Increased demand for BRCA testing is placing pressures on diagnostic laboratories to raise their mutation screening capacity and handle the challenges associated with classifying BRCA sequence ...variants for clinical significance, for example interpretation of pathogenic mutations or variants of unknown significance, accurate determination of large genomic rearrangements and detection of somatic mutations in DNA extracted from formalin-fixed, paraffin-embedded tumour samples. Many diagnostic laboratories are adopting next-generation sequencing (NGS) technology to increase their screening capacity and reduce processing time and unit costs. However, migration to NGS introduces complexities arising from choice of components of the BRCA testing workflow, such as NGS platform, enrichment method and bioinformatics analysis process. An efficient, cost-effective accurate mutation detection strategy and a standardised, systematic approach to the reporting of BRCA test results is imperative for diagnostic laboratories. This review covers the challenges of BRCA testing from the perspective of a diagnostics laboratory.
This paper examines two potential lacunae in understanding low‐income residents’ experiences of contemporary state‐led gentrification via a study of neighbourhood restructuring in Salford, UK, ...2004–2014. The first is the localised politics preparing the ground for neighbourhood “redevelopment” and housing demolition. The second is the blighted social landscape which emerges with the subsequent stalling of this project. A focus on “before” and “after” is adopted in order to disrupt the linear policy and “effects” temporalities that much qualitative gentrification research tends to inhabit. We see how state‐led neighbourhood restructuring does not simply displace, but carries residents from “empowerment” to abandonment and transfers them from active struggle into devitalised limbo. As such, the paper demarcates challenges and opportunities for resident mobilisation inherent in a vacillating urban renewal programme, powerful in its inception but which has since “hit the buffers” (Lees 2014, Antipode 46(4):921–947) in light of global and municipal fiscal crises.
Full Waveform LiDAR for Adverse Weather Conditions Wallace, Andrew M.; Halimi, Abderrahim; Buller, Gerald S.
IEEE transactions on vehicular technology,
07/2020, Letnik:
69, Številka:
7
Journal Article
Recenzirano
Odprti dostop
We present and discuss the case for full waveform pixel and image acquisition and processing to enable LiDAR sensors to penetrate and reconstruct 3D surface maps through obscuring media. To that end, ...we review work on signal propagation, on scanning and arrayed sensors, on signal processing strategies for independent pixels and employing spatial context, on reducing complexity and accelerating processing by sensor design, algorithmic changes, compressed sensing, and parallel processing. We report several experimental studies on LiDAR imaging through complex media, and how these can inform the automotive LiDAR scenario. We conclude with a discussion of future development and potential for full waveform LiDAR (FWL).
Selecting test populations by age and/or family history, failure to apply reference standard tests consistently, and poor conversion to definitive testing are all potential sources of bias 13. Most ...previous studies involve insurance-based healthcare systems; this is fraught with difficulty because fear of lack of reimbursement by services 17 and increased insurance premiums in individuals 18 influences testing decisions. ...the aims of this prospective study were to (1) establish the prevalence of LS and (2) evaluate the diagnostic accuracy of common LS testing strategies in an unselected EC population within a non–insurance-based healthcare system. All women gave written, informed consent to participate, providing blood-DNA, tumour, and clinical data (age, body mass index BMI, self-reported ethnicity) including detailed family histories (pedigrees). Diagnostic accuracy measures were conducted to establish the utility of clinical parameters and tumour triage strategies for risk stratifying women with EC for MMR germline sequencing, including age, family history, histological subtype, density of TILs, MMR deficiency by IHC, MSI status, and MLH1-methylation status.
According to one narrative, that received almost canonical status a century ago with Francis Haverfield, the orthogonal grid was the most important development of ancient town planning, embodying ...values of civilization in contrast to barbarism, diffused in particular by hundreds of Roman colonial foundations, and its main legacy to subsequent urban development was the model of the grid city, spread across the New World in new colonial cities. This book explores the shortcomings of that all too colonialist narrative and offers new perspectives. It explores the ideals articulated both by ancient city founders and their modern successors; it looks at new evidence for Roman colonial foundations to reassess their aims; and it looks at the many ways post-Roman urbanism looked back to the Roman model with a constant re-appropriation of the idea of the Roman.
