Showing papers by "Linköping University published in 1994"

BRCA1 mutations in primary breast and ovarian carcinomas

Abstract: Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.

A multiprojection algorithm using Bregman projections in a product space

Abstract: Generalized distances give rise to generalized projections into convex sets. An important question is whether or not one can use within the same projection algorithm different types of such generalized projections. This question has practical consequences in the area of signal detection and image recovery in situations that can be formulated mathematically as a convex feasibility problem. Using an extension of Pierra's product space formalism, we show here that a multiprojection algorithm converges. Our algorithm is fully simultaneous, i.e., it uses in each iterative stepall sets of the convex feasibility problem. Different multiprojection algorithms can be derived from our algorithmic scheme by a judicious choice of the Bregman functions which govern the process. As a by-product of our investigation we also obtain blockiterative schemes for certain kinds of linearly constraned optimization problems.

Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report.

Abstract: The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organised five workshops to discuss CSF analytical standards in the diagnosis of multiple sclerosis. This consensus report from 12 European countries summarises the results of those workshops. It is hoped that neurologists will confer with their colleagues in clinical chemistry to arrange the best possible local practice. The most sensitive method for the detection of oligoclonal immunoglobulin bands is isoelectric focusing. The same amounts of IgG in parallel CSF and serum samples are used and oligoclonal bands are revealed with IgG specific antibody staining. All laboratories performing isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and serum patterns. Quantitative measurements of IgG production in the CNS are less sensitive than isoelectric focusing. The preferred method for detection of blood-CSF barrier dysfunction is the albumin quotient. The CSF albumin or total protein concentrations are less satisfactory. These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/microliters. Among evolving optional tests, measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free light chains, IgM, IgA, or myelin basic protein concentrations.

Declining incidence of nephropathy in insulin-dependent diabetes mellitus

Abstract: Background The high relative mortality among patients with insulin-dependent diabetes mellitus results mainly from diabetic nephropathy. The cumulative incidence of nephropathy of 25 to 30 percent among patients who had had diabetes for 25 years remained stable from 1950 to the early 1980s. In a population study, we assessed recent trends in the incidence of diabetic nephropathy. Methods We studied all 213 patients in whom insulin-dependent diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in southeastern Sweden. Ninety-two percent of the patients were followed from the onset of diabetes to 1991 or to death. Patients with persistent albuminuria (positive Albustix test) were considered to have diabetic nephropathy. Glycosylated hemoglobin was measured periodically in all patients, beginning in 1980. Results The cumulative incidence of persistent albuminuria after 25 years of diabetes decreased from 30.0 percent among the patients in whom diabetes developed in th...

Power consumption estimation in CMOS VLSI chips

Abstract: Power consumption from logic circuits, interconnections, clock distribution, on chip memories, and off chip driving in CMOS VLSI is estimated. Estimation methods are demonstrated and verified. An estimate tool is created. Power consumption distribution between interconnections, clock distribution, logic gates, memories, and off chip driving are analyzed by examples. Comparisons are done between cell library, gate array, and full custom design. Also comparisons between static and dynamic logic are given. Results show that the power consumption of all interconnections and off chip driving can be up to 20% and 65% of the total power consumption respectively. Compared to cell library design, gate array designed chips consume about 10% more power, and power reduction in full custom designed chips could be 15%. >

A convergent iterative restricted complexity control design scheme

Abstract: In this contribution we propose an optimization approach to the design of a restricted complexity controller. The design criterion is of LQG type containing two terms. The first term is the quadratic norm of the error between the output of the true closed loop and a desired response. The second term is the quadratic norm of the input signal. It is shown that the minimization of this criterion does not require a model of the system. Closed loop experimental data can be used instead. The result is an iterative scheme of closed loop experiments and controller updates which converges to a local minimum of the design criterion under the condition of bounded signals. >

In vivo studies concerning a pH gradient in human stratum corneum and upper epidermis.

