A multitransmit external body array combined with a (1) H and (31) P endorectal coil to enable a multiparametric and multimetabolic MRI examination of the prostate at 7T

Item does not contain fulltextPURPOSE: In vivo (1) H and (31) P magnetic resonance spectroscopic imaging (MRSI) provide complementary information on the biology of prostate cancer. In this work we demonstrate the feasibility of performing multiparametric imaging (mpMRI) and (1) H and (31) P spectroscopic imaging of the prostate using a (31) P and (1) H endorectal radiofrequency coil (ERC) in combination with a multitransmit body array at 7 Tesla (T). METHODS: An ERC with a (31) P transceiver loop coil and (1) H receive (Rx) asymmetric microstrip ((31) P/(1) H ERC) was designed, constructed and tested in combination with an external 8-channel (1) H transceiver body array coil (8CH). Electromagnetic field simulations and measurements and in vivo temperature measurements of the ERC were performed for safety validation. In addition, the signal-to-noise (SNR) benefit of the (1) H microstrip with respect to the 8CH was evaluated. Finally, the feasibility of the setup was tested in one volunteer and three patients with prostate cancer by performing T2 -weighted and diffusion-weighted imaging in combination with (1) H and (31) P spectroscopic imaging. RESULTS: Electromagnetic field simulations of the (31) P loop coil showed no differences in the E- and B-fields of the (31) P/(1) H ERC compared with a previously safety validated ERC without (1) H microstrip. The hotspot of the specific absorption rate (SAR) at the feed point of the (31) P/(1) H ERC loop coil was 9.42 W/kg when transmitting on (31) P at 1 W. Additional in vivo measurements showed a maximum temperature increase at the SAR hotspot of 0.7 degrees C over 6 min on (31) P at 1.9 W transmit (Tx) power, indicating safe maximum power levels. When transmitting with the external (1) H body array at 40W for 2:30 min, the temperature increase around the ERC was < 0.3 degrees C. Up to 3.5 cm into the prostate the (1) H microstrip of the ERC provided higher SNR than the 8CH. The total coil combination allowed acquisition of an mpMRI protocol and the assessment of (31) P and (1) H metabolites of the prostate in all test subjects. CONCLUSION: We developed a setup with a (31) P transceiver and (1) H Rx endorectal coil in combination with an 8-channel transceiver external body array coil and demonstrated its safety and feasibility for obtaining multiparametric imaging and (1) H and (31) P MRSI at 7T in patients with prostate cancer within one MR examination

CYP2D6 Genotype is Not Associated with Survival in Breast Cancer Patients Treated with Tamoxifen: Results from a Population-based Study

Purpose: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy. Methods: Tumor-derived DNA was genotyped for common, functionally consequential CYP2D6 polymorphisms (*2, *3, *4, *6, *10, *41, and copy number variants) and assigned a CYP2D6 activity score (AS) ranging from none (0) to full (2). Patients with poor metabolizer (AS = 0) phenotype were compared to patients with AS > 0 and in secondary analyses AS was analyzed quantitatively. Clinical outcome of interest was recurrence free survival (RFS) and analyses using long-rank test were adjusted for relevant clinical covariates (nodal status, tumor size, etc.). Results: CYP2D6 AS was not associated with RFS in tamoxifen treated patients in univariate analyses (p > 0.2). In adjusted analyses, increasing AS was associated with inferior RFS (Hazard ratio 1.43, 95% confidence interval 1.00-2.04, p = 0.05). In patients that did not receive tamoxifen treatment, increasing CYP2D6 AS, and AS > 0, were associated with superior RFS (each p = 0.0015). Conclusions: This population-based study does not support the hypothesis that patients with diminished CYP2D6 activity achieve inferior tamoxifen benefit. These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice

Chemically modified dsRNA induces RNAi effects in insects in vitro and in vivo: a potential new tool for improving RNA-based plant protection

