| 1. |
- Asker, Claes
(author)
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Computer Assisted Video Microscopy : in Characterization of Capillary Ensembles
- 2000
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Doctoral thesis (other academic/artistic)abstract
- This thesis focuses on evaluation and analysis of capillary microcirculatory changes in the skin, that can be improved and extended by computer assisted video microscopy. Capillary microscopy has been used extensively, both in clinical practice and research, to study different phenomena in the microvasculature of the skin, mainly in the nailfold of fingers and toes where a large portion of the capillary loop can be observed.In the majority of the different skin regions, the nutritive capillary network approaches the skin surface perpendicularly and capillary microscopy in these sites reveals the apex of the capillary loop as a dark spot. The main approach in this work has been to study a large ensemble of capillary loops, in order to apply statistical and planar models whilst, at the same time, obtaining spatial parameters related to the capillary localization.The statistical models of proximity are based on nearest neighbour methods and triangulation techniques. The main reason for introducing these models is because of their capability to characterize the heterogeneity of the capillary ensemble.A computer assisted video microscopy system, that enables both capturing and evaluating of capillary bed images, was assembled and was, thereafter, successfully used in laboratory and clinical studies
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| 2. |
- Windahl, Charlotta, 1973-
(author)
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Integrated Solutions in the Capital Goods Sector : Exploring innovation, service and network perspectives
- 2007
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Doctoral thesis (other academic/artistic)abstract
- With varying degrees of success, a number of firms in the capital goods sector are experimenting with different ‘integrated solutions’ initiatives. Integrated solutions include product innovations which enable increased process control that allows the optimisation of the customers’ processes, as well as business innovations which change the firms’ business models and customer approach. It is not always easy to develop and commercialise these new offerings, especially for firms that have traditionally focused on developing and selling products. Integrated solutions challenge these firms to shift the focus from physical products, spare parts and support services to emphasis on delivery of performance optimisation and productivity.This thesis is a compilation of five papers and five supporting chapters that discuss and analyse the challenges with developing and commercialising integrated solutions in the capital goods sector. The research builds on case studies of firms experimenting with integrated-solution offerings. The firms produce complex, expensive industrial machinery to customers in the process and manufacturing industries. The main case is based on a five-year, in-depth longitudinal study of Alfa Laval, and more specifically of the developments within the wastewater industry. Other case studies include ITT Flygt and Atlas Copco.The thesis shows that the development and commercialisation of integrated solutions represent a multifaceted, iterative and complex process for the firms under study, who need to combine product, service and business innovations, create new business structures, and create new relationships with customers and possible partners. Consequently, the development of integrated solutions is not confined to or explained by one theoretical field in this thesis, but is linked to innovation, service and network perspectives.The thesis also shows that the three activities of innovating, organising and building relationships are dependent on changing market structures, customer demands and business cycles. Therefore it becomes important to manage the coexistence of different types of offerings, such as products, services and integrated solutions.
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| 3. |
- Ask, Per, 1950-
(author)
-
Oesophageal manometry : design and evaluation of measurement systems
- 1978
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Doctoral thesis (other academic/artistic)abstract
- The aim of this study was to investigate the technical characteristics of oesophageal manometry systems and to improve the performance of these systems.The investigation of the characteristics of oesophageal manometry systems with non-perfused catheters or catheters perfused with a flow generated by a syringe pump did not show properties which fullfilled the requirements for accurate pressure measurements. The bandwidth of the pressure mesurement system was limited by the high compliance of the syringe perfusion pump. The characteristics of perfused systems were improved by the design of a low-compliance perfusion pump. The frequency characteristics of a pressure measurement system utilizing the low-compliance perfusion pump seemed to be determined by the properties of the cathetermanometer system. The frequency content of oesophageal peristaltic pressure was studied by use of a measurement system including the low-compliance perfusion pump. This investigation showed that a bandwidth of about 8 Hz or more is necessary for accurate measurements, which bandwidth can only be obtained with a low-compliance system. In a clinical study a non-perfused system and a system perfused with a syringe pump were compared simultaneously to a system with the low-compliance perfusion pump. The non-perfused system and the system perfused with the syringe pump gave lower peristaltic and sphincter pressure amplitudes than the system with the low-compliance perfusion pump. Since the oesophageal sphincter pressure varies in different radial directions, a pressure transducer has been devised, the mechanical design of which gives an integration of a radial pressure profile. The transducer has a linear static and dynamic transfer function.