Abstract: Human skin has an acid mantle of pH 4-6, contrasting with the almost neutral pH of the interior body and implying the existence of a pH gradient over the horny layer that might influence a variety of epidermal processes. In an attempt to characterize the pH gradient, we applied a glass electrode to the volar surface of the forearm before and after consecutive strippings with sello-tape. Before stripping, the surface pH (mean +/- SD) was 4.5 +/- 0.2 in men (n = 7) and 5.3 +/- 0.5 in women (n = 7), the values gradually increasing to pH 6.9 +/- 0.4 in men and 6.8 +/- 0.5 in women after about 100-120 tape strippings, which completely removed the stratum corneum. When plotted against the number of strippings, the pH values usually conformed to a sigmoid curve with inflection (50% change) after about 60 strippings, at a level corresponding histologically to the lower third of stratum corneum. Similar gradients were found also in skin of the abdomen and calf. Stripping with cyanoacrylate resin produced a similar gradient, even though this form of stripping was 10 times more effective. The healing process after tape stripping was studied by determining pH and transepidermal water loss in 5 persons over a period of 14 days. The importance of the re-established pH gradient is discussed in relation to the many pH-dependent enzymes operating in stratum corneum.

Local multiscale frequency and bandwidth estimation

Abstract: This paper describes a robust algorithm for estimation of local signal frequency and bandwidth. The method is based on combining local estimates of instantaneous frequency over a large number of scales. The filters used are a set of lognormal quadrature wavelets. A novel feature is that an estimate of local frequency bandwidth can be obtained. The bandwidth can be used to produce a measure of certainty for the estimated frequency. The algorithm is applicable to multidimensional data and examples of the performance of the method are demonstrated for one-dimensional and two-dimensional signals. >

Masking of speech by amplitude‐modulated noise

Abstract: The masking of speech by amplitude‐modulated and unmodulated speech‐spectrum noise has been evaluated by the measurement of monaural speech recognition in such noise on young and elderly subjects with normal‐hearing and elderly hearing‐impaired subjects with and without a hearing aid Sinusoidal modulation with frequencies covering the range 2–100 Hz, as well as an irregular modulation generated by the sum of four sinusoids in random phase relation, was used Modulation degrees were 100%, ±6 dB, and ±12 dB Root mean‐square sound pressure level was equal for modulated and unmodulated maskers For the normal‐hearing subjects, essentially all types of modulated noise provided some release of speech masking as compared to unmodulated noise Sinusoidal modulation provided more release of masking than the irregular modulation The release of masking increased with modulation depth It is proposed that the number and duration of low‐level intervals are essential factors for the degree of masking The release of masking was found to reach a maximum at a modulation frequency between 10 and 20 Hz for sinusoidal modulation For elderly hearing‐impaired subjects, the release of masking obtained from amplitude modulation was consistently smaller than in the normal‐hearing groups, presumably related to changes in auditory temporal resolution caused by the hearing loss The average speech‐to‐noise ratio required for 30% correct speech recognition varied greatly between the groups: For young normal‐hearing subjects it was −15 dB, for elderly normal‐hearing it was −9 dB, for elderly hearing‐impaired subjects in the unaided listening condition it was +2 dB and in the aided condition it was +3 dB The results support the conclusion that within the methodological context of the study, age as well as sensorineural hearing loss, as such, influence speech recognition in noise more than what can be explained by the loss of audibility, according to the audiogram and the masking noise spectrum

Redistribution of intracellular Ca2+ stores during phagocytosis in human neutrophils

Abstract: Subcellular gradients of cytosolic free Ca2+ concentration, [Ca2+]i, are thought to be critical for the localization of functional responses within a cell. A potential but previously unexplored mechanism for the generation of gradients of [Ca2+]i is the accumulation of Ca2+ stores at the site of Ca2+ action. The distribution of the Ca2+ store markers Ca(2+)-dependent adenosine triphosphatase and calreticulin was investigated in resting and phagocytosing human neutrophils. Both proteins showed an evenly distributed fine granular pattern in nonphagocytosing cells, but became markedly concentrated in the filamentous actin-rich cytoplasmic area around the ingested particle during phagocytosis. This redistribution began at early stages of phagocytosis and did not depend on an increase in [Ca2+]i. Thus, accumulation of Ca2+ stores in a restricted area of the cell may contribute to the generation of localized increases in [Ca2+]i.

Reactive magnetron sputter-deposition of cnx films on si(001) substrates - film growth, microstructure and mechanical-properties

Abstract: There is currently considerable interest in producing new materials with extreme combinations of mechanical properties such as high hardnesses and moduli. One example of such a material is crystalline C3N4, which has been predicted to have a bulk modulus higher than that of diamond. In this paper we report on experiments carried out to synthesize CNx thin films. The films were grown in an unbalanced magnetron-sputtering system by reactive sputtering of C in N2 discharges. Si(001) substrates with the native oxide removed by thermal desorption and then kept at temperatures ranging from 150 to 600°C and substrate bias voltages Vs between 7.5 and -200 V were used. The films were analysed using X-ray diffraction, transmission electron microscopy (TEM). Auger electron spectroscopy, Rutherford backscattering and nano-indentation tests. Typically the films were grown at rates of 5 nm s−1 to total thicknesses of 300 nm. Owing to an extensive re-sputtering, only low negative bias voltages (−80

Case-control study of risk factors for disease in the neck and shoulder area.

