| 31. |
- Adler, Jan-Olof, et al.
(författare)
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The upgraded photon tagging facility at the MAX IV Laboratory
- 2013
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 715, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- A description is given of the upgraded photon tagging facility at the MAX IV Laboratory. Two magnetic spectrometers are used to momentum analyze post-bremsstrahlung electrons. The tagged photon range extends from 10 to 180 MeV with an energy resolution of about 300 keV. The system has been operated at rates up to 4 x 10(6) photons s(-1) MeV (-1). Different diagnostic tools are described as well as the experimental program.
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| 32. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Clinical management of gastric carcinoid tumors.
- 1994
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Ingår i: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
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| 33. |
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| 34. |
- Andersson, Håkan A., 1948-
(författare)
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Svenska småföretags användning av reserveringar för resultatutjämning och intern finansiering
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small firms often have inadequate access to the capital necessary for sucessful management. The Swedish Government introduced in the mid-1990s allowance rules that facilitate retention of profit for sole proprietorships and partnership firms. The tax credits arising from the allowances give certain benefits as a source of financing compared to traditional forms of credits. Among the more essential benefits are that the payment for some parts of the tax credit can be put on hold almost indefinitely, or alternatively never be paid. The firms are free to use these means, and the responsibility of future payment of the postponed tax debt stays with the individual firms. The comprehensive purpose of the dissertation may be stated as to increase the understanding of small Swedish firms, especially sole proprietorships, utilizing possibilities for allowances for income smoothing and internal financing. At the beginning the dissertation describes case studies, comprising a smaller selection of microfirms. With a starting-point from the accounted and reported income-tax returns, alternative calculations are made where additional positive tax and finance effects appear possible to obtain. One purpose of these studies is to increase the insight regarding the possibilities of income smoothing and internal financing that arise from utilizing these allowances. These studies also illuminate, to what extent and in what way they are being used in reality. Another objective of these studies is to give a more substantive insight into the technics behind the different allowances, appropriation to positive or negative interest rate allocation appropriation or dissolving of tax allocation reserve appropriation or dissolving of “expansion fund” Theories regarding the creation of resources, through building of capital, and theories on financial planning and strategy are studied. The purpose is to find support for the choice of theoretical grounded underlying independent variables that can be used in cross-sectional studies to explain the use of the possibilities of appropriations. Theories of finance that are of greatest interest, in the operationalisation of these variables, are theories that discuss the choices of different financing alternatives for small firms. The “pecking order theory”, describes the firm’s order of priority when choices of finance alternatives are made. The concept of “financial bootstrapping” expands the frame for different forms of financing choices that especially very small firms have at their disposal.The last part of the theoretical frame deals with the phenomenon of “income smoothing,” which can be translated as leveling out profits/losses. A number of financial and non-financial variables are supported by and operationalised from these financial theories e.g., return on sales, capital turnover, quick ratio and debt-to-equity ratio, respectively age, gender and line of business. Cross-sectional studies are implemented for the taxation years of 1996 and 1999, on databases that have been extracted from Statistics Sweden. The group of 87,276 sole proprietorships included in the study were required to complete tax returns and pay taxes for the business activity according to the supporting schedule, N2, information from the sole proprietorships’ income statement and balance sheet in an accounting statement that comes with the income tax return form. The possibilities of allowances are considered as dependent variables. The intention of the cross-sectional studies is to survey and describe the utilization of possible allowances, with the support of the financial and non-financial independent variables. The connection of these variables to the decision of sole proprietorships to appropriate to the tax allocation reserve is also summarized in a logistic regression model. A number of theoretically based propositions are made for the purpose of observing how the variables are connected to the chances that sole proprietorships actually appropriate to this form of allowance. Appropriation to the tax allocation reserve stands out as the most practiced form of allowance. The studies also clarify that utilization varies among different forms of allowances, but that not all firms that have the prerequisites to utilize the possibilities really do so to the full. A further utilization of the different possibilities of allowances is often conceivable. For the sole proprietorships that are not utilizing these possibilities, the allowances should be considered eligible as a contribution to internal financing and to increase access to capital.
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| 35. |
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| 36. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 37. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 38. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 39. |
- Israelsson, Charlotte, et al.
(författare)
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Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders
- 2010
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 31:5, s. 852-863
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) in the mouse results in the rapid appearance of scattered clusters of cells expressing the chemokine Cxcl10 in cortical and subcortical areas. To extend the observation of this unique pattern, we used neuropathological mouse models using quantitative reverse transcriptase-polymerase chain reaction, gene array analysis, in-situ hybridization and flow cytometry. As for TBI, cell clusters of 150–200 μm expressing Cxcl10 characterize the cerebral cortex of mice carrying a transgene encoding the Swedish mutation of amyloid precursor protein, a model of amyloid Alzheimer pathology. The same pattern was found in experimental autoimmune encephalomyelitis in mice modelling multiple sclerosis. In contrast, mice carrying a SOD1G93A mutant mimicking amyotrophic lateral sclerosis pathology lacked such cell clusters in the cerebral cortex, whereas clusters appeared in the brainstem and spinal cord. Mice homozygous for a null mutation of the Cxcl10 gene did not show detectable levels of Cxcl10 transcript after TBI, confirming the quantitative reverse transcriptase-polymerase chain reaction and in-situ hybridization signals. Moreover, unbiased microarray expression analysis showed that Cxcl10 was among 112 transcripts in the neocortex upregulated at least threefold in both TBI and ageing TgSwe mice, many of them involved in inflammation. The identity of the Cxcl10+ cells remains unclear but flow cytometry showed increased numbers of activated microglia/macrophages as well as myeloid dendritic cells in the TBI and experimental autoimmune encephalomyelitis models. It is concluded that the Cxcl10+ cells appear in the inflamed central nervous system and may represent a novel population of cells that it may be possible to target pharmacologically in a broad range of neurodegenerative conditions.
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| 40. |
- Kalimo, H., et al.
(författare)
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Details of neuropathology in Arctic Alzheimer's disease
- 2010
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Ingår i: Abstracts of the XVIIth International Congress of Neuropathology (ICN 2010), Salzburg, Austria, 11-15 September 2010. - : Wiley. ; , s. 22-23
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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