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Abstract The globe thermometer has been considered a reliable instrument to quantify mean radiant temperature (MRT) since Bedford & Warner isolated its readings from air movement in their 1934 paper so that radiation could be quantified. Recent expanded use of radiant heating and cooling systems has presented new challenges for the usage of globe thermometers in the built environment by causing additional radiant asymmetries and performance expectations. Therefore, we replicate the original Bedford & Warner work to reconsider and develop a more holistic understanding of black globe performance and the determination of MRT in buildings. We recreate the MRT and air temperature separation to investigate the accuracy of globe thermometers on measuring MRTs. A radiantly heated open-plan laboratory and a radiantly cooled conference room were selected and measured with multiple globe thermometers and non-contacting infrared sensors. The globe temperature results were then corrected with air movement to produce MRTs and compared against MRTs simulated from measured surface temperatures. We demonstrate a significant impact of air speed on the MRTs obtained from globe thermometers. We also illustrate a less-investigated non-graybody emissivity variation and spatial variation of MRTs of up to 5 °C at the same height. We believe the increasing temporal and spatial resolution of digital sensors may create new challenges for using globe thermometers to measure MRTs, since fluctuating readings may camouflage potential MRT changes. Through a validation of our spatial MRT distribution with experimental results, we believe there is a need for better sensors that could spatially resolve MRTs, and recognize issues with both air speed and emissivity. [ABSTRACT FROM AUTHOR]

Cancer is characterized by hypomethylation-associated silencing of large chromatin domains, whose contribution to tumorigenesis is uncertain. Through high-resolution genome-wide single-cell DNA methylation sequencing, we identify 40 core domains that are uniformly hypomethylated from the earliest detectable stages of prostate malignancy through metastatic circulating tumor cells (CTCs). Nested among these repressive domains are smaller loci with preserved methylation that escape silencing and are enriched for cell proliferation genes. Transcriptionally silenced genes within the core hypomethylated domains are enriched for immune-related genes; prominent among these is a single gene cluster harboring all five CD1 genes that present lipid antigens to NKT cells and four IFI16 -related interferon-inducible genes implicated in innate immunity. The re-expression of CD1 or IFI16 murine orthologs in immuno-competent mice abrogates tumorigenesis, accompanied by the activation of anti-tumor immunity. Thus, early epigenetic changes may shape tumorigenesis, targeting co-located genes within defined chromosomal loci. Hypomethylation domains are detectable in blood specimens enriched for CTCs. [Display omitted] • 40 core hypomethylated domains, shared across prostate CTCs, arise early in tumorigenesis • Hypomethylation silences immune-related genes, sparing adjacent proliferation genes • The CD1A-IFI16 immune locus is consistently silenced by hypomethylation in cancer • Hypomethylated domains are detected in CTC-enriched blood in localized prostate cancer Analysis of primary prostate cancer and circulating tumor cells reveals how DNA hypomethylation during early prostate tumorigenesis silences immune surveillance genes while sparing proliferation-associated genes. [ABSTRACT FROM AUTHOR]

The Thermoheliodome is an experimental pavilion that explores cooling without air conditioning. The two research aims were to explore the use of indirect evaporative cooling and the geometric reflection of radiant cooling. For evaporative cooling we utilize a cooling tower outside of the pavilion to indirectly supply water chilled near the wet-bulb temperature. The radiant cooling system is made up of 55 coaxial chilled pipes each located in the central axis of cones with reflective surfaces that spectrally reflect the surface of the pipes and expand their radiant view factor to the occupants inside the pavilion. The specific geometry was digitally fabricated using an industrial robot and hot-wire foam cutter. The mean radiant temperature (MRT) was shown to be significantly decreased using thermal imaging cameras and with a novel scanning MRT sensor. The radiant cooling delivered from the fluid is maximized by reflection and concentration of heat emitted by occupants on the pipes, while the convective cooling of the air is minimized because only the small pipes are cooled and the reflecting surfaces are not, so the convective heat transfer surface area is small. Under typical indoor office conditions the ratio of radiant to convective cooling is slightly greater than one. For the Thermoheliodome the radiant ratio was greater than 10. Occupant surveys found that although the air temperature was not modified, they felt that inside the space there is a cooling sensation ( p ≤ 0.01). The day of the survey they felt on average 3 °C cooler. [ABSTRACT FROM AUTHOR]

DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development. However, its dynamic patterns have not been analysed at the genome scale in human pre-implantation embryos due to technical difficulties and the scarcity of required materials. Here we systematically profile the methylome of human early embryos from the zygotic stage through to post-implantation by reduced representation bisulphite sequencing and whole-genome bisulphite sequencing. We show that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome is much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei is already lower than that in female pronuclei. The inverse correlation between promoter methylation and gene expression gradually strengthens during early embryonic development, reaching its peak at the post-implantation stage. Furthermore, we show that active genes, with the trimethylation of histone H3 at lysine 4 (H3K4me3) mark at the promoter regions in pluripotent human embryonic stem cells, are essentially devoid of DNA methylation in both mature gametes and throughout pre-implantation development. Finally, we also show that long interspersed nuclear elements or short interspersed nuclear elements that are evolutionarily young are demethylated to a milder extent compared to older elements in the same family and have higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Our work provides insights into the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements. [ABSTRACT FROM AUTHOR]

Deregulation of oncogenic signals in cancer triggers replication stress. Immediate early genes (IEGs) are rapidly and transiently expressed following stressful signals, contributing to an integrated response. Here, we find that the orphan nuclear receptor NR4A1 localizes across the gene body and 3′ UTR of IEGs, where it inhibits transcriptional elongation by RNA Pol II, generating R-loops and accessible chromatin domains. Acute replication stress causes immediate dissociation of NR4A1 and a burst of transcriptionally poised IEG expression. Ectopic expression of NR4A1 enhances tumorigenesis by breast cancer cells, while its deletion leads to massive chromosomal instability and proliferative failure, driven by deregulated expression of its IEG target, FOS. Approximately half of breast and other primary cancers exhibit accessible chromatin domains at IEG gene bodies, consistent with this stress-regulatory pathway. Cancers that have retained this mechanism in adapting to oncogenic replication stress may be dependent on NR4A1 for their proliferation. [Display omitted] • NR4A1 specifically localizes to IEG gene bodies suppressing transcriptional elongation • Acute replication stress triggers NR4A1 release, triggering burst of IEG expression • NR4A1 deletion deregulates expression of the IEG FOS , triggering mitotic catastrophe • The NR4A1-IEG pathway denotes differentiated cancers with a favorable prognosis Studying tumorigenesis by patient-derived breast cancer cells, Guo et al. identify NR4A1 as a master regulator of replication stress-induced immediate early gene expression through a transcriptional processing checkpoint. Suppression of NR4A1 in cancer cells dependent on this pathway triggers mitotic catastrophe through unregulated expression of the IEG family member FOS. [ABSTRACT FROM AUTHOR]

The optimization of the sintering process for ceramic stereolithography-based additive manufacturing is attracting high interest important due to its correlation with the final properties of the fabricated parts. In this work, a photosensitive zirconia suspension with low viscosity and high solid loading (48 vol%) was prepared using surface-modified zirconia ceramic powders, resulting in an improvement in long-term stability. The correlations between the sintering temperature (1400–1520 °C) and mechanical properties were investigated. The results showed that and the as-sintered zirconia parts exhibited a relatively high density of 99.5 ± 0.1 % and three-point flexural strength of 821 ± 65 MPa as well as excellent fracture toughness (4.37 ± 0.22 MPa m1/2) sintering at 1480 °C, which was attributed to the highly homogeneous microstructure without obvious pores or crack. The obtained insights regarding the correlation between sintering temperature, relative density, and flexural strength can provide practical guidance for the future applications of zirconia ceramics. [ABSTRACT FROM AUTHOR]