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| 4. |
- Hellgren, Johan, 1966-
(author)
-
Compensation for hearing loss and cancellation of acoustic feedback indigital hearing aids
- 2000
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Doctoral thesis (other academic/artistic)abstract
- The development of integrated circuits during the last decades has made it possible to incorporate digital signal processing in hearing aids that fit into the ear canal and are powered by small zink-air batteries. The digital signal processing provides new possibilities for the hearing aid to modify the signal to fit the impaired ear. A linear phase filter bank that is intended as a basic building block of the signal processing in digital hearing aids is introduced in this dissertation. The filterbank is computationally very efficient and divides the input signal into a number of narrow band signals for further signal processing. The filter bank was combined with band specific gains and two compressors to form the signal processing of a hearing aid. The compressors allow leveldependent gain. Three alternative fitting strategies used to adjust the characteristics of this hearing aid to the individual hearing impaired listener were evaluated. The three fitting strategies differed mainly in the characteristics of the compressors. The strategies were evaluated by hearing impaired subjects in a field test and in laboratory tests. When the subjects were grouped according to their preference among the fitting strategies, the results showed significant differences in the hearing loss configuration between the groups.One of the main tasks of a hearing aid is to amplify the signal to make it audible for the hearing impaired user. The maximum gain that can be used in a hearing aid will be controlled by the feedback from the output to the microphone, as the hearing aid will be a part of a closed loop system. The feedback path depends on several factors such as the position of the microphone (differs between hearing aid categories), size of vent, and the acoustics around the hearing aid. The feedback, and thus the maximum gain that can be used in a hearing aid, has been identified with a number of different hearing aids in a number of conditions that can be expected when the hearing aid is used under real-life conditions.Feedback cancellation can be used to reduce the negative effects of feedback on the performance of the hearing aid. An internal feedback in the hearing aid that is an estimate of the external feedback is then used to cancel the feedback signal. The external feedback path will vary as the hearing aid is used ( e.g. when a telephone set is placed by the ear). It is thus desirable to continuously identify the feedback path. One approach to do this is to utilize closed loop identification with the direct method and some recursive identification method. The output and input signals of the hearing aid are then considered as input and output signal of the system to be identified, i.e. the feedback path. An advantage with this method is that the identification can be done without modifying the output signal. A drawback is that the estimate may be biased, depending on the characteristics of the input signal. A difference from many other closed loop identification problems is that the data used for identification will depend on previous estimates of the system. A feedback cancellation algorithm where Filtered-X LMS is used with the direct method has been analyzed. Filtered-XLMS is computationally efficient and gives a possibility to incorporate known characteristics of the feedback path in the model set used. Prefiltering was also used in the algorithm as it can provide an unbiased estimate if the spectrum of the input signal is known.
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| 5. |
- Hällgren, Mathias, 1972-
(author)
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Hearing and cognition in speech comprehension. Methods and applications
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Central auditory processing is complex and can not be evaluated by a single method. This thesis focuses on assessment of some aspects of central auditory functions by the use of dichotic speech tests and cognitive tests that tax functions important for speech processing.Paper A deals with the cognitive effects in dichotic speech testing in elderly hearing-impaired subjects. It was found that different listening tasks in the dichotic tests put different demands on cognitive ability, shown by a varying degree of correlation between cognitive functions and dichotic test parameters. Age-related cognitive decline was strongly connected with problems to perceive stimuli presented to the left ear.Paper B presents a new cognitive test battery sensitive for functions important for speech processing and understanding, performed in text, auditory and audiovisual modalities. The test battery was evaluated in four groups, differing in age and hearing status, and has proven to be useful in assessing the relative contribution of different input-modalities and the effect of age, hearingimpairment and visual contribution on functions important for speech processing.In Paper C the test battery developed in Paper B was used to study listening situations with different kinds of background noise. Interfering noise at +10 dB signal-to-noise ratio has significant negative effects on performance in speech processing tasks and on the effort perceived. Hearing-impaired subjects showed poorer results in noise with temporal variations, and elderly subjects were more distracted by noise with temporal variations, especially by noise with meaningful content. In noise, all subjects, particularly those with impaired hearing, were more dependent upon visual cues than in the quiet condition.Hearing aid benefit in speech processing with and without background noise was studied in Paper D. The test battery developed in Paper B was used together with a standard measure of speech recognition. With hearing aids, speech recognition was improved in the background condition without noise and in the background condition of ordinary speech. Significantly less effort was perceived in the cognitive tests when hearing aids were used, although only minor benefits of hearing aid amplification were seen. This underlines the importance of considering perceived effort as a dimension when evaluating hearing aid benefit, in further research as well as in clinical practice.The results from the studies contribute to the knowledge about speech processing but also to the search for more specific evaluation of speech understanding, incorporating both sensory and cognitive factors.
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| 6. |
- Johansson, Magnus, 1973-
(author)
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On noise and hearing loss : Prevalence and reference data
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Noise exposure is one of the most prevalent causes of irreversible occupational disease in Sweden and in many other countries. In hearing conservation programs, aimed at preventing noise-induced hearing loss, audiometry is an important instrument to highlight the risks and to assess the effectiveness of the program. A hazardous working environment and persons affected by it can be identified by monitoring the hearing thresholds of individual employees or groups of employees over time. However, in order to evaluate the prevalence of occupational noise-induced hearing loss, relevant reference data of unexposed subjects is needed.The first part of this dissertation concerns the changes in hearing thresholds over three decades in two occupational environments with high noise levels in the province of Östergötland, Sweden: the mechanical and the wood processing industries. The results show a positive trend, with improving median hearing thresholds from the 1970s into the 1990s. However, the hearing loss present also in the best period, during the 1990s, was probably greater than if the occupational noise exposure had not occurred. This study made clear the need for a valid reference data base, representing the statistical distribution of hearing threshold levels in a population not exposed to occupational noise but otherwise comparable to the group under study.In the second part of the dissertation, reference data for hearing threshold levels in women and men aged from 20 to 79 years are presented, based on measurements of 603 randomly selected individuals in Östergötland. A mathematical model is introduced, based on the hyperbolic tangent function, describing the hearing threshold levels as functions of age. The results show an age-related gender difference, with poorer hearing for men in age groups above 50 years.The prevalence of different degree of hearing loss and tinnitus is described for the same population in the third part of the dissertation. The overall prevalence of mild, moderate, severe or profound hearing loss was 20.9% collectively for women and 25.0% collectively for men. Tinnitus was reported by 8.9% of the women and 17.6% of the men. Approximately 2.4% of the subjects under study had been provided with hearing aids. However, about 7.7% were estimated to potentially benefit from hearing aids as estimated from their degree of hearing loss.Noise-induced hearing loss primarily causes damage to the outer hair cells of the inner ear. The fourth and last part of the dissertation evaluates the outer hair cell function, using otoacoustic emission measurements (OAE). Prevalence results from three different measuring techniques are presented: spontaneous otoacoustic emissions (SOAE), transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). Gender and age effects on the recorded emission levels were also investigated. Women showed higher emission levels compared to men and for both women and men the emission levels decreased with increasing age. The results from the OAE recordings were shown to be somewhat affected by the state of the middle ear. The study included tympanometry, and the relation of the outcome ofthis test to the otoacoustic emissions is described, where high middle ear compliance resulted in low emission level. Reference data for the tympanometric measurements are also presented.The results of this project form an essential part of the important work against noiseinduced hearing loss, which needs continuous monitoring. The reference data presented here will provide a valid and reliable data base for the future assessment of hearing tests performed by occupational health centres in Sweden. This data base will in turn prove useful for comparison studies for Sweden as a responsible fellow EU member country setting high standards for work force safety. The statistical distribution of hearing threshold levels as a function of age for men and women in tabulated form is available on the Swedish Work Environment Authority (Arbetsmiljöverket) web site: http://www.av.se/publikationer/bocker/fysiskt/h293.shtm.
