| 1. |
|
|
| 2. |
- Alsanius, Beatrix, et al.
(author)
-
Decontamination of Irrigation Water under Field Conditions: Preliminary Results
- 2011
-
In: Acta Horticulturae. - 0567-7572 .- 2406-6168. ; 922, s. 61-66
-
Conference paper (peer-reviewed)abstract
- Outbreaks of foodborne diseases (Norovirus, Salmonella spp., verotoxin producing E. coli, Campylobacter spp., Shigella spp.) related to fruit and vegetable have increased worldwide. Microbial hazards cause considerable and in some cases life-long suffering. Contamination may occur during the entire farm-to-fork continuum with irrigation water as one of the major vehicles for contamination. Therefore, the potential of photocatalytic oxidation water treatment (POWT) to improve inferior irrigation water quality was studied. A prototype of a photocatalytic unit was installed on an irrigation ramp at a commercial field site growing leafy vegetables. Water samples were collected at five distinct sites within the water pipe namely from (i) the irrigation pond, (ii) after coarse filtration, (iii) at the beginning of the field water pipe as well as (iv) before and (v) after treatment using photocatalysis at three occasions with three independent replicates at each event. The water samples were analyzed with respect to indicator organisms for water quality (heterotrophic microorganisms at 22 degrees C, total coliform bacteria, thermotolerant coliform bacteria, E. coli, intestinal enterococci, Salmonella spp.). After the photocatalytic treatment, the number of indicator organisms in the irrigation water decreased with respect to all monitored organisms. This was also observed for Salmonella spp. which was detected at a couple of incidents at the sampling sites prior to the photocatalytic unit. Indicator organisms in the treated water at the irrigation ramp were beyond the thresholds stipulated by guidelines for irrigation water quality in examples such as British Columbia in Canada and Germany.
|
|
| 3. |
- Antoniou, Antonis C., et al.
(author)
-
Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
-
Journal article (peer-reviewed)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
|
|
| 4. |
- Bindler, Richard, et al.
(author)
-
Early medieval origins of iron mining and settlement in central Sweden : multiproxy analysis of sediment and peat records from the Norberg mining district
- 2011
-
In: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 38:2, s. 291-300
-
Journal article (peer-reviewed)abstract
- The historical Norberg mining district in central Sweden with its shallow, easily accessible iron ores figures prominently in the earliest documents from the 14th century concerning mining or metallurgy. This 1000-km2 district is considered to be one of the first areas in Sweden exploited for iron ores and, in fact, Europe’s oldest known blast furnace, Lapphyttan, is located in the Norberg district about 10 km from the mines in the village of Norberg (Norbergsby). Earlier archaeological excavations suggest the furnace was in operation as early as the 11th or 12th century (870 and 930 14C yr BP), and a number of other sites in the district have been dated to the 13th–15th centuries. Here, we have analyzed two lake sediment records (Kalven and Noren) from the village of Norberg and a peat record from Lapphyttan. The Lapphyttan peat record was radiocarbon dated, whereas the sediment from Kalven is annually laminated, which provides a fairly precise chronology. Our pollen data indicate that land use in the area began gradually as forest grazing by at least c. AD 1050, with indications of more widespread forest disturbance and cultivation from c. 1180 at Lapphyttan and 1250 at Kalven. Based on 206Pb/207Pb isotope ratios in Kalven’s varved sediment record, there is an indication of mining or metallurgy in the area c. 960, but likely not in immediate connection to our sites. Evidence of mining and metallurgy increases gradually from c. 1180 when there is a decline in 206Pb/207Pb ratios and an increase in charcoal particles at Lapphyttan, followed by increasing inputs of lithogenic elements in Noren’s sediment record indicating soil disturbance, which we attribute to the onset of mining the iron ore bodies surrounding Noren. From AD 1295 onwards evidence of mining and metallurgy are ubiquitous, and activities accelerate especially during the late 15th century; the maximum influence of Bergslagen ore lead (i.e., the minimum in 206Pb/207Pb isotope ratios) in both Kalven and Noren occurs c. 1490–1500, when also varve properties change in Kalven and in Noren sharp increases occur in the concentrations of a range of other ore-related metals (e.g., arsenic, cadmium, copper, iron, lead, mercury and zinc). From the 15th century onwards mining and metallurgy are the dominant feature of the sediment records.
|
|
| 5. |
- Ding, Yuan C, et al.
(author)
-
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
-
In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
-
Journal article (peer-reviewed)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
|
|
| 6. |
- Engen, Karin, et al.
(author)
-
Microwave Heated Flow Synthesis of Spiro-oxindole Dihydroquinazolinone Based IRAP Inhibitors
- 2014
-
In: Organic Process Research & Development. - : American Chemical Society (ACS). - 1083-6160 .- 1520-586X. ; 18:11, s. 1582-1588
-
Journal article (peer-reviewed)abstract
- A fast and convenient synthetic route towards spiro-oxindole dihydroquinazolinones as novel and drug-like insulin-regulated aminopeptidase (IRAP) inhibitors is reported. The synthesis is performed using a MW heated continuous flow system employing 200 mm X 3 mm i MW absorbing silicon carbide (SiC) or MW transparent borosilicate tubular reactors. A three-component MW-flow reaction to build up the spiro compounds (9 examples, 4087% yield), using the SiC reactor, as well as a SuzukiMiyaura cross-coupling reaction (71%), employing the borosilicate reactor, are presented with residence times down to 168 s. The continuous MW-flow routes provide a smooth and scalable synthetic methodology towards this class of IRAP inhibitors.
|
|
| 7. |
|
|
| 8. |
- Eriksson, Anna, et al.
(author)
-
Identification of AKN-032, a novel 2-aminopyrazine tyrosine kinase inhibitor, with significant preclinical activity in acute myeloid leukemia
- 2010
-
In: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 80:10, s. 1507-1516
-
Journal article (peer-reviewed)abstract
- Aberrant signal transduction by mutant or overexpressed protein kinases has emerged as a promising target for treatment of acute myeloid leukemia (AML). We here present a novel low molecular weight kinase inhibitor, AKN-032, targeting the FMS-like tyrosine kinase 3 (FLT3) and discovered in a new type of screening funnel combining the target therapy approach with sequential cellular screens. AKN-032 was identified among 150 selected hits from three different high throughput kinase screens. Further characterization showed inhibitory activity on FLT3 enzyme with an IC50 of 70 nM. Western blot analysis revealed reduced autophosphorylation of the FLT3-receptor in AML cell line MV4-11 cells after exposure to AKN-032. Flow cytometry disclosed cytotoxic activity against MV4-11, but not against non-malignant 3T3-L1 fibroblast cells. Using a fluorometric microculture cytotoxicity assay, AKN-032 was tested against 15 cell lines and displayed a potent cytotoxic activity in AML cell lines MV4-11 (IC50 = 0.4 mu M) and Kasumi-1 (IC50 = 2.3 mu M). AKN-032 was also highly cytotoxic in tumor cells from AML patients in vitro. Furthermore, AKN-032 demonstrated significant antileukemic effect in a relatively resistant in vivo hollow fiber mouse model. No major toxicity was observed in the animals. In conclusion. AKN-032 is a promising new kinase inhibitor with significant in vivo and in vitro activity in AML Results from the hollow fiber mouse assay suggest a favorable toxicity profile. Future studies will focus on pharmacokinetic properties, toxicity as well as further clarifying the mechanisms of action of AKN-032 in AML.
|
|
| 9. |
|
|
| 10. |
|
|
