Combustion of ammonia (NH3) blended fuels under elevated pressure conditions is critical for adopting this non-carbon fuel in the energy system for decarbonization. In the present work, laminar ...burning velocities of ammonia/methane(CH4)/air mixtures were measured using the heat-flux method at the pressure from 1 to 5 atm with the mixture equivalence ratios ranging from 0.6 to 1.6 and the mole fraction of NH3 ranging from 0 to 1.0. The relatively completed results obtained at elevated pressures were then used for validating and modifying the kinetic mechanisms (CEU-NH3-Mech 1.0) leading to a new version (CEU-NH3-Mech-1.1). Experimental results of NH3/H2/air in the present work, NH3/H2/CO/air mixtures measured on the same setup and reported in our previous works were also considered in the development of the kinetic mechanism. It was found that the CEU-NH3−Mech-1.1 can predict well the laminar flame speed, ignition delay time and species concentration in the ammonia oxidation at high temperatures for both NH3/CH4/air and NH3/H2/CO/air mixtures in a wide range of equivalence ratios and elevated pressures, including oxygen-enriched combustion conditions. The present experimental results also show that the value of pressure exponent (β) varies with the mole fraction of ammonia and behaves differently for the mixtures of ammonia blending into CH4 and H2. The kinetic and sensitivity analyses show that the sensitive reactions for β are weakly correlated to those for the laminar burning velocity, indicating that β can also work as a potential parameter for validating kinetic mechanisms. Ammonia content in the NH3/CH4/air mixtures determines the pressure exponent variation at over-rich equivalence ratios and reaction pathway variation in the post-flame zone. This work also clarifies the utilization of ammonia containing fuels in rich-lean combustion strategies.
Cells adapt to stressors by activating mechanisms that repair damage and protect them from further injury. Stress-induced damage accumulates with age and contributes to age associated diseases. ...Increased age attenuates the ability to mount a stress response, but little is known about the mechanisms by which this occurs. To begin addressing this problem, we studied hormesis in the nematode
Caenorhabditis elegans. When exposed to a low concentration of the xenobiotic juglone, young worms mount a robust hormetic stress response and survive a subsequent exposure to a higher concentration of juglone that is normally lethal to naïve animals. Old worms are unable to mount this adaptive response. Microarray and RNAi analyses demonstrate that an altered transcriptional response to juglone is responsible in part for the reduced adaptation of old worms. Many genes differentially regulated in young versus old animals are known or postulated to be regulated by the FOXO homologue DAF-16 and the Nrf2 homologue SKN-1. Activation of these pathways is greatly reduced in juglone stressed old worms. DAF-16- and SKN-1-like transcription factors play highly conserved roles in regulating stress resistance and longevity genes. Our studies provide a foundation for developing a molecular understanding of how age affects cytoprotective transcriptional pathways.
The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. ...Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of
PIK3R1
(NM_181523.2:c.1425 + 1G > A) found in three prior reports. All four had the Hyper IgM syndrome, lymphadenopathy and short stature, and one also had SHORT syndrome. They were investigated with in vitro immune studies, RT-PCR, and immunoblotting studies of the mutation’s effect on mTOR pathway signaling. All patients had very low percentages of memory B cells and class-switched memory B cells and reduced numbers of naïve CD4+ and CD8+ T cells. RT-PCR confirmed the presence of both an abnormal 273 base-pair (bp) size and a normal 399 bp size band in the patient and only the normal band was present in the parents. Following anti-CD40 stimulation, patient’s EBV-B cells displayed higher levels of S6 phosphorylation (mTOR complex 1 dependent event), Akt phosphorylation at serine 473 (mTOR complex 2 dependent event), and Akt phosphorylation at threonine 308 (PI3K/PDK1 dependent event) than controls, suggesting elevated mTOR signaling downstream of CD40. These observations suggest that amino acids 435–474 in PIK3R1 are important for its stability and also its ability to restrain PI3K activity. Deletion of Exon 11 leads to constitutive activation of PI3K signaling. This is the first report of this mutation and immunologic abnormalities in SHORT syndrome.
Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared ...results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen’s kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan–Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026–0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001–1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC.
The aim of this study was to assess the validity of categorization of chronic hepatitis B viral infection into stages or phases based upon measures of disease activity and viral load, assuming these ...phenotypes will be useful for prognostication and determining the need for antiviral therapy. We assessed the phenotype of hepatitis B of 1,390 adult participants enrolled in the Hepatitis B Research Network Cohort Study, using a computer algorithm. Only 4% were immune tolerant, while 35% had chronic hepatitis B (18% e antigen positive and 17% e antigen negative) while 23% were inactive carriers. Strikingly, 38% of participants did not fit clearly into any one of these groups and were considered indeterminant. The largest subset of indeterminants had elevated serum aminotransferases with low levels of HBV DNA (less than 10,000 iu/mL). Subsequent determination of hepatitis B phenotype on the next available laboratory tests showed that 64% remained indeterminant. These findings call into question the validity of conventional staging of hepatitis B, in large part because of the substantial proportion of patients who do not fit readily into one of the usual stages or phases. Further studies are needed of the indeterminant category of chronic hepatitis B viral infection, including assessments of whether patients in this group are perhaps in transition to another phase or if they are a distinct phenotype with a need to assess liver disease severity and need for antiviral therapy. (ClinicalTrials.gov identifier NCT01263587).
