Showing papers by "Uppsala University published in 1977"

The Internationalization Process of the Firm - A Model of Knowledge Development and Increasing Foreign Market Commitments

Abstract: On the basis of empirical research, a model of the internationalization process of the firm is developed. The model focuses on the gradual acquisition, integration and use of knowledge about foreign markets and operations, and on the incrementally increasing commitments to foreign markets. In particular, attention is concentrated on the increasing involvement in the individual foreign country.

Absorbing boundary conditions for the numerical simulation of waves

Abstract: In practical calculations, it is often essential to introduce artificial boundaries to limit the area of computation. Here we develop a systematic method for obtaining a hierarchy of local boundary conditions at these artifical boundaries. These boundary conditions not only guarantee stable difference approximations, but also minimize the (unphysical) artificial reflections that occur at the boundaries.

Absorbing boundary conditions for acoustic and elastic wave equations

Abstract: Boundary conditions are derived for numerical wave simulation that minimize artificial reflections from the edges of the domain of computation. In this way acoustic and elastic wave propagation in a limited area can be efficiently used to describe physical behavior in an unbounded domain. The boundary conditions are based on paraxial approximations of the scalar and elastic wave equations. They are computationally inexpensive and simple to apply, and they reduce reflections over a wide range of incident angles.

Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts

Abstract: Two types of host reactivities not requiring immunization in the mouse and not mediated by T lymphocytes were compared: resistance of irradiated and nonirradiated F1 hybrids to accept parental grafts of normal or malignant hemopoietic cells (Hh system), and the natural killer cell activity against mouse lymphomas (NK system). The effects of six independent variables known to influence resistance to marrow grafts were investigated in the NK system using YAC-1 lymphoma cells as targets. The following properties were shared: (a) maturation during the fourth week of life; (b) low sensitivity to acute total body irradiation; (c) dependence on the integrity of bone marrow as demonstrated by reduced reactivity in 89Sr-treated mice; (d) suppression by a single injection of rabbit anti-mouse bone marrow serum; (e) suppression by a single injection of the anti-macrophage agents silica and i-carrageenan; and (f) suppression by multiple injections of parental spleen cells into F1 mice. These positive correlations are particularly significant because most of the variables have either opposing or no effect on conventional immunity. F1 mice rendered specifically unresponsive to parental marrow grafts, could retain NK cell activity, and genetically susceptible mice could be rendered hyporeactive in terms of NK cells, indicating that the specificities of YAC-1 and Hh-1 incompatible targets were different. It is extremely unlikely that this remarkable parallelism is fortuitous. These results indicate that either a very similar, or more likely a common mechanism is operative in the two cell-mediated natural reactivities: effector cells in the NK and Hh systems do not bear B or T lymphocyte markers but are nevertheless endowed with “specificity”. They are dependent for generation in vivo (presumably by maturation or by recruitment) on the interaction with nonlymphoid accessory cells not endowed with specificity, capable of also interacting in vitro with Thy-1-positive F1 hybrid prekiller cells specific for parental targets. Because of thymus independence in vivo and apparent restriction to target cells of the hemopoietic system, these reactivities should be effective in the regulation of hemopoiesis and surveillance over leukemogenesis.

Absorbing Boundary Conditions for Numerical Simulation of Waves

Abstract: In practical calculations, it is often essential to introduce artificial boundaries to limit the area of computation. Here we develop a systematic method for obtaining a hierarchy of local boundary conditions at these artifical boundaries. These boundary conditions not only guarantee stable difference approximations, but also minimize the (unphysical) artificial reflections that occur at the boundaries.

On the possibility of “smart” perceptual mechanisms

Abstract: .— A basic feature of some modem theories of perception is the notion of complex or higher order variables which are considered basic for perception. A distinction between “rote” and “smart” mechanisms is introduced and it is suggested that perception consists of smart mechanisms which directly register complex variables. A model of a perceiver, based on the smart polar planimeter, is constructed and used to illustrate the possible consequences of smart perceptual mechanisms for research in areas such as psychophysics, cognition, attention, and perceptual development and learning.

Role of non-conventional natural killer cells in resistance against syngeneic tumour cells in vivo

Abstract: IMMUNE reactions of ‘conventional’ T and B lymphocytes are generally thought to constitute major parts of any measurable, ‘specific’ tumour resistance against autologous tumours. There is no doubt that protective immunity can be induced against subsequently transplanted syngeneic tumours in experimental systems1. But, there is only scanty evidence to suggest that conventional immune reactions can provide resistance against such tumour cells when transplantation is made into normal individuals. Yet, it is frequently found that even long-transplanted syngeneic tumour cells may require comparatively high numbers of cells to ensure tumour take in normal recipients. Mice failing to succumb to small numbers of tumour cells can frequently be shown to reject a second graft of the same tumour with similar vigour2. Thus, natural resistance against tumours may occur with no display of classical, immunological memory. That such natural protective forces do exist against tumours has been claimed for many years3, but its underlying basis is poorly understood. Here, we present data indicating that naturally occurring killer cells may play a decisive part in providing resistance against syngeneic tumour cells in vivo.

