STRmix™ put to the test: 300 000 non-contributor profiles compared to four-contributor DNA mixtures and the impact of replicates

Probabilistic genotyping approaches are increasingly used for the interpretation of DNA mixtures. To explore the specificity of one of these systems (STRmix^™), we conducted an extensive study using 24 complex mixtures: all were known or apparent 4-person mixtures with at least one contributor representing less than 20% of total DNA, and all mixtures had at least one contributor with suboptimal DNA quantity. Those mixtures were either generated in-house or from casework. All the mixtures were compared to 300,000 virtual non-contributors, resulting in a dataset of 7.2 million comparisons. The great majority of the non-contributor comparisons led to a LR lower than 1 for a specificity of 99.1%. The effect of using replicate amplifications to calculate the LR of non-contributors was also assessed as triplicates were used and led to an increased specificity of 99.8%. The very large extent of the analyzed data shows that STRmix^™ has an excellent ability to discriminate non-contributors from complex DNA mixtures.     

用反卷积法校正X线图像散射的方法

在数字Ｘ线摄影中，散射造成了图像对比度的下降，在影像增器－电视链成像系统中来自病人的散射和来自探测器系统的眩光更是恶化图像质量的主要原因。为了提高数字Ｘ线图像的质量，我们利用高斯曲线近似散射点扩展函数，并在一特定的系统上用实验的方法确定了散射量ρ和散射分布参数σ，     

Kinetics of the TL phenomenon in LiF:Mg irradiated to different dose of gamma radiation of 60Co using two different programs of deconvolution

In this work, the results on determination of kinetic parameters using the method of deconvolution of glow curves obtained from the LiF doped with Mg²⁺ ions, after having been irradiated to 5, 10 and 25 Gy of ⁶⁰Co gamma radiation, corresponding to the range of TL-vs-dose response linearity, are presented. The deconvolution is performed using two functions obtained by the method of asymptotic series and by the method based on the approximation of continued fractions. The glow curve of the studied material shows a dosimetric glow peak at 518 K and three peaks of very low intensity at 383, 423 and 463 K, all of a general-order kinetics. Kinetic parameters obtained with both methods showed that the values of kinetics, b, the energy of the traps, E, and the factor of frequency, s, do not differ significantly. However, the figure of merit, FOM, and the second derivative criteria indicate that the accuracy of the calculations with the second method improves considerably.     

Using big data from probabilistic genotyping to solve crime

Forensic Science South Australia (FSSA) has been using STRmix™ software to deconvolute all reported DNA mixtures since 2012. Almost a decade of deconvolutions had led to a substantial repository of analysed profile data that can be interrogated to observe trends in case type, location or occurrence. In addition, deconvolutions can be compared in order to identify common DNA donors and reveal new intelligence information in cases where DNA profiling has previously provided no investigative information. As a proof of concept all samples deconvoluted as part of criminal casework (suspect or no-suspect) were interrogated and compared to each other using the mixture-to-mixture comparison feature in STRmix™. Within the Adelaide region there were 32 groups of cases that had evidence samples linked by a common DNA donor with LR > 1 million which was in addition to direct links and mixture searching links identified previously. These groups of cases can then be interrogated to reveal additional information to inform Police intelligence gathering. Our paper reports on the findings of this proof-of-concept study.     

Proteomic screening of molecular targets of crocin

Background

Traditional drug discovery approaches are mainly relied on the observed phenotypic changes following administration of a plant extract, drug candidate or natural product. Recently, target-based approaches are becoming more popular. The present study aimed to identify the cellular targets of crocin, the bioactive dietary carotenoid present in saffron, using an affinity-based method.

Methods

Heart, kidney and brain tissues of BALB/c mice were homogenized and extracted for the experiments. Target deconvolution was carried out by first passing cell lysate through an affinity column prepared by covalently attaching crocin to agarose beads. Isolated proteins were separated on a 2D gel, trypsinized in situ and identified by MALDI-TOF/TOF mass spectrometry. MASCOT search engine was used to analyze Mass Data.

Results

Part of proteome that physically interacts with crocin was found to consist of beta-actin-like protein 2, cytochrome b-c1 complex subunit 1, ATP synthase subunit beta, tubulin beta-3 chain, tubulin beta-6 chain, 14-3-3 protein beta/alpha, V-type proton ATPase catalytic subunitA, 60 kDa heat shock protein, creatine kinase b-type, peroxiredoxin-2, cytochrome b-c1 complex subunit 2, acetyl-coA acetyltransferase, cytochrome c1, proteasome subunit alpha type-6 and proteasome subunit alpha type-4.

