Development and evaluation of time-resolved rapid immunofluorescence test for detection of TSOL18 specific antibody in porcine cysticercosis infections.

BACKGROUND: Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera. RESULTS: ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen's κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃. CONCLUSIONS: In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.

Spruce giga-genomes: structurally similar yet distinctive with differentially expanding gene families and rapidly evolving genes.

Spruces (Picea spp.) are coniferous trees widespread in boreal and mountainous forests of the northern hemisphere, with large economic significance and enormous contributions to global carbon sequestration. Spruces harbor very large genomes with high repetitiveness, hampering their comparative analysis. Here, we present and compare the genomes of four different North American spruces: the genome assemblies for Engelmann spruce (Picea engelmannii) and Sitka spruce (Picea sitchensis) together with improved and more contiguous genome assemblies for white spruce (Picea glauca) and for a naturally occurring introgress of these three species known as interior spruce (P. engelmannii × glauca × sitchensis). The genomes were structurally similar, and a large part of scaffolds could be anchored to a genetic map. The composition of the interior spruce genome indicated asymmetric contributions from the three ancestral genomes. Phylogenetic analysis of the nuclear and organelle genomes revealed a topology indicative of ancient reticulation. Different patterns of expansion of gene families among genomes were observed and related with presumed diversifying ecological adaptations. We identified rapidly evolving genes that harbored high rates of non-synonymous polymorphisms relative to synonymous ones, indicative of positive selection and its hitchhiking effects. These gene sets were mostly distinct between the genomes of ecologically contrasted species, and signatures of convergent balancing selection were detected. Stress and stimulus response was identified as the most frequent function assigned to expanding gene families and rapidly evolving genes. These two aspects of genomic evolution were complementary in their contribution to divergent evolution of presumed adaptive nature. These more contiguous spruce giga-genome sequences should strengthen our understanding of conifer genome structure and evolution, as their comparison offers clues into the genetic basis of adaptation and ecology of conifers at the genomic level. They will also provide tools to better monitor natural genetic diversity and improve the management of conifer forests. The genomes of four closely related North American spruces indicate that their high similarity at the morphological level is paralleled by the high conservation of their physical genome structure. Yet, the evidence of divergent evolution is apparent in their rapidly evolving genomes, supported by differential expansion of key gene families and large sets of genes under positive selection, largely in relation to stimulus and environmental stress response.

Enhancement of carbon nanotubes on microalgal-fungal consortium formation and wastewater treatment.

As a promising material with an efficient light capture capability, a low amount of carbon nanotubes can affect growth and photosynthesis by regulating microalgal cells, thereby enhancing the pollutant removal efficiency in wastewater. In this study, microalgal-fungal consortia of Chlorella vulgaris and Ganoderma lucidum were developed with different types and concentrations of carbon nanotubes. The treatment effect of microalgal-fungal consortia on simulated digestate was also studied. The results demonstrate that 1.5 mg/L of carboxylated multi-walled carbon nanotubes remarkably promoted the formation, growth and photosynthesis of consortium. The dry weight and chlorophyll a content reached 19.3 ± 0.53 mg/symbiont and 27.3 ± 0.52 µg/L, respectively. Moreover, the removal efficiency of chemical oxygen demand, total nitrogen, total phosphorus and tetracycline hydrochloride were 94.1%, 65.5%, 61.9% and 96.2%, respectively. Overall, these findings suggest a promising future for the use of carbon nanotubes in wastewater treatment by regulating microalgal-fungal consortia.

Whole-slide laser microdissection for tumour enrichment.

