Adjusting for covariates on a slippery slope: linkage analysis of change over time

BACKGROUND: We analyzed the Genetic Analysis Workshop 13 (GAW13) simulated data to contrast and compare different methods for the genetic linkage analysis of hypertension and change in blood pressure over time. We also examined methods for incorporating covariates into the linkage analysis. We used methods for quantitative trait loci (QTL) linkage analysis with and without covariates and affected sib-pair (ASP) analysis of hypertension followed by ordered subset analysis (OSA), using variables associated with change in blood pressure over time. RESULTS: Four of the five baseline genes and one of the three slope genes were not detected by any method using conventional criteria. OSA detected baseline gene b35 on chromosome 13 when using the slope in blood pressure to adjust for change over time. Slope gene s10 was detected by the ASP analysis and slope gene s11 was detected by QTL linkage analysis as well as by OSA analysis. Analysis of null chromosomes, i.e., chromosomes without genes, did not reveal significant increases in type I error. However, there were a number of genes indirectly related to blood pressure detected by a variety of methods. CONCLUSIONS: We noted that there is no obvious first choice of analysis software for analyzing a complicated model, such as the one underlying the GAW13 simulated data. Inclusion of covariates and longitudinal data can improve localization of genes for complex traits but it is not always clear how best to do this. It remains a worthwhile task to apply several different approaches since one method is not always the best

Self‐Assembly of Therapeutic Peptide into Stimuli‐Responsive Clustered Nanohybrids for Cancer‐Targeted Therapy

Clinical translation of therapeutic peptides, particularly those targeting intracellular protein–protein interactions (PPIs), has been hampered by their inefficacious cellular internalization in diseased tissue. Therapeutic peptides engineered into nanostructures with stable spatial architectures and smart disease targeting ability may provide a viable strategy to overcome the pharmaceutical obstacles of peptides. This study describes a strategy to assemble therapeutic peptides into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to tumor microenvironment. As a proof of concept, an anticancer peptide termed β‐catenin/Bcl9 inhibitors is copolymerized with gold ion and assembled into a cluster of nanohybrids (pCluster). Through a battery of in vitro and in vivo tests, it is demonstrated that pClusters potently inhibit tumor growth and metastasis in several animal models through the impairment of the Wnt/β‐catenin pathway, while maintaining a highly favorable biosafety profile. In addition, it is also found that pClusters synergize with the PD1/PD‐L1 checkpoint blockade immunotherapy. This new strategy of peptide delivery will likely have a broad impact on the development of peptide‐derived therapeutic nanomedicine and reinvigorate efforts to discover peptide drugs that target intracellular PPIs in a great variety of human diseases, including cancer.A strategy for clinical translation of therapeutic peptides by assembling them into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to the tumor microenvironment, is presented. An anticancer peptide termed β‐catenin/Bcl9 inhibitor is assembled into a cluster of nanohybrids termed pCluster, which potently inhibits tumor growth as well as metastasis, and synergizes with immunotherapy, while maintaining a highly favorable biosafety profile.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/1/adfm201807736.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/2/adfm201807736-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/3/adfm201807736_am.pd

Search for anomalous couplings in boosted WW/WZ -> l nu q(q)over-bar production in proton-proton collisions at root s=8TeV

Peer reviewe

Function of the Mitochondrial Transport Protein BcMtp1 in Regulating Vegetative Development, Asexual Reproduction, Stress Response, Fungicide Sensitivity, and Virulence of <i>Botrytis cinerea</i>

In model fungi, mitochondrial transport proteins (MTPs), also known as “mitochondrial carriers” (MC), are known to facilitate the exchange of biochemical substances across the mitochondrial inner membrane. In this study, we characterized an MTP in Botrytis cinerea homologous to the known MTPs in Saccharomyces cerevisiae designated BcMtp1. The BcMtp1 deletion mutant phenotype was strikingly defective in vegetative development, conidiation, and sclerotia production. In addition, ΔBcMtp1 showed increased sensitivity to osmotic stress, oxidative stress, and cell wall biogenesis inhibitors. In the pathogenicity assay, ΔBcMtp1 displayed compromised virulence on various host-plant tissues. The BcMtp1 deletion mutant phenotype was rescued by transforming the wild-type BcMtp1 variant into the mutant. Together, these data indicate that BcMtp1 is critical for vegetative development, asexual reproduction, stress tolerance, and virulence of B. cinerea

A Novel Transverse Flux Permanent Magnet Disk Wind Power Generator with H-Shaped Stator Cores

This paper presents a novel transverse flux permanent magnet disk generator (TFPMDG) for wind power generation. The main features of its structure are the modular H-shaped stator cores and two simple rotor disks. What is different from the structures introduced in the references is that each H-shaped stator core is formed by two T-shaped iron cores and a permanent magnet (PM) rather than a complete H-shaped core, which makes the manufacturing simpler and easier. Each rotor disk consists of a rotor holder and several rotor bars, resulting in high robustness and reliability. Moreover, two circular coils in the H-shaped stator cores together with the stator disk are sandwiched by the two rotor disks, which improves the utilization of PMs. In this paper, the proposed TFPMDG is investigated in detail. Firstly, the structure and operating principle are introduced. Then, the magnetic circuit method is used to analyze the TFPMDG. Next, the three-dimensional (3D) finite element method (FEM) is employed to compute the magnetic field distribution and EMF at no load. According to the calculation result, the other three TFPMDGs with different shapes of rotor cores are proposed and analyzed for better back EMF, and then a generator with good performance is selected for load analysis. Finally, a prototype is fabricated and tested, and the simulated results are compared with the measured ones, which proves the rationality of the simulated results

