Joint analysis of single-cell and bulk tissue sequencing data to infer intratumor heterogeneity

Many computational methods have been developed to discern intratumor heterogeneity (ITH) using DNA sequence data from bulk tumor samples. These methods share an assumption that two mutations arise from the same subclone if they have similar mutant allele-frequencies (MAFs), and thus it is difficult or impossible to distinguish two subclones with similar MAFs. Single-cell DNA sequencing (scDNA-seq) data can be very informative for ITH inference. However, due to the difficulty of DNA amplification, scDNA-seq data are often very noisy. A promising new study design is to collect both bulk and single-cell DNA-seq data and jointly analyze them to mitigate the limitations of each data type. To address the analytic challenges of this new study design, we propose a computational method named BaSiC (B ulk tumor a nd Si ngle C ell), to discern ITH by jointly analyzing DNA-seq data from bulk tumor and single cells. We demonstrate that BaSiC has comparable or better performance than the methods using either data type. We further evaluate BaSiC using bulk tumor and single-cell DNA-seq data from a breast cancer patient and several leukemia patients.     

Bayesian design of biosimilars clinical programs involving multiple therapeutic indications

In this paper, we propose a Bayesian design framework for a biosimilars clinical program that entails conducting concurrent trials in multiple therapeutic indications to establish equivalent efficacy for a proposed biologic compared to a reference biologic in each indication to support approval of the proposed biologic as a biosimilar. Our method facilitates information borrowing across indications through the use of a multivariate normal correlated parameter prior (CPP), which is constructed from easily interpretable hyperparameters that represent direct statements about the equivalence hypotheses to be tested. The CPP accommodates different endpoints and data types across indications (eg, binary and continuous) and can, therefore, be used in a wide context of models without having to modify the data (eg, rescaling) to provide reasonable information-borrowing properties. We illustrate how one can evaluate the design using Bayesian versions of the type I error rate and power with the objective of determining the sample size required for each indication such that the design has high power to demonstrate equivalent efficacy in each indication, reasonably high power to demonstrate equivalent efficacy simultaneously in all indications (ie, globally), and reasonable type I error control from a Bayesian perspective. We illustrate the method with several examples, including designing biosimilars trials for follicular lymphoma and rheumatoid arthritis using binary and continuous endpoints, respectively.     

Partial least squares for functional joint models with applications to the Alzheimer's disease neuroimaging initiative study

Many biomedical studies have identified important imaging biomarkers that are associated with both repeated clinical measures and a survival outcome. The functional joint model (FJM) framework, proposed by Li and Luo in 2017, investigates the association between repeated clinical measures and survival data, while adjusting for both high-dimensional images and low-dimensional covariates based on the functional principal component analysis (FPCA). In this paper, we propose a novel algorithm for the estimation of FJM based on the functional partial least squares (FPLS). Our numerical studies demonstrate that, compared to FPCA, the proposed FPLS algorithm can yield more accurate and robust estimation and prediction performance in many important scenarios. We apply the proposed FPLS algorithm to a neuroimaging study. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.     

Use of some emulsified plant seed oils as a safe alternative for the management of Meloidogyne incognita infecting tomato

Abstract

The aim of the present study was to formulate six different plant seed oils namely canola, cotton, flax, olive, sesame and soybean as emulsifiable concentrates. The composition of the formulation comprises at least one organic solvent, one surfactant and one plant oil. Physico-chemical properties of the formulated oils (emulsion stability test, cold stability and heat stability tests) were measured. The successfully emulsified oils were evaluated for nematicidal activity against Meloidogyne incognita infecting tomato plants under greenhouse conditions. Emulsified canola oil proved to be the most effective oil as a protectant against M. incognita infection to tomatoes followed by soybean, cotton, flax and sesame oil. In addition, employing a high rate of the tested emulsified oils gave higher activity in suppressing nematodes both in the soil and in tomato roots than using a low rate. Moreover, all tested formulated oils at both rates of application had no adverse effect on the growth of tomato plants except sesame oil which significantly decreased the shoot length when compared to the control. The prepared plant oils might be used as potential sources for sustainable eco-friendly botanical nematicides to protect plants from nematode attack.     

