Characteristics and survival of patients with advanced cancer and p53 mutations.

P53 mutations are associated with invasive tumors in mouse models. We assessed the p53mutations and survival in patients with advanced cancer treated in the Phase I Program. Of 691 tested patients, 273 (39.5%) had p53 mutations. Patients with p53 mutations were older (p<.0001) and had higher numbers of liver metastases (p=.005). P53 mutations were associated with higher numbers of other aberrations; PTEN (p=.0005) and HER2 (p=.003)aberrations were more common in the p53 mutation group. No survival difference was observed between patients with p53 mutations and those with wild-type p53. In patients with wild-type p53 and other aberrations, patients treated with matched-therapy against the additional aberrations had longer survival compared to those treated with non-matched-therapy or those who received no therapy (median survival, 26.0 vs. 11.8 vs. 9.8 months, respectively; p= .0007). Results were confirmed in a multivariate analysis (p= .0002). In the p53 mutation group with additional aberrations, those who received matched-therapy against the additional aberrations had survival similar to those treated with non-matched-therapy or those who received no therapy (p=.15). In conclusion, our results demonstrated resistance to matched-targeted therapy to the other aberrations in patients with p53 mutations and emphasize the need to overcome this resistance

Performance of Silica Gel in the Role of Residual Air Drying

Removal of carbon dioxide (CO2) is a necessary step in air revitalization and is often accomplished with sorbent materials. Since moisture competes with CO2 in sorbent materials, it is necessary to remove the water first. This is typically accomplished in two stages: bulk removal and residual drying. Silica gel is used as the bulk drying material in the Carbon Dioxide Removal Assembly (CDRA) in operation on ISS. There has been some speculation that silica gel may also be capable of serving as the residual drying material. This paper will describe test apparatus and procedures for determining the performance of silica gel in residual air drying

A Two-Amino Acid Difference in the Coat Protein of \u3ci\u3eSatellite panicum mosaic virus\u3c/i\u3e Isolates Is Responsible for Differential Synergistic Interactions with \u3ci\u3ePanicum mosaic virus\u3c/i\u3e

Panicum mosaic virus (PMV) (genus Panicovirus, family Tombusviridae) and its molecular parasite, Satellite panicum mosaic virus (SPMV), synergistically interact in coinfected proso and pearl millet (Panicum miliaceum L.) plants resulting in a severe symptom phenotype. In this study, we examined synergistic interactions between the isolates of PMV and SPMV by using PMV-NE, PMV85, SPMV-KS, and SPMV-Type as interacting partner viruses in different combinations. Coinfection of proso millet plants by PMV-NE and SPMV-KS elicited severe mosaic, chlorosis, stunting, and eventual plant death compared with moderate mosaic, chlorotic streaks, and stunting by PMV85 and SPMV-Type. In reciprocal combinations, coinfection of proso millet by either isolate of PMV with SPMV-KS but not with SPMV-Type elicited severe disease synergism, suggesting that SPMV-KS was the main contributor for efficient synergistic interaction with PMVisolates. Coinfection of proso millet plants by either isolate of PMV and SPMV-KS or SPMV-Type caused increased accumulation of coat protein (CP) and genomic RNA copies of PMV, compared with infections by individual PMV isolates. Additionally, CP and genomic RNA copies of SPMV-KS accumulated at substantially higher levels, compared with SMPV-Type in coinfected proso millet plants with either isolate of PMV. Hybrid viruses between SPMV-KS and SPMV-Type revealed that SPMV isolates harboring a CP fragment with four differing amino acids at positions 18, 35, 59, and 98 were responsible for differential synergistic interactions with PMV in proso millet plants. Mutation of amino acid residues at these positions in different combinations in SPMV-KS, similar to those as in SPMV-Type or vice-versa, revealed that A35 and R98 in SPMV-KS CP play critical roles in enhanced synergistic interactions with PMVisolates. Taken together, these data suggest that the two distinct amino acids at positions 35 and 98 in the CP of SPMV-KS and SPMV-Type are involved in the differential synergistic interactions with the helper viruses

Genetic (co)variation and accuracy of selection for resistance to viral mosaic disease and production traits in an inter-ecotypic switchgrass breeding population

