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- Bamberg, Krister, et al.
(författare)
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Electrolyte handling in the isolated perfused rat kidney : demonstration of vasopressin V2-receptor-dependent calcium reabsorption
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 125:4, s. 274-280
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Tidskriftsartikel (refereegranskat)abstract
- Background The most profound effect of vasopressin on the kidney is to increase water reabsorption through V-2-receptor (V2R) stimulation, but there are also data suggesting effects on calcium transport. To address this issue, we have established an isolated perfused kidney model with accurate pressure control, to directly study the effects of V2R stimulation on kidney function, isolated from systemic effects. Methods The role of V2R in renal calcium handling was studied in isolated rat kidneys using a new pressure control system that uses a calibration curve to compensate for the internal pressure drop up to the tip of the perfusion cannula. Results Kidneys subjected to V2R stimulation using desmopressin (DDAVP) displayed stable osmolality and calcium reabsorption throughout the experiment, whereas kidneys not administered DDAVP exhibited a simultaneous fall in urine osmolality and calcium reabsorption. Epithelial sodium channel (ENaC) inhibition using amiloride resulted in a marked increase in potassium reabsorption along with decreased sodium reabsorption. Conclusions A stable isolated perfused kidney model with computer-controlled pressure regulation was developed, which retained key physiological functions. The preparation responds to pharmacological inhibition of ENaC channels and activation of V2R. Using the model, the dynamic effects of V2R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption.
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| 3. |
- Aleksandrova, Krasimira, et al.
(författare)
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A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
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| 5. |
- Beser Hugosson, Muriel, 1968-
(författare)
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Issues in Estimation and Application of Long Distance Travel Demand Models
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Forecasts of the demand for long distance travel areessential for many decisions, such as infrastructureinvestments, operators´management policies etc. Manyresearch issues are related to this field, and the purpose ofthis thesis is to contribute to some of them. Paper I Modellingchoice of flight and booking class–a study using Stated Preference and Revealed Preference data goes into theinteresting issue of modelling departure time and ticket typechoices. The data used in the estimation process were acombination of revealed preference (RP) data and statedpreference (SP) data. A model was developed to estimaterecapture and buyup to improve the SAS (Scandinavian AirlinesSystem) yield management system. Paper II Endogenoussegmentation applied to long distance business trips in Swedenis related to the possibilities of identifying market segmentsthat differ in travel behaviour. The procedure of endogenoussegmentation has been explored to identify different tastesegments in a population. The results indicate that the methodis an efficient way of identifying market segments andoutperforms the traditional manual segmentation when modelefficiency is the objective. The restrictive assumption of independent distributed randomcomponents in the logit model utility function can be relaxedby finding a suitable nesting structure. The task ofestablishing such structures, another crucial issue in traveldemand model development, is further analysed in papers IIIExploring the HEV model to improve nesting structures of modelsfor Swedish long distance private trips and paper IV Enhancingmodel structure and treatment of incomplete geocodes in SAMPERSlong distance models. In paper III a technique to identifyscale parameters for separate alternatives is used. Based onthis, different nesting structures are tested and the resultsare compared with the old mode choice model for long distancetrips in Sweden. This paper leads to paper IV, where similarnesting structures were tested on the long distance mode anddestination choice model in the SAMPERS system. Paper IV alsodeals with data problems, as the destination coding wasincomplete. A final model formulation, related to these issuesis suggested. To turn the view a bit beside the pure estimationtechniques and structures used in the estimation of differentmodels, paper V Quantifying uncertainties in the SAMPERS longdistance forecasting model system considers uncertaintiesrelated to the fact that models are estimated on a sample of apopulation. The bootstrap method, a computer intensivestatistical method, can be used to compute statistical measuresfor very complex systems, without being bound to an analyticalapproach. The bootstrap method is applied on the SAMPERSsystem, and numerical results are presented on different modelsystem output levels.
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| 6. |
- Ciray, Ipek, et al.
(författare)
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Early response of breast cancer bone metastases to chemotherapy evaluated with MR imaging
- 2001
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 42:2, s. 198-206
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- PURPOSE: To compare T1-weighted spin-echo and fat-suppressed long echo time inversion recovery turbo spin-echo (long TE IR-TSE) MR images in the evaluation of early response of breast cancer bone metastases to chemotherapy. MATERIAL AND METHODS: Eighteen breast cancer patients with known bone metastases were investigated prospectively by MR, using T1-weighted and long TE IR-TSE sequences on the sternum, spine, pelvis and proximal femora, before and after a median of 6 courses of chemotherapy. Therapeutic response evaluation with MR was based on change in tumor size assessed quantitatively by measuring all focal metastases, and change in pattern and signal intensity (SI) of the metastases, assessed visually. Combined response evaluation based on clinical findings, conventional radiography, and scintigraphy was used as reference. RESULTS: Progressive disease (2 patients) and no change (4 patients) were assessed equally well on both MR sequences. Long TE IR-TSE demonstrated partial response with higher accuracy than T1-weighted images, 58% (7/12 patients) vs. 17% (2/12 patients). In patients without progression there was an SI increase in or around the metastases in 6 patients on T1-weighted images and in 7 patients on long TE IR-TSE images. CONCLUSION: The long TE IR-TSE sequence demonstrated early partial response of breast cancer bone metastases to chemotherapy more accurately than the T1-weighted sequence.