Field evaluation of some selected plant materials for the control of major insect pests of cowpea (Vigna unguiculata(L.) Walp.) in the Northern Guinea Savannah of Nigeria

Abstract

Field experiments were carried out at the Teaching and Research Farm of the Abubakar Tafawa Balewa University, Bauchi during the rainy season of 2005. The study was carried out with sole objective of evaluating the efficacy of six selected plant materials (sweetsop, red pepper, garlic, neem, mahogany and gmalina) against the major insect pests of cowpea variety, Dan Sokoto. The experiment was laid down in randomised complete block design with seven treatments. Each treatment was replicated three times. The results of the study showed that all the plant materials used were significantly (p < 0.05) better than control where no plant material was used in controlling the population of B. tabaci, E. dolichi, M. sjostedti and C. tomentosicollis at 1, 2 and 3 days after application of the treatments. Similarly the effects of these plant materials on the number of seeds/pod showed a significant (p < 0.05) difference between plots treated with plant materials and control. On the grain yield of the crop, all the plant materials showed significant effect except mahogany and the control which were statistically similar. Furthermore, the order of level of control indicated that sweet sop has (70.7%), garlic (69.3%), neem (61.0%), red pepper (54.0%), ash (30.9%), and mahogany (3.5%). The result of the present finding therefore recommends the use of sweet sop, garlic and neem as they were found to be the most promising in the control of major cowpea insect pests.     

A Comparison of Effects of Broad-Spectrum Antibiotics and Biosurfactants on Established Bacterial Biofilms

Current antibiofilm solutions based on planktonic bacterial physiology have limited efficacy in clinical and occasionally environmental settings. This has prompted a search for suitable alternatives to conventional therapies. This study compares the inhibitory properties of two biological surfactants (rhamnolipids and a plant-derived surfactant) against a selection of broad-spectrum antibiotics (ampicillin, chloramphenicol and kanamycin). Testing was carried out on a range of bacterial physiologies from planktonic and mixed bacterial biofilms. Rhamnolipids (Rhs) have been extensively characterised for their role in the development of biofilms and inhibition of planktonic bacteria. However, there are limited direct comparisons with antimicrobial substances on established biofilms comprising single or mixed bacterial strains. Baseline measurements of inhibitory activity using planktonic bacterial assays established that broad-spectrum antibiotics were 500 times more effective at inhibiting bacterial growth than either Rhs or plant surfactants. Conversely, Rhs and plant biosurfactants reduced biofilm biomass of established single bacterial biofilms by 74–88 and 74–98 %, respectively. Only kanamycin showed activity against biofilms of Bacillus subtilis and Staphylococcus aureus. Broad-spectrum antibiotics were also ineffective against a complex biofilm of marine bacteria; however, Rhs and plant biosurfactants reduced biofilm biomass by 69 and 42 %, respectively. These data suggest that Rhs and plant-derived surfactants may have an important role in the inhibition of complex biofilms.     

Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics

Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly. In this paper, we report a Saudi Arabian family with Liebenberg syndrome. Comparative genomic hybridization (CGH) revealed a 275-kb deletion within the cytogenetic band 5q31.1 which contains the H2AFY gene and 190,428 bp of its downstream region. The deleted region is upstream to the PITX1 gene. The radiological features in the upper limbs of all affected members of the family were almost identical to the phenotype in the mouse model with ectopic expression of Pitx1 in the forelimbs. We therefore re-define the phenotype of Liebenberg syndrome as a transformation of the upper limbs to reflect lower limb characteristics and speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds.     

Microbial maceration and carbonate dissolution on cold‐temperate shelves

Nummulites beaumonti d'Archiac & Haime, 1853, originally described from El Basatin, Gebel Mokattam, Greater Cairo, is redefined from a nummulitic bank at the base of the Maadi Formation from its type locality as neotype. Schaub (1981) described the species from Libya and the type example of this species is still unknown. N. discorbinus Schlotheim (1820) is described as neotype from a nummulitic bank in the Mokattam Formation, which is located in the site of the Citadel tombs, near the Salah El Din Citadel, Gebel Mokattam, Egypt. According to Schaub (1981), the type example of this species is also unknown. For this reason the establishment of the neotypes of these two widespread nummulites species: N. discorbinus (Late Lutetian) and N. beaumonti (Bartonian) is important and tackled in this paper. N. qurnensis n. sp. ( = N. sp. cf. beaumonti in Boukhary et al. 2002) is introduced as a new species from the lower Bartonian part of the Qurn Formation of Helwan. Biometrical studies are carried out on the three species to present up to date information on these Nummulites, with particular attention to their biostratigraphic correlation with the Shallow Benthic Zones (SBZ) of Serra-Kiel et al. 1998. The authors would like to stress the importance of a careful designation of a neotype to avoid the introduction of complicated and unnecessary taxonomic problems.     

Economic activity in the South-Asian population in Britain: the impact of ethnicity,religion, and class

This paper expands the existing literature on ethnicity and economic activity in Britain by studying the impact of religion and class. It argues that while the class location of the different South-Asian groups is important in determining their labour market outcomes, it does not operate independently from ethnicity; rather it is highly influenced by ethnicity in the process of determining the labour market participation of these groups. We use data obtained from the 2001 UK Census on Indian, Pakistani, and Bangladeshi men and women aged between twenty and twenty nine. Our findings confirm that class structure of the South-Asian groups is highly ethnicized, in that the ethno-religious background and class are interwoven to the extent that the separation between them is not easy, if not impossible.