No brain expansion in Australopithecus boisei

The endocranial volumes of robust australopithecine fossils appear to have increased in size over time. Most evidence with temporal resolution is concentrated in East African Australopithecus boisei. Including the KNM-WT 17000 cranium, this sample comprises 11 endocranial volume estimates ranging in date from 2.5 million to 1.4 million years ago. But the sample presents several difficulties to a test of trend, including substantial estimation error for some specimens and an unusually low variance. This study reevaluates the evidence, using randomization methods and a related test using an explicit model of variability. None of these tests applied to the A. boisei endocranial volume sample produces significant evidence for a trend in that species, whether or not the early KNM-WT 17000 specimen is included.     

Estimating the cumulative incidence of COVID-19 in the United States using influenza surveillance,virologic testing,and mortality data: Four complementary approaches

Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the prevalence of COVID-19 across the United States (US). Equipment shortages and varying testing capabilities have however hindered the usefulness of the official reported positive COVID-19 case counts. We introduce four complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 in each state in the US as well as Puerto Rico and the District of Columbia, using a combination of excess influenza-like illness reports, COVID-19 test statistics, COVID-19 mortality reports, and a spatially structured epidemic model. Instead of relying on the estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our four approaches emerges the consistent conclusion that on April 4, 2020, the estimated case count was 5 to 50 times higher than the official positive test counts across the different states. Nationally, our estimates of COVID-19 symptomatic cases as of April 4 have a likely range of 2.3 to 4.8 million, with possibly as many as 7.6 million cases, up to 25 times greater than the cumulative confirmed cases of about 311,000. Extending our methods to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 4.9 to 10.1 million, as opposed to 1.5 million positive test counts. The proposed combination of approaches may prove useful in assessing the burden of COVID-19 during resurgences in the US and other countries with comparable surveillance systems.     

A Statistical Test of a Neutral Model Using the Dynamics of Cytonuclear Disequilibria

In this paper we use cytonuclear disequilibria to test the neutrality of mtDNA markers. The data considered here involve sample frequencies of cytonuclear genotypes subject to both statistical sampling variation as well as genetic sampling variation. First, we obtain the dynamics of the sample cytonuclear disequilibria assuming random drift alone as the source of genetic sampling variation. Next, we develop a test statistic using cytonuclear disequilibria via the theory of generalized least squares to test the random drift model. The null distribution of the test statistic is shown to be approximately chi-squared using an asymptotic argument as well as computer simulation. Power of the test statistic is investigated under an alternative model with drift and selection. The method is illustrated using data from cage experiments utilizing different cytonuclear genotypes of Drosophila melanogaster. A program for implementing the neutrality test is available upon request.     

Test Samples for Optimizing STORM Super-Resolution Microscopy

STORM is a recently developed super-resolution microscopy technique with up to 10 times better resolution than standard fluorescence microscopy techniques. However, as the image is acquired in a very different way than normal, by building up an image molecule-by-molecule, there are some significant challenges for users in trying to optimize their image acquisition. In order to aid this process and gain more insight into how STORM works we present the preparation of 3 test samples and the methodology of acquiring and processing STORM super-resolution images with typical resolutions of between 30-50 nm. By combining the test samples with the use of the freely available rainSTORM processing software it is possible to obtain a great deal of information about image quality and resolution. Using these metrics it is then possible to optimize the imaging procedure from the optics, to sample preparation, dye choice, buffer conditions, and image acquisition settings. We also show examples of some common problems that result in poor image quality, such as lateral drift, where the sample moves during image acquisition and density related problems resulting in the ''mislocalization'' phenomenon.     

Composition and structure of a large online social network in The Netherlands

Limitations in data collection have long been an obstacle in research on friendship networks. Most earlier studies use either a sample of ego-networks, or complete network data on a relatively small group (e.g., a single organization). The rise of online social networking services such as Friendster and Facebook, however, provides researchers with opportunities to study friendship networks on a much larger scale. This study uses complete network data from Hyves, a popular online social networking service in The Netherlands, comprising over eight million members and over 400 million online friendship relations. In the first study of its kind for The Netherlands, I examine the structure of this network in terms of the degree distribution, characteristic path length, clustering, and degree assortativity. Results indicate that this network shares features of other large complex networks, but also deviates in other respects. In addition, a comparison with other online social networks shows that these networks show remarkable similarities.     