The practical application of genome-scale technologies to precision oncology research requires flexible tissue processing strategies that can be used to differentially select both tumour and normal cell populations from formalin-fixed, paraffin-embedded tissues. As tumour sequencing scales towards clinical implementation, practical difficulties in scheduling and obtaining fresh tissue biopsies at scale, including blood samples as surrogates for matched 'normal' DNA, have focused attention on the use of formalin-preserved clinical samples collected routinely for diagnostic purposes. In practice, such samples often contain both tumour and normal cells which, if correctly partitioned, could be used to profile both tumour and normal genomes, thus identifying somatic alterations. Here we report a semi-automated method for laser microdissecting entire slide-mounted tissue sections to enrich for cells of interest with sufficient yield for whole genome and transcriptome sequencing. Using this method, we demonstrated enrichment of tumour material from mixed tumour-normal samples by up to 67%. Leveraging new methods that allow for the extraction of high-quality nucleic acids from small amounts of formalin-fixed tissues, we further showed that the method was successful in yielding sequence data of sufficient quality for use in BC Cancer's Personalized OncoGenomics (POG) program. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Real-Time Φ-OTDR Vibration Event Recognition Based on Image Target Detection.

Accurate and fast identification of vibration signals detected based on the phase-sensitive optical time-domain reflectometer (Φ-OTDR) is crucial in reducing the false-alarm rate of the long-distance distributed vibration warning system. This study proposes a computer vision-based Φ-OTDR multi-vibration events detection method in real-time, which can effectively detect perimeter intrusion events and reduce personnel patrol costs. Pulse accumulation, pulse cancellers, median filter, and pseudo-color processing are employed for vibration signal feature enhancement to generate vibration spatio-temporal images and form a customized dataset. This dataset is used to train and evaluate an improved YOLO-A30 based on the YOLO target detection meta-architecture to improve system performance. Experiments show that using this method to process 8069 vibration data images generated from 5 abnormal vibration activities for two types of fiber optic laying scenarios, buried underground or hung on razor barbed wire at the perimeter of high-speed rail, the system mAP@.5 is 99.5%, 555 frames per second (FPS), and can detect a theoretical maximum distance of 135.1 km per second. It can quickly and effectively identify abnormal vibration activities, reduce the false-alarm rate of the system for long-distance multi-vibration along high-speed rail lines, and significantly reduce the computational cost while maintaining accuracy.

Metabolomics revealed the photosynthetic performance and metabolomic characteristics of Euglena gracilis under autotrophic and mixotrophic conditions.

Photosynthetic and metabolomic performance of Euglena gracilis was examined and compared under autotrophic and mixotrophic conditions. Autotrophic protozoa (AP) obtained greater biomass (about 33% higher) than the mixotrophic protozoa (MP) after 12 days of growth. AP maintained steady photosynthesis, while MP showed a remarkable decrease in photosynthetic efficiency and dropped to an extremely low level at day 12. In MP, low light absorption and photosynthetic electron transport efficiency, and high energy dissipation were reflected by the chlorophyll (chl a) fluorescence (OJIP) of the protozoa. The values of ΨO, ΦEo, and ETO/RC of MP decreased to extremely low levels, to 1/15, 1/46, and 1/9 those of AP, respectively, while DIO/RC increased to approximately 16 times that of AP. A total of 137 metabolites were showed significant differences between AP and MP. AP accumulated more monosaccharide, lipids, and alkaloids, while MP produced more amino acids, peptides, and long-chain fatty acids including poly-unsaturated fatty acids. The top nine most important enriched pathways obtained from KEGG mapping were related to ABC transporters, biosynthesis of amino acids, purine metabolism, and carbohydrate metabolism. There were significant differences between AP and MP in photosynthetic activity, metabolites, and metabolic pathways. This work presented useful information for the production of high value bioproducts in E. gracilis cultured under different nutritional conditions.

Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution.

Human cancers, including breast cancers, comprise clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However, the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours have not been systematically examined at single-cell resolution. Here we show, using deep-genome and single-cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all 15 cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (<5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single-cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies using patient-derived breast cancer xenoengraftment.

Radiomics Signature: A potential biomarker for the prediction of survival in Advanced Hepatocellular Carcinoma.