Obtaining good accuracy and reliability of estimated breeding values is essential to increase the efficiency of a plant breeding program. Genetic variation was assessed for categorical (Virc) and binary (Virb) mosaic (caused by Panicum mosaic virus), dry matter (DMY) and predicted ethanol (Etoh) yields, and lignin content (Klason or KL, and acid-detergent or ADL) in a Summer–Kanlow switchgrass (Panicum virgatum L.) population. Breeding values were predicted with the restricted maximum likelihood–best linear unbiased prediction (REML-BLUP) approaches using a multivariate phenotypic (PBLUP) and animal (ABLUP) models, integrating a three-generation pedigree (1,622 half-sibs) in ABLUP and not in PBLUP. Models were compared in their precision (accuracy and reliability) in assessing genetic parameters and estimating breeding values. The models were similar in most aspects, allocating the highest heritability (ℎ2i) values to DMY (.38 ± .035 vs. .41 ± .035), Etoh (.46 ± .031 vs. .42 ± .033), and Virc (.43 ± .046 vs. .37 ± .047) and the lowest (.17 ± .032 to .30 ± .044) to KL, ADL, and Virb. Genetic correlations were always larger than residual and phenotypic correlations. Intermediate or strong additive genetic control suggest that selecting for high-biomass genotypes will slightly increase lignin content and simultaneously impart mosaic tolerance. Mitigating an increase in lignin content will require including Etoh in a selection index based on its much stronger negative correlation (rG = −.63) with lignin. In this population, accuracy values ranged from .06 to .94 (PBLUP) and from .26 to .92 (ABLUP) and corresponding reliability ranged from .004 to .89 and from .07 to .87. However, ABLUP improved average reliability of DMY and Etoh by 11% and of other traits by 4–5% over the PBLUP model. The ABLUP was a better model over PBLUP, which is a valid analysis in the absence of a pedigree

\u3ci\u3eWheat streak mosaic virus\u3c/i\u3e alters the transcriptome of its vector, wheat curl mite (\u3ci\u3eAceria tosichella Keifer\u3c/i\u3e), to enhance mite development and population expansion

Wheat streak mosaic virus (WSMV; genus Tritimovirus; family Potyviridae) is an economically important wheat virus that is transmitted by the wheat curl mite (WCM; Aceria tosichella Keifer) in a persistent manner. Virus–vector coevolution may potentially influence vector gene expression to prolong viral association and thus increase virus transmission efficiency and spread. To understand the transcriptomic responses of WCM to WSMV, RNA sequencing was performed to assemble and analyse transcriptomes of WSMV viruliferous and aviruliferous mites. Among 7291 de novo-assembled unigenes, 1020 were differentially expressed between viruliferous and aviruliferous WCMs using edgeR at a false discovery rate ≤0.05. Differentially expressed unigenes were enriched for 108 gene ontology terms, with the majority of the unigenes showing downregulation in viruliferous mites in comparison to only a few unigenes that were upregulated. Protein family and metabolic pathway enrichment analyses revealed that most downregulated unigenes encoded enzymes and proteins linked to stress response, immunity and development. Mechanistically, these predicted changes in mite physiology induced by viral association could be suggestive of pathways needed for promoting virus–vector interactions. Overall, our data suggest that transcriptional changes in viruliferous mites facilitate prolonged viral association and alter WCM development to expedite population expansion, both of which could enhance viral transmission

Wheat streak mosaic virus alters the transcriptome of its vector, wheat curl mite (Aceria tosichella Keifer), to enhance mite development and population expansion

Wheat streak mosaic virus (WSMV; genus Tritimovirus; family Potyviridae) is an economically important wheat virus that is transmitted by the wheat curl mite (WCM; Aceria tosichella Keifer) in a persistent manner. Virus–vector coevolution may potentially influence vector gene expression to prolong viral association and thus increase virus transmission efficiency and spread. To understand the transcriptomic responses of WCM to WSMV, RNA sequencing was performed to assemble and analyse transcriptomes of WSMV viruliferous and aviruliferous mites. Among 7291 de novo-assembled unigenes, 1020 were differentially expressed between viruliferous and aviruliferous WCMs using edgeR at a false discovery rate 0.05. Differentially expressed unigenes were enriched for 108 gene ontology terms, with the majority of the unigenes showing downregulation in viruliferous mites in comparison to only a few unigenes that were upregulated. Protein family and metabolic pathway enrichment analyses revealed that most downregulated unigenes encoded enzymes and proteins linked to stress response, immunity and development. Mechanistically, these predicted changes in mite physiology induced by viral association could be suggestive of pathways needed for promoting virus–vector interactions. Overall, our data suggest that transcriptional changes in viruliferous mites facilitate prolonged viral association and alter WCM development to expedite population expansion, both of which could enhance viral transmission