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| 7. |
- Larsby, Birgitta, 1950-
(author)
-
Different neurophysiological methods for studying the vestibular system : evaluation of old methods and development of a new test procedure
- 1980
-
Doctoral thesis (other academic/artistic)abstract
- Different methods were used to study the physiology and anatomy of the vestibular system. 1) A primary vestibular cortical area in the cat was located and tested for somatosensory inflow by recordings of vestibular evoked potentials and extracellular single unit activity. 2) The enzyme horseradish peroxidase was used as a retrograde anatomical tracer to identify thalamo-cortical vestibular pathways. 3) Vestibular disturbances aused by the industrial solvents methylchloroform and styrene were recorded by electro-oculography. Positional nystagmus was seen above a concentration of 75 ppm of methylchloroform and 40 ppm of styrene in blood. 4) A clinical vestibular rotatory test procedure is described and evaluated in an animal model before and after unilateral labyrinthectomy. A long time reduction in gain is seen at higher rotational frequencies and a trend that serves to define the side of a peripheral lesion is superimposed on the oscillatory eye movements after unilateral vestibular damage.
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| 8. |
- Lövsund, Per, 1948-
(author)
-
Biological effects of alternating magnetic fields with special reference to the visual system
- 1980
-
Doctoral thesis (other academic/artistic)abstract
- The aims of the present investigation were to contribute to more knowledge of the interaction between extremely low frequency magnetic fields and excitable tissue and to widen the basic understanding of the mechanisms behind these effects. The human visual system and the frog retina were used as model systems.In order to ensure that industrial magnetic flux densities and frequencies were employed in the laboratory studies, the magnetic field levels in the welding and electrosteelindustries at the site ordinarily occupied by the operator were first measured. These processes usually generated fields with a frequency of 50 Hz and a magnetic flux density of 01-10 mT. In the laboratory magnetic fields (0-40 mT, 10-50Hz) were used to induce visual light phenomena, so-called magnetophosphenes, in volunteers. The threshold values for these phosphcnes were detennined as functions of magnetic field frequency as well as of colour and intensity of the background illumination. Maximum field sensitivity occurred at a frequency of approximately 20-30 Hz. With broad spectrum light the threshold flux density was about 10-12 mT. The thresholds were found to be dependent upon the intensity and the spectral distribution of the background light. During dark-adaptation the magnetic field sensitivity decreased. In certain respects volunteers with normal colour vision differed from colour defective ones as far as threshold values are concerned. Possible mechanisms for generation of magnetophosphenes are discussed. The threshold values for magnetophosphenes (0-40 mT) and electrophosphenes (0-0.3 mA) were compared under otherwise identical experimental conditions. In both broad spectrum and monochromatic background lighting the two types of phosphenes had a concurring sensitivity maximum at 20Hz. At higher frequencies there were significant differences in the threshold values. Applying electric current stimulation in different directions did not give rise to any great differences with regard to threshold values within the frequency range 10-30Hz. Frog retinas were exposed to magnetic fields (0-80 mT, 20-30 Hz). The electrical activity in the retina induced by the fields was registered from the ganglion cell layer with the aid of microelectrode technique, whereby a threshold value was obtained at approximately 20 mT and a sensitivity maximum was found at 20 Hz. The magnetic field response occurred within approximately 5 ms, while the light stimulus response occurred only after an average of approximately 85 ms. The latency from light stimulus to response in the ganglion cell layer was significantly prolonged if the preparation was simultaneously and continuously exposed to a magnetic field. Magnetic stimuli similar to light stimuli only induced a response upon 'on', 'off or 'on/off and not during continuous stimulation. Cells which were on-cells during light stimulation became off-cells during magnetic stimulation and vice versa. Addition of Na-aspartate or CoCl2 extinguished simultaneously the response both to light and to magnetic field stimuli. The results indicate that magnetophosphenes are generated in the retina and in the same channels that normally propagate signals induced by light.
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| 9. |
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| 10. |
- Nilsson, Gert, 1947-
(author)
-
On the measurement of evaporative water loss : methods and clinical applications
- 1977
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Doctoral thesis (other academic/artistic)abstract
- The new method for measurement of water loss by evaporation from the skin described in paper I, offers a high degree of accuracy and improved sensitivity in comparison with devices reported previously. Rapid recordings can be made by technically untrained persons both in clinical departments and in the laboratory.Using this method, the average insensible perspiration from the skin of healthy adult subjects at rest was found to be 381, 526 and 695 gr per day at ambient temperatures of 22°, 27° and 30°C, respectively. On the head, hands and feet the evaporation rate was high, while on other body surface areas more moderate values were recorded,In a clinical study on newborn infants, a linear relationship between the evaporative water loss from the skin and the ambient humidity was found. At an ambient temperature of 34.5°c and an ambient relative humidity of 50% the average transepidermal water loss was calculated to be 8.1 g/m2h.In burned patients high evaporation rates from about 140 g/m2h to over 220 g/m2h were recorded on the injured skin surfaces. Biological dressings were only slightly permeable to water vapour, while the permeability of the artificial dressings tested was generally high.By recording the rate of increase in vapour concentration in a closed measurement chamber placed over the exposed abdominal cavity during surgery, the water loss by evaporation from wounds and exteriorized viscera was determined. At incisions of minor extent the evaporative water loss was low, while at larger incisions with exteriorized viscera the water loss by evaporation from the wound exceeded the basal cutaneous perspiration of healthy adult subjects.
