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Search Results: 1 - 10 of 2205 matches for " Rainer Fagerholm "
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Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications
Taru A Muranen, Dario Greco, Rainer Fagerholm, Outi Kilpivaara, Kati K?mpj?rvi, Kristiina Aittom?ki, Carl Blomqvist, P?ivi Heikkil?, ?ke Borg, Heli Nevanlinna
Breast Cancer Research , 2011, DOI: 10.1186/bcr3015
Abstract: In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and gene-expression (GEX) experiments. After dimensionality reduction with CGHregions R package, CHEK2 1100delC-associated regions in the aCGH data were detected by the Wilcoxon rank-sum test. The linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by the bayesian method.We discovered four lost and three gained CHEK2 1100delC-related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2, and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3, and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors, nominating them as candidates for CHEK2 1100delC-associated tumor-progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM, and LRP1 on 12q13. Altogether, 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44, reduced expression levels.Our results suggest the WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC-mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC-associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time.We have shown that copy-number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions, we identified potential drivers of CHEK2 1100delC-associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene-expression signature highlights pathways that are likely to have a role in the development of metastatic disease in
Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients
Marjanka K Schmidt, Johanna Tommiska, Annegien Broeks, Flora E van Leeuwen, Laura J Van't Veer, Paul DP Pharoah, Douglas F Easton, Mitul Shah, Manjeet Humphreys, Thilo D?rk, Scarlett A Reincke, Rainer Fagerholm, Carl Blomqvist, Heli Nevanlinna
Breast Cancer Research , 2009, DOI: 10.1186/bcr2460
Abstract: We pooled data from four breast cancer cohorts within the Breast Cancer Association Consortium for which both TP53 R72P and MDM2 SNP309 were genotyped and follow-up was available (n = 3,749). Overall and breast cancer-specific survival analyses were performed using Kaplan-Meier analysis and multivariate Cox's proportional hazards regression models.Survival of patients did not differ by carriership of either germ-line variant, R72P (215G>C) or SNP309 (-410G>T) alone. Immunohistochemical p53 staining of the tumor was available for two cohorts (n = 1,109 patients). Survival was worse in patients with p53-positive tumors (n = 301) compared to patients with p53-negative tumors (n = 808); breast cancer-specific survival: HR 1.6 (95% CI 1.2 to 2.1), P = 0.001. Within the patient group with p53-negative tumors, TP53 rare homozygous (CC) carriers had a worse survival than G-allele (GG/GC) carriers; actuarial breast cancer-specific survival 71% versus 80%, P = 0.07; HR 1.8 (1.1 to 3.1), P = 0.03. We also found a differential effect of combinations of the two germ-line variants on overall survival; homozygous carriers of the G-allele in MDM2 had worse survival only within the group of TP53 C-allele carriers; actuarial overall survival (GG versus TT/TG) 64% versus 75%, P = 0.001; HR (GG versus TT) 1.5 (1.1 to 2.0), P = 0.01. We found no evidence for a differential effect of MDM2 SNP309 by p53 protein expression on survival.The TP53 R72P variant may be an independent predictor for survival of patients with p53-negative tumors. The combined effect of TP53 R72P and MDM2 SNP309 on survival is in line with our a priori biologically-supported hypothesis, that is, the role of enhanced DNA repair function of the TP53 Pro-variant, combined with increased expression of the Mdm2 protein, and thus overall attenuation of the p53 pathway in the tumor cells.Breast cancer outcome may be affected by germ-line variants in genes that play a role in DNA damage control and repair such as TP53 (R72P
Mapping and characterising children’s daily mobility in urban residential areas in Turku, Finland
Nora Charlotta Fagerholm,Anna Broberg
Fennia : International Journal of Geography , 2011,
Abstract: Independent mobility in a local environment is crucial for a child’s development and physical activity, contributing to overall health and well-being. This methodological article describes a study capturing children’s daily mobility in two residential areas in Turku, southwestern Finland, by combining the methods of GPS tracking, mobility diaries, interviews and questionnaires. Geographical positioning data enables analysis of spatial characteristics of children’s mobility, e.g. the comparison to land use structure and analysis of the travel speed, while the qualitative data sets reveal how, why and with whom the travel was realised and the level of children’s independence in mobility.The results show that children’s mobility is clustered around homes and schools and evident gender differences exist; boys travel longer distances and at higher speeds than girls. The children in Turku are relatively independent and have extensive mobility licenses. However, the travel undertaken to practise hobbies or participate in organised leisure activities is realised in adult company and significantly dominated by car transportation. The results strengthen the observation that Finnish children are allowed to travel rather independently and to explore the surrounding environment without adult company, using active forms of transportation. The significant level of independence is a consequence of the high perception of safety, both from the children and the parents in the residential areas. The described mixed methods approach, combining objective measurement of actual mobility with qualitative data sets, is applicable for further mobility studies and the results offer implications for planning child-friendly urban environments.
Supertranslations to All Orders*  [PDF]
Rainer Dick
Journal of Modern Physics (JMP) , 2010, DOI: 10.4236/jmp.2010.11007
Abstract: We calculate the transformation laws of the general linear superfield and chiral superfields under supertranslations to all orders in the translation parameters . We use the superfield formalism with complete expansions of the component fields in the coordinate shifts . The results show in particular how a general supertranslation transforms each component field of a supermultiplet into a complete superfield. The results also provide complete parametri-zations of orbits of component fields under supertranslations.