Some DNA-dependent RNA polymerases (DdRPs) possess RNA-dependent RNA polymerase activity, as was first discovered in the replication of Potato spindle tuber viroid (PSTVd) RNA genome in tomato ...(Solanum lycopersicum). Recent studies revealed that this activity in bacteria and mammals is important for transcriptional and posttranscriptional regulatory mechanisms. Here, we used PSTVd as a model to uncover auxiliary factors essential for RNA-templated transcription by DdRP. PSTVd replication in the nucleoplasm generates (2)-PSTVd intermediates and (+)-PSTVd copies. We found that the Nicotiana benthamiana canonical 9-zinc finger (ZF) Transcription Factor IIIA (TFIIIA-9ZF) as well as its variant TFIIIA-7ZF interacted with (+)-PSTVd, but only TFIIIA-7ZF interacted with (2)-PSTVd. Suppression of TFIIIA-7ZF reduced PSTVd replication, and overexpression of TFIIIA-7ZF enhanced PSTVd replication in planta. Consistent with the locale of PSTVd replication, TFIIIA-7ZF was found in the nucleoplasm and nucleolus, in contrast to the strictly nucleolar localization of TFIIIA- 9ZF. Footprinting assays revealed that only TFIIIA-7ZF bound to a region of PSTVd critical for initiating transcription. Furthermore, TFIIIA-7ZF strongly enhanced the in vitro transcription of circular (+)-PSTVd by partially purified Pol II. Together, our results identify TFIIIA-7ZF as a dedicated cellular transcription factor that acts in DdRP-catalyzed RNA-templated transcription, highlighting both the extraordinary evolutionary adaptation of viroids and the potential of DdRPs for a broader role in cellular processes.
Multispectral light detection and ranging (LiDAR) has the potential to recover structural and physiological data from arboreal samples and, by extension, from forest canopies when deployed on aerial ...or space platforms. In this paper, we describe the design and evaluation of a prototype multispectral LiDAR system and demonstrate the measurement of leaf and bark area and abundance profiles using a series of experiments on tree samples "viewed from above" by tilting living conifers such that the apex is directed on the viewing axis. As the complete recovery of all structural and physiological parameters is ill posed with a restricted set of four wavelengths, we used leaf and bark spectra measured in the laboratory to constrain parameter inversion by an extended reversible jump Markov chain Monte Carlo algorithm. However, we also show in a separate experiment how the multispectral LiDAR can recover directly a profile of Normalized Difference Vegetation Index (NDVI), which is verified against the laboratory spectral measurements. Our work shows the potential of multispectral LiDAR to recover both structural and physiological data and also highlights the fine spatial resolution that can be achieved with time-correlated single-photon counting.
Pathogenic variants in BRCA1 or BRCA2 are identified in ∼20% of families with multiple individuals affected by early-onset breast and/or ovarian cancer. Extensive searches for additional highly ...penetrant genes or alternative mutational mechanisms altering BRCA1 or BRCA2 have not explained the missing heritability. Here, we report a dominantly inherited 5′ UTR variant associated with epigenetic BRCA1 silencing due to promoter hypermethylation in two families affected by breast and ovarian cancer. BRCA1 promoter methylation of ten CpG dinucleotides in families who are affected by breast and/or ovarian cancer but do not have germline BRCA1 or BRCA2 pathogenic variants was assessed by pyrosequencing and clonal bisulfite sequencing. RNA and DNA sequencing of BRCA1 from lymphocytes was undertaken to establish allelic expression and the presence of germline variants. BRCA1 promoter hypermethylation was identified in 2 of 49 families in which multiple women are affected by grade 3 breast cancer or high-grade serous ovarian cancer. Soma-wide BRCA1 promoter hypermethylation was confirmed in blood, buccal mucosa, and hair follicles. Pyrosequencing showed that DNA was ∼50% methylated, consistent with the silencing of one allele, which was confirmed by clonal bisulfite sequencing. RNA sequencing revealed the allelic loss of BRCA1 expression in both families and that this loss of expression segregated with the heterozygous variant c.−107A>T in the BRCA1 5′ UTR. Our results establish a mechanism whereby familial breast and ovarian cancer is caused by an in cis 5′ UTR variant associated with epigenetic silencing of the BRCA1 promoter in two independent families. We propose that methylation analyses be undertaken to establish the frequency of this mechanism in families affected by early-onset breast and/or ovarian cancer without a BRCA1 or BRCA2 pathogenic variant.
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