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| 11. |
- Nilsson, Lena, 1950-
(author)
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Studies on skin blood flow and evaporative water loss : a bioengineering approach
- 1986
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Doctoral thesis (other academic/artistic)abstract
- Skin blood flow (SBF), temperature, evaporative water loss (EWL) and skin conductance (SC) measured during stimulus-response experiments reveal valuable information regarding the skin's regulatory capacity. SBF and EWL play powerful roles in keeping the human body within an adequate temperature range. EWL and SC reflect the thermal and mental state of the subject. SBF, EWL and SC were measured using noninvasive laser Doppler flowmetry, vapour pressure gradient estimation and a DC-voltage method, respectively.Short acoustic stimuli evoked responses in both EWL and SC at the palm; their response amplitudes were strongly correlated (r = 0.87). Both latency and time to the peak of EWL responses were delayed by 1.1 sec and 2.3 sec, respectively, in comparison to SC responses.EWL measurements at the forearm revealed rhythmical variations in the recorded signal. The period was approximately 0.74 sec at rest. At a higher evaporation rate, induced by exercise, a longer period (0.84 sec) was detected. The period was independent of the sex of the subject and ambient temperature, and remained unchanged for repeated measurements on the same subject.In the skin temperature range 12 to 38°C, the relationship between SBF and local temperature, at the thigh, palm and fingertip, was best fitted to exponential equations. For a narrower temperature interval (23 to 36°C), palmar SBF and temperature followed linear equations within subjects. However, a large variability in regression coefficients was revealed between subjects. When SBF values were normalized to room climate level, they correlated strongly to skin temperature values (r=0.88).Radiative cooling (17°C) of the palm from room climate conditions doubled local heat loss and left SBF virtually unchanged. When cold convective air currents (19°C, 0.5 or 1.0 m/s) were applied, SBF decreased to 60 and 53% while heat loss dropped to 68 and 70%. Rewarming after local cooling revealed discrepancies'in the restoration of both SBF and skin temperature between the measurement sites.
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| 12. |
- Nygårds, Mats-Erik, 1944-
(author)
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Computer-based detection of cardiac arrhythmias : methods and systems
- 1983
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Doctoral thesis (other academic/artistic)abstract
- The aim of this study was to develop methods and systems which could improve the accuracy or arrhythmia monitoring and analysis of long-term ECGs and eliminate or reduce the need for continuous visual ECG screening. The detection of arrhythmias was based on an automatic classification of heart beats, using waveform features obtained from a basis signals representation. Ventricular fibrillation, a condition in which individual QRS complexes cannot be discerned, was diagnosed from a spectral analysis of the ECG.The methods were put into practice in a computer-based system with the capacity for simultaneous monitoring of eight patients. The accuracy of the system with respect to arrhythmia alarms was studied during ten 24-h periods of clinical routine use, with 55 patients. monitored for a total time of about 1000 h. Seventy percent of the time during which an alarm message should have been present (134 h) a correct alarm was given. An incorrect alarm cause was reported 17% of the time, while 13% of the time no alarm at all was given. The ratio between true and false or incorrect alarms was 3:1.The methods for arrhythmia detection were also utilized in a computer program for offline analysis of long-term ECGs from ambulatory patients. Here, the automatic analysis was combined with a subsequent interactive examination of the analysis results for highest accuracy.
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| 13. |
- Rundquist, Ingemar, 1947-
(author)
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Cytofluorometry : technique and applications
- 1981
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Doctoral thesis (other academic/artistic)abstract
- The aims of this investigation were to examine the conditions for rapid fluorescence measurements on cellular material, to improve the performance of measurement systems for microscope fluorometry, and to apply this technique in studies on mast cell biology. Fluorescence fading, a general complication of cytofluorometry, was studied during illumination times in the millisecond range, and a new fading phenomenon characterized by short duration and rapid recovery was described. The findings of the study formed the basis for the construction of two instfurnent systems for microscope fluorometry based on Leitz MPV I and MPV II microscope photometers. Rapid fluorescence measurements were performed by a completely automatic measuring sequence, except forselectionandfocusing of the objects to be measured. Automation was mainly achieved by the integration of computers in the measurement systems, which also resulted in easily interchangeable programdetermined measuring routines and proper data processing and presentation of results. The systems were mainly used for rapid analysis of cell populations. The precision of the measurements was improved by different standardization techniques, and the measuring speed, about 500 cells per h on well prepared specimens, was high enough to permit analysis of relatively large cell populations within a reasonable time.The cytofluorometric technique was applied to studies on the biology of the connective tissue mast cell. Rat peritoneal mast cells were used for this purpose. The proliferation of mast cells was estimated by cytofluorometric measurements of DNA in mast cell populations after staining with the fluorescent dye Hoechst 33258. Formaldehyde-induced fluorescence was used to study the uptake and turnover of dopamine in mast cells in vivo. Measurements of the mast cell content of heparin, a constituent of the mast cell granule matrix, were performed by a combination of microscope fluorometry, which permits visual identification of the cells, and flow cytofluorometry, by which rapid measurements of large populations can be made.
