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This study reviewed the literature to assess the available evidence for the ability of biomarkers based on human papillomavirus (HPV) methylation (i.e., the detection of methyl groups in HPV DNA in cervical specimens) to screen for cervical precancerous and cancerous lesions. Scientific databases were searched, and abstracts screened for relevance. The quality of the included articles was assessed using a quality assessment tool called QUADAS-2. The main diagnostic performance parameter extracted from the included articles was the receiver operating characteristic (ROC), a measure of the ability of a biomarker to detect all true cases (true positives) while excluding all true non-cases (true negatives). After screening, nine articles were included, of which seven were of moderate quality and two were of high quality. ROC data were extracted for 27 biomarkers, of which four methylation biomarkers had high diagnostic ability (i.e., ROC 0.900), 17 had moderate diagnostic ability (ROC: 0.7000–0.8999) and six had low diagnostic ability (ROC 0.700). An umbrella meta-analysis (i.e., a weighted-average ROC for all HPV methylation biomarkers) revealed an ROC consistent with moderate diagnostic ability (0.770). The main conclusion from this study was that HPV methylation biomarkers, especially ones with high diagnostic ability, hold significant promise as independent screening tests for the detection of cervical precancerous and cancerous lesions.

Chop, DelRio, and GrandSlam are phage with a Siphoviridae morphotype isolated from soil in Arkansas using the host Gordonia terrae 3612. All three are temperate, and their genomes share at least 96% nucleotide identity. These phage are assigned to cluster DI based on gene content similarity to other sequenced actinobacteriophage.

In plants, host–pathogen coevolution often manifests in reciprocal, adaptive genetic changes through variations in host nucleotide-binding leucine-rich repeat immune receptors (NLR) and virulence-promoting pathogen effectors. In grass powdery mildew (PM) fungi, an extreme expansion of a RNase-like effector family, termed RALPH, dominates the effector repertoire, with some members recognized as avirulence (AVR) effectors by cereal NLR receptors. We report the structures of the sequence-unrelated barley PM effectors AVRA6, AVRA7and allelic AVRA10/AVRA22variants, which are detected by highly sequence-related barley NLRs MLA6, MLA7, MLA10, and MLA22, and of wheat PM AVRPM2detected by the unrelated wheat NLR PM2. The AVR effectors adopt a common scaffold, which is shared with the ribonuclease (RNase) T1/F1-family. We found striking variations in the number, position, and length of individual structural elements between RALPH AVRs, which is associated with a differentiation of RALPH effector subfamilies. We show that all RALPH AVRs tested have lost nuclease and synthetase activities of the RNase T1/F1- family and lack significant binding to RNA, implying that their virulence activities are associated with neo-functionalization events. Structure-guided mutagenesis identified six AVRA6residues that are sufficient to turn a sequence-diverged member of the same RALPH subfamily into an effector specifically detected by MLA6. Similar structure-guided information for AVRA10and AVRA22indicates that MLA receptors detect largely distinct effector surface patches. Thus, coupling of sequence and structural polymorphisms within the RALPH scaffold of PMs facilitated escape from NLR recognition and potential acquisition of diverse virulence functions.

The development of robust, high-performance integrated circuits (ICs) will enable numerous potential NASA missions of current interest, including long-duration robotic missions exploring the 460°C surface of Venus. Currently, NASA is looking towards SiC-based devices to provide such a solution. However, the current NASA silicon carbide (SiC) JFET device with a channel length of 6 μm (recently fabricated Gen. 11 ICs) limits mission-relevant circuit capabilities. In this study, we combined experiments with simulations to explore two straightforward fabrication strategies (shallow n−and extended n+) to reduce the SiC JFET channel length while maintaining the turn-off behavior needed to realize 500°C circuit operation. COMSOL Multiphysics was used to simulate the transfer characteristics and maximum potential below the gate of a 4H-SiC nJFET at 500°C, and a 1 μm gate length nJFET with turn-off performance comparable to the state-of-the-art is suggested.

