| 231. |
- Larsson, Rolf, et al.
(författare)
-
Testing for stationarity in heterogeneous panel data where the time dimension is finite
- 2005
-
Ingår i: Econometrics Journal. - 1368-4221. ; 8:1, s. 55-69
-
Tidskriftsartikel (refereegranskat)abstract
- This paper expands the tests of (2000, Econometrics Journal 3, 148-161) for the null of stationarity against the alternative of a unit root in panel data to the case where the time dimension of the panel is finite. This improves the finite sample properties of the tests for micro and macro panels. More importantly, the derivation of the tests for finite T as opposed to joint asymptotic where N and T simultaneously avoids the imposition of the rate condition N/T-> 0 and hence makes the test valid for any (T, N) combination. The asymptotic distributions of the tests are derived under the null and are shown to be normally distributed. Their moments for T fixed are derived analytically using (1994, Statistics and Probability letters 20, 313-319) lemma 1. Finite sample size and power are considered in a Monte Carlo experiment. The proposed tests have empirical sizes that are very close to the nominal 5% level. The Monte Carlo results clearly show that the power of the test statistics increases substantially with N, T and w (w being the number of unit root processes under the alternative). The results indicate that the assumption that T is asymptotic rather than fixed leads to tests that are substantially oversized particularly for relatively short panels with large N.
|
|
| 232. |
- Larsson, Rolf, 1962-, et al.
(författare)
-
What is the link between temperature, carbon dioxide and methane? : A multivariate Granger causality analysis based on ice core data from Dome C in Antarctica
- 2023
-
Ingår i: Journal of Theoretical and Applied Climatology. - : Springer Nature. - 0177-798X .- 1434-4483. ; 153:1-2, s. 49-55
-
Tidskriftsartikel (refereegranskat)abstract
- This paper continues the work of Kang and Larsson Theoretical and Applied Climatology 116:537-548 (2014) What is the link between temperature and carbon dioxide levels? A Granger causality analysis based on ice core data. Theoretical and Applied Climatology 116:537-548, by adding methane to the study of causality between temperature and carbon dioxide. The data used goes 800,000 years back in time which is possible due to it being extracted from ice cores located at Dome C in Antarctica. First we use linear interpolation to make the three data sets equidistant to be able to employ statistical methods. We adjust for a deterministic trend and find the best model fit to be an autoregressive model with lag two and a piecewise quadratic trend. By employing multivariate Granger causality tests we find strong evidence that temperature, carbon dioxide and methane all Granger cause each other in both directions i.e. carbon dioxide Granger causes temperature and temperature Granger causes carbon dioxide, etc. This is in accordance with the findings of Kang and Larsson, with the extension that we can add methane to establish a trivariate feedback system between temperature, carbon dioxide and methane.
|
|
| 233. |
- Larsson, Åke, et al.
(författare)
-
Immunohistochemistry of the B-cell Component in Lower Lip Salivary Glands of Sjögren's Syndrome and Healthy Subjects
- 2005
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:1, s. 98-107
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Serial sections of lower lip salivary gland (LSG) biopsies were examined by immunohistochemistry, using a battery of B- and partly T-related antibodies (CD5, CD20, CD21, CD27, CD38, CD45RO, CD79a, Bcl-2 and Bcl-6) in different groups of subjects: healthy controls and clinically verified smoking or nonsmoking cases of primary Sjögren's syndrome (SS). The purpose was to characterize the B-cell pattern of the lymphocytic foci and of the tiny perivascular infiltrates preceding the development of foci. Hyperplastic tonsil was used as stain control. In normal LSG, widely dispersed CD38+ and CD79a+ as well as some CD5+ cells are a normal constituent, with lack of staining with the other antibodies. In SS/LSG, the lymphocytic foci showed staining with all the antibodies, with variable degrees of overlapping or nonoverlapping. In SS/LSG of nonsmokers, CD20+ B cells make up a prominent part of the fully developed periductal lymphocytic foci, not overlapping with CD45RO. Also, CD20+ B cells did not overlap in the infiltrates with colocalized CD27+/CD38+ cells. CD20+ B cells and CD45RO+ T cells also occur as minute infiltrates perivascularly in areas of no foci in SS/LSG as well as in SS smokers lacking the typical foci. Smokers lack foci, but tiny infiltrates express CD20 as well CD45R0. Our findings suggest that CD20+ B cells and CD45RO+ T cells are early immigrants in the LSG of SS of smokers as well as nonsmokers and that another subgroup of CD27+/CD38+ B cells gradually mix with the first two to form the characteristic foci in SS/LSG. The simultaneous demonstration of CD20+ and CD27+ B cells in SS/LSG may constitute a significant diagnostic tool. Further, the findings suggest that the early immigrating lymphocytes may have been primed at a site remote from the glands before arriving via the blood to the gland tissue.