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| 14. |
- Salerud, Göran, 1954-
(author)
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Laser doppler tissue flowmetry : fiberoptic methods in microvascular research
- 1986
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Doctoral thesis (other academic/artistic)abstract
- Laser Doppler flowmetry (LDF) constitutes a method for measuring the flux of blood cells in the microcirculatory bed. Photons are scattered in the moving blood cells, where they undergo a frequency shift according to the Doppler principle. Light is brought to the tissue under study by one optical fiber and transmitted back to photodetectors by two separate fibers. LDF is a particulary useful method to study blood flow patterns and vascular regulatory mechanisms, since it is non-invasive and assesses blood flow in a very small volume of tissue (1 mm3).Blood flow recordings from skin areas, such as forearm and forehead, have revealed large spatial and temporal variations in microvascular blood flow. If the flowmeter probe is moved as little as 2.5 mm, the spatial heterogeneity of the vasculature result in a significant (p<0.001) difference in flowmeter output signal.Spontaneous rhythmical blood flow patterns (vasomotion) with different amplitudes, appeared in all of the 8 subjects studied. Some subjects had a continuous vasomotion pattern, while others showed only "bursts" of the pattern. Recorded blood flow in two juxtaposed skin sites sometimes demonstrated simultaneous variations in both sites, while in other instances the rhythmical flow patterns were out of phase or of different frequencies. To overcome the problem with a large spatial variation in skin blood flow in relation to the geometrical dimension of the probe, a multifiber probe was developed. It was designed to integrate the blood flow over an area enlarged approximately seven times compared to the standard probe. Measurements with this probe reduced the spatial differences as theoretically expected. No averaging effect was found, however, on the temporal variations.In skin, the capillary bed is located superficially, while in other tissues, such as the intestine, the inner wall (mucosa) is the most perfused. In an experiment on cat small intestine, the blood flow was measured both from the mucosal and serosal side. The results showed that it was possible to record the total blood flow of the intestinal wall, irrespective of whether the probe was placed on the mucosal or serosal side of the bowel wall.For tissues like muscle, liver and brain it may be of interest to assess the deep tissue perfusion. The LDF standard probes are, however, too large and blunt to be inserted into the tissue, without disturbing the flow. Therefore a single fiber LDF was developed, with oneoptical diber (Ø =0.5 mm) guiding the light to and from the tissue under study. In a flow model resembling tissue perfusion, the usefulness of the single fiber LDF based on the differential technique was evaluated. When a mathematical model was used to evaluate the single versus the differential channel operation, the differential technique was found most powerful if the laser broadband noise has a substantial rms-value or if many coherence areas are detected. The dynamic responses of the single fiber LDF were studied in a pig experimental model under different physiological conditions. The results agreed well with known reference blood flow patterns
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| 15. |
- Stål, Olle, 1952-
(author)
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Static and flow cytometry for tumor DNA analysis
- 1989
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Doctoral thesis (other academic/artistic)abstract
- The analysis of cellular DNA content in human tumors has shown to be of prognostic importance. The techniques used involve measurements in slide preparations by absorption cytophotometry and static cytofluorometry as well as the analysis of cell suspensions by flow cytometry. The aim of this work has been to improve these techniques by the development of computer aided systems in order to facilitate the use in a larger scale for clinical purposes. Another aim has been to study the prognostic significance of DNA analysis in breast cancer.Software for determination of DNA content and nuclear area by scanning absorption cytophotometry was developed. The system, HISTOSCAN, is insensitive to light scattering and may therefore be used in tissue sections. Thus, measurements in morphologically well-defined areas may be performed, but the method is less suitable for extensive use due to the slow procedure of the mechanical scanning.More rapid analyses are achieved by the system developed for static cytofluorometry in cytocentrifuged specimens. Cells to be measured are not positioned in the ordinary way, but are just passed through the excitation light beam as the specimen is visually scanned. DNA content and nuclear size are estimated simultaneously from the fluorescence recorded. For estimation of proliferative activity a sufficient number of cells may be analysed within a reasonable time.Similar results were obtained by static cytofluorometry and flow cytometry in a series of primary breast cancers. A close correlation was found for DNA index and, if 200 cells or more were measured, the same was true for S-phase fraction.Tumors from 472 women with primary breast cancer were analysed by flow cytometry. DNA ploidy showed significant association with disease recurrence and mortality but did not show a prognostic value in addition to that of traditional factors. The prognostic significance of S-phase fraction was independent of nodal status, tumor size and estrogen receptor content concerning early relapse and mortality. The survival of 116 women with recurrent breast cancer was correlated with both DNA ploidy and S-phase fraction in a multivariate analysis including nodal status, tumor size, ER content and site of recurrence.
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| 16. |
- Sundqvist, Tommy, 1949-
(author)
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Probing intestinal permeability in man using different-sized, low-molecular-weight polyethyleneglycols and mathematical modelling
- 1981
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Doctoral thesis (other academic/artistic)abstract
- Selective intestinal permeability as reflected by the urinary recovery of low-molecular-weight polyethylene glycols (PEG 400) of dlfferentsizes after oral administration was characterized with a mathematical filter-function. There was relative loss of both large and small PEG molecules on their way from the intestine to the urine. The reduced recovery of the large molecules is explained by selective intestinal absorption, since intravenous instillation abolished the effect. After curve-fitting to the experimental data, the mathematical procedure gives a quantitative measure of the fraction of selective and non-selective passage, and of filter-efficiency at different molecular weights. When applied to patients treated by bypass surgery for morbid obesity the method indicated a less permeable intestine with a reduced effective absorbtive surface area. In patients with rheumatoid arthritis a fasting diet gave a similar effect, which was accompanied by a reduction in disease activity. However, after changing to lactovegetarian diet the intestinal selectivity returned towards the control values, as did the inflammatory indices. Finally, to evaluate the importance of different physiological criteria for the outcome of the PEG 400 absorption test, a mathematical multi-compartment model was constructed and simulated on a computer.