Determining Optimum Soil Type and Salinity for Rearing the Federally Endangered Salt Creek Tiger Beetle, \u3ci\u3eCicindela (Ellipsoptera) nevadica lincolniana\u3c/i\u3e Casey (Coleoptera: Carabidae: Cicindelinae)

Effective rearing methods are needed to recover the federally endangered Salt Creek tiger beetle, Cicindela (Ellipsoptera) nevadica lincolniana Casey, a subspecies that occurs exclusively in saline wetlands and seeps along Little Salt Creek in Lancaster County, Nebraska. Experiments were initiated to determine soil type and salinity concentrations appropriate for stimulating female oviposition in laboratory settings to produce larvae and/or adults for reintroduction to native habitats. In 2013, there were highly significant differences between native soil and a sand/loess soil mixture, but no differences between two salinity levels, 0.354 M and 0.5 M. In 2014, using only a sand/loess soil mixture, there were again no differences between the test salinity levels. A sand/loess soil mixture of either 0.354M or 0.5M salinity was determined to be optimum for egg production

Determining Optimum Soil Type and Salinity for Rearing the Federally Endangered Salt Creek Tiger Beetle, \u3ci\u3eCicindela (Ellipsoptera) nevadica lincolniana\u3c/i\u3e Casey (Coleoptera: Carabidae: Cicindelinae)

Effective rearing methods are needed to recover the federally endangered Salt Creek tiger beetle, Cicindela (Ellipsoptera) nevadica lincolniana Casey, a subspecies that occurs exclusively in saline wetlands and seeps along Little Salt Creek in Lancaster County, Nebraska. Experiments were initiated to determine soil type and salinity concentrations appropriate for stimulating female oviposition in laboratory settings to produce larvae and/or adults for reintroduction to native habitats. In 2013, there were highly significant differences between native soil and a sand/loess soil mixture, but no differences between two salinity levels, 0.354 M and 0.5 M. In 2014, using only a sand/loess soil mixture, there were again no differences between the test salinity levels. A sand/loess soil mixture of either 0.354M or 0.5M salinity was determined to be optimum for egg production

Outcomes of patients with advanced cancer and KRAS mutations in phase I clinical trials.

BackgroundKRAS mutation is common in human cancer. We assessed the clinical factors, including type of KRAS mutation and treatment, of patients with advanced cancer and tumor KRAS mutations and their association with treatment outcomes.MethodsPatients referred to the Phase I Clinic for treatment who underwent testing for KRAS mutations were analyzed.ResultsOf 1,781 patients, 365 (21%) had a KRAS mutation. The G12D mutation was the most common mutation (29%). PIK3CA mutations were found in 24% and 10% of patients with and without KRAS mutations (p<0.0001). Of 223 patients with a KRAS mutation who were evaluable for response, 56 were treated with a MEK inhibitor-containing therapy and 167 with other therapies. The clinical benefit (partial response and stable disease lasting ≥6 months) rates were 23% and 9%, respectively, for the MEK inhibitor versus other therapies (p=0.005). The median progression-free survival (PFS) was 3.3 and 2.2 months, respectively (p=0.09). The respective median overall survival was 8.4 and 7.0 months (p=0.38). Of 66 patients with a KRAS mutation and additional alterations, higher rates of clinical benefit (p=0.04), PFS (p=0.045), and overall survival (p=0.02) were noted in patients treated with MEK inhibitor-containing therapy (n=9) compared to those treated with targeted therapy matched to the additional alterations (n=24) or other therapy (n=33).ConclusionsMEK inhibitors in patients with KRAS-mutated advanced cancer were associated with higher clinical benefit rates compared to other therapies. Therapeutic strategies that include MEK inhibitors or novel agents combined with other targeted therapies or chemotherapy need further investigation

Design and Test of the Payload Electronics and In Flight Sequence Development for the CSUNSAT1 Low Temperature Battery Experiment

No abstract availabl