Collapsing Schwarzschild Interior Solution  [PDF]
Rainer Burghardt
Journal of Modern Physics (JMP) , 2015, DOI: 10.4236/jmp.2015.613195
Abstract: We extend the static interior Schwarzschild solution to a collapsing model by applying geometrical methods. We examine the field quantities and field equations in the comoving and non-comoving observer systems. The collapsing stellar object contracts asymptotically to its minimum extent and needs an infinitely long time to arrive at the final state. The event horizon of the exterior Schwarzschild solution is not reached or even crossed. A geometric model of ECOs (eternally collapsing objects) is presented.
Einstein’s Elevator in Cosmology  [PDF]
Rainer Burghardt
Journal of Modern Physics (JMP) , 2016, DOI: 10.4236/jmp.2016.716203
Abstract: The metrics of gravitational and cosmological models are brought into canonical form in comoving coordinates. The FWR curvature parameter k is read from this and it is shown that k=0 does not correlate to a flat model, but for a spatially positively curved geometry in which reference systems which are in free fall exist. This also corresponds to Einstein’s elevator principle. Moreover, we will show that our subluminal cosmos is associated with the Rh=ct model of Melia, assuming that k=0 is related to a free-falling system in the sense described above.
Incidents with Dioxins and PCBs in Food and Feed-Investigative Work, Risk Management and Economic Consequences  [PDF]
Rainer Malisch
Journal of Environmental Protection (JEP) , 2017, DOI: 10.4236/jep.2017.86048
Abstract: The identification of contamination sources within the food chain with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs), (“dioxins”), and PCBs is difficult and complex. PCDD/PCDF can be formed as unintentional compounds in a number of chemical processes as well as in almost every combustion process. PCBs were intentionally produced chemicals that were manufactured for decades before the ban in marketing and use in many countries around 1985. The pattern of occurrence can change from the original source in particular via feedingstuffs to food of animal origin as result of bioaccumulation. A number of examples illustrate the challenging detective work and key scientific aspects for identification of the sources, for support of the risk management and for performance of monitoring programs. The contamination of milk and milk products in European countries with dioxins was caused by compound feeds containing citrus pulp pellets from Brazil which had high dioxin levels as a result of the use of heavily contaminated lime used for neutralization. The Belgian dioxin crisis was caused by a feed additive heavily contaminated with PCBs which were discharged into a recycled fat used in the production of animal feed. Guar gum from India was contaminated with sodium pentachlorophenate and dioxins. Clay was found to be possibly highly contaminated with dioxins possibly formed by geothermal processes over time; use of such clay as feed additive or for human intake led to elevated dioxin levels in food and humans. Bioanalytical screening in combination with comprehensive physicochemical investigations led to the detection of brominated flame retardants and brominated dioxins in a feed additive. Buffalo milk was contaminated in Italy presumably caused by illegal deposition of waste. High PCB levels in fuel oil for drying of breadcrumb used as a feed ingredient caused a major dioxin crisis with pork meat in Ireland. Fatty acids for technical purposes originating from a biodiesel company were used for production of feed fat which contaminated parts of the food chain in Germany. In addition to effects on human and animal health these incidents also have serious economic consequences which could be mitigated by more frequent control on food and feed. Addressing both these issues, the European Community has developed a strategy to reduce the presence of dioxins and PCBs in the environment and in feed and food comprising the establishment of maximum and action levels.
Generalization of the de Sitter Cosmos  [PDF]
Rainer Burghardt
Journal of Modern Physics (JMP) , 2018, DOI: 10.4236/jmp.2018.94047
Abstract: First of all, we investigate whether the transformation of Lemaître inevitably leads from the static de Sitter cosmos to an expanding cosmos. A Lorentz transformation which can be assigned to the Lemaître transformation results in a frame of reference that moves relatively to the static dS system. Because of the homogeneity of space, this applies to every point in the space which does not itself undergo any change. We interpret the “expansion” of the cosmos Milne-like. It is not the space that expands, but the mesh of the Lemaître coordinate system. The velocity parameter of the associated Lorentz transformation is geometrically based and shows that the joined observer systems are moving in free fall. We also discuss the question of whether the speed of light for free-falling observers in the universe can be reached or can be exceeded, respectively. We raise the question of whether the model can be extended in such a way that the motions take place with a velocity that is lower than the one of the free fall. We believe that the method we have derived can be generalized to models with genuine expansion.
Dark Matter without Matter  [PDF]
Rainer Burghardt
Journal of Modern Physics (JMP) , 2018, DOI: 10.4236/jmp.2018.913147
Abstract: We design a cosmological model that expands at a speed less than that of free fall and which allows accelerations of the recession velocity. In addition, the underlying geometry of the model can be adjusted in such a way that attractive forces arise in the cosmos, forces whose sources are not matter. This could explain dark matter as a property of space and one could also address the question of why galactic systems are not subject to expansion.
Drawing Kerr  [PDF]
Rainer Burghardt
Journal of Modern Physics (JMP) , 2019, DOI: 10.4236/jmp.2019.105036
Abstract: The Kerr metric is analyzed using strictly geometrical elements. A 4-dimensional surface representing the geometry of the Kerr model is embedded into a 5-dimensional flat space. The field strengths of the model are explicitly worked out and understanding of the theory is supported by numerous figures. The structure of the field equations is analyzed.
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