Study Question: Is it possible to evaluate the methylome of individual oocytes to investigate the DNA methylome alterations in metaphase II (MII) oocytes with reduced embryo developmental potential?Summary Answer: The DNA methylome of each human first polar body (PB1) closely mirrored that of its sibling MII oocyte; hypermethylated long interspersed nuclear element (LINE) and long terminal repeats (LTRs) and methylation aberrations in PB1 promoter regions may indicate poor embryo development.What Is Known Already: The developmental potential of an embryo is determined by the oocyte's developmental competence, and the PB1 is a good substitute to examine the chromosomal status of the corresponding oocyte. However, DNA methylation, a key epigenetic modification, also regulates gene expression and embryo development.Study Design, Size, Duration: Twelve pairs of PB1s and sibling MII oocytes were biopsied and sequenced to compare their methylomes. To further investigate the methylome of PB1s and the potential epigenetic factors that may affect oocyte quality, MII oocytes (n = 74) were fertilized through ICSI, while PB1s were biopsied and profiled to measure DNA methylation. The corresponding embryos were further cultured to track their development potential. The oocytes and sperm samples used in this study were donated by healthy volunteers with signed informed consent.Participants/materials, Setting, Methods: Single-cell methylome sequencing was applied to obtain the DNA methylation profiles of PB1s and oocytes. The DNA methylome of PB1s was compared between the respective group of oocytes that progressed to blastocysts and the group of oocytes that failed to develop. DNA methylation levels of corresponding regions and differentially methylated regions were calculated using customized Perl and R scripts. RNA-seq data were downloaded from a previously published paper and reanalysed.Main Results and the Role Of Chance: The results from PB1-MII oocyte pair validated that PB1 contains nearly the same methylome (average Pearson correlation is 0.92) with sibling MII oocyte. LINE and LTR expression increased markedly after fertilization. Moreover, the DNA methylation levels in LINE (including LINE1 and LINE2) and LTR were significantly higher in the PB1s of embryos that could not reach the blastocyst stage (Wilcoxon-Matt-Whitney test, P < 0.05). DNA methylation in PB1 promoters correlated negatively with gene expression of MII oocyte. Regarding the methylation status of the promoter regions, 66 genes were hypermethylated in the developmental arrested group, with their related functions (significantly enriched in several Gene Ontology terms) including transcription, positive regulation of adenylate cyclase activity, mitogen-activated protein kinase (MAPK) cascade and intracellular oestrogen receptor signalling pathway.Large Scale Data: N/A.Limitations, Reasons For Caution: Data analysis performed in this study focused on the competence of human oocytes and compared them with maternal genetic and epigenetic profiles. Therefore, data regarding the potential regulatory roles of paternal genomes in embryo development are lacking.Wider Implications Of the Findings: The results from PB1-oocyte pairs demonstrated that PB1s shared similar methylomes with their sibling oocytes. The selection of the good embryos for transfer should not only rely on morphology but also consider the DNA methylation of the corresponding PB1 and therefore MII oocyte. The application of early-stage analysis of PB1 offers an option for high-quality oocyte and embryo selection, which provides an additional tool for elective single embryo transfer in assisted reproduction.Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China (2018YFC1004003, 2017YFA0103801), the National Natural Science Foundation of China (81730038, 3187144, 81521002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020703). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Identifying expressed somatic mutations from single-cell RNA sequencing data de novo is challenging but highly valuable. We propose RESA – Recurrently Expressed SNV Analysis, a computational framework to identify expressed somatic mutations from scRNA-seq data. RESA achieves an average precision of 0.77 on three in silico spike-in datasets. In extensive benchmarking against existing methods using 19 datasets, RESA consistently outperforms them. Furthermore, we applied RESA to analyze intratumor mutational heterogeneity in a melanoma drug resistance dataset. By enabling high precision detection of expressed somatic mutations, RESA substantially enhances the reliability of mutational analysis in scRNA-seq. RESA is available at https://github.com/ShenLab-Genomics/RESA. [ABSTRACT FROM AUTHOR]

Summary Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental-stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation, with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes. [ABSTRACT FROM AUTHOR]

Measuring gene expression in individual cells is crucial for understanding the gene regulatory network controlling human embryonic development. Here we apply single-cell RNA sequencing (RNA-Seq) analysis to 124 individual cells from human preimplantation embryos and human embryonic stem cells (hESCs) at different passages. The number of maternally expressed genes detected in our data set is 22,687, including 8,701 long noncoding RNAs (lncRNAs), which represents a significant increase from 9,735 maternal genes detected previously by cDNA microarray. We discovered 2,733 novel lncRNAs, many of which are expressed in specific developmental stages. To address the long-standing question whether gene expression signatures of human epiblast (EPI) and in vitro hESCs are the same, we found that EPI cells and primary hESC outgrowth have dramatically different transcriptomes, with 1,498 genes showing differential expression between them. This work provides a comprehensive framework of the transcriptome landscapes of human early embryos and hESCs. [ABSTRACT FROM AUTHOR]