Inhibition of Influenza Virus Ribonucleic Acid Polymerase by Ribavirin Triphosphate

Abstract: Ribavirin 5′-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5′-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5′-triphosphate and guanosine 5′-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.

Tumorigenicity of human hematopoietic cell lines in athymic nude mice

Abstract: Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi-solid medium in vitro. Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein-Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of come of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines.

Studies on Visual Perception of Locomotion

Abstract: The problem about visual discrimination between seeing objects in motion and perception of motion of the perceiver (locomotion) was taken up. A flow of vertical motion was presented to limited areas of the far periphery (45 degrees-90 degrees) of the retina simultaneously with optical information about a stationary room over the rest of the retina. The result was that most subjects perceived themselves as sitting in an elevator continuously moving upward or downward. Thus, peripheral motion stimulation over a few percent of the retinal area determines locomotion perception in apparent competition with information about a static state over the rest of the retina. The same type of stimulus presented to the central part of the retina always brought about perception of object motion and a static perceiver. Effects of size and localization of the area stimulated with the motion flow was studied. Theoretical consequences and problems for further experimental analyses are discussed.

Antigen-Binding, Idiotypic T-Lymphocyte Receptors

Abstract: Specific immune cognition and recognition are intrinsic capacities of mature, immunocompetent lymphocytes. B and T lymphocyte populations can both be shown to display this ability with high discriminatory power. At the single-cell level, however, both B and T lymphocytes express antigen-binding receptors with extreme restriction (Raff et al., 1973; Binz and Wigzell, 1975a). It would seem likely that in fact all receptors for antigen on a single B (Raff et al., 1973) or T (Binz and Wigzell, 1975a) lymphocyte express the same antigen-binding specificity. When T and B lymphocytes are compared with respect to their capacity to react against various epitopes, largely overlapping recognition spectra of antigenic specificities are found (Rajewsky and Mohr, 1974). Comparable mechanisms for the generation of diversity at the single-cell level of T and B cells would thus seem logical and economical. Whereas the biochemistry and underlying genetics of the B-cell receptors for antigen are by now relatively well understood, considerably less is known of the T-cell system.

On model structure testing in system identification

Abstract: In system identification it is assumed in many cases that the order of the system is known. Thus it is important to perform tests for determining the correct model order. For a single-input, single-output system the order is the only structural parameter, but for multivariable systems there are several structural parameters. It is in such cases not enough to test only for the order but to investigate if a model structure is appropriate or not. The paper contains a brief review of some methods for model structure testing. Two methods proposed by Akaike and the F-test are compared and it is shown that they are asymptotically equivalent. The methods are analysed theoretically through analytical calculations. The results are also illustrated with simulations.

alpha-Fetoprotein induces suppressor T cells in vitro.

Abstract: THE ability of α-fetoprotein (AFP) of mouse or human origin to suppress certain T cell-dependent immune reactions in vitro is well documented1–4. These findings on a tumour-associated embryonic substance5 have potentially important implications as to our understanding of the maternal–foetal immunological relationship6, the development of immune capabilities in the foetus and newborn7, and of certain diseases8 where immunological hyporeactivity and elevations in AFP often occur concomitantly. The mechanism(s) through which AFP is exerting its immunoregulatory influence is largely unknown, however, previous studies1 have shown that AFP must be added at the initiation of antigen-stimulated spleen cell cultures for maximal inhibition of primary antibody synthesis to occur. Continued presence of AFP in the cultures for 8–12 h was sufficient to maintain suppression in an AFP-free environment for at least 5 d in vitro1 and 10 d in vivo using adoptive transfer experiments (unpublished). These observations suggested that AFP may inhibit immune responses indirectly by activating regulatory suppressor cells. Here we report that AFP does indeed induce the formation of highly efficient suppressor T cells with capacity to inhibit helper T cells, but with no effect on B cells responding to thymus independent antigens.

Blood Flow in the Rabbit Tracheal Mucosa under Normal Conditions and under the Influence of Tracheal Intubation

Abstract: Isotope labelled microspheres were used to study the capillary blood perfusion of the rabbit tracheal mucosa. Under resting conditions the perfusion was about 0.3 ml/min - g (i.e. about 60% of the relative cerebral blood flow). Irritation of the tracheal mucosa by an endotracheal tube caused a steep rise in blood flow, tenfold or more. This was probably due to relaxation of the arterioles caused by a release of histamine-like substances. When an endotracheal tube is equipped with a small cuff (small resting diameter, low residual volume), the part of the mucosa in contact with the cuff, i.e. the mucosa covering the surface and edges of the cartilages, will be ischaemic at a cuff to tracheal wall pressure (C-T pressure) of greater than 30 millimeters of mercury. This abrupt ischaemia threshold contributes to the risk of deep mucosal damage with subsequent tracheal scarring, possibly proceeding to stenosis. Our present studies indicate that the ideal large cuff, with properties resembling those of an air cushion, will allow the major part of the arterial pressure to be propagated as far down as the capillaries. Under these conditions the cuff would permit some of the capillary blood perfusion of the tracheal mucosa covering the cartilages also at C-T pressures exceeding 30 mmHg. Although this investigation supports the concept that the ideal thin-walled large cuff interferes much less with the mucosal blood perfusion than the small cuff, we recommend that the cuff pressure be monitored and kept below 20 mmHg.