Objectives: To develop and validate radiomics nomograms for the pretreatment predictions of overall survival (OS) and time to progression (TTP) in the patients with advanced hepatocellular carcinoma (HCC) treated with apatinib plus transarterial chemoembolization (TACE), and to assess the incremental value of the clinical-radiomics nomograms for estimating individual OS and TTP. Methods: A total of 60 patients with advanced HCC (BCLC stage C) treated with apatinib plus TACE were divided into a training set (n=48) and a validation set (n=12). The predictors identified from the clinical variables and the radiomics signature constructed from the computed tomography images, such as ɑ-fetoprotein level (AFP), formfactor, the grey level co-occurrence matrix, the gray level size zone matrix, and the gray level run-length matrix, were used to build the clinical-radiomics nomograms and the radiomics nomograms for the prediction of OS and TTP. Results: Apatinib plus TACE benefited the patients with advanced HCC, with a 579-day median OS and a 270-day median TTP. The nomograms were built with the radiomics signature and AFP, and achieved favorable prediction efficacy with acceptable calibration curves. Decision curve analyses demonstrated that the clinical-radiomics nomograms outperformed the radiomics nomograms for the predictions of OS and TTP. Conclusions: Apatinib plus TACE may improve OS and prolonged TTP in the patients with advanced HCC. The clinical-radiomics nomograms, a noninvasive pretreatment prediction tool that incorporate radiomics signature and AFP, demonstrated good prediction accuracy for OS and TTP in these patients. These results indicate that the clinical-radiomics nomograms may provide novel insight for precise personalized medicine approaches in the patients with advanced HCC.

Sources of erroneous sequences and artifact chimeric reads in next generation sequencing of genomic DNA from formalin-fixed paraffin-embedded samples.

Tissues used in pathology laboratories are typically stored in the form of formalin-fixed, paraffin-embedded (FFPE) samples. One important consideration in repurposing FFPE material for next generation sequencing (NGS) analysis is the sequencing artifacts that can arise from the significant damage to nucleic acids due to treatment with formalin, storage at room temperature and extraction. One such class of artifacts consists of chimeric reads that appear to be derived from non-contiguous portions of the genome. Here, we show that a major proportion of such chimeric reads align to both the 'Watson' and 'Crick' strands of the reference genome. We refer to these as strand-split artifact reads (SSARs). This study provides a conceptual framework for the mechanistic basis of the genesis of SSARs and other chimeric artifacts along with supporting experimental evidence, which have led to approaches to reduce the levels of such artifacts. We demonstrate that one of these approaches, involving S1 nuclease-mediated removal of single-stranded fragments and overhangs, also reduces sequence bias, base error rates, and false positive detection of copy number and single nucleotide variants. Finally, we describe an analytical approach for quantifying SSARs from NGS data.

Removal of atrazine in catalytic degradation solutions by microalgae Chlorella sp. and evaluation of toxicity of degradation products via algal growth and photosynthetic activity.

Degradation solutions containing atrazine need to be further purified before they are discharged into the aquatic environment. With the objectives of evaluating removal capacity of the microalga Chlorella sp. toward atrazine in degradation solutions and toxicity of the degradation products, we investigated the removal efficiency (RE) and bioaccumulation of atrazine in the microalgae after an 8 d exposure to diluted degraded solutions containing 40 µg/L and 80 µg/L of atrazine as well as degradation products in the present study. Moreover, pure atrazine solutions with similar concentrations were simultaneously inoculated with the microalgae in order to distinguish the influence of the products. The photocatalytic degradation results showed that 31.4% of atrazine was degraded after 60 min, and three degradation products, desisopropyl-atrazine (DIA), desethyl-atrazine (DEA), and desethyl-desisopropyl-atrazine (DEIA) were detected. After an 8-d exposure, 83.0% and 64.3% of atrazine were removed from the degraded solutions containing 40 µg/L and 80 µg/L of atrazine, respectively. In comparison with the control, i.e., pure atrazine solution with equal concentration, Chlorella sp. in the degraded atrazine solution showed lower RE and growth rate. The photosynthetic parameters, especially performance index (PIABS), clearly displayed the differences between treatments. The values of PIABS of Chlorella sp. cultured in degradation atrazine for 8 days were significantly lower (P < 0.01) than that in the corresponding pure atrazine, suggesting potential inhibitory effect of degradation products on the microalgae. Atrazine and the degradation products inhibited algal photosynthesis via depressed light absorption and electron transport, and reduced utilization of light energy via energy dissipation. Our results demonstrated that microalgae Chlorella sp. had an encouraging atrazine removal potential and the degradation products of atrazine may inhibit algal growth and removal capability. This study may be useful for the application of microalgae in herbicide wastewater treatment and understanding algal removal of atrazine in natural aquatic environment.

