Variance components estimation in agricultural experiments with possible application to ICRISAT data

In agricultural experiments, especially in plant breeding quite often interest lies in estimating different components of genetic variance either for the purpose of studying their relative magnitudes of for estimating certain functions of them e.g. heritability (see Kempthorne and Tandon 1953), average degree of dominance (see Comstock and Robinson 1948) etc..

Limiting Behaviour of the Mean Residual Life

In survival or reliability studies, the mean residual life or life expectancy is an important characteristic of the model. Here, we study the limiting behaviour of the mean residual life, and derive an asymptotic expansion which can be used to obtain a good approximation for large values of the time variable. The asymptotic expansion is valid for a quite general class of failure rate distributions--perhaps the largest class that can be expected given that the terms depend only on the failure rate and its derivatives.Comment: 19 page

Characterizing the hygroscopicity of growing particles in the Canadian Arctic summer

The impact of aerosols on clouds is a well-studied, although still poorly constrained, part of the atmospheric system. New particle formation (NPF) is thought to contribute 40 %-80 % of the global cloud droplet number concentration, although it is extremely difficult to observe an air mass from NPF to cloud formation. NPF and growth occurs frequently in the Canadian Arctic summer atmosphere, although only a few studies have characterized the source and properties of these aerosols. This study presents cloud condensation nuclei (CCN) concentrations measured on board the CCGS Amundsen in the eastern Canadian Arctic Archipelago from 23 July to 23 August 2016 as part of the Network on Climate and Aerosols: Addressing Uncertainties in Remote Canadian Environments (NETCARE). The study was dominated by frequent ultrafine particle and/or growth events, and particles smaller than 100 nm dominated the size distribution for 92 % of the study period. Using kappa-Kohler theory and aerosol size distributions, the mean hygroscopicity parameter (kappa) calculated for the entire study was 0.12 (0.06-0.12, 25th-75th percentile), suggesting that the condensable vapours that led to particle growth were primarily slightly hygroscopic, which we infer to be organic. Based on past measurement and modelling studies from NETCARE and the Canadian Arctic, it seems likely that the source of these slightly hygroscopic, organic, vapours is the ocean. Examining specific growth events suggests that the mode diameter (D-max) had to exceed 40 nm before CCN concentrations at 0.99 % supersaturation (SS) started to increase, although a statistical analysis shows that CCN concentrations increased 13-274 cm(-3) during all ultrafine particle and/or growth times (total particle concentrations > 500 cm(-3 ), D-max < 100 nm) compared with background times (total concentrations < 500 cm(-3)) at SS of 0.26 %-0.99 %. This value increased to 25-425 cm(-3) if the growth times were limited to times when D-max was also larger than 40 nm. These results support past results from NETCARE by showing that the frequently observed ultrafine particle and growth events are dominated by a slightly hygroscopic fraction, which we interpret to be organic vapours originating from the ocean, and that these growing particles can increase the background CCN concentrations at SS as low as 0.26 %, thus pointing to their potential contribution to cloud properties and thus climate through the radiation balance.Peer reviewe

Employing the Metabolic “Branch Point Effect” to Generate an All-or-None, Digital-like Response in Enzymatic Outputs and Enzyme-Based Sensors

Here, we demonstrate a strategy to convert the graded Michaelis−Menten response typical of unregulated enzymes into a sharp, effectively all-or-none response. We do so using an approach analogous to the “branch point effect”, a mechanism observed in naturally occurring metabolic networks in which two or more enzymes compete for the same substrate. As a model system, we used the enzymatic reaction of glucose oxidase (GOx) and coupled it to a second, nonsignaling reaction catalyzed by the higher affinity enzyme hexokinase (HK) such that, at low substrate concentrations, the second enzyme outcompetes the first, turning off the latter’s response. Above an arbitrarily selected “threshold” substrate concentration, the nonsignaling HK enzyme saturates leading to a “sudden” activation of the first signaling GOx enzyme and a far steeper dose−response curve than that observed for simple Michaelis−Menten kinetics. Using the well-known GOx-based amperometric glucose sensor to validate our strategy, we have steepen the normally graded response of this enzymatic sensor into a discrete yes/no output similar to that of a multimeric cooperative enzyme with a Hill coefficient above 13. We have also shown that, by controlling the HK reaction we can precisely tune the threshold target concentration at which we observe the enzyme output. Finally, we demonstrate the utility of this strategy for achieving effective noise attenuation in enzyme logic gates. In addition to supporting the development of biosensors with digital-like output, we envisage that the use of all-or-none enzymatic responses will also improve our ability to engineer efficient enzyme-based catalysis reactions in synthetic biology applications

Tigers of Sundarbans in India: Is the Population a Separate Conservation Unit?

The Sundarbans tiger inhabits a unique mangrove habitat and are morphologically distinct from the recognized tiger subspecies in terms of skull morphometrics and body size. Thus, there is an urgent need to assess their ecological and genetic distinctiveness and determine if Sundarbans tigers should be defined and managed as separate conservation unit. We utilized nine microsatellites and 3 kb from four mitochondrial DNA (mtDNA) genes to estimate genetic variability, population structure, demographic parameters and visualize historic and contemporary connectivity among tiger populations from Sundarbans and mainland India. We also evaluated the traits that determine exchangeability or adaptive differences among tiger populations. Data from both markers suggest that Sundarbans tiger is not a separate tiger subspecies and should be regarded as Bengal tiger (P. t. tigris) subspecies. Maximum likelihood phylogenetic analyses of the mtDNA data revealed reciprocal monophyly. Genetic differentiation was found stronger for mtDNA than nuclear DNA. Microsatellite markers indicated low genetic variation in Sundarbans tigers (He= 0.58) as compared to other mainland populations, such as northern and Peninsular (Hebetween 0.67- 0.70). Molecular data supports migration between mainland and Sundarbans populations until very recent times. We attribute this reduction in gene flow to accelerated fragmentation and habitat alteration in the landscape over the past few centuries. Demographic analyses suggest that Sundarbans tigers have diverged recently from peninsular tiger population within last 2000 years. Sundarbans tigers are the most divergent group of Bengal tigers, and ecologically non-exchangeable with other tiger populations, and thus should be managed as a separate "evolutionarily significant unit" (ESU) following the adaptive evolutionary conservation (AEC) concept.Wildlife Institute of India, Dehra Dun (India)

Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions

BackgroundTargeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing.ResultsAll panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden.ConclusionThis comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.Peer reviewe

The apicomplexan plastid and its evolution

Protistan species belonging to the phylum Apicomplexa have a non-photosynthetic secondary plastid—the apicoplast. Although its tiny genome and even the entire nuclear genome has been sequenced for several organisms bearing the organelle, the reason for its existence remains largely obscure. Some of the functions of the apicoplast, including housekeeping ones, are significantly different from those of other plastids, possibly due to the organelle’s unique symbiotic origin

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children &lt;18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p&lt;0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p&lt;0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p&lt;0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer