The Role of Funding Programs in Promotion of Best Management Practices for Effective Stream Restoration

Large amounts of money are spent on stream restoration projects across the United States every year. Restoration researchers and professionals commonly recommend a suite of Best Management Practices (BMPs), including project goals, objectives, monitoring, consideration of future conditions, adaptive management, and public reporting of results, which are widely recognized as contributing to effective projects. Studies over the last two decades demonstrated that these BMPs were not consistently incorporated into restoration projects, which highlighted the need to improve practices and for funding programs to incorporate BMPs into funding requirements. I reviewed 28 programs that fund stream restoration in the Rocky Mountain region to determine whether programs require information associated with BMPs in the application and evaluation process and if this varies with funding program size. Additionally, I reviewed budget restrictions and timelines to investigate impediments to achieving BMPs. Previous studies typically found few restoration plans included goals and objectives, but 91% of the current funding programs in my survey required both goals and objectives as part of the application process. The larger (project costs \u3e $300,000) funding programs in this study had more comprehensive BMP requirements: all of the large funding programs required goals, objectives, and public reporting of project results, while none of the smaller (\u3c$25,000 per project) funding programs required consideration for future conditions or adaptive management. Even though post-project monitoring is commonly indicated to be required, many funding timelines are less than two years which is too short to evaluate whether the restoration successfully achieved their objectives. To evaluate project success, smaller funding programs need to expand their BMP requirements. Overall, the field may need to consider alternatives for funding approaches that would better facilitate monitoring and adaptive management

Double quantum dot with tunable coupling in an enhancement-mode silicon metal-oxide semiconductor device with lateral geometry

We present transport measurements of a tunable silicon metal-oxide-semiconductor double quantum dot device with lateral geometry. Experimentally extracted gate-to-dot capacitances show that the device is largely symmetric under the gate voltages applied. Intriguingly, these gate voltages themselves are not symmetric. Comparison with numerical simulations indicates that the applied gate voltages serve to offset an intrinsic asymmetry in the physical device. We also show a transition from a large single dot to two well isolated coupled dots, where the central gate of the device is used to controllably tune the interdot coupling.Comment: 4 pages, 3 figures, to be published in Applied Physics Letter

Enhancement mode double top gated MOS nanostructures with tunable lateral geometry

We present measurements of silicon (Si) metal-oxide-semiconductor (MOS) nanostructures that are fabricated using a process that facilitates essentially arbitrary gate geometries. Stable Coulomb blockade behavior free from the effects of parasitic dot formation is exhibited in several MOS quantum dots with an open lateral quantum dot geometry. Decreases in mobility and increases in charge defect densities (i.e. interface traps and fixed oxide charge) are measured for critical process steps, and we correlate low disorder behavior with a quantitative defect density. This work provides quantitative guidance that has not been previously established about defect densities for which Si quantum dots do not exhibit parasitic dot formation. These devices make use of a double-layer gate stack in which many regions, including the critical gate oxide, were fabricated in a fully-qualified CMOS facility.Comment: 11 pages, 6 figures, 3 tables, accepted for publication in Phys. Rev.

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers