Rare Decays of \Lambda_b->\Lambda + \gamma and \Lambda_b ->\Lambda + l^{+} l^{-} in the Light-cone Sum Rules

Within the Standard Model, we investigate the weak decays of $\Lambda_b \to \Lambda + \gamma$ and $\Lambda_b \to \Lambda + l^{+} l^{-}$ with the light-cone sum rules approach. The higher twist distribution amplitudes of $\Lambda$ baryon to the leading conformal spin are included in the sum rules for transition form factors. Our results indicate that the higher twist distribution amplitudes almost have no influences on the transition form factors retaining the heavy quark spin symmetry, while such corrections can result in significant impacts on the form factors breaking the heavy quark spin symmetry. Two phenomenological models (COZ and FZOZ) for the wave function of $\Lambda$ baryon are also employed in the sum rules for a comparison, which can give rise to the form factors approximately 5 times larger than that in terms of conformal expansion. Utilizing the form factors calculated in LCSR, we then perform a careful study on the decay rate, polarization asymmetry and forward-backward asymmetry, with respect to the decays of $\Lambda_b \to \Lambda \gamma$, $\Lambda l^{+}l^{-}$.Comment: 38 pages, 15 figures, some typos are corrected and more references are adde

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

Background Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. Methods and results Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both crosssectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and allcause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Biogeochemical responses to nutrient, moisture and temperature manipulations of soil from Signy Island, South Orkney Islands in the Maritime Antarctic

We have investigated how the microbially-driven processes of carbon (C) mineralization (respiration) and nitrogen (N) mineralization/immobilization in a soil from the northern Maritime Antarctic respond to differences in water availability (20% and 80% water-holding capacity) and temperature (5°C and 15°C) in the presence and absence of different organic substrates (2 mg C as either glucose, glycine or tryptone soy broth (TSB) powder (a complex microbial growth medium)) in a controlled laboratory experiment over 175 days. Soil respiration and N mineralization/immobilization in the presence of a C-rich substrate (glucose) increased with increases in water and temperature. These factors were influential individually and had an additive effect when applied together. For the N-rich substrates (glycine and TSB), microbial responses to increased water or temperature alone were weak or not significant, but these factors interacted to give significantly positive increases when applied together. These data indicate that under the expected changes in environmental conditions in the Maritime Antarctic, where temperature and the availability of water and organic substrates will probably increase, soil microbial activity will lead to more rapid C and N cycling and have a positive feedback on these biogeochemical processes, particularly where or when these factors increase concurrently

Evaluation of water-compatible molecularly imprinted polymers as solid-phase extraction sorbents for the selective extraction of sildenafil and its desmethyl metabolite from plasma samples

The evaluation of molecularly imprinted polymers (MIPs) as selective sorbents for the solid-phase extraction of sildenafil and its principal metabolite, desmethylsildenafil, was investigated. Two MIPs were synthesised using structural analogues of sildenafil as templates, and a comparison of the performance of the two MIP sorbents in organic and aqueous media was performed. Additionally, the feasibility of applying molecularly imprinted solid-phase extraction (MISPE) to the clean-up of plasma samples containing sildenafil and desmethylsildenafil was investigated. A preliminary, quantitative MISPE for the determination of both compounds in plasma was also performed. The results showed that the MIPs used for the selective extraction of sildenafil gave better compound recovery when aqueous samples were used in comparison to organic-based samples. A preliminary, quantitative MISPE of sildenafil and desmethylsildenafil indicated that the imprinted materials could be used successfully as SPE sorbents for sample pre-treatment for the determination of sildenafil, and related compounds, in plasma

Ensuring planetary survival: the centrality of organic carbon in balancing the multifunctional nature of soils

Not only do soils provide 98.7% of the calories consumed by humans, they also provide numerous other functions upon which planetary survivability closely depends. However, our continuously increasing focus on soils for biomass provision (food, fiber, and energy) through intensive agriculture is rapidly degrading soils and diminishing their capacity to deliver other vital functions. These tradeoffs in soil functionality – the increased provision of one function at the expense of other critical planetary functions – are the focus of this review. We examine how land-use change for biomass provision has decreased the ability of soils to regulate the carbon pool and thereby contribute profoundly to climate change, to cycle the nutrients that sustain plant growth and ecosystem health, to protect the soil biodiversity upon which many other functions depend, and to cycle the Earth’s freshwater supplies. We also examine how this decreasing ability of soil to provide these other functions can be halted and reversed. Despite the complexity and the interconnectedness of soil functions, we show that soil organic carbon plays a central role and is a master indicator for soil functioning and that we require a better understanding of the factors controlling the behavior and persistence of C in soils. Given the threats facing humanity and their economies, it is imperative that we recognize that Soil Security is itself an existential challenge and that we need to increase our focus on the multiple functions of soils for long-term human welfare and survivability of the planet