Showing papers by "Aarhus University published in 1990"

Unbiased stereological estimation of the number of neurons in the human hippocampus

Abstract: The total numbers of neurons in five subdivisions of human hippocampi were estimated using unbiased stereological principles and systematic sampling techniques. The method addresses the problems associated with the results and conclusions of previous quantitative studies, virtually all of which have been based on biased estimates of neuron densities. For each subdivision, the total number of neurons was calculated as the product of the estimate of the volume of the neuron-containing layers and the estimate of the numerical density of neurons in the layers. Each hippocampus was cut into 3-mm-thick slabs, transverse to the rostrocaudal axis. One 70-micron-thick section from each slab was used in the analysis. The volumes of the layers containing neurons in five major subdivisions of the hippocampus (granule cell layer, hilus, CA3-2, CA1, and subiculum) were estimated with point-counting techniques after delineation of the layers on each section. The numerical densities of neurons in each subdivision were estimated on the same sections with optical disectors. The sampling used in both estimates was performed systematically in all three dimensions. In an example of five hippocampi, the mean numbers of neurons (CV = SD/mean) in the different subdivisions were as follows: granule cells 15 X 10(6) (0.28), hilus 2.0 X 10(6) (0.16), CA3-2 2.7 X 10(6) (0.22), CA1 16 X 10(6) (0.32), subiculum 4.5 X 10(6) (0.19). The stereological measurements contributed approximately 25% of the observed variance. Among the five subjects there was a significant inverse relationship between age (which ranged from 47 to 85 years) and the total number of neurons in CA1 (which ranged from 24 to 11 X 10(6)). An optimized sampling scheme for studies of the number of neurons in the human hippocampus has been designed on the basis of an analysis of variance of the estimates at different levels of the sampling scheme. Counting neurons in the five subdivisions of the human hippocampus with the optimized sampling scheme takes less than 4 hours.

Structure and function of small arteries

Abstract: The small arteries (prearteriolar vessels with lumen diameter less than approximately 500 microns) contribute importantly to and participate actively in the regulation of the peripheral resistance. New techniques, building on the classic histological and hemodynamic techniques, have enabled detailed in vitro investigation of small arteries. At present, research in small arteries is in its infancy, and our understanding of the heterogeneity of small arteries within vascular beds, between vascular beds, and between species is extremely limited. This review attempts to describe the current status of the field. New techniques, based primarily on a wire myograph (where the vessels are mounted as ring preparations) and a pressure myograph (where vessels are cannulated and pressure-lumen relations are determined), have allowed in vitro investigations of small arteries. The more physiological arrangement of the pressure myograph allows, for example, investigation of the vasoconstrictor response to raised intravascular pressure (the Bayliss response), whereas the less-sophisticated wire myograph is similar to use and may be more useful in certain situations where particular mechanisms are being investigated. Both techniques allow simultaneous measurements of vessel tone and a variety of parameters (e.g., membrane potential and intracellular ion activities) and thus allow precise determination of the relation between small artery structure and function. The vessels appear to remain fully viable with regard to the contractility of their smooth muscle cells as well as to the function of their perivascular nerves and their endothelium. The evidence suggests that the monovalent transport mechanisms in the plasma membrane, in particular potassium channels, play an important role in the determination of the membrane potential in small arteries, although the relation is more complex than indicated by the Goldman equation. Confirmation of these findings requires, however, simultaneous determinations of ion transport and vascular tone under conditions where vessels are subjected to mechanical loading. The membrane potential, through its effect on potential-dependent calcium channels, plays an important role in the determination of vascular tone. With regard to calcium homeostasis, current knowledge is hampered by the lack of direct measurements of the relation between cytoplasmic calcium and vascular tone. The evidence, however, suggests that besides potential-dependent calcium channels, receptor-operated calcium channels are present in the plasma membrane, although this still requires confirmation. The role of the sarcoplasmic reticulum is not clarified.(ABSTRACT TRUNCATED AT 400 WORDS)

Microalbuminuria as predictor of increased mortality in elderly people.

Abstract: OBJECTIVE--Correlation of the urinary albumin excretion rate and the risk of death among elderly subjects. DESIGN--216 Subjects aged 60-74 whose urinary albumin excretion rate had been determined were followed up 62-83 months later. SETTING--Municipality of Fredericia, Denmark. SUBJECTS--223 People who had been selected as control subjects for diabetics found during a systematic screening for diabetes of all people aged 60-74 living in the municipality of Fredericia, Denmark. Of these subjects, 216 had an extensive clinical and biochemical examination within a few weeks of selection. MAIN OUTCOME MEASURE--Death. RESULTS--The median urinary albumin excretion rate was 7.52 micrograms/min. Eight of those with a rate below the median died compared with 23 with a rate equal to or greater than the median (p = 0.0078). The median albumin excretion rate in the 31 who died was 15.00 micrograms/min. Cardiovascular disease was the most common cause of death in both groups. A multivariate regression analysis of survival data was performed using the proportional hazards model. Besides albumin excretion rate, male sex, serum creatinine concentration, and hypertension were found to be of prognostic value. CONCLUSIONS--The association between the albumin excretion rate and mortality that has been described in recent years in patients with diabetes mellitus may be present in elderly people in general, even when other known risk factors are taken into account.

Excitation energies from the coupled cluster singles and doubles linear response function (CCSDLR). Applications to Be, CH+, CO, and H2O

Abstract: The linear response function for a coupled cluster singles and doubles wave function is used to calculate vertical electronic energies for the closed shell system Be, CH+, CO, and H2O. It is shown that excitations of single electron replacement character can be described accurately in such an approach. Improved convergence is obtained using a preconditioned form of the coupled cluster linear response matrix.

Structure and ligand binding properties of human serum albumin

Abstract: UNLABELLED 1 INTRODUCTION Serum albumin possesses a unique capability to bind, covalently or reversibly, a great number of various endogenous and exogenous compounds Several different transport proteins exist in blood plasma but albumin only is able to bind a wide diversity of ligands reversibly with high affinity The subject of the present thesis is these binding properties In 1981 the author proposed in a review a model for binding of ligands to serum albumin In the model, binding of ligands to at least 6 distinct regions was considered The purpose of the experimental work described here was to test the validity of the model This was done by performing a large number of competition experiments From these new data a revised model for ligand binding is presented 2 STRUCTURE AND CONFORMATIONAL CHANGES OF SERUM ALBUMIN Human serum albumin consists of 585 amino acids forming a single polypeptide of known sequence A number of well characterized genetic variants have been reported The physico-chemical characteristics of the protein are well-established By contrast, the complete secondary and tertiary structures are not known; information about major structural features only has been obtained The albumin molecule seems to have an overall ellipsoidal shape (about 140 x 40 A) and to be composed of domains On the basis of the amino acid sequence, Brown (1977a) proposed a 3-domain model for the protein Each domain is believed to consist of 6 helices forming a hydrophobic channel with basic and hydrophobic amino acid residues placed at the ends Experimental data, however, indicate that the domains cannot be identical Long-chain fatty acid ions are proposed to bind with high affinity within the channels The ability to fluctuate between isomeric forms in aqueous solution could assist in adapting the albumin molecule to bind ligands with a diverse nature with high affinity This possibility is discussed on the basis of several physico-chemical techniques including hydrogen-deuterium exchanges Also the importance of the N-B transition for ligand binding is considered 3 PRELIMINARY BINDING MODEL OF SERUM ALBUMIN Single binding of ligands to serum albumin is usually described as high-affinity binding to one or two sites and weaker binding to a larger number of sites In this chapter, the original binding model for high-affinity binding is elaborated Region 1 seems to be specific for binding of one, or possibly two, ions of long-chain fatty acids Region 2 is somewhat less specific and includes binding of octanoate, tryptophan, chlorazepate, thyroxine, p-iodobenzoate and possibly also chloride Region 3 accommodates bilirubin, Phenol Red, Bromophenol Blue and iopanoate Region 4 is a special site for strong binding of metal ions such as Cu++ and Ni++ Evidence is presented for placing the primary haemin site in a separate region (no 5) The existence of additional binding regions, well-suited for high-affinity binding of drugs, is discussed

Transition-metal oxides in the self-interaction-corrected density-functional formalism.

Abstract: We present a method for performing fully self-consistent, ab initio, self-interaction\char21{}corrected, local-spin-density calculations. We demonstrate that the formalism correctly predicts that MnO, FeO, CoO, NiO, and CuO are antiferromagnetic insulators, and that VO is a nonmagnetic metal. The band gaps and moments are drastically improved compared with the local-spin-density approximation.

A Thiosulfate Shunt in the Sulfur Cycle of Marine Sediments

Abstract: The oxidation of sulfide, generated by bacterial sulfate reduction, is a key process in the biogeochemistry of marine sediments, yet the pathways and oxidants are poorly known. By the use of 35 S-tracer studies of the S cycle in marine and freshwater sediments, a novel shunt function of thiosulfate (S 2 O 3 2- ) was identified. The S 2 O 3 2- constituted 68 to 78 percent of the immediate HS - -oxidation products and was concurrently (i) reduced back to HS - , (ii) oxidized to SO 4 2- , and (iii) disproportionated to HS - + SO 4 2- . The small thiosulfate pool is thus involved in a dynamic HS - - S 2 O 3 2- cycle in anoxic sediments. The disproportionation of thiosulfate may help account for the large difference in isotopic composition ( 34 S/ 32 S) of sulfate and sulfides in sediments and sedimentary rocks.