|
|
| 234. |
- Larsson, Å., et al.
(författare)
-
Ku protein and DNA strand breaks in lip glands of normal and primary Sjogren's syndrome subjects: Lack of correlation with apoptosis
- 2001
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 54:3, s. 328-334
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to examine tissue expression of Ku protein in lower lip salivary gland (LSG) biopsies from cases of primary Sjogren's syndrome (SS) and from normal subjects. Methods: immunohistochemistry was used with antibodies to Ku70/86 and also Ki67, PCNA and p53. In addition, the Klenow method was applied in order to detect evidence of apoptosis. Sections of hyperplastic tonsil served as additional controls. Results: in normal controls, LSG acinar cells stained negatively whereas LSG excretory duct cell nuclei stained positively with Ku and Klenow and occasionally with PCNA but negatively with Ki67 and p53. In LSG focal sialadenitis of SS cases, some lymphocytic cells showed staining with Ku, Ki67, PCNA, Klenow and p53. In addition to duct cell Ku and Klenow as well as PCNA staining which was not much different from normals, a few ductal epithelial and also mononuclear cells stained with p53. In focal sialadenitis, some acinar cells showed staining with PCNA as well as with Klenow. Conclusions: our findings in LSG biopsies of SS cases added little to an increased understanding about the pathogenetic mechanisms in the development of focal sialadenitis in SS. However. in normal LSG. ductal epithelial but not acinar cells seem to express a constitutively specific Ku protein and Klenow profile, suggestive of DNA strand breaks but not clearly associated with ongoing apoptotic events. It may reflect an enhanced stress response, which may be pathogenetically important in the early events of focal sialadenitis development in primary Sjogren's syndrome.
|
|
| 235. |
- Laryea, Daniel, et al.
(författare)
-
Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumour cell lines and primary cultures of tumour cells from patients
- 2009
-
Ingår i: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 27:5, s. 402-411
-
Tidskriftsartikel (refereegranskat)abstract
- The plant derived indoloquinoline alkaloid cryptolepine was investigated for its cytotoxic properties in 12 human tumour cell lines and in primary cultures of tumour cells from patients. The fluorometric microculture cytotoxicity assay was used to assess cytotoxicity and DNA micro-array analysis to evaluate gene expression. Cryptolepine mean IC(50) in the cell line panel was 0.9 muM compared with 1.0 and 2.8 muM in haematological and solid tumour malignancies, respectively. Among patient solid tumour samples, those from breast cancer were the most sensitive and essentially as sensitive as haematological malignancies. Cryptolepine activity showed highest correlations to topoisomerase II and microtubule targeting drugs. In the cell lines cryptolepine activity was essentially unaffected by established mechanisms of drug resistance. A number of genes were identified as associated with cryptolepine activity. In conclusion, cryptolepine shows interesting in vitro cytotoxic properties and its further evaluation as an anti-cancer drug seems warranted.
|
|
| 236. |
- Laryea, Daniel, et al.
