| 1. |
- Adman, Per, et al.
(author)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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In: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Journal article (pop. science, debate, etc.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 2. |
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| 3. |
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| 4. |
- Brändstedt, Johan, et al.
(author)
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Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case-control study.
- 2012
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 23:8, s. 1377-1385
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the risk of prostate cancer in relation to pre-diagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH, and calcium. METHODS: Nine hundred forty-three incident prostate cancer cases were identified in the Malmö Diet and Cancer Study cohort, and each was matched with one control using incidence density matching with age as the underlying timescale. We also matched for calendar time and age at inclusion. Logistic regression analysis yielded odds ratios with 95 % confidence intervals for different quartiles and deciles. All analyses were repeated stratified for age and body mass index (BMI). RESULTS: We found a weak trend toward increasing prostate cancer risk with rising vitamin D levels (p-trend across quartiles, 0.048). Dividing the cohort into deciles showed a nonlinear association. Compared to decile one, the prostate cancer risk was highest in deciles seven and eight, which corresponded to vitamin D levels of 91-97 nmol/L (1.68; 1.06-2.68), and 98-106 nmol/L (1.80; 1.13-2.85). In the other deciles, there was no association between prostate cancer risk and vitamin D levels. Albumin-adjusted calcium was positively associated with an increased risk for prostate cancer among men aged 55-65 with a BMI <25 (2.07; 1.08-3.97). No association was observed between pre-diagnostic PTH and subsequent prostate cancer incidence, and the stratified analyses revealed no other convincing relationships. CONCLUSIONS: This study suggests a possible weak positive nonlinear association between vitamin D and the risk of prostate cancer.
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| 5. |
- Brändstedt, Johan, et al.
(author)
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Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case-control study.
- 2016
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 27:1, s. 69-80
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Journal article (peer-reviewed)abstract
- Epidemiological studies suggest that low levels of vitamin D (25OHD) constitute a risk factor for more aggressive prostate cancer. We examined the relationship between pre-diagnostic serum levels of vitamin D, parathyroid hormone (PTH), and calcium and risk of prostate cancer according to tumor aggressiveness.
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| 6. |
- Brändstedt, Johan, et al.
(author)
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Vitamin D, PTH, and calcium in relation to survival following prostate cancer
- 2016
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 27:5, s. 669-677
-
Journal article (peer-reviewed)abstract
- PURPOSE: Epidemiological studies suggest that low levels of vitamin D constitute a risk factor for prostate cancer. However, the results are conflicting, perhaps because prostate cancer is a very heterogeneous disease. More recent studies have focused on cancer progression and mortality. Vitamin D is closely related to both calcium metabolism and parathyroid hormone (PTH) levels, and all three factors have been implicated in prostate cancer.METHODS: We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and the risk of death from prostate cancer was analyzed using Cox proportional hazard analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models were adjusted for season and year of inclusion, age at baseline, age at diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason score).RESULTS: We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85-102 nmol/L) compared to the first (<68 nmol/L), HR 0.54 (0.34-0.85) when adjusting for age, time of inclusion, and BMI. The association was further strengthened when adjusted for age at diagnosis, Gleason score, and TNM classification with a HR in Q3 0.36 (0.22-0.60). p for trend was 0.03. Regarding calcium, there was a significantly lower HR for the second quartile (2.35-2.39 mmol/L) compared to the first (≤2.34 mmol/L) with a HR of 0.54 (0.32-0.86) in the unadjusted analysis. However, this association disappeared when adjusting for tumor characteristics. There were no associations between levels of PTH and prostate cancer mortality.CONCLUSION: This study shows that levels of pre-diagnostic vitamin D above 85 nmol/L may improve survival in men with prostate cancer.
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| 7. |
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| 8. |
- Eklund, Anders, et al.
(author)
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Dependence of the colored frequency noise in spin torque oscillators on current and magnetic field
- 2014
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 104:9, s. 092405-
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Journal article (peer-reviewed)abstract
- The nano-scale spin torque oscillator (STO) is a compelling device for on-chip, highly tunable microwave frequency signal generation. Currently, one of the most important challenges for the STO is to increase its longer-time frequency stability by decreasing the 1/f frequency noise, but its high level makes even its measurement impossible using the phase noise mode of spectrum analyzers. Here, we present a custom made time-domain measurement system with 150MHz measurement bandwidth making possible the investigation of the variation of the 1/f as well as the white frequency noise in a STO over a large set of operating points covering 18-25GHz. The 1/f level is found to be highly dependent on the oscillation amplitude-frequency non-linearity and the vicinity of unexcited oscillation modes. These findings elucidate the need for a quantitative theoretical treatment of the low-frequency, colored frequency noise in STOs. Based on the results, we suggest that the 1/f frequency noise possibly can be decreased by improving the microstructural quality of the metallic thin films.
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| 9. |
- Eklund, Anders J., et al.
(author)
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Triple mode-jumping in a spin torque oscillator
- 2013
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In: 2013 22nd International Conference on Noise and Fluctuations, ICNF 2013. - New York : IEEE conference proceedings. - 9781479906680 ; , s. 6578965-
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Conference paper (peer-reviewed)abstract
- In a nano-contact Co/Cu/NiFe spin torque oscillator, mode-jumping between up to three frequencies within 22.5-24.0 GHz is electrically observed in the time domain. The measurements reveal toggling between two states with differing oscillation amplitude, of which the low-amplitude state is further divided into two rapidly alternating modes. Analysis of the mode dwell time statistics and the total time spent in each mode is carried out, and it is found that in both aspects the balance between the modes is greatly altered with the DC drive current.
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| 10. |
- Fedirko, V., et al.
(author)
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Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study
- 2014
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In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 60:4, s. 1222-1230
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Journal article (peer-reviewed)abstract
- The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. © 2014 by the American Association for the Study of Liver Diseases.
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| 11. |
- Malm, Gunilla, et al.
