the pathomorphological substrate of AIDS-related dementia. Moreover, it confirms by quantitative means damage to the cerebral cortex in AIDS which has been described only qualitatively as diffuse poliodystrophy.

The biochemistry of cell death by apoptosis.

Abstract: In higher organisms homeostatic control of cell number is thought to be the result of the dynamic balance between cell proliferation and cell death. While the process of proliferation has received a great deal of attention over the past 20 years, much less emphasis has been placed on the biochemical events that occur before and during cell death. In higher organisms cell death can be classified into one of three different categories: necrosis, which occurs as a result of massive tissue damage; terminal differentiation of specialized tissues such as the skin, intestine, and red blood cells; and apoptosis, which is a process of active cellular selfdestruction that requires the expression of a number of genes. The latter process was originally recognized and described by Wyllie who coined the term "apoptosis" to describe the sequence of events that lead to cell death in a variety of different systems (Kerr et al., Br. J . Cancer, 26, 239-257, 1972), specifically to distinguish this form of cell death from necrosis. Apoptosis is induced in the terminally differentiated cells of hormone-dependent tissues, such as the prostate and mammary gland in the absence of the appropriate trophic hormones, resulting in the regression of the tissue. In other tissues apoptosis can be induced by positive modulators, such as Mullerian duct inhibiting substance (MIS) in the Mullerian ducts, tumor necrosis factor (TNF) in adipocytes, and a variety of cell lines and glucocorticoids in lymphocytes and thymocytes. It can also be induced in cells that retain their proliferative potential (such as hepatocytes) to maintain homeostasis of cell numbers in organs such as the liver. In both proliferating and nonproliferating systems, apoptosis requires specific gene transcription and protein synthesis in the affected cell prior to death, although the biochemical sequence of events may vary slightly from one tissue to another.

The evolution of stochastic strategies in the Prisoner's Dilemma

Abstract: The evolution of reactive strategies for repeated 2×2-games occurring in biology is investigated by means of an adaptive dynamics

Interstitial lung disease in progressive systemic sclerosis: High-resolution CT versus radiography

Abstract: High-resolution computed tomographic (HRCT) scans and chest radiographs were obtained in 23 patients with progressive systemic sclerosis (PSS) to assess the diagnostic merits of HRCT compared with chest radiography in detecting interstitial lung involvement in these patients. HRCT scans showed interstitial disease in 21 patients (91%). The most frequent finding was the so-called subpleural lines, which were demonstrated in 17 patients (74%). Honeycombing was seen in seven patients (30%), while parenchymal bands were seen in six patients (26%). Chest radiographs, on the other hand, showed definite interstitial opacification patterns in only nine patients (39%); six patients (26%) had equivocal reticular areas of attenuation, while eight patients (35%) had normal chest radiographs. Thus, HRCT is much more sensitive than chest radiography when assessing minimal interstitial lung involvement in patients with PSS.

The initiation of meiotic chromosome pairing: the cytological view.

Abstract: Opposing views are held with respect to the time when and the mechanisms whereby homologous chromosomes find each other for meiotic synapsis. On the one hand, some evidence has been presented for somatic homologous associations or some other kind of relationship between chromosomes in somatic cells as a preliminary to meiotic pairing. On the other hand, it is argued by many that homologous contacts are first established at meiotic prophase prior to, or in the course of, synaptonemal complex formation. The present paper reviews the controversial cytological evidence, hypotheses, and ideas on how the first contact between homologous chromosomes comes about.

DNA Synthesis, Apoptosis, and Phenotypic Expression as Determinants of Growth of Altered Foci in Rat Liver during Phenobarbital Promotion

Abstract: Carcinogenesis was initiated in female rat liver by a single dose of N-nitrosomorpholine; subsequently phenobarbital (PB) was administered via the diet at a daily dose of 50 mg/kg body weight for up to 49 weeks. Subgroups of rats were left untreated after 10 or 28 weeks on PB. PB produced the following changes: (a) accelerated appearance of neoplastic nodules and hepatocellular carcinoma (from 28 weeks onwards); (b) phenotypic changes in altered foci such as a shift from clear to eosinophilic appearance, enhanced expression of gamma-glutamyltranspeptidase and other markers, and more distinct borders from surrounding liver; (c) an increase in foci number; and (d) accelerated foci enlargement. The increase in foci number was found to be due to increased phenotypic expression of foci. DNA synthesis was measured by [3H]thymidine labeling at multiple time points. The rate of DNA synthesis was always approximately 10-fold higher in foci than in surrounding liver tissue. Despite this, after N-nitrosomorpholine alone foci grew little before 18-24 weeks. Continuous treatment with PB did not produce a persistent further increase of DNA synthesis in foci, although it accelerated foci growth. Furthermore, at early stages small and larger foci showed similar DNA synthesis activity. These findings indicate that the rate of cell replication as measured by DNA synthesis is not the only determinant of the growth rate of foci. Further studies showed that foci with indistinct borders (reflecting weak expression of the altered phenotype) grew much less than foci with distinct borders; this was at least in part due to an increased rate of cell death by apoptosis found in foci with indistinct borders. In conclusion, besides cell replication, apoptosis and the extent of phenotypic expression (remodeling) determine the growth rate of foci. Foci with weak phenotypic expression predominated after N-nitrosomorpholine alone; in these, a high incidence of apoptosis counterbalanced cell replication. In contrast, during PB treatment foci with strong phenotypic expression predominated; in these, apoptotic activity was lower and the high replicative activity could manifest itself. Finally, all effects of PB on foci were largely although not completely reversible upon cessation of treatment; as a result phenotypic expression declined, and "remodeling" foci with high apoptotic activity predominated again.

Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system.

Abstract: Intrathecal injection of interferon-gamma induced a significant increase of the number of class I and class II major histocompatibility complex (MHC)-expressing cells within the rat nervous system. A progressive appearance of MHC-antigen-positive cells was found by light- and electron microscopic immune histology. The first level comprised cells that constitutively expressed MHC antigens in normal animals (meningeal and endoneural monocytes, some perivascular dendritic cells, and few parenchymal microglia cells, especially in the lumbar spinal cord and in the cerebellar white matter). The second level represented cells readily expressing MHC antigens after stimulation with interferon-gamma (all perivascular, dendritic cells, and microglia). The third level included ependymal cells, astrocytes, and Schwann cells. After stimulation with interferon-gamma, these neuroectodermal cells expressed MHC antigens inconsistently, usually in a low density and patchy distribution. The progressive appearance of MHC antigens may be reflected by the variances of lesional patterns found in experimental allergic encephalomyelitis of different histologic severity.

Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia.

Abstract: A strong immunoreactivity for ferritin was observed in the neuritic (senile) plaques in Alzheimer's disease hippocampus. The ferritin accumulation was almost exclusively associated with the microglia, which appeared to have proliferated greatly. These cells were also positive for HLA-DR, a putative marker for reactive microglia. In contrast, in the diffuse plaques, which were without neuritic pathology, the ferritin-stained microglia appeared to be normal. Microglia were seen frequently in contact with neurons undergoing neurofibrillary changes but only the tangles in the extracellular space were ferritin positive. No ferritin was detected, by Western blots, in paired helical filaments isolated from Alzheimer's disease brain, suggesting that ferritin was most likely weakly associated with and was not a constituent of these fibrils. No correlation between increased ferritin/microglia activity and blood-brain barrier leakage was detected. Ferritin, an iron-storage protein, might have a role in the formation of amyloid through the action of free radicals generated during the release of iron from the ferritin molecule. Alternatively, the ferritin/microglia system might be secondarily involved in the removal and processing of the amyloid.

Isolation of Borrelia burgdorferi from the myocardium of a patient with longstanding cardiomyopathy.

Abstract: LYME borreliosis (or Lyme disease) is a systemic disorder caused by the spirochete Borrelia burgdorferi, a newly discovered species of borrelia.1 , 2 The disease usually begins with a characteristic skin lesion; neurologic, cardiac, and joint involvement may develop weeks to months later. Some manifestations may last for years or even decades.3 Lyme borreliosis is transmitted by arthropods, especially by ticks of the genus ixodes and by some tabanid species. The area in which it is endemic includes most of the United States,4 all of Europe,5 the European and Asian parts of Russia,6 China,7 and Japan.8 Cardiac abnormalities induced by Lyme . . .

Ki-1-positive large cell lymphoma. A clinicopathologic study of 41 cases.

Abstract: We report the clinicopathologic findings of 41 patients with Ki-1 (CD30)-positive large cell lymphoma. The median age was 50 years; 13 patients were under 40 years of age. Ten patients presented with extranodal disease. Fifty-five percent of the patients presented with stage I or II disease, and bone marrow involvement was histologically documented in 30% and occurred exclusively in patients over 40 years of age. Two cytomorphologically distinct groups of Ki-1--positive large cell lymphomas could be separated. Group A lymphomas consisted of pleomorphic large cells, sometimes with wreathlike and embryo-like nuclei, whereas group B lymphomas displayed a rather monomorphic appearance. Clinically the two groups of lymphomas differed with respect to stage of disease, frequency of bone marrow involvement, and median survival. On paraffin sections, the Ki-1--related antibody Ber-H2 provided excellent staining results in all cases. Immunologic phenotyping disclosed a T cell type in the majority of cases, revealed marked loss of differentiation antigens, and frequent expression of HLA-DR and IL-2 receptor. The overall median survival was 13 months. Age below 40 years, limited stage of disease (I and II), and, although not statistically significant, lymphoma morphology were associated with longer survival. We conclude, that Ki-1--positive large cell lymphomas represent a morphologically and immunologically heterogeneous category of hematolymphoid neoplasms derived from dedifferentiated and activated lymphoid cells with marked age-dependent prognosis.

Molecular characterization and functional analysis of the leukocyte surface protein CD31.