PDF file - 9.7MB, Hematoxylin and eosin stained sections of ovarian tumors in Gclm+/+ and Gclm-/- F1 females prenatally exposed to BaP

Evidence showing a relationship between the mouse gut microbiome and properties such as phenotype and reaction to therapeutic agents and other treatments has increased significantly over the past 20 to 30 y. Recent concerns regarding the reproducibility of animal experiments have underscored the importance of understanding this relationship and how differences in husbandry practices can affect the gut microbiome. The current study focuses on effects of different barrier practices in 2 barrier facilities at the same institution on the fecal microbiome of breeding C57Bl/6J mice. Ten female and 10 male C57Bl/6J mice were obtained in one shipment from Jackson Laboratories and were housed under different barrier conditions upon arrival. Fecal samples were collected on arrival and periodically thereafter and were sent to TransnetYX for microbiome analysis. Mice used for collection of feces were housed as breeding pairs, with a total of 5 breeding pairs per barrier. An additional fecal sample was collected from these mice at 8 wk after arrival. One F1 female and one F1 male from each breeding cage were housed as brother-sister breeding pairs and a fecal sample was collected from them at 8 wk of age. Brother-sister breeding colonies were continued through F3, with fecal samples for microbiome analysis were collected from each generation at 8 wk of age. Breeding colonies in the 2 barriers showed differences in relative abundance, α -diversity, and β -diversity. Our data indicate that differences in barrier husbandry practices, including the use of autoclaved cages, the degree of restricted access, feed treatment practices, and water provision practices, can affect fecal microbiome divergence in both the parental and filial generations of different breeding colonies. To our knowledge, this is the first study to examine the effect of barrier husbandry practices on the microbiome of breeding colonies through the F3 generation.

Introgressions of chromosomal segments from related species into wheat are important sources of resistance against fungal diseases. The durability and effectiveness of introgressed resistance genes upon agricultural deployment is highly variable-a phenomenon that remains poorly understood, as the corresponding fungal avirulence genes are largely unknown. Until its breakdown, the

Recent experimental and computational evidence indicates that singlet oxygen (1O2) attacks the ethylene group (-CH2-CH2-) in ethylene carbonate (EC) leading to degradation in Li-ion batteries employing EC as the electrolyte solvent [J. Phys. Chem. A2018, 122, 8828-8839]. Here, we employ computational quantum chemistry to explore this mechanism in detail for a large set of organic molecules. Benchmark calculations comparing density functional theory to the complete active space second-order perturbation theory and internally contracted multireference configuration interaction indicate that the M11 functional adequately captures trends in the transition-state energies for this mechanism. Based on our results, we recommend that solvents which include the ethylene group should be avoided in Li-ion and Li-O2 batteries where 1O2 is generated unless neighboring functional groups raise the reaction barrier to avoid this decomposition pathway.

Research centres in low- and middle-income countries are routinely circumvented in the production of cross-cultural research on human behaviour. Where local contributions are made, collaboration is rarely equitable and often uncredited in co-authorship. Efforts to decolonize the social sciences will remain inadequate until these norms are overturned.

The marriage of older men to younger women is common across cultures. On one hand, husband-older marriage may serve the interests of both sexes, a conclusion broadly consistent with reported gender differences in mate preferences. On the other hand, men alone may benefit from such marriages at a cost to women if seniority enables men to exert dominance in conflicts of interest. Indeed, in public health large spousal age gaps are generally deemed “pathological”, both as a cause and consequence of gender inequalities harmful to women. We investigate these alternative models of spousal age gap using data from a cross-sectional survey of women in Mwanza, northwestern Tanzania (n = 993). Consistent with the notion that spousal age gaps are a product of sexual conflict, women typically married with a larger age gap than stated ideals. However, adjusting for potential confounds, spousal age gap was not associated with fertility or the risk of divorce. Furthermore, women's mental health and autonomy in household decision-making was higher in husband-older marriages compared to rare cases of same-age or wife-older marriage. Beyond this comparison, the magnitude of spousal age gaps was unrelated to either measure of women's wellbeing among the overwhelming majority of marriages where the husband was older. Together these findings suggest husband-older marriage does not influence marital stability, relatively large spousal age gaps are neither especially costly nor beneficial to women, and that alternative sociodemographic factors are more important in driving variation in women's wellbeing and reproductive success in this context. Our results support neither a model of mutual benefits, nor a pathological conceptualization of spousal age gaps. We conclude by both encouraging evolutionary human scientists to engage more fully with models of sexual conflict in future studies of marriage and mating, and suggesting that public health scholars consider more neutral interpretations of spousal age differences.