Pre-analytical requirements

Correct test selection: a test must have the potential to alter patient management and have the specificity and sensitivity appropriate to the pretest probability of disease. Correct dynamic test procedure: dynamic tests may assist diagnosis and protocols must be readily available. Correct patient preparation: fasting, or other patient preparation, may reduce variability. Clear communication, to both patients and staff, of any such requirements is essential. Correct sample collection: the tube type (for blood) or container (for urine) must be appropriate for the analyte; there must be sufficient volume, avoidance of venous stasis, contaminants and haemolysis; and adequate labelling. Correct sample handling: the time and temperature before and after separation, and the centrifugation and separation procedures, must be suitable for the analyte. Accept/reject criteria must be defined. Methods require thorough evaluation of patient-related pre-analytical factors, and quantification of the effects of time, temperature, haemolysis, anticoagulant type and minimum allowable volume on sample suitability.     

新型冠状病毒肺炎:实验室检测、治疗及疫苗

新型冠状病毒肺炎(2019 novel coronavirus disease,COVID-19),一种由动物来源的新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SRAS-CoV-2)感染所致的疾病在全球范围内急速传播,严重的危害人类的健康.快速、准确的诊...     

Robust, integrated computational control of NMR experiments to achieve optimal assignment by ADAPT-NMR

ADAPT-NMR (Assignment-directed Data collection Algorithm utilizing a Probabilistic Toolkit in NMR) represents a groundbreaking prototype for automated protein structure determination by nuclear magnetic resonance (NMR) spectroscopy. With a [(13)C,(15)N]-labeled protein sample loaded into the NMR spectrometer, ADAPT-NMR delivers complete backbone resonance assignments and secondary structure in an optimal fashion without human intervention. ADAPT-NMR achieves this by implementing a strategy in which the goal of optimal assignment in each step determines the subsequent step by analyzing the current sum of available data. ADAPT-NMR is the first iterative and fully automated approach designed specifically for the optimal assignment of proteins with fast data collection as a byproduct of this goal. ADAPT-NMR evaluates the current spectral information, and uses a goal-directed objective function to select the optimal next data collection step(s) and then directs the NMR spectrometer to collect the selected data set. ADAPT-NMR extracts peak positions from the newly collected data and uses this information in updating the analysis resonance assignments and secondary structure. The goal-directed objective function then defines the next data collection step. The procedure continues until the collected data support comprehensive peak identification, resonance assignments at the desired level of completeness, and protein secondary structure. We present test cases in which ADAPT-NMR achieved results in two days or less that would have taken two months or more by manual approaches.     

A mini core subset for capturing diversity and promoting utilization of chickpea genetic resources in crop improvement

A core collection is a chosen subset of large germplasm collection that generally contains about 10% of the total accessions and represents the genetic variability of entire germplasm collection. The purpose of a core collection is to improve the use of genetic resources in crop improvement programs. In many crops the number of accessions contained in the genebank are several thousands, and a core subset consisting of 10% of total accessions would be an unwieldy proposition. In this article we have suggested a two-stage strategy to select a chickpea mini core subset consisting of only about 1% of the entire collection held in trust at ICRISAT’s genebank (16,991 accessions). This mini core subset still represents the diversity of the entire core collection. The first stage involves developing a representative core subset (about 10%) from the entire collection using all the available information on origin, geographical distribution, and characterization and evaluation data of accessions. The second stage involves evaluation of the core subset for various morphological, agronomic, and quality traits, and selecting a further subset of about 10% accessions from the core subset. At both stages standard clustering procedure was used to separate groups of similar accessions. A mini core subset consisting 211 accessions from 1,956 core subset accessions, using data on 22 morphological and agronomic traits, was selected. Newman- Keuls’ test for means, Levene’s test for variances, the chi-square test and Wilcoxon’s rank-sum non-parametric test for frequency distribution analysis for different traits indicated that the variation available in the core collection has been preserved in the mini core subset. The most important phenotypic correlations which may be under the control of coadapted gene complexes, were also preserved in the mini core. This mini core subset, due to its drastically reduced size, will prove to be a point of entry to proper exploitation of chickpea genetic resources. Received: 20 August 2000 / Accepted: 25 September 2000     

New Concept to Non-Invasively Screen Iron Deficiency in Patients

Nearly two billion people are afflicted with iron deficiency and approximately 300 million children globally have anemia. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency requires a blood test. It is becoming increasingly important to screen these individuals to reduce medical cost and avoid chronic disease conditions. There are limited settings of laboratory infrastructure for standard blood-based tests around the world to routinely accomplish this important screening test. We propose a new concept to use either human hair or nail as a screening method to detect steady state iron content in patients utilizing a sensitive portable magnetometer. The optimum hair/ nail sample weight should be determined for acceptable detection resolution (i.e., acceptable correlation with the results of blood test). The advantages of a portable device are as follows: non-invasive approach, point of care (on the spot) response with patient hair/nail sample to make screening much faster, and make screening for iron deficiency more available and affordable for patients around the world by eliminating current shortcomings of blood-based iron screening. The potential outcome of this concept is of great value to iron deficient patients. An easy, and cost-effective screening system will reduce morbidity, chronic diseases and medical cost substantially throughout the world.     