Contribution of vitamin B12 to biogas upgrading and nutrient removal by different microalgae-based technology.

The algae-based technology has a positive effect on the treatment of biogas slurry and the purification of biogas, while vitamin B12 (VB12) is one of the important regulatory substances in the algae-based cultivation system. In this study, different concentrations of VB12 were used in three microalgal treatment technologies to assess their effect on simultaneous removal of nutrients from biogas slurry and removal of CO2 from raw biogas. Results showed that Chlorella vulgaris exhibited higher growth rate, mean daily productivity, chlorophyll a content, carbonic anhydrase activity and better photosynthetic properties when co-cultivated with Ganoderma lucidum, rather than when co-cultivated with activated sludge or under mono-cultivation. Maximum mean chemical oxygen demand, total nitrogen, total phosphorus and CO2 removal efficiencies were found to be 84.29 ± 8.28%, 83.27 ± 8.14%, 85.27 ± 8.46% and 65.71 ± 6.35%, respectively when microalgae were co-cultivated with Ganoderma lucidum under 100 ng L-1 of VB12. This study shows the potential of microalgae and fungi co-cultivation supplemented with VB12 for the simultaneous upgradation of biogas production as well as for the purification of biogas slurry.

Continuous positive airway pressure effectively ameliorates arrhythmias in patients with obstructive sleep apnea-hypopnea via counteracting the inflammation.

INTRODUCTION: This work is aimed at evaluating the therapeutic effect of continuous positive airway pressure (CPAP) in treatment of patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) combined with arrhythmias as well as clarifying the possible mechanism underpinning such an intervention. METHODS: Through exclusions, a total of 108 OSAHS patients combined with arrhythmias were enrolled from June 2017 to June 2019 with full clinical information in this work. A computerized permuted block design with varying block stratification and size according to age, sex, AHI and type of arrhythmia was used to randomize 108 patients to CPAP versus sham CPAP for a period of 12-week. All were subjected to unchanged pharmacological anti-arrhythmia therapy combined with CPAP. Before and after CPAP treatment, the improvement of various arrhythmias was compared between the CPAP group and the sham-CPAP group. The levels of CRP, IL-6 and TNF-ɑ were measured simultaneously. RESULTS: During follow-up, the mean (±SD) CPAP pressure used in the CPAP group was 12.3 (±3.1) cm H2O. The use of CPAP and sham CPAP was on average of 5.2 ± 0.56 and 5.1 ± 0.63 h/night, respectively. After 12 weeks of CPAP therapy, the AHI was significantly decreased and the lowest blood oxygen saturation was notably elevated in the CPAP group compared to the sham-CPAP group, P < 0.05. The CPAP therapy, compared with the sham-CPAP group, significantly reduced the incidence of all types of arrhythmia in patients with OSAHS. The level of the c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was significantly lower in the CPAP group than in the sham-CPAP group (P < 0.05). Pearson correlation analysis showed that the reduction in the incidence of total arrhythmias was positively correlated with the decrease of CRP, IL-6 and TNF-ɑ levels, respectively. CONCLUSION: Findings from this work suggest that proper use of CPAP significantly benefits to OSAHS patients combined with arrhythmias, possibly via counteracting the inflammation.

[Versa HD Volume-modulated Accelerator High Voltage Circuit Fault Maintenance].