Abstract: A case-control study was performed to elucidate the strength of the relation between musculoskeletal disorders in the neck and shoulders and physical, organisational, and psychosocial aspects of the work environment. Cases were identified as those persons who consulted a physician in a community in southern Sweden for new musculoskeletal disorders in the neck and shoulders during a study period from August 1988 to the end of October 1989. One hundred and nine cases were collected and clinically examined. The cases also answered the Nordic questionnaire on symptoms as well as a questionnaire on work conditions and background factors. Controls were drawn as a random sample of the working population in the community where the cases appeared. A total of 637 controls answered the same questionnaires as the cases. Odds ratios (ORs) were calculated by logistic regression. The odds ratios were 11.4 for women, 4.9 for immigrant background, and 3.7 for current smoking. To exercise rarely, compared with often, appeared as a preventive factor with an OR of 0.3. The ORs for various determinants of physical work load were 7.5 for repetitive movements demanding precision, 13.6 for light lifting, 3.6 for uncomfortable sitting positions, 4.8 for work with lifted arms, and 3.5 for a rushed work pace. Regarding work organisational determinants, the ORs were 16.5 for ambiguity of work role (uncertainty whether the person could manage the work) 2.6 for low quality work, and 3.8 for high demands on attention. Several of the determinants showed a significant dose-response relation with disease. It seems that work organisation and psychosocial work conditions are as important determinants for disease in the neck and shoulders as are the physical work conditions.

Mechanisms of action of nitrates.

Abstract: Glyceryl trinitrate, isosorbide dinitrate, and isosorbide-5-mononitrate are organic nitrate esters commonly used in the treatment of angina pectoris, myocardial infarction, and congestive heart failure. Organic nitrate esters have a direct relaxant effect on vascular smooth muscles, and the dilation of coronary vessels improves oxygen supply to the myocardium. The dilation of peripheral veins, and in higher doses peripheral arteries, reduces preload and afterload, and thereby lowers myocardial oxygen consumption. Inhibition of platelet aggregation is another effect that is probably of therapeutic value. Effects on the central nervous system and the myocardium have been shown but not scrutinized for therapeutic importance. Both the relaxing effect on vascular smooth muscle and the effect on platelets are considered to be due to a stimulation of soluble guanylate cyclase by nitric oxide derived from the organic nitrate ester molecule through metabolization catalyzed by enzymes such as glutathione S-transferase, cytochrome P-450, and possibly esterases. The cyclic GMP produced by the guanylate cyclase acts via cGMP-dependent protein kinase. Ultimately, through various processes, the protein kinase lowers intracellular calcium; an increased uptake to and a decreased release from intracellular stores seem to be particularly important.

Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22)

Abstract: It has been shown that the gene ERG in 21q22 is rearranged in the t(16;21)(p11;q22) associated with acute myeloid leukemia (AML). ERG is a member of the ETS gene family and is fused with EWS in a subset of Ewing's sarcomas. EWS in 22q12 has a very high homology with FUS (also called TLS) in 16p11; the latter gene is rearranged in the t(12;16)(q13;p11) that characterizes myxoid liposarcoma. To investigate whether FUS is involved in the t(16;21) of AML, we used the Southern blot technique and polymerase chain reaction (PCR) to examine the bone marrow of a 3-year-old boy with a t(16;21)(p11;q22)-positive AML. Hybridization of Southern blot filters containing digested DNA with probes for FUS and ERG showed both germline and aberrant fragments. Using specific primers for the 5' part of FUS and the 3' part of ERG, we amplified a 4.4 kb genomic FUS/ERG DNA fragment from the leukemic sample. In a second PCR experiment, in which we used primers upstream of the 5' part of ERG and downstream of the 3' part of FUS, a 5.6 kb fragment was amplified. Blotting and hybridization with specific probes for FUS and ERG revealed that the amplified fragments consisted of FUS/ERG and ERG/FUS hybrid DNA. Both PCR fragments, when used as probes, detected germline ERG and FUS as well as aberrant fragments on Southern blot filters. The results suggest that the t(16;21) in AML leads to rearrangement and fusion of the FUS and ERG genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Image sequence coding at very low bit rates: a review