Introgressions of chromosomal segments from related species into wheat are important sources of resistance against fungal diseases. The durability and effectiveness of introgressed resistance genes upon agricultural deployment is highly variable—a phenomenon that remains poorly understood, as the corresponding fungal avirulence genes are largely unknown. Until its breakdown, the Pm17 resistance gene introgressed from rye to wheat provided broad resistance against powdery mildew ( Blumeria graminis ). Here, we used quantitative trait locus (QTL) mapping to identify the corresponding wheat mildew avirulence effector AvrPm17 . It is encoded by two paralogous genes that exhibit signatures of reoccurring gene conversion events and are members of a mildew sublineage specific effector cluster. Extensive haplovariant mining in wheat mildew and related sublineages identified several ancient virulent AvrPm17 variants that were present as standing genetic variation in wheat powdery mildew prior to the Pm17 introgression, thereby paving the way for the rapid breakdown of the Pm17 resistance. QTL mapping in mildew identified a second genetic component likely corresponding to an additional resistance gene present on the 1AL.1RS translocation carrying Pm17. This gene remained previously undetected due to suppressed recombination within the introgressed rye chromosomal segment. We conclude that the initial effectiveness of 1AL.1RS was based on simultaneous introgression of two genetically linked resistance genes. Our results demonstrate the relevance of pathogen-based genetic approaches to disentangling complex resistance loci in wheat. We propose that identification and monitoring of avirulence gene diversity in pathogen populations become an integral part of introgression breeding to ensure effective and durable resistance in wheat.

Almost 75 years of research has been devoted to producing superalloys capable of higher operating temperatures in jet turbine engines, and there is an ongoing need to increase operating temperature further. Here, a new disk Nickel-base superalloy is designed to take advantage of strengthening atomic-scale dynamic complexions. This local phase transformation strengthening provides the alloy with a three times improvement in creep strength over similar disk superalloys and comparable strength to a single crystal blade alloy at 760 °C. Ultra-high-resolution chemical mapping reveals that the improvement in creep strength is a result of atomic-scale η (D024) and χ (D019) formation along superlattice stacking faults. To understand these results, the energy differences between the L12 and competing D024 and D019 stacking fault structures and their dependence on composition are computed by density functional theory. This study can help guide researchers to further optimize local phase transformation strengthening mechanisms for alloy development. There is an ongoing need to increase the operating temperature of jet engines, requiring new high-temperature materials. Here, local phase transformations at superlattice stacking faults contribute to a three times improvement in creep strength in a Ni-based superalloy.

Malaria in pregnancy remains a major problem of public health concern in Sub-Saharan Africa due to its endemicity and the diverse consequences on both the mother and the baby. Much attention, therefore, is needed to fully understand the epidemiology of the disease and to mitigate the devastating outcomes. The present study aimed at investigating malaria in pregnancy, its adverse effects on pregnant women and the impact on birthweight of babies. A total of 222 pregnant women gave their consent and were recruited into the study during their routine Antenatal care visits. This study employed a combination of cross-sectional and longitudinal cohort study designs. For 122 women in the cross-sectional arm, blood samples and data were obtained once, whilst 100 women in the longitudinal cohort arm were followed up from recruitment until delivery. Demographic information, obstetric history and risk factors were obtained by administering questionnaires. About 1.0 ml of venous blood was drawn to determine malaria parasitaemia and anaemia status of the participants. The birthweights of the babies were also taken at delivery. The prevalence of malaria and anaemia was 19.8% and 27.0% respectively at registration for all 222 participants. All infections wereP. falciparummalaria. One hundred and forty-six (65.8%) of participants had ITN but only 72 (32.4%) used it the previous night. Young age and rural settings were risk factors for malaria. Young age and malaria positive pregnant women had increased risk of anaemia. In the follow-up group which ended with 54 participants, the overall prevalence of malaria and anaemia were 18.7% and 32.4% respectively. Fifty-two (96.3%) of pregnant women attended ANC ≥ 4 times and 55.6% took ≥ 3 doses of SP. There were two cases of miscarriage. Low birthweight occurred in 5.6% of babies. Both malaria and anaemia during pregnancy had no significant impact on birthweight of the babies. Although few of the babies had low birthweight, this number can be further reduced when pregnant women attend ANC and take SP at the recommended number of times.

Reynoutria japonica (Japanese knotweed) is a problematic invasive plant found in many areas of Europe and North America. Notably, in the UK, the species can cause issues with mortgage acquisition. Control of R. japonica is complicated by its ability to regenerate from small fragments of plant material; however, there remains uncertainty about how much (in terms of mass) rhizome is required for successful regeneration. This study investigated the ability of crowns and rhizomes with different numbers of nodes to regenerate successfully from three sites in the north of England, UK. Two of the sites had been subject to herbicide treatment for two years prior to sampling and the third site had no history of herbicide treatment. No significant differences were observed in regenerated stem diameter, maximum height of stem and maximum growth increments among crowns. All traits measured from the planted crowns were significantly greater than those of the planted rhizome fragments and at least one node was necessary for successful regeneration of rhizomes. The smallest initial fragment weight to regenerate and survive the experiment was 0.5 g. Subjecting all plant material to desiccation for 38 days resulted in no regrowth (emergence or regeneration) after replanting. These findings suggest that desiccation could be a valuable management strategy for small to medium scale infestations common in urban settings.

