| 1. |
- Barausse, Enrico, et al.
(författare)
-
Prospects for fundamental physics with LISA
- 2020
-
Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
|
|
| 2. |
- Bicak, Mesude, et al.
(författare)
-
Genetic signature of prostate cancer mouse models resistant to optimized hK2 targeted α-particle therapy
- 2020
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:26, s. 15172-15181
-
Tidskriftsartikel (refereegranskat)abstract
- Hu11B6 is a monoclonal antibody that internalizes in cells expressing androgen receptor (AR)-regulated prostate-specific enzyme human kallikrein-related peptidase 2 (hK2; KLK2). In multiple rodent models, Actinium-225-labeled hu11B6-IgG1 ([225Ac]hu11B6-IgG1) has shown promising treatment efficacy. In the present study, we investigated options to enhance and optimize [225Ac]hu11B6 treatment. First, we evaluated the possibility of exploiting IgG3, the IgG subclass with superior activation of complement and ability to mediate FC-γ-receptor binding, for immunotherapeutically enhanced hK2 targeted α-radioimmunotherapy. Second, we compared the therapeutic efficacy of a single high activity vs. fractionated activity. Finally, we used RNA sequencing to analyze the genomic signatures of prostate cancer that progressed after targeted α-therapy. [225Ac]hu11B6-IgG3 was a functionally enhanced alternative to [225Ac]hu11B6-IgG1 but offered no improvement of therapeutic efficacy. Progression-free survival was slightly increased with a single high activity compared to fractionated activity. Tumor-free animals succumbing after treatment revealed no evidence of treatment-associated toxicity. In addition to up-regulation of canonical aggressive prostate cancer genes, such as MMP7, ETV1, NTS, and SCHLAP1, we also noted a significant decrease in both KLK3 (prostate-specific antigen ) and FOLH1 (prostate-specific membrane antigen) but not in AR and KLK2, demonstrating efficacy of sequential [225Ac]hu11B6 in a mouse model.
|
|
| 3. |
- Bicak, Mesude, et al.
(författare)
-
Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB
- 2020
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 29:10, s. 1581-1591
-
Tidskriftsartikel (refereegranskat)abstract
- How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis.
|
|
| 4. |
- Li, Weiqiang, et al.
(författare)
-
Genome-wide association study identifies novel single nucleotide polymorphisms having age-specific effect on prostate-specific antigen levels
- 2020
-
Ingår i: Prostate. - : Wiley. - 0270-4137. ; 80:16, s. 1405-1412
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Testing for prostate-specific antigen (PSA) levels in blood are widely used and associated with prostate cancer risk and outcome. After puberty, PSA levels increase by age and multiple single nucleotide polymorphisms (SNPs) have been found to be associated with PSA levels. However, the relationship between the effects of SNPs and age on PSA remains unknown. Methods: To test for SNP × age interaction, we conducted a genome-wide association study using 2394 men without prostate cancer diagnosis from Malmö, Sweden as a discovery set and 2137 men from the eMERGE study (USA) for validation. Linear regression was used to identify significant interactions between SNP and age (p < 1 × 10−4 for discovery, p <.05 for validation). Results: The 15 SNPs from three different loci (8p11.22, 8p12, 3q25.31) are found to have age-specific effect on PSA levels. Expression quantitative trait loci (eQTLs) analysis shows that 12 SNPs from 3q25.31 locus affect the expression level of three genes: KCNAB1, SLC33A1, PLCH1. Conclusions: Our results suggest that SNPs may have age-specific effect on PSA levels, which provides new direction to study genetic markers for PSA.
|
|