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| 17. |
- Tenland, Torsten, 1952-
(author)
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On laser Doppler flowmetry : methods and microvascular applications
- 1982
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Doctoral thesis (other academic/artistic)abstract
- A laser Doppler flowmeter for non-invasive microcirculatory blood flow studies has been developed. The tissue under study is illuminated by laser light (helium-neon laser, output power 2 mW) via an optical fibre and the Doppler shift oflight scattered in moving red cells is analysed. By the use of two photodetectors for detection of the backscattered light, the influences of mode interference and broadband noise from the laser and noise from surrounding light sources have been suppressed. The instrument is designed to give a continuous, stable and linear real-time measure of the flux of red cells (i.e. the number of red cells times their velocity) in the outermost layer (1 mm) of tissue, in which the red cell volume fractions are low or moderate. Linearity, measuring depth and the influence of blood oxygen tension were evaluated in a flow model with optical properties similar to those of human skin. Laser Dopplerflowmetry was found to be versatile for measurements of blood flow in human skin and rat testis and did not influence the flow under study.An extensive study of spatial and temporal variations of human skin blood flow was performed. As it was found that skin blood flow shows wide day-to-day variations and significant differences between adjacent probe sites, earlier reported "normal" values of skin blood flow were seriously questioned. It is proposed that this study can serve as a base for further functional studies.Testicular blood flow in rats was studied in order to evaluate acute effects of stress-linked substances such as adrenaline and noradrenaline. Both substances lowered the blood flow at high doses.Rhythmical variations of blood flow (frequency 5-12 min-1) in human skin and rat testis were observed and found to be in agreement with earlier findings in microscopic studies on other types of tissue. The nature and origin of this rhythmicity point towards a local regulatory mechanism operating also under "steady state" conditions.
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| 18. |
- Åhlfeldt, Hans, 1955-
(author)
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Computer-based modeling and simulation in the analysis of cardiac arrhythmias and cardiac pacing
- 1989
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Doctoral thesis (other academic/artistic)abstract
- Most systems for ECG analysis deal with QRS classification and arrhythmia detection but do not address the problem of finding the underlying mechanism responsible for the manifest arrhythmia. Although it is possible to distinguish among different arrhythmogenic mechanisms on the cellular level, it is far more difficult in the clinic based on ECG recordings. A computer model which is well suited for rhythm studies has been developed. The heart is modeled as a network of finite elements in which the impulse propagation is described mathematically, as well as several arrhythmogenic mechanisms. These include modulated parasystole, macro and micro reentry and different kinds of block. Since modulated parasystole provides a unified explanation of a variety of different arrhythmias, a stepwise procedure is presented by which this mechanism can be detected. Modulated parasystole can be described mathematically with a phase response curve, and the model has proven valuable for deduction of biand triphasic phase response curves from clinical cases with frequent ventricular premature complexes.Cardiac pacing is a very important therapy for rhythm disorders and since modern pacemakers interact with the heart in a complex way, the problem of cardiac pacing and pacemaker follow-up has also been studied. An ambulatory recording system has been developed, including a pacemaker spike detector and a computer program which can detect possible events of pacemaker malfunction. The computer model has been used to analyse the interaction between the heart and different types of pacemakers. The model has also been integrated with a hypertext system, allowing the system to be used for computer-aided education of cardiac pacing and cardiac arrhythmias.
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| 19. |
- Farnana, Zohra, 1978-
(author)
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The Double Obstacle Problem on Metric Spaces
- 2009
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Doctoral thesis (other academic/artistic)abstract
- In this thesis we investigate the double obstacle problem for p-harmonic functions on metric spaces. We minimize the p-energy integral among all functions which have prescribed boundary values and lie between two given obstacles. This is a generalization of the Dirichlet problem for p-harmonic functions, in which case the obstacles are —∞ and ∞.We show the existence and uniqueness of solutions, and their continuity when the obstacles are continuous. Moreover we show that the continuous solution is p-harmonic in the open set where it does not touch the continuous obstacles. If the obstacles are not continuous, but satisfy a Wiener type regularity condition, we prove that the solution is still continuous. The Hölder continuity for solutions is shown, when the obstacles are Hölder continuous. Boundary regularity of the solutions is also studied.Furthermore we study two kinds of convergence problems for the solutions. First we let the obstacles and the boundary values vary and show the convergence of the solutions. We also consider generalized solutions for insoluble obstacle problems, using the convergence results. Moreover we show that for soluble obstacle problems the generalized solution coincides, locally, with the standard solution.Second we consider an increasing sequence of open sets, with union Ω, and fix the obstacles and the boundary values. We show that the solutions of the obstacle problems in these sets converge to the solution of the corresponding problem in Ω.