(författare)
-
Characterization of the cytotoxic properties of the benzimidazole fungicides, benomyl and carbendazim, in human tumour cell lines and primary cultures of patient tumour cells
- 2010
-
Ingår i: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 21:1, s. 33-42
-
Tidskriftsartikel (refereegranskat)abstract
- The benzimidazoles, benomyl and carbendazim, are fungicides suggested to target microtubules. Benomyl is metabolized to carbendazim, which has already been explored as an anticancer drug in phase 1 clinical trials. We further characterized the cytotoxic properties of benomyl and carbendazim in 12 human cell lines and in primary cultures of patient tumour cells with the overall aims of elucidating mechanisms of action and anticancer activity spectrum. Cytotoxicity was assessed in the short-term fluorometric microculture cytotoxicity assay and was correlated with the activity of other anticancer drugs and gene expression assessed by cDNA microarray analysis. Benomyl was generally more potent than its metabolite, carbendazim. Both showed high drug activity correlations with several established and experimental anticancer drugs, but modest association with established mechanisms of drug resistance. Furthermore, these benzimidazoles showed high correlations with genes considered relevant for the activity of several mechanistically different standard and experimental anticancer drugs, indicating multiple and broad mechanisms of action. In patient tumour samples, benomyl tended to be more active in haematological compared with solid tumour malignancies, whereas the opposite was observed for carbendazim. In conclusion, benomyl and carbendazim show interesting and diverse cytotoxic mechanisms of action and seem suitable as lead compounds for the development of new anticancer drugs.
|
|
| 237. |
- Leijon, Jonas, et al.
(författare)
-
Attachment of macromolecular heparin conjugate to gelatin scaffolds improves endothelial cell infiltration
- 2013
-
Ingår i: Tissue Engineering. Parts A, B and C. - 2152-4947 .- 2152-4955. ; 19:11-12, s. 1336-1348
-
Tidskriftsartikel (refereegranskat)abstract
- Long-term survival of implanted cells requires oxygen and nutrients, the need for which is met by vasculari- zation of the implant. The use of scaffolds with surface-attached heparin as anchoring points for angiogenic growth factors has been reported to improve this process. We examined the potential role of surface modification of gelatin scaffolds in promoting endothelial cell infiltration by using a unique macromolecular conjugate of heparin as a coating. Compared to other heparin coatings, this surface modification provides flexible heparin chains, representing a new concept in heparin conjugation. In vitro cell infiltration of scaffolds was assessed using a three-dimensional model in which the novel heparin surface, without growth factors, showed a 2.5-fold increase in the number of infiltrating endothelial cells when compared to control scaffolds. No additional improvement was achieved by adding growth factors (vascular endothelial growth factor and/or fibroblast growth factor-2) to the scaffold. In vivo experiments confirmed these results and also showed that the addition of angiogenic growth factors did not significantly increase the endothelial cell infiltration but increased the number of inflammatory cells in the implanted scaffolds. The endothelial cell-stimulating ability of the heparin surface alone, combined with its growth factor-binding capacity, renders it an interesting candidate surface treatment to create a prevascularized site prepared for implantation of cells and tissues, in particular those sensitive to inflammation but in need of supportive revascularization, such as pancreatic islets of Langerhans.
|
|
| 238. |
- Leuchowius, Karl-Johan, et al.
(författare)
-
High content screening for inhibitors of protein interactions and post-translational modifications in primary cells by proximity ligation
- 2010
-
Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 9:1, s. 178-183
-
Tidskriftsartikel (refereegranskat)abstract
- The cost of developing new drugs is a major obstacle for pharmaceutical companies and academia with many drugs identified in the drug discovery process failing approval for clinical use due to lack of intended effect or because of severe side effects. Since the early 1990 s, high throughput screening of drug compounds has increased enormously in capacity but has not resulted in a higher success rate of the identified drugs. Thus, there is a need for methods that can identify biologically relevant compounds and more accurately predict in vivo effects early in the drug discovery process. To address this, we developed a proximity ligation-based assay for high content screening of drug effects on signaling pathways. As a proof of concept, we used the assay to screen through a library of previously identified kinase inhibitors, including six clinically used tyrosine kinase inhibitors, to identify compounds that inhibited the platelet-derived growth factor (PDGF) receptor beta signaling pathway in stimulated primary human fibroblasts. Thirteen of the 80 compounds were identified as hits, and the dose responses of these compounds were measured. The assay exhibited a very high Z' factor (0.71) and signal to noise ratio (11.7), demonstrating excellent ability to identify compounds interfering with the specific signaling event. A comparison with regular immunofluorescence detection of phosphorylated PDGF receptor demonstrated a far superior ability by the in situ proximity ligation assay to reveal inhibition of receptor phosphorylation. In addition, inhibitor-induced perturbation of protein-protein interactions of the PDGF signaling pathway could be quantified, further demonstrating the usefulness of the assay in drug discovery.
|
|
| 239. |
- Levenfors, Jolanta, et al.