A review of early Homo in southern Africa focusing on cranial, mandibular and dental remains, with the description of a new species (Homo gautengensis sp. nov.)

The southern African sample of early Homo is playing an increasingly important role in understanding the origins, diversity and adaptations of the human genus. Yet, the affinities and classification of these remains continue to be in a state of flux. The southern African sample derives from five karstic palaeocave localities and represents more than one-third of the total African sample for this group; sampling an even wider range of anatomical regions than the eastern African collection. Morphological and phenetic comparisons of southern African specimens covering dental, mandibular and cranial remains demonstrate this sample to contain a species distinct from known early Homo taxa. The new species Homo gautengensis sp. nov. is described herein: type specimen Stw 53; Paratypes SE 255, SE 1508, Stw 19b/33, Stw 75-79, Stw 80, Stw 84, Stw 151, SK 15, SK 27, SK 45, SK 847, SKX 257/258, SKX 267/268, SKX 339, SKX 610, SKW 3114 and DNH 70. H. gautengensis is identified from fossils recovered at three palaeocave localities with current best ages spanning ∼2.0 to 1.26-0.82 million years BP. Thus, H. gautengensis is probably the earliest recognised species in the human genus and its longevity is apparently well in excess of H. habilis.     

GREEN-DB: a framework for the annotation and prioritization of non-coding regulatory variants from whole-genome sequencing data

Non-coding variants have long been recognized as important contributors to common disease risks, but with the expansion of clinical whole genome sequencing, examples of rare, high-impact non-coding variants are also accumulating. Despite recent advances in the study of regulatory elements and the availability of specialized data collections, the systematic annotation of non-coding variants from genome sequencing remains challenging. Here, we propose a new framework for the prioritization of non-coding regulatory variants that integrates information about regulatory regions with prediction scores and HPO-based prioritization. Firstly, we created a comprehensive collection of annotations for regulatory regions including a database of 2.4 million regulatory elements (GREEN-DB) annotated with controlled gene(s), tissue(s) and associated phenotype(s) where available. Secondly, we calculated a variation constraint metric and showed that constrained regulatory regions associate with disease-associated genes and essential genes from mouse knock-outs. Thirdly, we compared 19 non-coding impact prediction scores providing suggestions for variant prioritization. Finally, we developed a VCF annotation tool (GREEN-VARAN) that can integrate all these elements to annotate variants for their potential regulatory impact. In our evaluation, we show that GREEN-DB can capture previously published disease-associated non-coding variants as well as identify additional candidate disease genes in trio analyses.     

A Monte Carlo Permutation Test for Random Mating Using Genome Sequences

Testing for random mating of a population is important in population genetics, because deviations from randomness of mating may indicate inbreeding, population stratification, natural selection, or sampling bias. However, current methods use only observed numbers of genotypes and alleles, and do not take advantage of the fact that the advent of sequencing technology provides an opportunity to investigate this topic in unprecedented detail. To address this opportunity, a novel statistical test for random mating is required in population genomics studies for which large sequencing datasets are generally available. Here, we propose a Monte-Carlo-based-permutation test (MCP) as an approach to detect random mating. Computer simulations used to evaluate the performance of the permutation test indicate that its type I error is well controlled and that its statistical power is greater than that of the commonly used chi-square test (CHI). Our simulation study shows the power of our test is greater for datasets characterized by lower levels of migration between subpopulations. In addition, test power increases with increasing recombination rate, sample size, and divergence time of subpopulations. For populations exhibiting limited migration and having average levels of population divergence, the statistical power approaches 1 for sequences longer than 1Mbp and for samples of 400 individuals or more. Taken together, our results suggest that our permutation test is a valuable tool to detect random mating of populations, especially in population genomics studies.     