Conclusion

The present findings revealed that crocin physically binds to a wide range of cellular proteins such as structural proteins, membrane transporters, and enzymes involved in ATP and redox homeostasis and signal transduction.     

Unwrapping of transient responses from high rate overlapping pattern electroretinograms by deconvolution

Objective

Due to overlapping, temporal information is mostly lost in high rate steady-state pattern electroretinograms (PERG_SS). This study develops a deconvolution method and a display/recording system to “unwrap” PERG_SS and obtain a transient, “per stimulus” response (PERG_tr) regardless of reversal rate.

Methods

Processing and instrumentation, including high temporal resolution display and acquisition were developed for deconvolving PERGs acquired at high rates by slight jittering of reversal onsets at a given mean rate.

Results

The system was successfully tested at eight rates from 2.2 to 78.1 rps. At medium rates (17.4–41.2 rps) recordings with conventional morphology (N35–P50–N95) but earlier peaks and higher amplitudes were extracted up to 40 rps. At higher rates, smaller triphasic responses were obtained, exhibiting similar peak latencies, but reversed polarity. Oscillating potentials (OPs) were also recorded at all rates after deconvolution.

Conclusions

Transient PERGs and OPs can be extracted from quasi steady-state PERG recordings obtained at high rates with a deconvolution algorithm using high temporal resolution display and acquisition systems.

Significance

The methodology to extract transient and oscillatory responses from steady-state PERGs could be useful in understanding high rate responses and diagnosis of various retinal diseases by revealing temporal information on waveform components which cannot be normally observed.     

Method for the deconvolution of auditory steady-state responses

The potential evoked by a ‘train’ of N equally spaced auditory clicks, with an inter-click period shorter than the duration of the response to an isolated click, is said to be a steady-state response (SSR). Extracting the individual responses evoked by the clicks of the train during steady state can be key to understanding of the neurophysiological mechanisms underlying SSR generation. In the literature, this task has been dealt with only under the (unwarranted) assumption that the response of the system does not vary during the presentation of the clicks, i.e. no neurophysiological adaptation is present. In this work, a new, non-parametric algorithm is proposed that, relaxing the time-invariance hypothesis, allows the extraction from the SSR of the N waveforms individually evoked by the N clicks of the train. The performance of the approach is evaluated on simulated SSRs and on real data recorded from the temporal cortex of awake rats. Results show that the method is able to detect and assess possible adaptation of the neurophysiological system in the generation of SSRs.     

A new method for imaging and 3D reconstruction of mammalian cochlea by fluorescent confocal microscopy

Traditional methods for anatomical and morphometric studies of cochlear tissues have relied upon either microdissection of the organ of Corti or the generation of serial sections of the cochlea. Such methods are time-consuming, disruptive to three-dimensional relationships and often restrict sampling to very limited numbers of cells. We have found that cells and tissue components of the cochlear duct may be labelled by fluorescent markers within intact cochleae, which are then embedded in epoxy resin for subsequent viewing by fluorescent microscopy methods. This approach allows imaging through thick optical volumes with preservation of three-dimensional relationships. Unlike sectioned tissue, alignment of the sample relative to the focal axis may be easily corrected by re-orientation of the optical volume with common image processing software. Fluorescently labelled cochleae embedded in epoxy can be viewed by most fluorescent microscopy methods including laser scanning confocal microscopy, multi-photon confocal microscopy and widefield epi-fluorescence microscopy with deconvolution. Furthermore, semi-thin sections made from these preparations are compatible with traditional histological stains, as well as allowing brightly labelled epi-fluorescent images.     

Using semi‐parametric methods in an analysis of earnings mobility

Summary This paper describes a dynamic random effects econometric model from which inferences on earnings mobility may be made. It answers questions such as, given some initial level of observed earnings, what is the probability that an agent with certain characteristics will remain below a specified level of earnings (for example the poverty level) for a specified number of time periods? Existing research assumes that the distributions of the unobserved permanent and transitory shocks in the model are known up to finitely many parameters. However, predictions of earnings mobility are highly sensitive to assumptions about these distributions. The present paper estimates the distributions of the random effects non‐parametrically. The results are used to predict the probabilities of remaining in a low state of earnings. The results from the non‐parametric distributions are contrasted to those obtained under a normality assumption. Using the non‐parametrically estimated distributions gives estimated probabilities that are smaller than those obtained under the normality assumption. Through a Monte Carlo experiment and by examining unconditional predicted earnings distributions, it is demonstrated that the non‐parametric method is likely to be considerably more accurate, and that assuming normality may give quite misleading results.