Abstract: The CD31 Ag is a surface glycoprotein of 130 kDa with a broad cellular distribution. We show that among peripheral human blood cells, it is expressed on monocytes, granulocytes, platelets, and a subpopulation of lymphocytes. Activation of granulocytes leads to down-regulation of CD31 molecule expression. Sequence analysis and quantitative measurements of the relatedness of the CD31 molecule to other known proteins demonstrate that it consists of six Ig constant domains and that each domain bears substantial similarity to Fc gamma R domains. We find, however, that the CD31 molecule does not bind Ig Fc domains. On human monocytes we demonstrate that CD31 mAb recognizing certain epitopes of the CD31 molecule induce the generation of reactive oxygen metabolites. No such effect was seen with human granulocytes. By using two CD31 mAb, termed 1B5 and 7E4, we analyzed the requirements for activation of the monocyte respiratory burst via CD31 Ag in more detail. We show that signal transduction occurs via formation of a CD31 Ag-mAb-Fc gamma R complex involving either Fc gamma RI (CD64) or Fc gamma RII (CDw32) molecules.

Plasma fibrinogen--an independent cardiovascular risk factor.

Abstract: Apart from being an acute phase reactant, fibrinogen appears to play an important although not widely recognized role in athero-/thrombogenesis Arteriosclerotic diseases are associated with elevated levels of plasma fibrinogen Strategies that lower the cardiovascular risk also lower fibrinogen levels Virtually all accepted risk factors are associated with hyperfibrinogenaemia, while low risk populations usually have low fibrinogen levels Epidemiological studies show that fibrinogen is a predictor of arteriosclerotic diseases Its predictive power seems to be as high as or higher than accepted risk factors These findings and other circumstantial, as well as experimental, evidence suggest that fibrinogen is a powerful, independent cardiovascular risk factor

Cortical endoplasmic reticulum in plants

Abstract: Structural observations provide persuasive evidence for the existence of a cortical network of endoplasmic reticulum (ER) in a large number of plant and animal cells. The network in plants generally possesses a polygonal pattern in which smooth, tubular elements are joined by intervening lamellar segments. The individual elements of ER are often positioned extremely close to the plasma membrane (PM), and may form appositional contacts, but fusion does not occur. The network arises at cytokinesis and establishes continuity between the cortical ER of daughter cells in the form of tightly furled membrane tubules that traverse the plasmodesmata. The specific function of the cortical ER complex is unknown but different possibilities seem attractive. It may serve key roles in anchoring the cytoskeleton and in facilitating secretion. The cortical ER might also participate in the communication of signals between the exterior of the cell and cytoplasm. As a consequence of its ability to release and/or sequester Ca, the ER could control the cytoplasmic activity of this ion and thus a host of physiologically and developmentally important reactions.

Immunocytochemical Localization of Estrogen and Progesterone Receptor and Prognosis in Human Primary Breast Cancer

Abstract: An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA-positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance.

A review of stroke rehabilitation and physiotherapy.

Abstract: Most of the members of the therapeutic team in stroke rehabilitation take the effectiveness of physical treatments after stroke for granted. Yet, published data show that the evidence is not so straightforward or easy to evaluate. The majority of the hard evidence, however, does imply that stroke patients benefit from rehabilitation with physiotherapy. This benefit may be statistically small, but for a given individual, it could mean the difference between living at home or in an institution. Few studies address the question of the optimal physiotherapy in stroke rehabilitation. The evidence available today suggests that it does not matter which form of treatment is chosen and that any of the available approaches will improve the patient's functional status. In other words, if an optimal treatment exists, we have, so far, failed to identify it. Until further evidence emerges, we should therefore select therapies that are most cost-effective and that can be given to the largest number of patients. Well-planned clinical trials aimed at finding the best approach and discriminating potential responders from nonresponders are urgently needed.

Sleep laboratory investigations on hypnotic properties of melatonin.

Abstract: Melatonin (MLT), a pineal hormone, has some sedative and hypnotic properties. To explore this effect further 20 young, healthy volunteers exposed to artificial insomnia participated in a double-blind, placebo controlled, parallel group design study. They slept in a sleep laboratory for several consecutive nights and were polygraphically monitored and subjected to a battery of psychometric tests and standardized self-report questionnaires each morning. One night all subjects received only placebo (21:00 hours) and on a second night half of them were subjected to placebo and half to MLT. On the later night blood MLT levels were measured. Polygraphic recordings revealed that MLT at bedtime decreased the time the subjects were awake before sleep onset (P<0.025), sleep latency (P<0.05), and the number of awakenings during the total sleep period (P<0.025), and increased sleep efficiency (P<0.05). In addition, it decreased sleep stage 1 (P<0.05) and increased sleep stage 2 (P<0.025). On the morning following the treatment most objective and subjective measures for awakening quality showed a trend towards improvement after MLT. One hour after its oral administration, serum MLT rose to a high pharmacological level (25817 pg/ml; median), but individual peak serum MLT levels varied by a factor of 300. From the data collected it is concluded that a single pharmacological dose of MLT exerts a hypnotic effect by accelerating sleep initiation, improving sleep maintenance and altering sleep architecture in a similar manner to anxiolytic sedatives; objective and subjective measures for awakening qualitiy indicate good tolerance of one dose of MLT without hangover problems on the following morning. Oral administration of crystalline MLT, however, results in high interindividual differences in absorption.