Global agriculture loses over $100 billion of produce annually to crop pests such as insects. Many of these crop pests either are not currently controlled by artificial means or have developed resistance against chemical pesticides. Long dsRNAs are capable of inducing RNAi in insects and are emerging as novel, highly selective alternatives for sustainable insect management strategies. However, there are significant challenges associated with RNAi efficacy in insects. In this study, we synthesized a range of chemically modified long dsRNAs in an approach to improve nuclease resistance and RNAi efficacy in insects. Our results showed that dsRNAs containing phosphorothioate modifications demonstrated increased resistance to southern green stink bug saliva nucleases. Phosphorothioate-modified and 2′-fluoro-modified dsRNA also demonstrated increased resistance to degradation by soil nucleases and increased RNAi efficacy in Drosophila melanogaster cell cultures. In live insects, we found chemically modified long dsRNAs successfully resulted in mortality in both stink bug and corn rootworm. These results provide further mechanistic insight into the dependence of RNAi efficacy on nucleotide modifications in the sense or antisense strand of the dsRNA in insects and demonstrate for the first time that RNAi can successfully be triggered by chemically modified long dsRNAs in insect cells or live insects

Deficiency of Pkc1 activity affects glycerol metabolism in Saccharomyces cerevisiae

In pressProtein kinase C is apparently involved in the control of many cellular systems: the cell wall integrity pathway, the synthesis of ribosomes, the appropriated reallocation of transcription factors under specific stress conditions and also the regulation of N-glycosylation activity. All these observations suggest the existence of additional targets not yet identified. In the context of the control of carbon metabolism, previous data demonstrated that Pkc1 p might play a central role in the control of cellular growth and metabolism in yeast. In particular, it has been suggested that it might be involved in the derepression of genes under glucose-repression by driving an appropriated subcellular localization of transcriptional factors, such as Mig1 p. In this work, we show that pkc1∆ mutant is unable to grow on glycerol because it cannot perform the derepression of GUT1 gene that encodes for glycerol kinase. Additionally, active transport is also partially affected. Using this phenotype, we were able to isolate a new pkc1∆ revertant. We also isolated two transformants identified as the nuclear exportin Msn5 and the histone deacetylase Hos2 extragenic suppressors of this mutation. Based on these results, we postulate that Pkc1 p may be involved in the control of the cellular localization and/or regulation of the activity of nuclear proteins implicated in gene expression.Fundação Universidade Federal de Ouro Preto (FUFOP). Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) - CBS-1875/95. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - 300998/89-9 to R.L.B., 301255/01-6 to L.G.F

The mineralogical composition of calcium and calcium-magnesium carbonate pedofeatures of calcareous soils in the European prairie ecodivision in Hungary

Abstract There is little data on the mineralogy of carbonate pedofeatures in the calcareous soils in Hungary which belong to the European prairie ecodivision. The aim of the present study is to enrich these data. The mineralogical composition of the carbonate pedofeatures from characteristic profiles of the calcareous soils in Hungary was studied by X-ray diffractometry, thermal analysis, SEM combined with microanalysis, and stable isotope determination. Regarding carbonate minerals only aragonite, calcite (+ magnesian calcite) and dolomite (+proto-dolomite) were identified in carbonate grains, skeletons and pedofeatures. The values relating, respectively, to stable isotope compositions (C13, O18) of carbonates in chernozems and in salt-affected soils were in the same range as those for recent soils (latter data reported earlier). There were no considerable differences between the values for the carbonate nodules and tubules from the same horizons, nor were there significant variations between the values of the same pedofeatures from different horizons (BC-C) of the same profile. Thus it can be assumed that there were no considerable changes in conditions of formation. Tendencies were recognized in the changes of (i) carbonate mineral associations, (ii) the MgCO3 content of calcites, (iii) the corrected decomposition temperatures, and (iv) the activation energies of carbonate thermal decompositions among the various substance-regimes of soils. Differences were found in substance-regimes types of soils rather than in soil types

Tensor Polarization of the phi meson Photoproduced at High t

As part of a measurement of the cross section of $\phi$ meson photoproduction to high momentum transfer, we measured the polar angular decay distribution of the outgoing $K^+$ in the channel $\phi \to K^+K^-$ in the $\phi$ center-of-mass frame (the helicity frame). We find that s-channel helicity conservation (SCHC) holds in the kinematical range where $t$-channel exchange dominates (up to $-t \sim 2.5$ GeV$^2$ for $E_{\gamma}$=3.6 GeV). Above this momentum, $u$-channel production of a $\phi$ meson dominates and induces a violation of SCHC. The deduced value of the $\phi NN$ coupling constant lies in the upper range of previously reported values.Comment: 6 pages; 5 figure