The M50 electrophysiological auditory evoked response time can be measured at the superior temporal gyrus with magnetoencephalography (MEG) and its latency is related to the conduction velocity of ...auditory input passing from ear to auditory cortex. In children with autism spectrum disorder (ASD) and certain genetic disorders such as XYY syndrome, the auditory M50 latency has been observed to be elongated (slowed).
The goal of this study is to use neuroimaging (diffusion MR and GABA MRS) measures to predict auditory conduction velocity in typically developing (TD) children and children with autism ASD and XYY syndrome.
Non-linear TD support vector regression modeling methods accounted for considerably more M50 latency variance than linear models, likely due to the non-linear dependence on neuroimaging factors such as GABA MRS. While SVR models accounted for ~80% of the M50 latency variance in TD and the genetically homogenous XYY syndrome, a similar approach only accounted for ~20% of the M50 latency variance in ASD, implicating the insufficiency of diffusion MR, GABA MRS, and age factors alone. Biologically based stratification of ASD was performed by assessing the conformance of the ASD population to the TD SVR model and identifying a sub-population of children with unexpectedly long M50 latency.
Multimodal integration of neuroimaging data can help build a mechanistic understanding of brain connectivity. The unexplained M50 latency variance in ASD motivates future hypothesis generation and testing of other contributing biological factors.
Animal-assisted interventions (AAIs) use human-animal interactions to positive effect in various contexts including cancer care. As the first installment of a 2-part series, this systematic ...literature review focuses on the research methods and quantitative results of AAI studies in oncology. We find methodological consistency in the use of canines as therapy animals, in the types of high-risk patients excluded from studies, and in the infection precautions taken with therapy animals throughout cancer wards. The investigated patient endpoints are not significantly affected by AAI, with the exceptions of improvements in oxygen consumption, quality of life, depression, mood, and satisfaction with therapy. The AAI field in oncology has progressed significantly since its inception and has great potential to positively affect future patient outcomes. To advance the field, future research should consistently improve the methodological design of studies, report data more completely, and focus more on the therapy animal’s well-being.
Background:
Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X ...chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of 46, XX females to balance the gene expression with 46, XY males. Age acquired XCI-skew describes the preferential selection of cells across a tissue resulting in an imbalance of XCI, which is particularly prevalent in blood tissues of ageing females, and yet its clinical consequences are unknown.
Methods:
We assayed XCI in 1575 females from the TwinsUK population cohort using DNA extracted from whole blood. We employed prospective, cross-sectional, and intra-twin study designs to characterise the relationship of XCI-skew with molecular and cellular measures of ageing, cardiovascular disease risk, and cancer diagnosis.
Results:
We demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10 year follow-up study, XCI-skew is predictive of future cancer incidence.
Conclusions:
Our study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk.
Funding:
KSS acknowledges funding from the Medical Research Council MR/M004422/1 and MR/R023131/1. JTB acknowledges funding from the ESRC ES/N000404/1. MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.
Abstract Rearing animals in captivity for conservation translocation is a complex undertaking that demands interdisciplinary management tactics. The maladapted behaviors that captive animals can ...develop create unique problems for wildlife managers seeking to release these animals into the wild. Often, released captive animals show decreased survival due to predation and their inability to display appropriate anti-predator, vigilance, and risk-analysis behaviors. Additionally, released animals may have poor foraging skills, further increasing their vulnerability to predation. Often conservation translocation programs use anti-predator training to ameliorate these maladapted behaviors before release but find mixed results in behavioral responses. The behavioral scope of analyzing the effect of anti-predator trainings is frequently narrow; the effect of this training on an animal’s risk-analysis competency, or ability to assess the predation risk of a foraging patch and subsequently adjust its behavior, remains unstudied. Using a captive-reared passerine species, the American robin (Turdus migratorius) (46 individuals), we applied an experimental giving up density test (GUD) to analyze the effect of anti-predator training on the robins’ vigilance/risk-analysis behaviors, patch choice, and the GUD of food left behind after one foraging session. Robins moved and foraged freely between 3 foraging patches of differing predation risk before and after a hawk silhouette was presented for 1 min. Results indicate that after anti-predator training, robins displayed increased vigilance across most foraging patches and better foraging efficiency (higher vigilance and latency to forage with simultaneous lower GUD) in the safest patch. These results can have positive survival implications post-release, however, more research on this training is needed because anti-predator training has the potential to elicit indiscriminate increased vigilance to the detriment of foraging gains. Further research is required to standardize GUD’s application in translocation programs with multigenerational captive-bred animals to fully comprehend its effectiveness in identifying and correcting maladaptive behaviors. GUD tests combined with behavioral analysis should be used by conservation translocation managers to examine the need for anti-predator and foraging trainings, the effects of trainings, and a group’s suitability for release.
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