All-solid-state batteries with Li metal anode can address the safety issues surrounding traditional Li-ion batteries as well as the demand for higher energy densities. However, the development of solid electrolytes and protective anode coatings possessing high ionic conductivity and good stability with Li metal has proven to be a challenge. Here, we present our informatics approach to explore the Li compound space for promising electrolytes and anode coatings using high-throughput multi-property screening and interpretable machine learning. To do this, we generate a database of battery-related materials properties by computing $$\hbox {Li}^+$$ Li + migration barriers and stability windows for over 15,000 Li-containing compounds from Materials Project. We screen through the database for candidates with good thermodynamic and electrochemical stabilities, and low $$\hbox {Li}^+$$ Li + migration barriers, identifying promising new candidates such as $$\hbox {Li}_9\hbox {S}_3$$ Li 9 S 3 N, $$\hbox {LiAlB}_2\hbox {O}_5$$ LiAlB 2 O 5 , $$\hbox {LiYO}_2$$ LiYO 2 , $$\hbox {LiSbF}_4$$ LiSbF 4 , and $$\hbox {Sr}_4\hbox {Li}(\hbox {BN}_2)_3$$ Sr 4 Li ( BN 2 ) 3 , among others. We train machine learning models, using ensemble methods, to predict migration barriers and oxidation and reduction potentials of these compounds by engineering input features that ensure accuracy and interpretability. Using only a small number of features, our gradient boosting regression models achieve $$\mathrm {R}^2$$ R 2 values of 0.95 and 0.92 on the oxidation and reduction potential prediction tasks, respectively, and 0.86 on the migration barrier prediction task. Finally, we use Shapley additive explanations and permutation feature importance analyses to interpret our machine learning predictions and identify materials properties with the largest impact on predictions in our models. We show that our approach has the potential to enable rapid discovery and design of novel solid electrolytes and anode coatings.

The abstraction of a proton by OH-, O2-, and XO2- from DME n···X+, where X is Li, Na, or K, is studied using density functional theory. Both the gas phase and the solution phase are studied. In general, when explicit solvent molecules are added, the difference between the gas-phase and solution results becomes rather small. While the DME n···X+ binding energies differ significantly for various alkali cations, the reaction energies and transition-state energies are far less sensitive to the choice of an alkali cation. XO2- has a lower barrier height than OH-, which, in turn, has a lower barrier height than O2-. The reaction energies follow the same trends.

Approximately 40% of women in sub-Saharan Africa marry before their eighteenth birthday1. Within the international development sector, this phenomenon is referred to as 'child marriage', widely equated to forced marriage, and recognized as damaging to multiple dimensions of female well-being1,2. An escalating global campaign to end early marriage typically assumes that its high prevalence is driven by a conflict of interests between parents and daughters, with parents coercing daughters to marry early for the parents' economic benefit3. However, a parent-offspring conflict model of early marriage has not been explicitly tested. Here we present a study of marriage transitions in rural Tanzania, where marriage before or just after 18 years of age is normative. Consistent with parental coercion, we find that bridewealth transfers are highest for younger brides. However, autonomy in partner choice is very common at all ages, relationships between age at marriage and female well-being are largely equivocal, and women who marry early achieve relatively higher reproductive success. We conclude that, in contexts in which adolescents have autonomy in marriage choices and in which marriage promotes economic and social security, early marriage may be better understood as serving the strategic interests of both parents and daughters.

A global campaign to end “child marriage” has emerged over the last decade as part of growing international commitments to address gender inequities and improve female wellbeing. Campaigns typically assert that young brides have negligible autonomy in the marriage process and that marrying under 18 years has resolutely negative impacts on wellbeing. Yet, surprisingly few studies explore local attitudes towards marriage and its timing within contexts where early marriage is most common. As such our understanding of motivations and potential conflicts of interest leading female adolescents into marriage remain poorly informed by viewpoints of people purportedly at risk. We present an exploratory study of attitudes to early marriage in northwestern Tanzania where marriage before or shortly after 18 years is normative. We use focus group discussions, complimented by a survey of 993 women, to investigate local views on marriage. We explore (i) why people marry, (ii) when marriage is deemed appropriate, and (iii) who guides the marriage process. Contrary to dominant narratives in the end child marriage movement, we find that women are frequently active rather than passive in the selection of when and who to marry. Furthermore, marriage is widely viewed as instrumental in acquiring social status within one’s local community. Our conclusions illuminate why rates of early marriage remain high despite potential negative wellbeing consequences and increasingly restrictive laws. We discuss our results in relation to related qualitative studies in other cultural contexts and consider the policy implications for current efforts to limit early marriage in Tanzania and beyond.

Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are ubiquitous environmental contaminants formed during incomplete combustion of organic materials. Our prior work showed that transplacental exposure to BaP depletes ovarian follicles and increases prevalence of epithelial ovarian tumors later in life. We used the MutaMouse transgenic rodent model to address the hypothesis that ovarian mutations play a role in tumorigenesis caused by prenatal exposure to BaP. Pregnant MutaMouse females were treated with 0, 10, 20, or 40 mg/(kg day) BaP orally on gestational days 7-16, covering critical windows of ovarian development. Female offspring were euthanized at 10 weeks of age; some ovaries with oviducts were processed for follicle counting; other ovaries/oviducts and bone marrow were processed for determination of lacZ mutant frequency (MF). Mutant plaques were pooled within dose groups and sequenced to determine the mutation spectrum. BaP exposure caused highly significant dose-related decreases in ovarian follicles and increases in ovarian/oviductal and bone marrow mutant frequencies at all doses. Absence of follicles, cell packets, and epithelial tubular structures were observed with 20 and 40 mg/(kg day) BaP. Depletion of ovarian germ cells was inversely associated with ovarian MF. BaP induced primarily G > T and G > C transversions and deletions in ovaries/oviducts and bone marrow cells and produced a mutation signature highly consistent with that of tobacco smoking in human cancers. Overall, our results show that prenatal BaP exposure significantly depletes ovarian germ cells, causes histopathological abnormalities, and increases the burden of ovarian/oviductal mutations, which may be involved in pathogenesis of epithelial ovarian tumors. Environ. Mol. Mutagen. 60:410-420, 2019. © 2018 Her Majesty the Queen in Right of Canada.

Recent experimental and computational evidence indicates that singlet oxygen (

Achieving gender equality fundamentally requires a transfer of power from men to women. Yet data on men's support for women's empowerment (WE) remains scant and limited by reliance on self-report methodologies. Here, we examine men's support for WE as a sexual conflict trait, both via direct surveys (n = 590) and indirectly by asking men's wives (n = 317) to speculate on their husband's views. Data come from a semi-urban community in Mwanza, Tanzania. Consistent with reduced resource competition and increased exposure to relatively egalitarian gender norms, higher socioeconomic status predicted greater support for WE. However, potential demographic indicators of sexual conflict (high fertility, polygyny, large spousal age gap) were largely unrelated to men's support for WE. Contrasting self- and wife-reported measures suggests that men frequently exaggerate their support for women in self-reported attitudes. Discrepancies were especially pronounced among men claiming the highest support for WE, but smallest among men who held a professional occupation and whose wife participated in wage labour, indicating that these factors predict genuine support for WE. We discuss the implications of these results for our understanding of both individual variation and patriarchal gender norms, emphasising the benefits of greater exchange between the evolutionary human sciences and global health research on these themes.

BackgroundGenotype independent transformation and whole plant regeneration through somatic embryogenesis relies heavily on the intrinsic ability of a genotype to regenerate. The critical genetic architecture of non-embryogenic callus (NEC) cells and embryogenic callus (EC) cells in a highly regenerable cotton genotype is unknown.ResultsIn this study, gene expression profiles of a highly regenerableGossypium hirsutumL. cultivar, Jin668, were analyzed at two critical developmental stages during somatic embryogenesis, non-embryogenic callus (NEC) cells and embryogenic callus (EC) cells. The rate of EC formation in Jin668 is 96%. Differential gene expression analysis revealed a total of 5333 differentially expressed genes (DEG) with 2534 genes upregulated and 2799 genes downregulated in EC. A total of 144 genes were unique to NEC cells and 174 genes were unique to EC. Clustering and enrichment analysis identified genes upregulated in EC that function as transcription factors/DNA binding, phytohormone response, oxidative reduction, and regulators of transcription; while genes categorized in methylation pathways were downregulated. Four key transcription factors were identified based on their sharp upregulation in EC tissue;LEAFY COTYLEDON 1(LEC1),BABY BOOM(BBM),FUSCA(FUS3) andAGAMOUS-LIKE15with distinguishable subgenome expression bias.ConclusionsThis comparative analysis of NEC and EC transcriptomes gives new insights into the genes involved in somatic embryogenesis in cotton.