(author)
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Maternal serum vitamin D level in early pregnancy and risk for preeclampsia : A casecontrol study in Southern Sweden
- 2023
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:2 February
-
Journal article (peer-reviewed)abstract
- Background Preeclampsia is considered a major cause of maternal and fetal morbidity and mortality. The aim of the present case-control study in Sweden was to assess the hypothesized association between low serum vitamin D concentrations in early pregnancy and the risk of developing preeclampsia since vitamin D may play a role in early placental development. Methods The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Serum samples were obtained from a biobank of samples collected in early pregnancy including almost all pregnancies in Southern Sweden. Concentrations of 25-hydroxyvitamin D3 (vitamin D) were analyzed using liquid chromatography-tandemmass- spectrometry (LC/MS/MS). The cases were divided into two categories: i) infants were born before gestational week 34 (early onset) and/or born small-for-gestational age (SGA)(n = 51), ii) and others defined as late onset (n = 245). Vitamin D concentrations were analyzed both as a continuous and a categorized variable. Results When all preeclampsia cases were included in the analyses no consistent patterns were observed. However, the median serum concentrations of vitamin D were significantly lower among the cases who were early onset and/or were born SGA (median 39.2 nmol/L, range 1.2-93.6) as compared to the controls (49.0 nmol/L, 0.1-219; p = 0.01). In addition, high concentrations were statistically significantly associated with a decreased risk of preeclampsia (>66.9 vs ≤30.1 nmol/L; crude OR 0.39, 95% CI 0.16-0.96). When potential confounders were included in the models the associations were even more pronounced. Conclusions Our results support the hypothesis that vitamin D deficiency is a risk factor for preeclampsia, but only in preeclampsia cases who were early-onset and/or were born SGA. Preeclampsia is not a homogenous condition and more studies are needed before vitamin D supplementation during pregnancy can be recommended.
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| 12. |
- Malm, Gunilla, et al.
(author)
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Reproductive function during summer and winter in Norwegian men living north and south of the Arctic circle.
- 2004
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 89:9, s. 4397-4402
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Journal article (peer-reviewed)abstract
- Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69° north latitude) and 112 in Oslo (60° north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49 × 106/ml in summer and 54 × 106/ml in winter. Corresponding values for Oslo were 59 × 106/ml and 54 × 106/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P = 0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter).The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility.
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| 13. |
- Malm, Johan, et al.
(author)
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Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: Data from the malmö preventive project
- 2018
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:5, s. 5778-5785
-
Journal article (peer-reviewed)abstract
- Objectives: To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results: After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods: In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions: Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multivariable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. © Assel et al.
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| 14. |
- Pirhonen, Juho, et al.
(author)
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Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer
- 2022
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In: Cancer Research. - 0008-5472. ; 82:21, s. 3932-3949
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Journal article (peer-reviewed)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignancies and potentially curable only with radical surgical resection at early stages. The tumor microenvironment has been shown to be central to the development and progression of PDAC.A better understanding of how early human PDAC metabolically communicates with its environment and differs from healthy pancreas could help improve PDAC diagnosis and treatment. Here we performed deep proteomic analyses from diagnostic specimens of operable, treatment-naive PDAC patients (n 14), isolating four tissue compartments by laser-capture microdissection: PDAC lesions, tumor-adjacent but morphologically benign exocrine glands, and connective tissues neighboring each of these compartments. Protein and pathway levels were compared between compartments and with control pancreatic proteomes. Selected targets were studied immunohistochemically in the 14 patients and in additional tumor microarrays, and lipid deposition was assessed by nonlinear label-free imaging (n = 16). Widespread downregulation of pancreatic secretory functions was observed, which was paralleled by high cholesterol biosynthetic activity without prominent lipid storage in the neoplastic cells. Stromal compartments harbored ample blood apolipoproteins, indicating abundant microvasculature at the time of tumor removal. The features best differentiating the tumor-adjacent exocrine tissue from healthy control pancreas were defined by upregulation of proteins related to lipid transport. Importantly, histologically benign exocrine regions harbored the most significant prognostic pathways, with proteins involved in lipid transport and metabolism, such as neutral cholesteryl ester hydrolase 1, associating with shorter survival. In conclusion, this study reveals prognostic molecular changes in the exocrine tissue neighboring pancreatic cancer and identifies enhanced lipid transport and metabolism as its defining features.
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| 15. |
- Ruhayel, Yasir, et al.
(author)
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Seasonal variation in serum concentrations of reproductive hormones and urinary excretion of 6-sulfatoxymelatonin in men living north and south of the Arctic Circle: a longitudinal study.
- 2007
-
In: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 67:1, s. 85-92
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Journal article (peer-reviewed)abstract
- bjective Seasonal variation in photoperiod or temperature may influence human reproductive biology. The present study evaluated whether seasonal changes occurred in the levels of reproductive hormones and the major melatonin metabolite, 6-sulfatoxymelatonin (aMT6s), in populations exposed to extreme variation in photoperiod and temperature. Design Two separate cohorts of Norwegian men were recruited from the general population in either of two locations: Tromso (69.5 degrees N, n = 92) or Oslo (60 degrees N, n = 112), located north and south of the Arctic Circle (66.5 degrees N), respectively. Measurements Four blood and 12-h overnight urine samples were obtained on separate occasions over a 12-month period, including during the photoperiod maximum and minimum. Serum concentrations of FSH, LH, testosterone (T), oestradiol (E-2), SHBG and the urinary excretion of aMT6s were assessed. Results Statistical analysis using generalized estimating equations indicated that LH levels were lowest during early winter in both locations (both P = 0.01). In Tromso, free T and E-2 concentrations peaked during early winter (P = 0.02 and 0.003, respectively). In Oslo, free T levels were lowest during early winter (P = 0.06) whereas E-2 levels were lowest during late summer (P < 0.001). Urinary aMT6s concentrations were lowest during early summer in Tromso and Oslo. Concentrations peaked during early winter in Tromso (P < 0.001) and during late winter in Oslo (P < 0.001). Conclusion LH levels exhibited similar changes in both locations, whereas the patterns of changes of the sex steroid concentrations differed, possibly indicating different underlying mechanisms. Excretion of aMT6s was lowest during early summer in both locations, indicating that the long natural photoperiod was sufficient to cause suppression of melatonin secretion. Whether these changes have any biological significance remains uncertain.
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| 16. |
- Rylander, Lars, et al.
(author)
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Single semen analysis as a predictor of semen quality: clinical and epidemiological implications.