The computer reaches out: the historical continuity of interface design

Abstract: This paper examines the evolution of the focus of user interface research and development from the first production of commercial computer systems in the 1950s through the present. The term “user interface” was not needed in the beginning, when most users were engineers and programmers; it may again become inappropriate when more applications are written for groups than for individuals. But there is a continuity to the outward movement of the computer's interface to its external environment, from hardware to software to increasingly higher-level cognitive capabilities and finally to social processes. As the focus shifts, the approaches to design and the skills required of practitioners changes. In this paper five foci or levels of development are identified. Most development today is positioned in the third level and considerable research is directed at the fourth. Some attention is now being given to the fifth: repositioning the interface in the work group or organization itself. Work at the different levels is not entirely independent, so establishing a comprehensive framework may enable us to position existing research and development efforts and plan future work more effectively.

Electronic structure of beta -FeSi2.

Abstract: Ab initio calculations of the electronic structure of \ensuremath{\beta}-${\mathrm{FeSi}}_{2}$ show that this material, in agreement with experiment, is a semiconductor. The calculated hole and electron masses of the band-edge states are \ensuremath{\simeq}0.8${\mathit{m}}_{0}$. A particularly strong coupling of the band-edge states to the lattice is suggested. This may cause the mobilities, even in pure \ensuremath{\beta}-${\mathrm{FeSi}}_{2}$ samples, to be very low at ambient temperature.

Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q.

Abstract: The serum lectin, mannan binding protein (MBP), was isolated in a yield of 40 micrograms/liter from pooled normal human serum by affinity chromatography on mannan-Sepharose, followed by gel-filtration and ion-exchange chromatography and finally by passage down an anti-IgM Sepharose column. A rabbit antiserum was prepared against the purified MBP and an enzyme-linked immunoassay developed that used both the specificity of the polyclonal antibody and the Ca+(+)-dependent carbohydrate binding property of MBP. Assay of the sera from 103 blood-donors showed a wide range of MBP levels, ranging from 0 to 870 micrograms/liter. MBP, after interaction with zymosan, caused efficient activation of a C1r2 125I-C1s2 complex that was prepared by incubation of 125I-C1s2 with serum, from a patient with a complete genetic deficiency of C1q, followed by gel-filtration on Sepharose 6B. The purified MBP is composed of a mixture of trimers, tetramers, pentamers, and hexamers of an approximate 90-kDa structural unit as judged by chromatography, SDS-PAGE and electron microscopy studies. Only the molecules in the pentamer/hexamer fraction, which have a similar overall structure to that of C1q, appeared to cause efficient, zymosan-dependent, activation of C1s within the C1r2C1s2 complex. The pentamer/hexamer form of MBP may therefore play an important role in antibody-independent activation of the C system during the early stages of certain infections.

Microstructure of diffusive boundary layers and the oxygen uptake of the sea floor

Abstract: THE diffusive boundary layer (DBL) is a thin (≲1 mm) film of water that covers the sea floor, and through which molecular diffusion is the dominant transport mechanism for dissolved material. The diffusive fluxes are a measure of the rate of remineralization of organic matter in the sea bed, and of the dissolution or precipitation of minerals such as carbonates or metal oxides. Here we report detailed in situ analyses of chemical microgradients within the DBL, using a microelectrode profiling instrument with a spatial resolution of 25–50 µm. Over a Danish coastal sediment at 15 m water depth, the DBL was 0.5-0.7 mm thick and showed both stochastic fluctuations of oxygen distribution owing to boundary-layer turbulence and harmonic oscillations resulting from surface waves. A three-dimensional mapping of the DBL and the corresponding sediment surface showed that the DBL was spatially well defined and followed surface contours, but smoothed out sediment microtopographic features smaller than 100 µm. The three-dimensional oxygen diffusive flux across the sediment/water interface was about 2.5 times higher than that calculated from a simple one-dimensional diffusion model. These results indicate that benthic oxygen consumption and other fluxes can be studied by direct measurement of DBL microgradients at the undisturbed sea floor.

Reactive, generative, and stratified models of probabilistic processes

Abstract: Reactive, generative, and stratified models are considered within the framework of PCCS, a specification language for probabilistic processes. A structural operational semantics of PCCS, given as a set of inference rules for each of the models, a notion of bisimulation semantics, and some conference proofs are presented. >

The total number of neurons in the human neocortex unbiasedly estimated using optical disectors.