This paper introduces a fast repair methods of Versa HD volume-modulated accelerator's high voltage circuit fault:the key points test method. To identify five key points:①Enter maintenance mode to check for AFC deviation; ② The magnetron waveform MI and PFN waveform PFN V are detected on the maintenance terminal board; ③ Detect thyratron waveform; ④ Check the supply voltage of thyratron; ⑤ HT PSU 600 V DC test 600 V normal or not. The waveform or voltage is also measured to efficiently narrow the fault range to find out the cause of the fault, quickly remove the fault.

The shaping and functional consequences of the microRNA landscape in breast cancer.

MicroRNAs (miRNAs) show differential expression across breast cancer subtypes, and have both oncogenic and tumour-suppressive roles. Here we report the miRNA expression profiles of 1,302 breast tumours with matching detailed clinical annotation, long-term follow-up and genomic and messenger RNA expression data. This provides a comprehensive overview of the quantity, distribution and variation of the miRNA population and provides information on the extent to which genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture, suggesting an important role for post-transcriptional regulation. The key clinical parameters and cellular pathways related to the miRNA landscape are characterized, revealing context-dependent interactions, for example with regards to cell adhesion and Wnt signalling. Notably, only prognostic miRNA signatures derived from breast tumours devoid of somatic copy-number aberrations (CNA-devoid) are consistently prognostic across several other subtypes and can be validated in external cohorts. We then use a data-driven approach to seek the effects of miRNAs associated with differential co-expression of mRNAs, and find that miRNAs act as modulators of mRNA-mRNA interactions rather than as on-off molecular switches. We demonstrate such an important modulatory role for miRNAs in the biology of CNA-devoid breast cancers, a common subtype in which the immune response is prominent. These findings represent a new framework for studying the biology of miRNAs in human breast cancer.

DOA Estimation and Self-Calibration under Unknown Mutual Coupling.

In practical applications, the assumption of omnidirectional elements is not effective in general, which leads to the direction-dependent mutual coupling (MC). Under this condition, the performance of traditional calibration algorithms suffers. This paper proposes a new self-calibration method based on the time-frequency distributions (TFDs) in the presence of direction-dependent MC. Firstly, the time-frequency (TF) transformation is used to calculate the space-time-frequency distributions (STFDs) matrix of received signals. After that, the estimated steering vector and corresponding noise subspace are estimated by the steps of noise removing, single-source TF points extracting and clustering. Then according to the transformation relationship between the MC coefficients, steering vector and MC matrix, we deduce a set of linear equations. Finally, with two-step alternating iteration, the equations are solved by least square method in order to estimate DOA and MC coefficients. Simulations results show that the proposed algorithm can achieve direction-dependent MC self-calibration and outperforms the existing algorithms.

Refining Inaccurate Transmitter and Receiver Positions Using Calibration Targets for Target Localization in Multi-Static Passive Radar.

Transmitter and receiver position errors have been known to significantly deteriorate target localization accuracy in a multi-static passive radar (MPR) system. This paper explores the use of calibration targets, whose positions are known to the MPR system, to counter the loss in target localization accuracy arising from transmitter/receiver position errors. This paper firstly evaluates the Cramér-Rao lower bound (CRLB) for bistatic range (BR)-based target localization with calibration targets, which analytically indicates the potential of calibration targets in enhancing localization accuracy. After that, this paper proposes a novel closed-form solution, which includes two steps: calibration step and localization step. Firstly, the calibration step is devoted to refine the inaccurate transmitter and receiver locations using the BR measurements from the calibration targets, and then in the calibration step, the target localization can be accurately achieved by using the refined transmitter/receiver positions and the BR measurements from the unknown target. Theoretical analysis and simulation results indicate that the proposed method can attain the CRLB at moderate measurement noise level, and exhibits the superiority of localization accuracy over existing algorithms.

SOX9 modulates the expression of key transcription factors required for heart valve development.