Bubble Stability Test Compared with Lecithin Assay in Prediction of Respiratory Distress Syndrome

A simple test for surfactant, utilizing bubble stability in ethanol, was performed in 106 samples of amniotic fluid obtained from 94 patients. Of these patients 80 delivered within 48 hours of the collection of the sample. The results were compared with the lecithin concentration in the same amniotic fluid samples and with the quality of respiration in the neonate. The test was “positive,” indicating fetal pulmonary maturity, in 37 cases and none of these infants developed respiratory distress syndrome (R.D.S.). In only one of these cases, however, was gestation less than 37 weeks. The test was “intermediate” or “negative” in 43 cases but in 35 of these infants respiration at birth was perfectly normal.Performed by the method described by its originators, this simple test gives too many false negative results to be of value in routine clinical practice, although a positive result is helpful. The concept of the test is ingenious, however, and further developments may be expected.     

Insects attracted to Maple Sap: Observations from Prince Edward Island, Canada

The collection of maple sap for the production of maple syrup is a large commercial enterprise in Canada and the United States. In Canada, which produces 85% of the world's supply, it has an annual value of over $168 million CAD. Over 38 million trees are tapped annually, 6.5% of which use traditional buckets for sap collection. These buckets attract significant numbers of insects. Despite this, there has been very little investigation of the scale of this phenomenon and the composition of insects that are attracted to this nutrient source. The present paper reports the results of a preliminary study conducted on Prince Edward Island, Canada. Twenty-eight species of Coleoptera, Lepidoptera, and Trichoptera were found in maple sap buckets, 19 of which are known to be attracted to saps and nectars. The physiological role of sap feeding is discussed with reference to moths of the tribe Xylenini, which are active throughout the winter, and are well documented as species that feed on sap flows. Additionally, 18 of the 28 species found in this study are newly recorded in Prince Edward Island.     

Test of genetical isochronism for longitudinal samples of DNA sequences

Longitudinal samples of DNA sequences, the DNA sequences sampled from the same population at different time points, have increasingly been used to study the evolutionary process of fast-evolving organisms, e.g., RNA virus, in recent years. We propose in this article several methods for testing genetical isochronism or detecting significant genetical heterochronism in this type of sample. These methods can be used to determine the necessary sample size and sampling interval in experimental design or to combine genetically isochronic samples for better data analysis. We investigate the properties of these test statistics, including their powers of detecting heterochronism, assuming different evolutionary processes using simulation. The possible choices and usages of these test statistics are discussed.     

DiffVar: a new method for detecting differential variability with application to methylation in cancer and aging

Methylation of DNA is known to be essential to development and dramatically altered in cancers. The Illumina HumanMethylation450 BeadChip has been used extensively as a cost-effective way to profile nearly half a million CpG sites across the human genome. Here we present DiffVar, a novel method to test for differential variability between sample groups. DiffVar employs an empirical Bayes model framework that can take into account any experimental design and is robust to outliers. We applied DiffVar to several datasets from The Cancer Genome Atlas, as well as an aging dataset. DiffVar is available in the missMethyl Bioconductor R package.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0465-4) contains supplementary material, which is available to authorized users.     

Visual detection of filaria-specific IgG4 in urine using red-colored high density latex beads

The use of urine for the immunodiagnosis of lymphatic filariasis has a definite advantage: the sample collection is not invasive and thus well accepted by people. Urine-based ELISA to detect filaria-specific IgG4 has been used successfully. However, ELISA requires equipment such as a microplate reader, which is often not available in most endemic areas. We have developed a new visual immunodiagnosis that detects urinary IgG4 using red-colored latex beads (bead test). The sensitivity was 87.2% when ICT antigen test positive people were regarded as the standard (136/156), and the specificity was 97.2% with the non-endemic people in Japan and Bangladesh, and the urine ELISA negatives in Sri Lanka (1264/1300). In a prevalence study, the bead test could detect filarial infection more effectively than ICT test among young children in Sri Lanka, indicating the usefulness of the visual test in epidemiological studies.     

Choosing the Best Plant for the Job: A Cost-Effective Assay to Prescreen Ancient Plant Remains Destined for Shotgun Sequencing

DNA extracted from ancient plant remains almost always contains a mixture of endogenous (that is, derived from the plant) and exogenous (derived from other sources) DNA. The exogenous ‘contaminant’ DNA, chiefly derived from microorganisms, presents significant problems for shotgun sequencing. In some samples, more than 90% of the recovered sequences are exogenous, providing limited data relevant to the sample. However, other samples have far less contamination and subsequently yield much more useful data via shotgun sequencing. Given the investment required for high-throughput sequencing, whenever multiple samples are available, it is most economical to sequence the least contaminated sample. We present an assay based on quantitative real-time PCR which estimates the relative amounts of fungal and bacterial DNA in a sample in comparison to the endogenous plant DNA. Given a collection of contextually-similar ancient plant samples, this low cost assay aids in selecting the best sample for shotgun sequencing.