- 2009
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In: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 11, s. 723-730
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Journal article (peer-reviewed)abstract
- It is generally thought that a single ejaculate is a bad predictor of semen quality of a subject, because of significant intra-individual variation. Therefore, we investigated the degree to which the results of a first semen analysis differ from that of a second analysis among men from a general population in Norway. In addition, we analysed how the two different semen results mirrored the overall semen quality assessment. A total of 199 volunteers participated in the study and delivered two semen samples with an interval of 6 months. The semen parameters were determined according to the World Health Organization (WHO) 1999 guidelines, which were also used to determine whether semen quality was normal or abnormal. In addition, the DNA fragmentation index (DFI) was determined using the Sperm Chromatin Structure Assay. The two samples from each individual were very similar with regard to standard semen parameters and DFI (r(s:) 0.67-0.72), and there were no significant systematic differences between the two samples. The result of the first sample (normal/abnormal) was highly predictive of the overall conclusion based on the two samples (sperm concentration: in 93% of the cases (95% confidence interval [CI]: 89%-96%); sperm motility: in 85% of the cases (95% CI: 79%-89%); overall semen quality: in 85% of the cases (95% CI: 80%-90%). In epidemiological studies, one ejaculate is a sufficient indicator of semen quality in a group of subjects. In a clinical situation, when the question is whether the semen quality is normal or not, the first ejaculate will, in at least 85% of cases, give a correct overall conclusion.
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| 17. |
- Sävblom, C, et al.
(author)
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Association between polymorphisms in the prostate-specific antigen (PSA) promoter and release of PSA
- 2009
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In: International Journal of Andrology. - : Wiley-Blackwell. - 0105-6263 .- 1365-2605. ; 32:5, s. 479-485
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Journal article (peer-reviewed)abstract
- Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte DNA was extracted from 291 conscripts and genotyping performed with the Sequenom Mass Array System. PSA was measured with an immunofluorometric assay. Linear regression analysis was used to test the association of polymorphism frequencies with serum and seminal plasma levels of PSA. PSA gene polymorphisms at -158 bp or -4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in blood. Homozygotes for the A-allele at -158 bp in combination with CAG > 22 had significantly higher serum levels of tPSA than subjects carrying the G-allele (p = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by interactions between PSA promoter variants and AR CAG polymorphism.
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| 18. |
- Thalén, Niklas, 1985-, et al.
(author)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Other publication (other academic/artistic)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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| 19. |
- Thalén, Niklas, et al.
(author)
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Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold
- 2024
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In: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 81, s. 157-166
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Journal article (peer-reviewed)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.
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| 20. |
- Theodorsson, Elvar, 1953-, et al.
(author)
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Salt-Vattenbalansen
- 2003. - 9
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In: Laurells Klinisk kemi i Praktisk Medicin. - Lund : Studentlitteratur. - 9144007663 - 9789144047874 ; , s. 47-70
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Book chapter (other academic/artistic)abstract
- Klinisk kemi i praktisk medicin används som kurslitteratur för läkare, biomedicinska analytiker och biomedicinare sedan 40 år tillbaka. Den finns på avdelningar, mottagningar och vårdcentraler - överallt där man behöver ta prover för kliniskt kemiska analyser och tolka deras resultat. Nu föreligger den i sin nionde upplaga efter omfattande revision och med nyskrivna kapitel. I denna upplaga har innehållet organiserats med tydlig anknytning till kliniska problemområden. Alla kapitel har grundligt reviderats. Avsnitten om tolkning av analysresultat, allergi och autoimmunitet, hjärtinfarkt och hjärtskademarkörer, digestionsorganens sjukdomar, graviditet, infertilitet och prenataldiagnostik samt läkemedel, förgiftningar och missbruk är helt nyskrivna. Boken kan användas både för att slå upp fakta om specifika analyser och för att förstå de sjukdomsmekanismer som är av betydelse för tolkningen av laboratorieresultat. Modern medicinsk praxis är patientcentrerad och har sitt fundament i ett nära samspel mellan klinik, laboratorier och patienter. Kunskapsfragment inom klinisk kemi är lättillgängliga för alla och envar på nätet, men ger sällan den helhetsbild som behövs för grundlig förståelse och därmed optimal användning av laboratorieanalyser. Denna bok ger sådan helhetsbild.
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| 21. |
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| 22. |
- Åkerman, Johan, et al.
(author)
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Impact of intragrain spin wave reflections on nanocontact spin torque oscillators
- 2021
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In: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 103:21
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Journal article (peer-reviewed)abstract
- We investigate the origin of the experimentally observed varying current-frequency nonlinearity of the propagating spin wave mode in nanocontact spin torque oscillators. Nominally identical devices with 100 nm diameter are characterized by electrical microwave measurements and show large variation in the generated frequency as a function of drive current. This quantitative and qualitative device-to-device variation is described in terms of continuous and discontinuous nonlinear transitions between linear current intervals. The thin-film grain microstructure in our samples is determined using atomic force and scanning electron microscopy to be on the scale of 30 nm. Micromagnetic simulations show that the reflection of spin waves against the grain boundaries results in standing wave resonance configurations. For a simulated device with a single artificial grain, the frequency increases linearly with the drive current until the decreased wavelength eventually forces another spin wave antinode to be formed. This transition results in a discontinuous step in the frequency versus current relation. Simulations of complete, randomly generated grain microstructures additionally shows continuous nonlinearity and a resulting device-to-device variation in frequency that is similar to the experimental levels. The impact of temperature from 4 to 300 K on the resonance mode-transition nonlinearity and frequency noise is investigated using simulations and it is found that the peak levels of the spectral linewidth as a function of drive current agree quantitatively with typical levels found in experiments at room temperature. The impact of the grain microstructure on the localized oscillation modes is also investigated. © 2021 authors.
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| 23. |
- Ahmad Tajudin, Asilah, et al.
(author)
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Integrated acoustic immunoaffinity-capture (IAI) platform for detection of PSA from whole blood samples.
- 2013
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In: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 13:9, s. 1790-1796
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Journal article (peer-reviewed)abstract
- On-chip detection of low abundant protein biomarkers is of interest to enable point-of-care diagnostics. Using a simple form of integration, we have realized an integrated microfluidic platform for the detection of prostate specific antigen (PSA), directly in anti-coagulated whole blood. We combine acoustophoresis-based separation of plasma from undiluted whole blood with a miniaturized immunoassay system in a polymer manifold, demonstrating improved assay speed on our Integrated Acoustic Immunoaffinity-capture (IAI) platform. The IAI platform separates plasma from undiluted whole blood by means of acoustophoresis and provides cell free plasma of clinical quality at a rate of 10 uL/min for an online immunoaffinity-capture of PSA on a porous silicon antibody microarray. The whole blood input (hematocrit 38-40%) rate was 50 μl min(-1) giving a plasma volume fraction yield of ≈33%. PSA was immunoaffinity-captured directly from spiked female whole blood samples at clinically significant levels of 1.7-100 ng ml(-1) within 15 min and was subsequently detected via fluorescence readout, showing a linear response over the entire range with a coefficient of variation of 13%.
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| 24. |
- Ahmad Tajudin, Asilah, et al.