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| 7. |
- Dam, Mads
(författare)
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Decidability and proof systems for language-based noninterference relations
- 2006
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Ingår i: SIGPLAN notices. - : Association for Computing Machinery (ACM). - 0362-1340 .- 1558-1160. ; 41:1, s. 67-78
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Tidskriftsartikel (refereegranskat)abstract
- Noninterference is the basic semantical condition used to account for confidentiality and integrity-related properties in programming languages. There appears to be an at least implicit belief in the programming languages community that partial approaches based on type systems or other static analysis techniques are necessary for noninterference analyses to be tractable. In this paper we show that this belief is not necessarily true. We focus on the notion of strong low bisimulation proposed by Sabelfeld and Sands. We show that, relative to a decidable expression theory, strong low bisimulation is decidable for a simple parallel while-language, and we give a sound and relatively complete proof system for deriving noninterference assertions. The completeness proof provides an effective proof search strategy. Moreover, we show that common alternative noninterference relations based on traces or input-output relations are undecidable. The first part of the paper is cast in terms of multi-level security. In the second part of the paper we generalize the setting to accommodate a form of intransitive interference. We discuss the model and show how the decidability and proof system results generalize to this richer setting.
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| 8. |
- Dias Batista, Edgard, 1975-
(författare)
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Etanolens hållbarhet – en litteraturöversikt
- 2012
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Rapport (populärvet., debatt m.m.)abstract
- Etanol är ett omdebatterat bränsle bland miljödebattörer och politiker, men även bland forskare. I denna studie har 192 vetenskapligt granskade artiklar om etanol studerats och slutsatserna kvantifierats. Slutsatserna har delats in i sex frågeområden, utöver de övergripande slutsatser om etanol som hållbart drivmedel. Litteraturstudien visar att en majoritet av artiklarna har slutsatser som är positiva till att använda etanol som biodrivmedel. Sammanställningen över artiklarnas övergripande slutsatser, som är den viktigaste frågan i studien, visar att 65 procent av slutsatserna är positiva eller mycket positiva, 10 procent av artiklarna är neutrala eller ofullständiga, medan summan av de negativa och helt negativa slutsatserna är 25 procent. Inom samtliga sex områden är andelen positiva slutsatser högre än de negativa. Frågan där fördelningen är jämnast gäller den om etanolens inverkan på livsmedelspriser och livsmedelsproduktion där 54 procent av artiklarna var positiva eller mycket positiva till använda etanol som drivmedel. 43 procent var negativa eller mycket negativa.
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| 10. |
- Liminga, Gunnar
(författare)
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Functional studies of calcein acetoxymethyl ester in human tumor cells
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A fluorometric assay for functional measurement of P-glycoprotein 170 (Pgp) mediated transport in cell lines, using the acetoxymethyl ester of calcein (calcein/AM) as a probe was established. The myeloma cell line RPMI 8226/S and the two Pgp-expressing doxorubicin resistant subcell lines 8226/dox6 (low) and 8226/dox40 (high) were used. There was significantly lower accumulation of fluorescent calcein in both dox6 and dox40 cells compared to 8226/S. The calcein/AM uptake assay also detected membrane transport related to themultidrug resistance associated protein, MRP1.Furthermore, the in vitro cytotoxic activity of calcein/AM was investigated in cell lines and in primary cultures of patient tumor cells derived from both solid and hematological tumors. Calcein/AM was cytotoxic in the µg/ml (µM) range to both cell lines and patient samples. At 2.5 µg/ml, calcein/AM produced a cell kill greater than 50% in 94% of the hematological and in 63% of the solid tumor samples.In the histiocytic lymphoma cell line, U-937 GTB, calcein/AM at 2.5 µg/ml, induced an almost complete inhibition of DNA synthesis and a partial disruption of the mitochondrial membrane potential within one hour of incubation. This was followed by an increase of caspase-3 activity and an increasing cell fraction judged as apoptotic by morphological and TUNEL evaluation at 3 and 6 h of incubation, respectively.High coefficients of correlation were observed between cytotoxicity of calcein/AM, topoisomerase II active/intercalating agents and mitochondria active compounds, using a cell line panel consisting of 10 cell lines expressing defined mechanisms of resistance. Kinetic studies of extracellular metabolism and confocal microscopy evaluation further supported the notion that calcein/AM interacts with nuclear and/or mitochondrial DNA to induce cytotoxicity and apoptosis.The rapid and potent induction of tumor cell apoptosis in combination with the esterase dependent delivery mechanism makes calcein/AM a candidate for further in vivo evaluation.
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