Abstract: This paper presents a review of promising techniques for very low bit-rate, below 64 kb/s, image sequence coding. Image sequence coding at such low rates will be a crucial technique in forthcoming visual services, e.g., visual information transmission and storage. A typical application is to transmit moving videophone scenes through the existing analog telephone lines or via a mobile channel. Two types of potential coding techniques are addressed: waveform-based image sequence coding and model-based image sequence coding. >

Food-induced lowering of blood-ethanol profiles and increased rate of elimination immediately after a meal

Abstract: In a two-part crossover study, ten healthy men drank a moderate dose of ethanol (0.80 g/kg) in the morning after an overnight fast or immediately after breakfast. The breakfast consisted of orange juice (150 mL), fruit yogurt (250 mL), two cheese sandwiches, one boiled egg, and one cup of coffee with milk and sugar. Ethanol was determined in venous blood at various times after the start of drinking by headspace gas chromatography. All subjects felt less intoxicated when alcohol was ingested after breakfast compared with drinking on an empty stomach. The peak BAC (+/- SD) was 67 +/- 9.5 mg/dL (ethanol + food) compared with 104 +/- 16.5 mg/dL when the drinking occurred after an overnight fast (P 6h) was 398 +/- 56 mg/dL x h in the fasting state compared with 241 +/- 34 mg/dL x h when subjects drank alcohol after the meal (P < 0.001). The time required to metabolize the dose of ethanol was approximately two hours shorter after the subjects had eaten breakfast. These results suggest that food in the stomach before drinking not only leads to a lowering of the peak BAC and diminishes the feelings of intoxication, but also boosts the rate of ethanol metabolism. A food-induced increase in the rate of disposal of ethanol was also confirmed when subjects ate a meal 5 h after drinking, that is, when the postabsorptive phase of ethanol metabolism was well established. The mean rate of disappearance of alcohol from blood was increased by between 36 and 50%.

Assignment of the contribution of the tryptophan residues to the circular dichroism spectrum of human carbonic anhydrase ii

Abstract: The circular dichroism (CD) spectrum of human carbonic anhydrase II (HCAII) has been investigated using various mutants of the enzyme in which tryptophans have been replaced by site-directed mutagenesis. HCAII contains seven tryptophans which are believed to significantly contribute to the CD spectrum in both the near- and far-UV regions. By substituting the tryptophans one at a time, the spectral effects of the individual tryptophans were studied. The near-UV spectrum of HCAII is very complex, with multiple Cotton effects. This complexity has been attributed to aromatic amino acids, especially tryptophans, located in asymmetric aromatic clusters in the molecule. CD spectra of the individual tryptophans were calculated as difference spectra between the CD spectrum of HCAII and those of the tryptophan mutants. These spectra showed that the tryptophans contributed to the CD spectrum in almost the entire wavelength region investigated (180-310 nm). Summation of the individual tryptophan CD spectra in the near-UV region yielded a spectrum that was qualitatively very similar to that of HCAII, showing that the tryptophans are the major determinant for this part of the CD spectrum. Since tryptophans were also demonstrated to contribute significantly in the far-UV region, tryptophans can interfere considerably with the assignment of changes in CD bands to changes in secondary structure content during folding reactions. Moreover, because of this substantial interference, predictions of the amount of various types of secondary structure from CD data from the far-UV region are made more difficult. These findings are probably of general importance for proteins that, like HCAII, contain several tryptophans.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic factors in thin cutaneous malignant melanoma.

Abstract: Background. Thin melanomas can metastasize and be lethal. The predictive importance of tumor thickness in thin melanomas and the specific features identifying the patients at risk have not been investigated fully. Methods. Prognostic factors were analyzed in 585 patients with clinical Stage I invasive cutaneous malignant melanoma with a thickness of less than or equal to 0.8 mm. The patients were included in a population-based cancer registry in Stockholm county during 1976–1987. They constituted about 64% of all patients with thin melanomas who were diagnosed in the region during the study period. Information was available on age, sex, anatomic site of the tumor, histologic type of melanoma, level of invasion, tumor thickness, and tumor regression. In a Cox regression analysis, the prognostic importance of each factor was studied. By a case-control technique with individual matching for the identified independent predictors of recurrence, the additional prognostic information given by type and grade of inflammatory response, presence of vertical growth phase, mitotic rate/mm2, and histologic ulceration of the tumor was assessed. Results. After a median follow-up time of 50 months, recurrent disease developed in 26 patients (4%). There was no difference in recurrence rate between patients treated with narrow (1–2 cm) or wide (5 cm) excision. Anatomic site, tumor thickness, level of invasion, and tumor regression were found to be independent prognostic factors in the multivariate analysis. In the case-control study, only grade of inflammatory reaction added significant prognostic information. No subgroup could be identified that was without risk of recurrent disease. Conclusions. Thin melanomas do not seem to constitute a separate form of melanoma, but compose one end of a continuous spectrum of biologic behavior.

Automated transformation of algorithms into register-transfer level implementations

Abstract: This paper describes a high-level synthesis system, called CAMAD, for transforming algorithms into hardware implementation structures at register-transfer level. The algorithms are used to specify the behaviors of the hardware to be designed. They are first translated into a formal representation model which is based on timed Petri nets and consists of separate but related descriptions of control and data path. The formal model is used as an intermediate design representation and supports an iterative transformation approach to high-level synthesis. The basic idea is that once the behavioral specification is translated into the initial design representation, it can be viewed as a primitive implementation. Correctness-preserving transformations are then used to successively transform the initial design into an efficient implementation. Selection of transformations is guided by an optimization strategy which makes design decisions concerning operation scheduling, data path allocation, and control allocation simultaneously. The integration of these several synthesis subtasks has resulted in a better chance to reach the globally optimal solution. Experimental results show that our approach produces improved register-transfer designs, especially in the cases when the designed hardware consists of data paths and control logics that are tightly coupled. >

Updated and expanded Swedish cohort study on trichloroethylene and cancer risk.

Abstract: There is limited evidence for mutagenicity and carcinogenicity of trichloroethylene (TRI) in experimental test systems. Whether TRI is a human carcinogen is unclear, however. This paper presents an update and extension of a previously reported cohort of workers exposed to TRI, in total 1670 persons. Among men (n = 1421), the overall standardized mortality ratio (SMR) and cancer morbidity ratio (SIR) were close to the expected, with SMR, 0.97; 95% confidence interval (CI), 0.86 to 1.10; and SIR, 0.96; 95% CI, 0.80 to 1.16, respectively. The cancer mortality was significantly lower than expected (SMR, 0.65; 95% CI, 0.47 to 0.89), whereas an increased mortality from circulatory disorders (cardiovascular, cerebrovascular) was of borderline significance (SMR, 1.17; 95% CI, 1.00 to 1.37). No significant increase of cancer of any specific site was observed, except for a doubled incidence of nonmelanocytic skin cancer without correlation with the exposure categories. In the small female subcohort (n = 249), a nonsignificant increase of cancer and circulatory deaths was observed (SMR, 1.53 and 2.02, respectively). For both genders, however, excess risks were largely confined to groups of workers with lower exposure levels or short duration of exposure or both. It is concluded that this study provides no evidence that TRI is a human carcinogen, ie, when the exposure is as low as for this study population.

Childhood Asthma in Four Countries: A Comparative Survey

Abstract: BACKGROUND: Asthma mortality among young people varies widely between different countries. Geographical differences in asthma prevalence are also believed to exist, but evidence is sparse owing to the lack of multicentre surveys using common protocols. A survey was conducted of 12-year-old children living in defined areas of New Zealand, Wales, South Africa and Sweden, in order to see whether asthma prevalence and mortality rates in children show parallel differences. METHODS: Questionnaires enquiring about a history of asthma and respiratory symptoms were issued to the parent. The children performed a simple exercise challenge test. RESULTS: Information was obtained for 4353 children. A history of asthma at any time was reported for 16.8% of children in New Zealand, 12.0% in Wales, 11.5% in South Africa and 4.0% of Sweden, and a similar pattern was shown by several other indices of asthma (various relevant symptoms, inhaler use, response to exercise challenge, and asthma mortality at ages 5-19 years). In Sweden wheezing was negatively associated with pet ownership; elsewhere there was a positive (though non-significant) association. Cat ownership was highest in New Zealand and lowest in Sweden. CONCLUSIONS: The prevalence of asthma in children shows geographical variation which is parallel to that of asthma mortality, being high in New Zealand and low in Sweden. Differential exposure to animal allergens is a possible factor in this variation.