(author)
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MALDI-target integrated platform for affinity-captured protein digestion.
- 2014
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In: Analytica Chimica Acta. - : Elsevier BV. - 1873-4324 .- 0003-2670. ; 807:Jan 7, s. 1-8
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Journal article (peer-reviewed)abstract
- To address immunocapture of proteins in large cohorts of clinical samples high throughput sample processing is required. Here a method using the proteomic sample platform, ISET (integrated selective enrichment target) that integrates highly specific immunoaffinity capture of protein biomarker, digestion and sample cleanup with a direct interface to mass spectrometry is presented. The robustness of the on-ISET protein digestion protocol was validated by MALDI MS analysis of model proteins, ranging from 40fmol to 1pmol per nanovial. On-ISET digestion and MALDI MS/MS analysis of immunoaffinity captured disease-associated biomarker PSA (prostate specific antigen) from human seminal plasma are presented.
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| 25. |
- Akselsson, Cecilia, et al.
(author)
-
Impact of harvest intensity on long-term base cation budgets in Swedish forest soils
- 2007
-
In: Water, Air, & Soil Pollution: Focus. - : Springer Science and Business Media LLC. - 1573-2940 .- 1567-7230. ; 7:1, s. 201-210
-
Journal article (peer-reviewed)abstract
- Abstract in UndeterminedThe effects of harvesting on the long-term mass balances of calcium (Ca), magnesium (Mg) and potassium (K) were evaluated on a regional level in Sweden. A new high-resolution weathering database was used together with estimates of total deposition, losses through harvest and leaching. Estimates were made for pine and spruce separately and for two harvesting intensity scenarios: stem harvesting and whole-tree harvesting. The mass balance calculations showed net losses of Ca and Mg in almost the whole country for both scenarios. The losses were smaller for pine than for spruce. The K balances were mainly positive for pine but negative for spruce. Leaching was a main factor in the mass balances, especially for Ca and Mg. Whole-tree harvesting in spruce forests led to substantially higher net losses of K and Ca than stem harvesting, according to the calculations. In the whole-tree harvesting scenario in spruce forests the estimated yearly net losses of Ca, Mg and K corresponded to at least 5%, 8% and 3% of the pools of exchangeable base cations, respectively, at 25% of the analysed sites. If losses of this magnitude continue the depletion of the pools of Ca, Mg and K may lead to very low base saturation of the soils, possibly accompanied by negative effects on soil fertility, runoff water quality, tree vitality and tree growth within a forest rotation in parts of Sweden. Avoiding whole-tree harvesting can improve the situation substantially for K, but the losses of Ca and Mg will still be significant.
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| 26. |
- Akselsson, Cecilia, et al.
(author)
-
Regional övervakning av nedfall och effekter av luftföroreningar :
- 2000
-
Reports (other academic/artistic)abstract
- IVL har tillsammans med länen (Luftvårdsförbund och Länsstyrelser) och Naturvårdsverket utförtett projekt under tre år (1997 till 1999) där de framtida metoderna för att övervaka luftföroreningarmed regional upplösning har utretts och utvecklats. Utredningen har resulterat i ett förslag till framtidaregional miljöövervakning av luftföroreningar som omfattar en kombination av mätningar ochresultat från andra program. Samordningen innebär att resultatredovisningen blir mer komplett ochanpassad till nya krav på indikatorer och uppföljningsmått. Programmet omfattar följande moment;deposition, halter i luft och markvatten, modellberäkningar, lagring, bearbetning och utvärdering avdata, redovisning samt samordning, kvalitetssäkring och programutveckling. Samarbetsprojektet harutvärderat de olika momenten och utvecklat rutiner för lagring, bearbetning och redovisning avresultat i form av länsrapporter och en hemsida. Förbättrade metoder att mäta och beräkna den totaladepositionen av baskatjoner och kväve till skog har utvecklats inom projektet.
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| 27. |
- Akselsson, Cecilia, et al.
(author)
-
Regional övervakning av nedfall och effekter av luftföroreningar - Sammanfattande slutrapport från ett samarbetsprojekt mellan IVL, länen och Naturvårdsverket.
- 2000
-
Reports (other academic/artistic)abstract
- IVL har tillsammans med länen (Luftvårdsförbund och Länsstyrelser) och Naturvårdsverket utfört ett projekt under tre år (1997 till 1999) där de framtida metoderna för att övervaka luftföroreningar med regional upplösning har utretts och utvecklats. Utredningen har resulterat i ett förslag till framtida regional miljöövervakning av luftföroreningar som omfattar en kombination av mätningar och resultat från andra program. Samordningen innebär att resultatredovisningen blir mer komplett och anpassad till nya krav på indikatorer och uppföljningsmått. Programmet omfattar följande moment; deposition, halter i luft och markvatten, modellberäkningar, lagring, bearbetning och utvärdering av data, redovisning samt samordning, kvalitetssäkring och programutveckling. Samarbetsprojektet har utvärderat de olika momenten och utvecklat rutiner för lagring, bearbetning och redovisning av resultat i form av länsrapporter och en hemsida. Förbättrade metoder att mäta och beräkna den totala depositionen av baskatjoner och kväve till skog har utvecklats inom projektet
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| 28. |
- Almeida, Natália, et al.
(author)
-
Mapping the melanoma plasma proteome (MPP) using single-shot proteomics interfaced with the WiMT database
- 2021
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 13:24
-
Journal article (peer-reviewed)abstract
- Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom protein databases for ID generation. This entails a multi-level dynamic protein database with different immunodepletion strategies by applying single-shot proteomics. The highest number of melanoma plasma proteins from undepleted and unfractionated plasma was reported, mapping >1200 proteins from >10,000 protein sequences with confirmed significance scoring. Of these, more than 660 proteins were annotated by WiMT from the resulting ~5800 protein sequences. We could verify 4000 proteins by MS1t analysis from HeLA extracts. The WiMT platform provided an output in which 12 previously well-known candidate markers were identified. We also identified low-abundant proteins with functions related to (i) cell signaling, (ii) immune system regulators, and (iii) proteins regulating folding, sorting, and degradation, as well as (iv) vesicular transport proteins. WiMT holds the potential for use in large-scale screening studies with simple sample preparation, and can lead to the discovery of novel proteins with key melanoma disease functions.
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| 29. |
- Almquist, Martin, et al.
(author)
-
Reproductive history, lifestyle factors and season as determinants for serum calcium concentrations in women.
- 2008
-
In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 777-785
-
Journal article (peer-reviewed)abstract
- Objective. Serum calcium concentrations have been associated with the risk of malignant disease, especially breast cancer. Thus, determinants of serum calcium concentrations, with special regard to risk factors of breast cancer, are of great interest. Material and methods. Previous studies have either been small or they have not focused on reproductive factors. The present study examined serum calcium concentrations in relation to reproductive history, selected lifestyle factors and screening season in a large population-based cohort study comprising 8,114 women. ANOVA followed by the Bonferroni t-test were used for comparison of means, and logistic regression and multiple regression analysis were used to test associations. Results. Serum calcium concentrations were lower in hormone replacement therapy users versus non-users (2.321 mmol/L versus 2.364; p<0.001) and in users of oral contraceptives versus non-users (2.304 versus 2.348; p<0.001). They were higher in peri-/postmenopausal versus premenopausal women (2.357 versus 2.319; p<0.001). Overweight and obese women had higher mean calcium concentrations (2.350 and 2.355) than women with body mass index between 20 and 25 (2.342; p<0.001). Serum calcium concentrations were higher in spring and autumn than in winter (2.352 and 2.353 versus 2.343; p = 0.002). Both younger (40-45 years) (2.334; p = 0.001) and older age groups (>55 years) (2.363; p<0.001) had higher mean calcium concentrations compared to those of women aged 45-50 years (2.320), even when adjusting for menopausal status, suggesting that age has an independent influence on calcium concentrations. Conclusions. It is concluded that reproductive factors such as menopausal status, use of oral contraceptives or hormone-replacement therapy, and age, BMI and season are associated with serum calcium concentrations.
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| 30. |
- Almquist, Martin, et al.
(author)
-
Serum calcium and tumour aggressiveness in breast cancer: a prospective study of 7847 women.
- 2009
-
In: European Journal of Cancer Prevention. - 1473-5709. ; 18, s. 354-360
-
Journal article (peer-reviewed)abstract
- Experimental, epidemiological and clinical studies suggest that calcium and/or its regulating hormones affect breast cancer risk. There has been no prospective cohort study investigating serum calcium levels and breast cancer aggressiveness, as determined by tumour histology and stage. Dichotomized prediagnostic serum calcium levels were investigated in relation to breast cancer aggressiveness as determined by grade (mitotic frequency, tubule formation, nuclear atypia) and stage (tumour size and axillary lymph node status). Cox's proportional hazards analysis and heterogeneity analysis were used to investigate the associations between low/high calcium and grade/stage in a prospective cohort study of 7847 women, out of whom 462 women were diagnosed with incident breast cancer during a mean follow-up of 17.2 years. All analyses were stratified for body mass index and menopausal status. Prediagnostic serum calcium levels in premenopausal women were positively associated with increased tumour aggressiveness as determined by a higher risk of nodal metastasis; relative risk (RR) for calcium above median as compared with calcium below median was 1.88 with a 95% confidence interval (CI) of 1.04-3.38. In overweight women, prediagnostic serum calcium levels were also associated with tumour aggressiveness, as determined by both a higher risk of nodal metastasis [RR (95% CI) 1.69 (0.95-3.02)] and severe nuclear atypia [RR (95% CI) 2.06 (1.10-3.86)]. Results also indicate that, in overweight women, calcium is positively associated with worse grade as determined by tubule formation and mitotic frequency. In conclusion, prediagnostic serum calcium levels are positively associated with increased tumour aggressiveness in premenopausal and/or overweight women.
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| 31. |
- Almquist, Martin, et al.
(author)
-
Serum levels of vitamin D, PTH, calcium and breast cancer risk - a prospective nested case-control study.
- 2010
-
In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 127:9, s. 2159-2168
-
Journal article (peer-reviewed)abstract
- Previous studies indicate that calcium and its regulating hormones, i.e. parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to pre-diagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH and calcium using a nested case-control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analysed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD(3), PTH and calcium. There was a weak, non-significant inverse association between breast cancer risk and 25OHD(3), and the OR for the 2(nd), 3(rd) and 4(th) quartiles, as compared to the first, were 0.84(0.60-1.15), 0.84(0.60-1.17), and 0.93(0.66-1.33). Serum calcium was positively associated with breast cancer in pre-menopausal women (OR for the 4(th) quartile = 3.10:1.33-7.22 and p for quartile trend=0.04), and in women with BMI>25 (OR for the 4(th) quartile=1.94:1.12-3.37 and p for trend<0.01). There was no association between baseline serum PTH and breast cancer risk. (c) 2010 UICC.
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| 32. |
- Alveteg, Mattias, et al.
(author)
-
Vad räknas som belägg för studenters måluppfyllelse?
- 2018
-
In: 10:e Pedagogiska Inspirationskonferensen 2018. - 2003-3761 .- 2003-377X. ; 10
-
Conference paper (peer-reviewed)abstract
- Universitetskanslerämbetet (UKÄ) ställer numera krav på svenska lärosäten att vi ska utvärdera oss själva. Vi på LTH bör då gemensamt försöka hitta sätt att uppfylla UKÄs krav som även ger de verktyg vi själva behöver för att förbättra våra utbildningars kvalitét.Hur tar vi reda på våra utbildningars styrkor och svagheter och vad vi kan göra för att förbättra dem ytterligare? Ett sätt är att undersöka hur väl studenterna uppfyller examensmålen. Vad som ska räknas som belägg för studenters måluppfyllelse är dock svårt, av flera olika skäl. Vår rekommendation blir att triangulera olika typer av belägg samt att tydligt involvera institutionerna i arbetet.
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| 33. |
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| 34. |
- Andersson, E., et al.
(author)
-
Isolation of human cationic antimicrobial protein-18 from seminal plasma and its association with prostasomes.
- 2002
-
In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 17:10, s. 34-2529
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cathelicidins are a group of antibiotic peptides with broad antimicrobial activity. They are considered to be an essential part of the innate immune system. The only known human cathelicidin is the human cationic antimicrobial protein (hCAP-18), from which the antimicrobial peptide LL-37 is released. METHODS AND RESULTS: In the present study, we purified hCAP-18 from seminal plasma and confirmed its identity by N-terminal amino acid sequencing. Gel filtration of seminal plasma showed the presence of hCAP-18 in both a low and a high molecular weight peak. Fractions corresponding to the high molecular form of hCAP-18 also contained dipeptidyl peptidase IV (CD26), a prostasome marker. This finding suggested that hCAP-18 found in fractions corresponding to high molecular weight molecules, is prostasome-associated. Flow cytometry confirmed the association of hCAP-18 with prostasomes and indicated that the molecule is surface bound. Western blot showed the presence of intact hCAP-18 in sperm, prostasomes and ultracentrifuged seminal plasma. CONCLUSIONS: These findings suggest that hCAP-18 may have an important role in antimicrobial defence during human reproduction. The binding of hCAP-18 to prostasomes indicates that protasomes can serve as a reservoir of this precursor of the antibiotic peptide LL-37.
