| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 3. |
- Bost, Jeremy P., et al.
(författare)
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Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
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| 4. |
- Evans Axelsson, Susan, et al.
(författare)
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Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.
- 2014
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Ingår i: American journal of nuclear medicine and molecular imaging. - 2160-8407. ; 4:4, s. 311-323
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.
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| 5. |
- Evans Axelsson, Susan, et al.
(författare)
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Radioimmunotherapy for Prostate Cancer-Current Status and Future Possibilities.
- 2016
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Ingår i: Seminars in Nuclear Medicine. - : Elsevier BV. - 0001-2998. ; 46:2, s. 165-179
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Forskningsöversikt (refereegranskat)abstract
- Prostate cancer (PCa) is one of the most common cancers in men and is the second leading cause of cancer-related deaths in the USA. In the United States, it is the second most frequently diagnosed cancer after skin cancer, and in Europe it is number one. According to the American Cancer Society, approximately 221,000 men in the United States would be diagnosed with PCa during 2015, and approximately 28,000 would die of the disease. According to the International Agency for Research on Cancer, approximately 345,000 men were diagnosed with PCa in Europe during 2012, and despite more emphasis placed on early detection through routine screening, 72,000 men died of the disease. Hence, the need for improved therapy modalities is of utmost importance. And targeted therapies based on radiolabeled specific antibodies or peptides are a very interesting and promising alternative to increase the therapeutic efficacy and overall chance of survival of these patients. There are currently several preclinical and some clinical studies that have been conducted, or are ongoing, to investigate the therapeutic efficacy and toxicity of radioimmunotherapy (RIT) against PCa. One thing that is lacking in a lot of these published studies is the dosimetry data, which are needed to compare results between the studies and the study locations. Given the complicated tumor microenvironment and overall complexity of RIT to PCa, old and new targets and targeting strategies like combination RIT and pretargeting RIT are being improved and assessed along with various therapeutic radionuclides candidates. Given alone or in combination with other therapies, these new and improved strategies and RIT tools further enhance the clinical response to RIT drugs in PCa, making RIT for PCa an increasingly practical clinical tool.
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| 6. |
- Hilling, Axel, et al.
(författare)
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Equal taxation as a basis for classifying financial instruments as debt or equity - a Swedish case study
- 2015
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Ingår i: eJournal of Tax Research. - 1448-2398. ; 13:3, s. 677-715
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Tidskriftsartikel (refereegranskat)abstract
- This article examines the way in which classification of financial instruments as debt or equity has developed in the Swedish income taxation system over the past 25 years. Although the structure of the tax system is based on the assumption that debt instruments are financial instruments with low risk, legal developments have not shared that assumption, resulting in several types of high-risk derivative instruments being covered by the definition of legal debt. This article illustrates how those developments, which can be recognized in most income-tax systems within OECD countries, seriously threatens the fundament of the tax system: equal taxation for capital income and income from labor. The article concludes by illustrating how the standard solution to the problem of classifying financial instruments as debt and equity – by treating them alike – does not fulfill the challenged principle of equal taxation, but actually intensifies the development towards unequal taxation.
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| 7. |
- Hilling, Axel, et al.
(författare)
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Lagen är lika för alla, men är alla verkligen lika inför lagen? : En studie av Skatteverkets processföring i PwC-målet
- 2018
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Ingår i: Förvaltningsrättslig tidskrift. - 0015-8585. ; :2, s. 269-286
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Tidskriftsartikel (refereegranskat)abstract
- För korrekt beskattning i komplicerade mål är det viktigt att Skatteverket kan utvärdera och presentera sakomständigheter på ett kvalificerat sätt. Skattebetalare med hög kompetens har annars större möjligheter att hävda sin rätt jämfört med skattebetalare som saknar sådan kompetens, vilket står i konflikt med likabehandlingsprincipen. I artikeln illustreras vikten av en kvalificerad förvaltningsmyndighet för att rättssäkerhet ska säkerställas. Det sker genom en studie av det s.k. PwC-målet, där sakfrågan rör marknadsvärdering av finansiella instrument. Artikeln visar att sakfrågan i målet inte kom att prövas av domstol som följd av att Skatteverket inte presenterade sakomständigheterna på ett övertygande och prövningsbart sätt. En motpart med stora ekonomiska resurser hade möjlighet att visa på bristerna i Skatteverkets argumentation, något som inte nödvändigtvis en motpart med mindre resurser hade kunnat göra. Lagen är då förvisso lika för alla, men alla är inte lika inför lagen.
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| 8. |
- Hulthén, Erik, 1980, et al.
(författare)
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Implementing Real-time Optimization on a secondary Cone Crusher for Iron Ore Production, part 1
- 2013
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Ingår i: Preprints Conference in Minerals Engineering, Luleå, 5-6 February 2013. ; , s. 71-80
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Cone crushers are often used as an intermediate comminution step in the mining industry. Real-time feedback data on the product streams can be obtained by applying mass-flow sensors to the process. Systems used for controlling the Closed Side Setting (CSS) on cone crushers are widely used to compensate for wear of the manganese crushing liners and to protect the machines from overloads. With a frequency converter also the eccentric speed in a cone crusher can be adjusted in real-time in addition to the CSS. The eccentric speed affects the dynamic interaction between the rock material and the crusher liners. The adjustment of these two online parameters in real time can result in an increased potential for production yield; however, a nontrivial optimization problem with a large solution space also arises. As the feed material also varies, and the wear is highly evident, the optimal setting for the parameters varies in time. In this paper we report on the preparation of a secondary cone crusher for real-time optimization. The cone crusher, a Sandvik CH680, has got a frequency converter installed and the temperature in the crusher is measured in order to ensure that the crusher as a mechanical machine is working under good operating conditions. The conveyor belts around the crusher have all been equipped with mass-flow meters. Thus the different product yields from the crushing plant can be monitored continuously. The results of the electrical and instrumental installations are that both the CSS and now also the eccentric speed can be operated and monitored in real time without interrupting the process at one of LKAB Malmbergets secondary cone crushers. The first guiding tests indicate a more beneficial operating point, where a higher power consumption can be achieved in the crusher without increasing the pressure as much. The results of the capacities, both the crusher and the crushing stage, indicate the same direction. There are operating points which are more beneficial than others, and it is not the nominal one that is the best. The range of the change in capacity of the circuit is -6.1% to +2.3% from the nominal point.
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| 9. |
- Kristiansson, Amanda, et al.
(författare)
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177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging
- 2021
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.
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| 10. |
- Kristiansson, Amanda, et al.
(författare)
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Hematological and renal toxicity in mice after three cycles of high activity [177Lu]Lu-PSMA-617 with or without human α1-microglobulin
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.
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