Adaptation to Climate Change Effects by Cultivar and Sowing Date Selection for Maize in the Northeast China Plain

Cultivar and sowing date selection are major factors in determining the yield potential of any crop and in any region. To explore how climate change affects these choices, this study performed a regional scale analysis using the well-validated APSIM-maize model for the Northeast China Plain (NEC) which is the leading maize (Zea mays L.) producing area in China. Results indicated that high temperature had a significantly negative effect on grain yield, while effective accumulated temperature and solar radiation had significant positive effects on grain yield and kernel number. Cloudy and rainy weather in flowering stage had significant negative effects on kernel number. Delayed sowing led to less cloudy and rainy weather during flowering and reduced the negative effect on kernel number. Higher diurnal thermal range and less precipitation during the grain-filling stage also increased the 1000-kernel weight. Delayed sowing, however, also significantly increased the risk of early senescence and frost (&gt;80%) in middle and high latitude areas. In the middle and high latitude areas of the NEC, the grain yield of a long-season cultivar (LS) under early sowing (I) (6.2&ndash;19.9%) was significantly higher than under medium sowing (II) or late sowing (III), and higher than that of an early sown (I) short-season (SS) and medium-season cultivar (MS). In the low latitude area of the NEC, the grain yield of MS under medium sowing date (II) was higher than that under I and III, meanwhile, this was also higher than that of SS and LS. Therefore, under climate warming, LS sown earlier in high and medium latitudes and MS sown medium in low latitude were the appropriate cultivar and sowing date choices, which could mitigate the stress of high temperatures and reduce the risk of early senescence and frost. Cultivar and sowing date selection are effective measures to alleviate negative effects of climate change on maize production in the NEC, and provides valuable advice for breeders on cultivar selection, and the choice of varieties and sowing dates for farmers in actual production

Adaptation to Climate Change Effects by Cultivar and Sowing Date Selection for Maize in the Northeast China Plain

Cultivar and sowing date selection are major factors in determining the yield potential of any crop and in any region. To explore how climate change affects these choices, this study performed a regional scale analysis using the well-validated APSIM-maize model for the Northeast China Plain (NEC) which is the leading maize (Zea mays L.) producing area in China. Results indicated that high temperature had a significantly negative effect on grain yield, while effective accumulated temperature and solar radiation had significant positive effects on grain yield and kernel number. Cloudy and rainy weather in flowering stage had significant negative effects on kernel number. Delayed sowing led to less cloudy and rainy weather during flowering and reduced the negative effect on kernel number. Higher diurnal thermal range and less precipitation during the grain-filling stage also increased the 1000-kernel weight. Delayed sowing, however, also significantly increased the risk of early senescence and frost (>80%) in middle and high latitude areas. In the middle and high latitude areas of the NEC, the grain yield of a long-season cultivar (LS) under early sowing (I) (6.2–19.9%) was significantly higher than under medium sowing (II) or late sowing (III), and higher than that of an early sown (I) short-season (SS) and medium-season cultivar (MS). In the low latitude area of the NEC, the grain yield of MS under medium sowing date (II) was higher than that under I and III, meanwhile, this was also higher than that of SS and LS. Therefore, under climate warming, LS sown earlier in high and medium latitudes and MS sown medium in low latitude were the appropriate cultivar and sowing date choices, which could mitigate the stress of high temperatures and reduce the risk of early senescence and frost. Cultivar and sowing date selection are effective measures to alleviate negative effects of climate change on maize production in the NEC, and provides valuable advice for breeders on cultivar selection, and the choice of varieties and sowing dates for farmers in actual production

 Polygonatum praecox (Asparagaceae), a new species from mid-eastern China revealed by morphological and molecular evidence

A new species, Polygonatum praecox Y.F.Hu & J.W.Shao (Asparagaceae), is described and illustrated. This species is similar to P. cyrtonema, P. odoratum and P. caulialatum, but can be distinguished from P. cyrtonema by its racemose inflorescence, cylindrical hairless filaments and apex without a retrorse spur; from P. odoratum by its stout moniliform rhizome, straight stem and longer (1.7–2.2 cm long) floral tube; and from P. caulialatum by its upper part straight stem, yellowish-green corolla, lobes excurved and earlier flowering. The complete chloroplast genome of this new species is 155,115–155,256 bp in length. Phylogenetic analysis revealed that P. praecox is not genetically related to the above three morphological similar species, but is closely related to the two European species (P. multiforum and P. latifolium). This species is relatively common in mid-eastern China and has previously been confused with P. cyrtonema. As its wild resources have decreased in recent years due to over-exploitation for medicinal or edible purposes, we classify it as Near Threatened (NT) according to the IUCN Red List Criteria