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| 35. |
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| 36. |
- Andrée, Martin, et al.
(author)
-
Slutrapport för projektet Smart planering för byggande : Delprojekt 3 - BIM som informationsstöd för 3D fastighetsbildning
- 2018
-
Reports (other academic/artistic)abstract
- Samhällsbyggnadsprocessen behöver utvecklas och bli smartare, öppnare och mer effektiv för ett ökat bostadsbyggande. En digitalisering av samhällsbyggnadsprocessen kan ge ett effektivare samarbete mellan kommun, fastighetsägare, byggherrar, medborgare, näringsliv och myndigheter.Vid bildande av tredimensionellt avgränsade fastigheter eller fastighetsutrymmen (3D-fastigheter) behöver gränsernas läge redovisas både verbalt och i kartor och ritningar, detsamma gäller berörda rättigheter. Det är idag ofta svårt att korrekt redovisa en 3D-volym med enbart dagens pappersritningar och även svårt att läsa en registerkarta i 2D med fastigheter och rättigheter beslutade i 3D. Beslutsunderlagen i fastighetsbildnings-processen behöver bli mer enhetliga och entydiga samt fastighetsinformationen behöver bli återanvändningsbar i hela samhällsbyggnadsprocessen.I detta projekt har vi studerat informationsbehovet i de olika tidpunkterna under fastighetsbildningsprocessen för 3D-fastigheter med fokus på vem som är ansvarig för att tillhandahålla informationsunderlag för att identifiera krav på utformning av 3D-modeller (t.ex BIM) och 3D-stöd för fastighetsbildning.Internationellt finns det ett stort intresse och många frågeställningar gällande samspelet mellan BIM och Fastighetsinformation; det är däremot ganska få fall som har identifierats där man har arbetat praktiskt med BIM i relation till redovisning av 3D-fastigheter.Projektethar även tittat på behov av visualisering och tillhandahållande av fastighetsinformation i 3D, hur informationen bör utformas för att kunna tolkas korrekt samt nyttjas vidare av andra aktörer i samhällsbyggnadsprocessen.Slutsatsen i projektetär att en framtida arbetsmodell där man i samband med myndighetsutövningen för fastighetsbildning samverkar med stöd av BIM och geografisk information i ärendehandläggningen kan ge stora effekter på både myndighetens effektivitet och i ärendeutövningen och för förståelsen av fastighetbildningsbeslutet hos samtliga intressenter i processen. För att det arbete som genomförts i denna utredning skall få genomslag i den dagliga verksamheten rekommenderar vibland annatatt de statliga och kommunala lantmäterimyndigheterna arbetar vidare med att utveckla arbetsprocessen och rekommendationerna för 3D-fastighetsbildning baserat på resultatet från detta projekt och redan i dagens modell efterfrågar att man i handläggningsprocessen kan arbeta BIM-baserat även om kommande beslutshandlingar under en övergångsperiod fortfarande kommer att vara baserade på ritningsbilagor i 2D.
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| 37. |
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| 38. |
- Aniander, Gustav
(author)
-
Improved candidate screening through tailored co-culture assays and precise tuning of protein expression
- 2024
-
Licentiate thesis (other academic/artistic)abstract
- The field of biopharmaceuticals is a rapidly growing one. In the last ten years the number of approved biopharmaceuticals has more than doubled. A major hurdle to overcome for increased availability of all the new, effective biopharmaceuticals is the cost of treatment. Much of this can be attributed to the sheer time required for their development. Owing to this, interest in improvements to the biopharmaceuticals and their development process has also rapidly increased. As costs increase the further into development a drug candidate progresses, increasing the fidelity of screening at early stages could alleviate some of the exorbitant costs of development.In paper I, we showcase a novel way of targeting the tumor microenvironment (TME) to allow for TMElocalized CD40 activation. This is of interest as CD40 agonists have shown great potential for immune activation, but with systemic activation leading to severe adverse effects. The localized activation is achieved through the construction of an affinity fusion protein termed an AffiMab through fusion of a platelet derived growth factor receptor beta (PDGFRβ) targeting affibody to the heavy chain of a CD40 agonistic monoclonal antibody (mAb). We demonstrate PDGFRβ-dependent activation in a variety of assays, showing that the approach merits further investigation.Building on the activation assays set up in paper I, we aim to generate an in vitro screening platform for immune cell engagers in paper II. Screening candidates for on-target off-tumor activation is essential, as such activation would lead to adverse effects and be a doselimiting factor. To screen for this, we construct a series of plasmids which upon transfecting cells allow for different levels of a cell-surface target protein to be expressed, a so-called target density panel. This is achieved through the use of hairpin forming elements in the 5’ untranslated region of the mRNA dubbed regulatory elements (RgEs). Through use of different RgEs, we show that a target density panel can be generated and validate it in activation assays with the AffiMab developed in paper I. The platforms’ uniform cell surface background due to all different levels of target being expressed in the same host cell line and tunability through use of different RgEs are features that make it interesting for further research.Finally in paper III, we construct and test an improved translation initiation site (TIS) sequence. Using previous studies on the impact of the nucleotides in the sequence on the efficacy of the TIS, we constructed a novel sequence, TISNOV. This sequence enhanced titer and quality for recombinant production of IgG1 and IgG4 in both stable and transient settings. Further research into other TIS sequences and their uses in regulating protein expression, as well as usage of the TISNOV to improve expression of difficult to express proteins such as bispecifics remain interesting.In conclusion this thesis focuses on different manners to improve and hasten development of new biopharmaceuticals through usage of new workflows, platforms, and genetic engineering strategies.
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| 39. |
- Augustsson, Per, et al.