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| 20. |
- Caporaletti, Francesca, 1990-
(author)
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MYC and MexR interactions with DNA : a Small Angle Scattering perspective
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Protein-DNA complexes govern transcription, that is, the cellular mechanism that converts the information stored in the DNA into proteins. These complexes need to be highly dynamic to respond to external factors that regulate their functions in agreement with what the cells need at that time. Macromolecular X-ray crystallography is very useful for structural studies of large molecular assemblies, but its general application is limited by the difficulties in crystallising highly dynamic and transient complexes. Furthermore, crystal lattices constrain the macromolecular conformation and do not entirely reveal the conformational ensemble adopted by protein-DNA complexes in the solution.Small-Angle X-Ray Scattering (SAXS) and Small-Angle Neutron Scattering (SANS) are two complementary techniques known jointly as Small-angle Scattering (SAS). SAS is a powerful tool for analysing the shape and changes of molecules in solution in their native state. It is beneficial if the variability of conformation or disorder complements high-resolution methods such as NMR or crystallography. With SANS, we can explore non-crystallisable protein-DNA complexes in solution without restrictions of artificially symmetrised DNA and limitations of a protein sequence. Neutrons are well-suited probes for studying protein-DNA complexes for the capability of the neutrons to scatter common atoms in biomolecules differentially and can thereby distinguish between hydrogen and deuterium. Together with varying the solvent deuterium ratio, the contrast variation approach can reveal shapes of distinct components within a macromolecular complex.The goal of this thesis is to explore unchartered territories of regulatory protein-DNA interactions by studying such complexes by SAS, with a specific focus on the flexibility of the complexes. In my study of the MexR-DNA complex, I try to elucidate the molecular mechanism by which the MexR repressor regulates the expression of the MexAB-OPrM efflux pump through DNA binding. This pump is one of the multidrug-resistant tools of the pathogen Pseudomonas Aeruginosa (P. Aer.). It can extrude antibacterial drugs from the bacteria enabling them to survive in hostile environments. In the second project, I strive to explore the MYC:MAX:DNA complex. This heterodimer assembly functions as a central hub in cellular growth control by regulating many biological functions, including proliferation, apoptosis, differentiation and transformation. Overexpression or deregulation of MYC is observed in up to 70% of human aggressive cancer forms, including prostate and breast cancers. By combining SAS with biophysical methods, the work presented in this thesis reveals novel information on the shape and dynamics of biomolecular assemblies critical to health and disease.This thesis comprises five chapters, each dealing with a different aspect of the work in those years. The first chapter introduces the reader to the motivations of this research, and it will give the reader a brief state of the art of the two projects. In the second chapter, I will give you all the theoretical instruments to understand better all the methods used in this thesis, I write first to provide an overview regarding the proteins and their capability to bind other macromolecules. I then will exploit the basics of the small-angle technique, focusing on the neutron contrast variation: the fundamental technique used throughout this thesis and the ab-initio modelling.In the third chapter, Methods, I will discuss the SAS measurements and the requirements for the experiments themselves, the procedure for the data reduction and the data processing and analysis to obtain the structural information.The fourth chapter is a summary of the results of the submitted papers and my contributions:Small-angle X-ray and neutron scattering of MexR and its complex with DNA supports a conformational selection binding modelResolving the DNA interaction of the MexR antibiotic resistance regulatory proteinUpgraded D22 SEC-SANS set-up dedicated to the biology communitySAS studies on the regulation of MYC303:MAX:DNA and MAX:MAX:DNA binding in cancer.
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| 21. |
- Andersson, Jesper
(author)
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Dynamic Software Architectures
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Software architecture is a software engineering discipline that provides notations and processes for high-level partitioning of systems' responsibilities early in the software design process. This thesis is concerned with a specific subclass of systems, systems with a dynamic software architecture. They have practical applications in various domains such as high-availability systems and ubiquitous computing. In a dynamic software architecture, the set of architectural elements and the configuration of these elements may change at run-time. These modifications are motivated by changed system requirements or by changed execution environments. The implications of change events may be the addition of new functionality or re-configuration to meet new Quality of Service requirements. This thesis investigates new modeling and implementation techniques for dynamic software architectures. The field of Dynamic Architecture is surveyed and a common ground defined. We introduce new concepts and techniques that simplify understanding, modeling, and implementation of systems with a dynamic architecture, with this common ground as our starting point. In addition, we investigate practical use and reuse of quality implementations, where a dynamic software architecture is a fundamental design principle. The main contributions are a taxonomy, a classification, and a set of architectural patterns for dynamic software architecture. The taxonomy and classification support analysis, while the patterns affect design and implementation work directly. The investigation of practical applications of dynamic architectures identifies several issues concerned with use and reuse, and discusses alternatives and solutions where possible. The results are based on surveys, case studies, and exploratory development of dynamic software architectures in different application domains using several approaches. The taxonomy, classification and architecture patterns are evaluated through several experimental prototypes, among others, a high-performance scientific computing platform.
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| 22. |
- Montebelli, Alberto
(author)
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Modeling the Role of Energy Management in Embodied Cognition
- 2012
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Doctoral thesis (other academic/artistic)abstract
- The quest for adaptive and autonomous robots, flexible enough to smoothly comply with unstructured environments and operate in close interaction with humans, seems to require a deep rethinking of classical engineering methods. The adaptivity of natural organisms, whose cognitive capacities are rooted in their biological organization, is an obvious source of inspiration. While approaches that highlight the role of embodiment in both cognitive science and cognitive robotics are gathering momentum, the crucial role of internal bodily processes as foundational components of the biological mind is still largely neglected.This thesis advocates a perspective on embodiment that emphasizes the role of non-neural bodily dynamics in the constitution of cognitive processes in both natural and artificial systems. In the first part, it critically examines the theoretical positions that have influenced current theories and the author's own position. The second part presents the author's experimental work, based on the computer simulation of simple robotic agents engaged in energy-related tasks. Proto-metabolic dynamics, modeled on the basis of actual microbial fuel cells for energy generation, constitute the foundations of a powerful motivational engine. Following a history of adaptation, proto-metabolic states bias the robot towards specific subsets of behaviors, viably attuned to the current context, and facilitate a swift re-adaptation to novel tasks. Proto-metabolic dynamics put the situated nature of the agent-environment sensorimotor interaction within a perspective that is functional to the maintenance of the robot's overall `survival'. Adaptive processes tend to convert metabolic constraints into opportunities, branching into a rich and energetically viable behavioral diversity.
