| 1. |
- Botling, Johan, et al.
(författare)
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Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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| 2. |
- Burke, Derek G., et al.
(författare)
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Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes
- 2013
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 36:5, s. 869-872
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Tidskriftsartikel (refereegranskat)abstract
- Lysosomal glucocerebrosidase (GBA1) deficiency is causative for Gaucher disease. Not all individuals with GBA1 mutations develop neurological involvement raising the possibility that other factors may provide compensatory protection. One factor may be the activity of the non-lysosomal beta-glucosidase (GBA2) which exhibits catalytic activity towards glucosylceramide and is reported to be highly expressed in brain tissue. Here, we assessed brain GBA2 enzymatic activity in wild type, heterozygote and GBA1 deficient mice. Additionally, we determined activity in leucocytes obtained from 13 patients with Gaucher disease, 10 patients with enzymology consistent with heterozygote status and 19 controls. For wild type animals, GBA2 accounted for over 85 % of total brain GBA activity and was significantly elevated in GBA1 deficient mice when compared to heterozygote and wild types (GBA1 deficient; 92.4 +/- 5.6, heterozygote; 71.5 +/- 2.4, wild type 76.8 +/- 5.1 nmol/h/mg protein). For the patient samples, five Gaucher patients had GBA2 leucocyte activities markedly greater than controls. No difference in GBA2 activity was apparent between the control and carrier groups. Undetectable GBA2 activity was identified in four leucocyte preparations; one in the control group, two in the carrier group and one from the Gaucher disease group. Work is now required to ascertain whether GBA2 activity is a disease modifying factor in Gaucher disease and to identify the mechanism(s) responsible for triggering increased GBA2 activity in GBA1 deficiency states.
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| 3. |
- Wu, Xuping, et al.
(författare)
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Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks
- 2012
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier BV. - 0167-4889 .- 1879-2596. ; 1823:12, s. 2130-2135
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Tidskriftsartikel (refereegranskat)abstract
- Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1. week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1 h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer.
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| 4. |
- Calles, Olle, 1974-, et al.
(författare)
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Evaluating technical improvements for downstream migrating diadromous fish at a hydroelectric plant
- 2012
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Ingår i: Ecological Engineering - The Journal of Ecosystem Restoration. - : Elsevier. - 0925-8574. ; 48, s. 30-37
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Tidskriftsartikel (refereegranskat)abstract
- Technical improvements to ameliorate downstream passage for diadromous fish have rarely been eval-uated in regulated rivers in northern Europe. The current study evaluated rehabilitative measures for downstream migrating Atlantic salmon, brown trout and European eel at a hydroelectric plant in south-ern Sweden. Smolts (N= 66), kelts (N= 20) and silver eels (N= 55) were caught, radio-tagged and tracked whilst passing the facilities in spring (salmonids) and fall (eels) of 2007. A surface gate in combination with a 90 mm-spaced turbine intake rack had a fish guidance efficiency ranging from no effect for eels and trout smolts to 50% for trout kelts. A siphon discharging water from the bottom of the same 90 mm rack did not bypass any tagged fish, and only a few untagged eels. The poor function of the measures was attributed to the failure of the rack to stop smolts and eels from entering the turbines. The kelts, on the other hand, could not pass through the rack, and instead took a long time to locate the surface bypass entrance. The conditions for downstream migrating fish have improved at the hydroelectric plant, but the total losses remain quite high for the studied groups (10–67%), and there is a need for a new rehabilitative measure that effectively allows all fish to bypass the turbines.
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| 5. |
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| 6. |
- Calles, Olle, 1974-, et al.
(författare)
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Success of a low-sloping rack for improving downstream passage of silver eels at a hydroelectric plant
- 2013
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Ingår i: Freshwater Biology. - : John Wiley & Sons. - 0046-5070 .- 1365-2427. ; 58, s. 2168-2179
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Tidskriftsartikel (refereegranskat)abstract
- 1. The European eel (Anguilla anguilla) is a critically endangered species, and one major threat is thesurvival of silver eels migrating downstream towards the sea from lake and river rearing areas. Duringthis migration, many eels are impinged and die on intake racks, or are injured or killed whenpassing through turbines.2. Intake racks at a hydroelectric plant were modified to avoid impingement and to collect eels withoutinjury; high mortality on both racks and in turbines was previously documented. Modificationsconsisted of reducing the rack gap width from 20 to 18 mm, decreasing the rack slope from 63 to 35degrees, increasing the rack surface area by 58% and installing six openings in the rack leading totraps.3. Downstream passage conditions for silver eels at the hydroelectric plant were significantlyimproved, reducing mortality from >70% at the old steep 20 mm racks to <10% at the modified18 mm rack collection facility. No tagged eels were impinged and killed on the racks, and 80%entered the collection facility.4. Survival can probably be improved even more, as the individuals that passed the facility mostlikely escaped through holes in the traps. Moreover, injured untagged eels were still encountered atthe modified racks, illustrating the need for rehabilitative measures to be implemented at all obstaclesbetween the main eel rearing areas and the sea.
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| 7. |
- Ginks, Matthew R., et al.
(författare)
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Relationship between intracardiac impedance and left ventricular contractility in patients undergoing cardiac resynchronization therapy
- 2011
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 13:7, s. 984-991
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Tidskriftsartikel (refereegranskat)abstract
- Aims Cardiac resynchronization therapy (CRT) has dramatically improved the symptoms and prognosis of patients with heart failure in large randomized clinical trials. Optimization of device settings may maximize benefit on an individual basis, although the best method for this is not yet established. We evaluated the use of cardiogenic impedance measurements (derived from intracardiac impedance signals) in CRT device optimization, using invasive left ventricular (LV) dP/dt(max) as the reference. Methods and results Seventeen patients underwent invasive haemodynamic assessment using a pressure wire placed in the LV cavity at the time of CRT device implantation. Intracardiac impedance measurements were made at different atrioventricular (AV) and interventricular (VV) delays and compared with LV dP/dt(max). We assessed the performance of patient-specific and generic impedance-based models in predicting acute haemodynamic response to CRT. In two patients, LV catheterization with the pressure wire was unsuccessful and in two patients LV lead delivery was unsuccessful; therefore, data were acquired for 13 out of 17 patients. Left ventricular dP/dt(max) was 919 +/- 182 mmHg/s at baseline and this increased acutely (by 24%) to 1121 +/- 226 mmHg/s as a result of CRT. The patient-specific impedance-based model correctly predicted the optimal haemodynamic response (to within 5% points) for AV and VV delays in 90 and 92% of patients, respectively. Conclusion Cardiogenic impedance measurements are capable of correctly identifying the maximum achievable LV dP/dt(max) as measured by invasive haemodynamic assessment. This study suggests that cardiogenic impedance can potentially be used for CRT optimization and may have a role in ambulatory assessment of haemodynamics.
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| 8. |
- Isaksson, Johan, 1983, et al.
(författare)
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Possibilities to implement pinch analysis in the steel industry – a case study at SSAB EMEA in Luleå
- 2011
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Ingår i: Proceedings of WREC - World Renewable Energy Congress, 8-11 May 2011, Linköping, Sweden. - : Linköping University Electronic Press.
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Konferensbidrag (refereegranskat)abstract
- Steelmaking is an energy intensive industry. Much development work has been accomplished during the past years to make the processes more efficient. Process integration has come to play an important role for identifying efficiency measures, using mathematical programming as general tool. So far only a few minor process integration studies using pinch analysis have been made in this type of industry, and only on smaller subsystems. This paper presents the results of a pinch targeting study that was conducted at the Swedish steel making company SSAB EMEA in Luleå. The pinch analysis methodology was originally developed to study heating, cooling and heat exchange in process systems with many streams. In the steel industry there are relatively few streams that are appropriate for heat exchange. This limits the use of pinch analysis. However, this study demonstrates that pinch analysis is a powerful tool for certain subsystems, especially the gas cleaning unit of the coke plant. The paper includes several suggestions for improved energy efficiency in this section of the steel plant.
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| 9. |
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| 10. |
- Karlsson, Kristian, 1973, et al.
(författare)
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Doppler Spread in Reverberation Chamber Predicted From Measurements During Step-Wise Stationary Stirring
- 2010
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Ingår i: IEEE Antennas and Wireless Propagation Letters. - 1548-5757 .- 1536-1225. ; 9, s. 497 - 500
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Tidskriftsartikel (refereegranskat)abstract
- We propose a simple method to accurately predict Doppler spread in a reverberation chamber (RC) by using frequency domain S-parameters measured with a vector network analyzer (VNA) at many fixed stirrer positions (step-wise stationary mode). Thus, the measurements are done under repeatable stationary conditions, so no Doppler shift is present during the actual measurements. Still, this letter shows that the measured S-parameters in step-wise stationary mode can be used to determine Doppler spread appearing during continuous movement of the stirrers. This can be done by computation for any stirrer speed by assuming that the fixed stirrer position steps are the time steps of a continuous movement of the stirrers, and by adding a virtual stirrer speed between the positions corresponding to the desired continuous movement of the stirrers. The computed Doppler spreads are validated over a large frequency band by measuring the time-varying S-parameters for a given stirrer speed.
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