Development of Specifications for Modified Engineered Cementitious Composites (MECC) for use as Bridge Deck Overlays in Nevada

Engineered cementitious composite (ECC) material is a high-strength, fiber-reinforced, ductile mortar mixture that can exhibit tensile strains of up to 5%. The durability and mechanical properties of ECC make it a desirable construction material. This study presents an extensive evaluation of modified engineered cementitious composite (MECC) using locally sourced raw materials for use as a bridge-deck-overlay material. MECC is a mixture of cement, fly ash, water, concrete sand, and poly-vinyl alcohol fibers. The concrete sand used in this study was used in lieu of the typically used silica sand to reduce the high material cost, which makes MECC a modified ECC mix. Currently, the Nevada Department of Transportation (NDOT) uses a polymer concrete for bridge-deck-overlays in Nevada. While NDOT has had good performance with the polymer concrete overlays, the polymer concrete material is an expensive proprietary material. NDOT believes that MECC may be a viable alternative to the polymer concrete as a bridge-deck-overlay material.In this study, three different representative aggregates from throughout Nevada were selected to understand how the local aggregates would perform in MECC mixes. In total, eighteen different MECC mixes were evaluated using a total of thirteen different tests to determine the fresh and hardened properties of the MECC material. These tests included compressive strength, freeze-thaw durability, resistance to chloride ion penetration, and drying shrinkage. Additionally, a uniaxial tensile test was developed to test the tensile strengths and tensile strains of these different MECC mixes. In addition to evaluating MECC, samples of the polymer concrete and of a traditional Portland cement concrete mix were also tested. These results were used to determine how the performance of the MECC material compares with polymer concrete and traditional concrete. The laboratory test results were then analyzed using several different statistical analyses. First, all of the MECC mixes were compared with each other, and the polymer concrete and traditional concrete mixes. This showed how many mixes had statistically significantly higher/lower performance that both the polymer concrete and traditional concrete. Second, linear regressions were used to determine the standardized regression coefficients (or beta coefficients) which were used to determine which variables (mix proportions, aggregate source, fiber type) influenced the MECC’s properties. Third, additional MECC mixes were batched to determine which aggregate properties would influence the MECC’s properties. From this analysis, several predictive models were developed to predict the properties of an MECC mix that used a specific fine aggregate stockpile. After the completion of the laboratory phase, three different field trials were conducted to determine the feasibility of batching large amounts of MECC at commercial concrete batch plants. In these trials, approximately 6 cubic yards of MECC was mixed using different plant configurations to determine if any special measures would be needed to mix MECC on a large-scale. Additionally, a trial slab of MECC was placed at each of these field trials to determine how easy the MECC material would be to place, consolidate, and finish.The findings of this study are that MECC has many desirable qualities of a bridge-deck-overlay material. MECC has higher compressive strengths, higher tensile strengths and strains, high resistance to chloride ion penetration, and higher abrasion resistance than traditional concrete. Additionally, MECC has similar performance to the polymer concrete, meaning there is not a significant drop in performance between the materials. The large-scale trial batches showed that MECC could be mixed on a large-scale without any special measures. While MECC is harder to place than traditional concrete, it is not expected to require any specialty equipment for placement. The findings of this study were used to draft a specification for NDOT for the use of MECC as a bridge-deck-overlay material. This specification will be used in an upcoming field project by NDOT where a bridge-deck-overlay measuring approximately 28 feet by 140 feet by 4 inches thick will be placed in the spring of 2016 in Northern Nevada

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

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

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PAM, 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 pArg1931* 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