(author)
-
Acoustophoretic microfluidic chip for sequential elution of surface bound molecules from beads or cells
- 2012
-
In: Biomicrofluidics. - : AIP Publishing. - 1932-1058. ; 6:3
-
Journal article (peer-reviewed)abstract
- An acoustophoresis-based microfluidic flow-chip is presented as a novel platform to facilitate analysis of proteins and peptides loosely bound to the surface of beads or cells. The chip allows for direct removal of the background surrounding the beads or cells, followed by sequential treatment and collection of a sequence of up to five different buffer conditions. During this treatment, the beads/cells are retained in a single flow by acoustic radiation force. Eluted peptides are collected from the outlets and subsequently purified by miniaturized solid-phase extraction and analyzed with matrix assisted laser desorption mass spectrometry. Fundamental parameters such as the system fluidics and dispersion are presented. The device was successfully applied for wash and sequential elution of peptides bound to the surface of microbeads and human spermatozoa, respectively. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4749289]
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| 40. |
- Axelsson, Ida, et al.
(author)
-
Does microbiological contamination of homografts prior to decontamination affect the outcome after right ventricular outflow tract reconstruction?
- 2021
-
In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9293 .- 1569-9285. ; 33:4, s. 605-613
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Homografts are often in short supply. Today, European guidelines recommend that all tissues contaminated by any of 18 different bacteria and fungi be discarded before antibiotic decontamination has been conducted. The tissue bank in Lund uses more liberal protocols: It accepts all microbes prior to decontamination except multiresistant microbes and Pseudomonas species. The aim of this study was to analyse the effect of contamination on the long-term outcome and occurrence of endocarditis in recipients. METHODS: Data were collected on homografts and on recipients of homografts in the right ventricular (RV) outflow tract who were operated on between 1995 and 2018 in Lund. The long-term outcome of recipients was analysed in relation to different types of contamination using Cox proportional hazard regression. The proportion of patients with endocarditis was analysed with the χ2 test. RESULTS: The study included 509 implanted homografts. Follow-up was a maximum of 24 years and 99% complete. A total of 156 (31%) homografts were contaminated prior to antibiotic decontamination. Homografts contaminated with low-risk microbes had the lowest reintervention rate, but there was no significant difference compared to no contamination [hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.73-1.7] or contamination with high-risk microbes (HR 1.6, 95% CI 0.87-2.8) in the multivariable analysis. There was no significant difference in the proportion of cases of endocarditis during the follow-up period between recipients of homografts contaminated prior to decontamination and recipients of homografts with no contamination (P = 0.83). CONCLUSIONS: Contamination of homograft tissue prior to decontamination did not show any significant effect on the long-term outcome or the occurrence of endocarditis after implantation in the RV outflow tract. Most contaminated homografts can be used safely after approved decontamination.
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| 41. |
- Axelsson, Ida, et al.
(author)
-
Impact of storage time prior to cryopreservation on mechanical properties of aortic homografts
- 2024
-
In: Cell and Tissue Banking. - : Springer Science and Business Media LLC. - 1389-9333 .- 1573-6814.
-
Journal article (peer-reviewed)abstract
- Optimal time spans in homograft procurement are still debatable among tissue banks and needs to be further investigated. Cell viability decreases at longer preparation intervals, but the effect on collagen and elastic fibers has not been investigated to the same extent. These fibers are of importance to the homograft elasticity and strength. The objective of this study was to analyze the mechanical properties of homograft tissue at different time spans in the procurement process. Ten aortic homografts were collected at the Tissue Bank in Lund. Twelve samples were obtained from each homograft, cryopreserved in groups of three after 2–4 days, 7–9 days, 28–30 days, and 60–62 days in antibiotic decontamination. Mechanical testing was performed with uniaxial tensile tests, calculating elastic modulus, yield stress and energy at yield stress. Two randomly selected samples were assessed with light microscopy. Procurement generated a total of 120 samples, with 30 samples in each time group. Elastic modulus and yield stress was significantly higher in samples cryopreserved after 2–4 days (2.7 MPa (2.5-5.0) and 0.78 MPa (0.68-1.0)) compared to 7–9 days (2.2 MPa (2.0-2.6) and 0.53 MPa (0.46–0.69)), p = 0.008 and 0.011 respectively. Light microscopy did not show any difference in collagen and elastin at different time spans. There was a significant decrease in elastic modulus and yield stress after 7 days of decontamination at 4 °C compared to 2–4 days. This could indicate some deterioration of elastin and collagen at longer decontamination intervals. Clinical significance of these findings remains to be clarified.
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| 42. |
- Axelsson, Ida, et al.
(author)
-
Impact of valve fenestrations and structural changes in homografts on the long-term outcome in the recipient
- 2021
-
In: Cell and Tissue Banking. - : Springer Science and Business Media LLC. - 1389-9333 .- 1573-6814. ; 22:3, s. 399-408
-
Journal article (peer-reviewed)abstract
- Homografts have long been used for right ventricular outflow tract (RVOT) reconstruction. Tissue banks struggle to meet the clinical demand of tissue, with insufficient donor availability and strict recommendations on tissue quality with high proportions of discards. This study analyzes the long-term outcome of patients receiving a homograft with small fenestrations of the cusps or other structural changes, to evaluate if minor impairment of the homograft affects the durability. Homograft characteristics and patient outcome were described. Follow-up was maximum 24 years. Structural changes of the homografts were analyzed in relation to patient outcome, using univariable and multivariable Cox proportional hazard regression. Between 1995 and 2018, 468 patients received 535 homografts in the RVOT in Lund. Median recipient age was 13 years. There were 137 (26.9%) reinterventions. Freedom from reintervention was 75.8% (95% CI 71.3–79.7%) at 10 years and 57.4% (95% CI 50.0–64.0%) at 20 years. Small fenestrations of the cusps, fibrosis of the cusps and minor atheromatosis of the vessel did not show any statistically significant impact on long-term outcome, hazard ratio = 0.46 (95% CI 0.11–1.87, p = 0.276) and hazard ratio = 0.80 (95% CI 0.25–2.56, p = 0.704). Minor structural changes of the homografts seem to be acceptable without affecting the long-term durability.
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| 43. |
- Banuazizi, Seyed Amir Hossein, et al.
(author)
-
Control of thermal budget in nanocontact spin-torque nano-oscillators
-
Other publication (other academic/artistic)abstract
- We investigate the influence of the bottom Cu electrode thickness (tCu) in nanocontact spin-torque nano-oscillators (NC-STNOs) based on Si/SiO2/Pd(8)/Cu(tCu)/Co(8)/Cu(7)/NiFe(4.5)/Cu(3)/Pd(3) GMR stacks on the thermal budget of the magnetodynamically active region. Increasing tCu from 10 to 70 nm results in a ~50% reduction in Joule heating in both the Co and NiFe layers, which directly improves the microwave output stability and linewidth. Numerical simulations of the NC-STNO current distribution suggest that this improvement originates from a strongly reduced lateral current spread in the top ferromagnetic layer and a reduction in the device's resistance.