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| 23. |
- Peters, Björn
(author)
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Evaluation of Adapted Passenger Cars for Drivers with Physical Disabilities
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Driving can provide independent and efficient mobility. However, according to the driving license directive (91/439/EEC) are persons with locomotor impairments are only allowed drive if their disabilities can be compensated. Compensation can be realised by vehicle adaptations. The directive provides meagre guidance on how vehicles should be adapted or how to verify that the compensatory requirements are fulfilled. This is a gap in the current process for licensing drivers with physical disabilities. Furthermore, the Swedish process from driver assessment to driver licensing and adaptation approval is complex, fragmented, and suffer from lack of communication between involved authorities. The objective of this thesis was to contribute to the development of a method to evaluate vehicle adaptations for driver with physical disabilities. The focus was on the evaluation of adaptations for steering, accelerating and braking. Three driving simulator experiments and one manoeuvre test with adapted vehicles were conducted. A group of drivers with tetraplegia driving with hand controls were compared to able-bodied drivers in the first experiment. Even if the drivers with tetraplegia had a longer brake reaction time they performed comparable to the able-bodied drivers. However, they spent more effort and were more tired in order to perform as well as the able-bodied drivers. It was concluded that the adaptation was not sufficient. An Adaptive Cruise Controller (ACC) was tested in the second experiment in order to find out if it could alleviate the load on drivers using hand controls. It was found that the ACC decreased the workload on the drivers. However, ACC systems need to be adjustable and better integrated. The results from the first two experiments were used to provide some guidelines for ACCsystems to be used by drivers with disabilities. The third experiment was preceded by a manoeuvre test with joystick controlled cars. The test revealed some problems, which were attributed to time lags, control interference, and lack of feedback. Four joystick designs were tested with a group of drivers with tetraplegia in the third experiment. It was concluded that time lags should be made similar to what is found in standard cars. Lateral and longitudinal control should be separated. Active feedback can improve vehicle control but should be individually adjusted. The experiments revealed that drivers with the same diagnose can be functionally very diverse. Thus, an adaptation evaluation should be made individually. Furthermore, the evaluation should include a manoeuvre test. Finally, it was concluded that the evaluation approach applied in the experiments was relevant but needs to be further developed.
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| 24. |
- Rambusch, Jana
(author)
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Mind Games Extended : Understanding Gameplay as Situated Activity
- 2010
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Doctoral thesis (other academic/artistic)abstract
- This thesis addresses computer gameplay activities in terms of the physical handling of a game, players’ meaning-making activities, and how these two processes are closely interrelated. It is examined in greater detail which role the body plays in gameplay, but also how gameplay is shaped by sociocultural factors outside the game, including different kind of tools and players’ participation in community practices. An important step towards an understanding of these key factors and their interaction is the consideration of gameplay as situated activity where players who actively engage with games are situated in both the physical world and the virtual in-game world. To analyse exactly how players interact with both worlds, two case studies on two different games have been carried out, and three different levels of situatedness are identifed and discussed in detail in this thesis, on the basis of existing theories within situated cognition research.
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| 25. |
- Stenlund, Jörgen, 1959-
(author)
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Visualizing the abyss of time : Students’ interpretation of visualized deep evolutionary time
- 2023
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Doctoral thesis (other academic/artistic)abstract
- The immense time scales involved in Deep evolutionary time (DET) is a threshold concept in biology and interpreting temporal aspects of DET is demanding. DET is communicated through various visualizations that include static two-dimensional representations, low interactivity animations, as well as high interactivity interfaces. Given the importance of DET as fundamental scientific knowledge of potential societal application, there is a need for educational research on students’ interpretation of visually communicated DET. This thesis explores students’ interpretation of different forms of visualized DET along a continuum of interactivity. The research aim is four-fold, and probes how students interpret DET visualizations in terms of temporal aspects, communicated evolutionary concepts, degree of visualization interactivity, and generated affective responses.The work comprises four studies, which as a collective, adopt exploratory and multi-method designs. A total of 505 students participated. Data were collected from questionnaires, task-based questions, and semi-structured interviews. Data analysis was qualitative and quantitative, and incorporated deductive and inductive approaches. In analysing students' interpretation of static two-dimensional DET visualizations, an instrument for measuring knowledge about the visual representation of deep evolutionary time (DET-Vis) was developed. Emergence of a unidimensional construct during validation represents knowledge about the visual communication of DET. Inspection of item performance suggests that interpreting visualized DET requires both procedural and declarative knowledge. Analysis of students’ interpretation of a low interactivity DET animation, communicating hominin evolution revealed five temporal aspects influencing interpretation: events at specific times, relative order, concurrent events, time intervals, and time interval durations. A further shift across the continuum involved analysing students’ interpretation of a high-interactivity DET visualization of a three-dimensional phylogenetic tree. Finger-based zooming was associated with movement within the tree itself, or as movement in time, respectively, and related to identified misinterpretations. Further analysis showed that interpreting DeepTree evoked the epistemic affective responses of awe, curiosity, surprise, and confusion. Affective responses were expressed in relation to five evolutionary conceptual themes, namely biological relationships, evolutionary time, biological diversity, common descent, and biological structure or terminology. The thesis findings have implications for teaching, visualization design and future research. Exposing students to various DET visualizations across the continuum could support DET teaching. Visual communication of temporal aspects should be carefully considered in DET visualization design. Future work on relationships between affect, highly interactive visualizations, and evolution concepts will provide further insight for leveraging learning and teaching of DET.
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