Abstract: An efficient method is presented for obtaining, in under 4 h, an unbiased estimate of the total number of neurons in the human neocortex, with a coefficient of error on the estimate of approximately 5%. The novel sampling scheme used in this study is unbiased and was designed so that only a small amount of neocortical grey matter had to be removed. Hence, the majority of the cerebral grey matter and all the internal grey matter was left intact for further resampling and analysis. Each cerebral hemisphere was subdivided into the four major neocortical regions, sliced coronally at 7-mm intervals and the volume of the neocortex determined using Cavalieri's principle. Uniform sampling of neocortex was performed in the hemisphere followed by regional subsampling with a varying sampling fraction being taken from each region. Neuronal density estimates were made in thick plastic sections using optical disectors. Shrinkage estimates were made in parallel with the number estimates and found to be negligible. The total number of neocortical neurons in the right hemisphere of five normal 80-year-old men was found to be 13.7 x 10(9) with an inter-individual coefficient of variation of 12%.

Surface reconstruction of Cu(110) induced by oxygen chemisorption.

Abstract: The dynamics of the reconstruction of the Cu(110) surface induced by oxygen chemisorption has been studied by scanning tunneling microscopy. The nucleation and growth of the CU(110)-(2\ifmmode\times\else\texttimes\fi{}1)O reconstructed phase shows up as ``added rows'' of Cu-O atoms which grow preferentially in the [001] direction. The Cu atoms are supplied by diffusion from terrace edges.

Leukemia Following Chemotherapy for Ovarian Cancer

Abstract: An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known.

Zinc-containing neurons in hippocampus and related CNS structures.

Abstract: Recent advances in metallohistochemistry have substantiated the identification of a distinct class of neurons in the brain, the zinc-containing neurons. These neurons sequester peculiar amounts of zinc in their presynaptic boutons and show both high-affinity uptake and calcium- and impulse-dependent release of the cation. It is thought that the zinc may act to stabilize the storage of certain macromolecules in presynaptic vesicles, but there is also mounting evidence that zinc released from vesicles can produce a broad spectrum of neuromodulatory effects upon target cells. Zinc-containing neurons are found predominantly in limbic and cerebrocortical regions, and a possible role of these neurons in the modification of synaptic strength is considered.

Coupled cluster energy derivatives. Analytic Hessian for the closed‐shell coupled cluster singles and doubles wave function: Theory and applications

Abstract: Expressions for coupled cluster molecular energy derivatives up to third order are presented and the molecular gradient and Hessian are implemented in a computer code for the CCSD wave function. Sample calculations on water and hydrogen peroxide indicate that significant savings are obtained by calculating the Hessian analytically rather than by finite differences.

Structural Changes and New Cleavages: the Progress Parties in Denmark and Norway:

Abstract: The Progress parties have been variously dubbed 'flash party, protest party', 'tax-revolt party', petty bourgeois protest movement populist party, 'extreme right-wing party' None of these labels pa...

Convertible Undeniable Signatures

Abstract: We introduce a new concept called convertible undeniable signature schemes In these schemes, release of a single bit string by the signer turns all of his signatures, which were originally undeniable signatures, into ordinary digital signatures We prove that the existence of such schemes is implied by the existence of digital signature schemes Then, looking at the problem more practically, we present a very efficient convertible undeniable signature scheme This scheme has the added benefit that signatures can also be selectively converted

Effects of a growth hormone pulse on total and forearm substrate fluxes in humans.

Abstract: Under physiological circumstances growth hormone (GH) is secreted in bursts after the onset of sleep and a few hours postprandially. Because most relevant studies have employed constant or repeated infusion of high doses of GH, the possible metabolic effects of such bursts are largely unknown. We have studied seven healthy, male subjects for 7 h after an intravenous bolus of 1) 140 micrograms GH and 2) saline. When injected, serum GH rose to a peak of 21 +/- 3 micrograms/l 10 min after injection. GH caused 1) a rapid, sustained 55% decrease in forearm glucose uptake (P less than 0.05) followed by increases toward control values, 2) a delayed 5 mg/100 ml decrease in plasma glucose (P less than 0.05), and 3) significant 60-250% increases (P less than 0.05) in all measured lipid intermediates (nonesterified fatty acids, 3-hydroxybutyrate, and glycerol) 120-160 min after administration followed by decreases to below control values (P less than 0.05). GH did not influence circulating levels of insulin, C-peptide, glucagon, or insulin-like growth factor I (IGF-I), or isotopically determined glucose turnover. Physiological bursts of GH secretion appear to have acute insulin antagonistic effects with maximal effect on lipolysis after 2 h. These effects are reversed after 4 h. Therefore, GH could play a key role in regulation of diurnal rhythms of substrate levels and fuel utilization in humans.