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| 44. |
- Banuazizi, Seyed Amir Hossein, et al.
(author)
-
Order of magnitude improvement of nano-contact spin torque nano-oscillator performance
- 2017
-
In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 9:5, s. 1896-1900
-
Journal article (peer-reviewed)abstract
- Spin torque nano-oscillators (STNO) represent a unique class of nano-scale microwave signal generators and offer a combination of intriguing properties, such as nano sized footprint, ultrafast modulation rates, and highly tunable microwave frequencies from 100 MHz to close to 100 GHz. However, their low output power and relatively high threshold current still limit their applicability and must be improved. In this study, we investigate the influence of the bottom Cu electrode thickness (t(Cu)) in nano-contact STNOs based on Co/Cu/NiFe GMR stacks and with nano-contact diameters ranging from 60 to 500 nm. Increasing t(Cu) from 10 to 70 nm results in a 40% reduction of the threshold current, an order of magnitude higher microwave output power, and close to two orders of magnitude better power conversion efficiency. Numerical simulations of the current distribution suggest that these dramatic improvements originate from a strongly reduced lateral current spread in the magneto-dynamically active region.
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| 45. |
- Banuazizi, Seyed, et al.
(author)
-
Order of magnitude improvement of nano-contact spin torque nano-oscillator performance
- 2017
-
In: 2017 IEEE International Magnetics Conference, INTERMAG 2017. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538610862
-
Conference paper (peer-reviewed)abstract
- Spin torque nano-oscillators [1,2] (STNO) represent a unique class of nano-scale microwave signal generators where spin transfer torque [3-5] (STT) from a direct spin-polarized current drives and controls the auto-oscillation of the local free layer magnetization, which through its oscillating magnetoresistance transforms the direct current into a tunable microwave voltage.
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| 46. |
- Barbara Sahlin, K., et al.
(author)
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Short-term effect of induced alterations in testosterone levels on fasting plasma amino acid levels in healthy young men
- 2021
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In: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
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Journal article (peer-reviewed)abstract
- Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term T alterations were induced. We designed a human model of 30 healthy young males with pharmacologically induced T changes, which resulted in three time points for blood collection: (A) baseline, (B) low T (3 weeks post administration of gonadotropin releasing hormone antagonist) and (C) restored T (2 weeks after injection of T undecanoate). The influence of T on AAs was analyzed by spectrophotometry on plasma samples. Levels of 9 out of 23 AAs, of which 7 were essential AAs, were significantly increased at low T and are restored upon T supplementation. Levels of tyrosine and phenylalanine were most strongly associated to T changes. Short-term effect of T changes suggests an increased protein breakdown that is restored upon T supplementation. Fasting AA levels are able to monitor the early metabolic changes induced by the T fluctuations.
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| 47. |
- Bauer, Mikael, et al.
(author)
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Zn2+ binding to human calbindin D(28k) and the role of histidine residues.
- 2008
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In: Protein Science. - : Wiley. - 1469-896X .- 0961-8368. ; 17:4, s. 760-767
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Journal article (peer-reviewed)abstract
- We have studied the binding of Zn2+ to the hexa EF-hand protein, calbindin D(28k)-a strong Ca2+-binder involved in apoptosis regulation-which is highly expressed in brain tissue. By use of radioblots, isothermal titration calorimetry, and competition with a fluorescent Zn2+ chelator, we find that calbindin D(28k) binds Zn2+ to three rather strong sites with dissociation constants in the low micromolar range. Furthermore, we conclude based on spectroscopic investigations that the Zn2+-bound state is structurally distinct from the Ca2+-bound state and that the two forms are incompatible, yielding negative allosteric interaction between the zinc- and calcium-binding events. ANS titrations reveal a change in hydrophobicity upon binding Zn2+. The binding of Zn2+ is compatible with the ability of calbindin to activate myo-inositol monophosphatase, one of the known targets of calbindin. Through site-directed mutagenesis, we address the role of cysteine and histidine residues in the binding of Zn2+. Mutation of all five cysteines into serines has no effect on Zn2+-binding affinity or stoichiometry. However, mutating histidine 80 into a glutamine reduces the binding affinity of the strongest Zn2+ site, indicating that this residue is involved in coordinating the Zn2+ ion in this site. Mutating histidines 5, 22, or 114 has significantly smaller effects on Zn2+-binding affinity.
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| 48. |
- Bech-Hanssen, Odd, 1956, et al.
(author)
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Pressure reflection in the pulmonary circulation in patients with severe mitral regurgitation indicates adverse postoperative outcome.
- 2013
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In: European Journal Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 44:6, s. 1037-1044
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Severe pulmonary hypertension (PH) is a known risk factor in valvular surgery. In the present study, we hypothesized that the assessment of pressure reflection (PR) in the pulmonary circulation, indicating increased pulmonary vascular resistance, might improve the identification of patients with increased morbidity and mortality following surgery for severe mitral regurgitation. METHODS: A total of 103 patients without atrial fibrillation were divided into three groups: Group 1 (n = 48), patients without PR; Group 2 (n = 36), patients with PR and pulmonary artery systolic pressure (PASP) ≤60 mmHg and Group 3 (n = 19), patients with PR and PASP >60 mmHg. Three variables related to PR were selected: the acceleration time in the right ventricular outflow tract (RVOT), the interval between peak velocity in the RVOT and peak tricuspid regurgitant jet velocity and the right ventricular pressure increase after peak RVOT velocity. RESULTS: There were no differences between groups in age, ejection fraction, need for coronary bypass grafting or creatinine. Patients with PR (Groups 2 and 3) had more use of vasoactive drugs (overall P < 0.0001, Group 1 vs Group 2 P = 0.018). The proportion of patients with >24 h in the intensive care unit was 27% in Group 1, 54% in Group 2 and 84% in Group 3 (overall P < 0.0001, Group 1 vs Group 2 P = 0.006). The in-hospital mortality in patients without PR (n = 49) was 0% compared with 10.9% in patients with PR (P = 0.029). CONCLUSIONS: Echocardiography assessment of PR in the pulmonary circulation and severe PH may identify patients with adverse outcome following mitral surgery.
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| 49. |
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| 50. |
- Berkenstam, Anders, et al.
(author)
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The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans
- 2008
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:2, s. 663-667
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Journal article (peer-reviewed)abstract
- Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115, (3-[[3,5-dibromo-4- [4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis. © 2007 by The National Academy of Sciences of the USA.
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