Structural Studies on the Four Repetitive Fc‐Binding Regions in Protein A from Staphylococcus aureus

Abstract: The covalent structures of the four highly homologous Fc-binding regions in protein A, regions D, A, B, and C, have been studied by enzymic fragmentations of previously isolated fragments originating from these regions and subsequent isolation of the generated peptides by ion-exchange chromatography, molecular-sieve chromatography, high-voltage paper electrophoresis and paper chromatography. The complete sequence of region B was elucidated by combining the results of Edman degradations on isolated fragment B peptides with the previously reported N-terminal sequence of the same fragment. Furthermore, Edman degradations of fragment D, A and C peptides differing from the region B sequence provided the structures of subregions not identical to corresponding subregions within region B. Thus, it is possible to propose a highly probable covalent structure for the N-terminal 27000-molecular-weight portion of protein A responsible for the IgG-Fc-binding activities. However, it was not possible to assign the activities to specific structures within the regions. The sequence data indicate that not only mutual homology between the four regions exists, but also internal homologies within the regions. Furthermore, the data strongly supports the hypothesis of a stepwise gene fusion procedure being involved in the evolution of the protein.

Transepidermal water loss in newborn infants. I. Relation to ambient humidity and site of measurement and estimation of total transepidermal water loss.

Abstract: Insensible water loss (IWL) is an important factor in the thermoregulation and water balance of the newborn infant. A method for direct measurement of the rate of evaporation from the skin surface has been developed. The method, which is based on determination of the vapour pressure gradient close to the skin surface, allows free evaporation. From measurements performed on 19 newborns placed in incubators, a linear relation was found between the evaporation rate (ER) and the humidity of the environment at a constant ambient temperature. A 40% lower ER was recorded at a high relative humidity (60%) than at a low one (20%) in the incubator. At measurements on different sites of the body, a high ER was observed on the face and peripheral parts of the extremities, while ER at other sites was relatively low. By determining ER from different parts of the body and calculating the areas of the corresponding surfaces, the total cutaneous insensible water loss for the infant in question could be obtained. The transepidermal water loss (TEWL) for the whole body surface area was calculated to be 8.1 g/m2h. On the basis of measurements performed it was found that the total cutaneous insensible water loss can be estimated with a reasonable degree of accuracy by recording ER from only three easily accessible measurement points.

Continuum orbitals, complex scaling problem, and the extended virial theorem

Abstract: A complex scale transformation of the time-independent Schr\"odinger equation leads to a symmetric eigenvalue problem containing both bound states and resonance (complex) eigenvalues as solutions. An extended virial theorem is stated, and its necessary fulfillment is pointed out. The latter, in conjunction with a symmetric stationary principle, allows for determination of resonance (complex) eigenvalues by means of elementary matrix manipulations. Application to the Stark effect in the hydrogen atom shows agreement with previous calculations based on numerical integration.

Growth Pattern of Pancreatic Islets in Animals

Abstract: The efficiency with which the pancreatic islet organ maintains the blood sugar homeostasis is determined both by the total islet mass and the hormonal release of individual islet cells in response to changes in the blood sugar concentration. Alterations in islet mass caused by cell loss or proliferation may well lead to disturbances in hormone production which will contribute to the development of either diabetes mellitus or hypoglycemic states. Factors which cause damage or loss of various islet cell types have attracted much attention in the past, and studies of this kind have greatly expanded our knowledge on the pathogenesis of diabetes. In comparison, little is known so far about the kinetics and regulation of islet cell proliferation and the significance of this process for the manifestations of the diabetic syndrome. The following review is an attempt to summarize the relevant literature in this latter field with regard to the growth of the islet organ both in normal conditions and in spontaneous and experimental diabetes.

Ionic selectivity, saturation and block in gramicidin A channels:

Abstract: A model for the gramicidin A channel is proposed which extends existing models by adding a specific cationic binding site at each entrance to the channel. The binding of ions to these outer channel sites is assumed to shift the energy levels of the inner sites and barriers and thereby alter the channel conductance. The resulting properties are analyzed theoretically for the simplest case of two inner sites and a single energy barrier. This four-site model (two outer and two inner) predicts that the membrane potential at zero current (U0) should be described by a Goldman-Hodgkin-Katz equation with concentration-dependent permeability ratios. The coefficients of the concentration-dependent terms are shown to be related to the peak energy shifts of the barrier and to the binding constants of the outer sites. The theory also predicts the channel conductance in symmetrical solutions to exhibit three limiting behaviors, from which the properties of the outer and inner sites can be characterized. In two-cation symmetrical mixtures the conductance as a function of mole fraction is shown to have a minimum, and the related phenomenon of inhibition and block exerted by one ion on the other is explained explicitly by the theory. These various phenomena, having ion interactions in a multiply occupied channel as a common physical basis, are all related (by the theory) through a set of measurable parameters describing the properties of the system.