(författare)
-
Antibacterial pyrrolidinyl and piperidinyl substituted 2,4-diacetylphloroglucinols from Pseudomonas protegens UP46
- 2020
-
Ingår i: Journal of antibiotics (Tokyo. 1968). - : SPRINGERNATURE. - 0021-8820 .- 1881-1469. ; 73:11, s. 739-747
-
Tidskriftsartikel (refereegranskat)abstract
- In the search for new antibiotic compounds, fractionation of Pseudomonas protegens UP46 culture extracts afforded several known Pseudomonas compounds, including 2,4-diacetylphloroglucinol (DAPG), as well as two new antibacterial alkaloids, 6-(pyrrolidin-2-yl)DAPG (1) and 6-(piperidin-2-yl)DAPG (2). The structures of 1 and 2 were determined by nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1 and 2 were found to have antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus, with minimal inhibitory concentration (MIC) 2 and 4 mu g ml(-1), respectively, for 1, and 2 mu g ml(-1) for both pathogens for 2. The MICs for 1 and 2, against all tested Gram-negative bacteria, were >32 mu g ml(-1). The half maximal inhibitory concentrations against HepG2 cells for compounds 1 and 2 were 11 and 18 mu g ml(-1), respectively, which suggested 1 and 2 be too toxic for further evaluation as possible new antibacterial drugs. Stable isotope labelling experiments showed the pyrrolidinyl group of 1 to originate from ornithine and the piperidinyl group of 2 to originate from lysine. The P. protegens acetyl transferase (PpATase) is involved in the biosynthesis of monoacetylphloroglucinol and DAPG. No optical rotation was detected for 1 or 2, and a possible reason for this was investigated by studying if the PpATase may catalyse a stereo-non-specific introduction of the pyrrolidinyl/piperidinyl group in 1 and 2, but unless the PpATase can be subjected to major conformational changes, the enzyme cannot be involved in this reaction. The PpATase is, however, likely to catalyse the formation of 2,4,6-triacetylphloroglucinol from DAPG.
|
|
| 240. |
- Li, Shi-Sheng, et al.
(författare)
-
Ligatoxin B, a new cytotoxic protein with a novel helix-turn-helix DNA-binding domain from the mistletoe Phoradendron liga
- 2002
-
Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 366:Pt 2, s. 405-13
-
Tidskriftsartikel (refereegranskat)abstract
- A new basic protein, designated ligatoxin B, containing 46 amino acid residues has been isolated from the mistletoe Phoradendron liga (Gill.) Eichl. (Viscaceae). The protein's primary structure, determined unambiguously using a combination of automated Edman degradation, trypsin enzymic digestion, and tandem MS analysis, was 1-KSCCPSTTAR-NIYNTCRLTG-ASRSVCASLS-GCKIISGSTC-DSGWNH-46. Ligatoxin B exhibited in vitro cytotoxic activities on the human lymphoma cell line U-937-GTB and the primary multidrug-resistant renal adenocarcinoma cell line ACHN, with IC50 values of 1.8 microM and 3.2 microM respectively. Sequence alignment with other thionins identified a new member of the class 3 thionins, ligatoxin B, which is similar to the earlier described ligatoxin A. As predicted by the method of homology modelling, ligatoxin B shares a three-dimensional structure with the viscotoxins and purothionins and so may have the same mode of cytotoxic action. The novel similarities observed by structural comparison of the helix-turn-helix (HTH) motifs of the thionins, including ligatoxin B, and the HTH DNA-binding proteins, led us to propose the working hypothesis that thionins represent a new group of DNA-binding proteins. This working hypothesis could be useful in further dissecting the molecular mechanisms of thionin cytotoxicity and of thionin opposition to multidrug resistance, and useful in clarifying the physiological function of thionins in plants.
|
|