Heart valve formation initiates when endothelial cells of the heart transform into mesenchyme and populate the cardiac cushions. The transcription factor SOX9 is highly expressed in the cardiac cushion mesenchyme, and is essential for heart valve development. Loss of Sox9 in mouse cardiac cushion mesenchyme alters cell proliferation, embryonic survival, and valve formation. Despite this important role, little is known about how SOX9 regulates heart valve formation or its transcriptional targets. Therefore, we mapped putative SOX9 binding sites by ChIP-Seq in E12.5 heart valves, a stage at which the valve mesenchyme is actively proliferating and initiating differentiation. Embryonic heart valves have been shown to express a high number of genes that are associated with chondrogenesis, including several extracellular matrix proteins and transcription factors that regulate chondrogenesis. Therefore, we compared regions of putative SOX9 DNA binding between E12.5 heart valves and E12.5 limb buds. We identified context-dependent and context-independent SOX9-interacting regions throughout the genome. Analysis of context-independent SOX9 binding suggests an extensive role for SOX9 across tissues in regulating proliferation-associated genes including key components of the AP-1 complex. Integrative analysis of tissue-specific SOX9-interacting regions and gene expression profiles on Sox9-deficient heart valves demonstrated that SOX9 controls the expression of several transcription factors with previously identified roles in heart valve development, including Twist1, Sox4, Mecom and Pitx2. Together, our data identify SOX9-coordinated transcriptional hierarchies that control cell proliferation and differentiation during valve formation.

Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas.

Programmed death ligands (PDLs) are immune-regulatory molecules that are frequently affected by chromosomal alterations in B-cell lymphomas. Although PDL copy-number variations are well characterized, a detailed and comprehensive analysis of structural rearrangements (SRs) and associated phenotypic consequences is largely lacking. Here, we used oligonucleotide capture sequencing of 67 formalin-fixed paraffin-embedded tissues derived from primary B-cell lymphomas and 1 cell line to detect and characterize, at base-pair resolution, SRs of the PDL locus (9p24.1; harboring PDL1/CD274 and PDL2/PDCD1LG2). We describe 36 novel PDL SRs, including 17 intrachromosomal events (inversions, duplications, deletions) and 19 translocations involving BZRAP-AS1, CD44, GET4, IL4R, KIAA0226L, MID1, RCC1, PTPN1 and segments of the immunoglobulin loci. Moreover, analysis of the precise chromosomal breakpoints reveals 2 distinct cluster breakpoint regions (CBRs) within either CD274 (CBR1) or PDCD1LG2 (CBR2). To determine the phenotypic consequences of these SRs, we performed immunohistochemistry for CD274 and PDCD1LG2 on primary pretreatment biopsies and found that PDL SRs are significantly associated with PDL protein expression. Finally, stable ectopic expression of wild-type PDCD1LG2 and the PDCD1LG2-IGHV7-81 fusion showed, in coculture, significantly reduced T-cell activation. Taken together, our data demonstrate the complementary utility of fluorescence in situ hybridization and capture sequencing approaches and provide a classification scheme for PDL SRs with implications for future studies using PDL immune-checkpoint inhibitors in B-cell lymphomas.

The clonal and mutational evolution spectrum of primary triple-negative breast cancers.

Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.

A Bias Compensation Method for Distributed Moving Source Localization Using TDOA and FDOA with Sensor Location Errors.

Current bias compensation methods for distributed localization consider the time difference of arrival (TDOA) and frequency difference of arrival (FDOA) measurements noise, but ignore the negative influence by the sensor location uncertainties on source localization accuracy. Therefore, a new bias compensation method for distributed localization is proposed to improve the localization accuracy in this paper. This paper derives the theoretical bias of maximum likelihood estimation when the sensor location errors and positioning measurements noise both exist. Using the rough estimate result by MLE to subtract the theoretical bias can obtain a more accurate source location estimation. Theoretical analysis and simulation results indicate that the theoretical bias derived in this paper matches well with the actual bias in moderate noise level so that it can prove the correctness of the theoretical derivation. Furthermore, after bias compensation, the estimate accuracy of the proposed method achieves a certain improvement compared with existing methods.