Miracle-dz/UniFAR-FTUs huggingface dataset:
Constraining the propagation of the 17O-excess of ozone in the troposphere: Towards a quantitative interpretation of the oxygen isotopic composition of atmospheric nitrate

The unique and distinctive 17O-excess (Δ17O) of ozone (O3) serves as a valuable tracer for oxidative processes in both modern and ancient atmospheres. This isotopic signature is propagated throughout the atmospheric reactive nitrogen (NOx = NO + NO2) cycle and preserved in nitrate (NO3-) aerosols and mineral deposits, providing a conservative tracer for the relative importance of ozone and other key oxidant involved in NOx cycling. However, despite the intense research effort dedicated to the interpretation of Δ17O(NO3-) measurements, the atmospheric processes responsible for the transfer of Δ17O to nitrate and their overall influence on nitrate isotopic composition on different spatial and temporal scales are not well understood. Furthermore, due to the inherent complexity of extracting ozone from ambient air, the absolute magnitude and spatiotemporal variability of Δ17O(O3) remains poorly constrained, a problem that has confounded the interpretation of Δ17O measurements for over a decade. The research questions that have been pursued in this thesis were formulated to address these knowledge gaps. The primary analytical tool used was the bacterial denitrifier method followed by continuous-flow isotope ratio mass spectrometry (CF-IRMS), which allows for the comprehensive isotopic analysis of nitrate (i.e., δ15N, δ18O, Δ17O). This method was applied to the isotopic analysis of nitrate samples in two case studies: (i) an investigation of the diurnal and spatial features of atmospheric nitrate isotopic composition in coastal California; and (ii) a study of the seasonality and air-snow transfer of nitrate stable isotopes on the Antarctic plateau. Furthermore, the method was adapted to the isotopic characterization of ozone via chemical conversion of its terminal oxygen atoms to nitrate. During the course of this thesis, a large dataset of tropospheric Δ17O(O3) measurements has been obtained, including a full annual record from Grenoble, France (45°N) and a ship-based latitudinal profile from 50°S to 50°N in the Atlantic marine boundary layer (MBL). This observational dataset represents a two-fold increase in the number of existing tropospheric Δ17O(O3) observations and a dramatic expansion in the global representation of this key isotopic variable. Additionally, the two case studies presented reveal novel and often unexpected aspects of the isotope dynamics of atmospheric nitrate, with potentially important implications for air quality modeling and the interpretation of isotopic information preserved in the polar ice core record.
Antinoise in U.S. equity markets

There are many well documented behavioral biases in financial markets. Yet, analyzing U.S. equities reveals that less than 1% of returns are predictable in recent years. Given the high number of biases, why are returns not more predictable? We provide new evidence in support of one possible explanation. In the long-run, low correlations across signals that trigger biases may create sufficient antinoise which mutes more sizable patterns in returns. However, in the short-run, correlation spikes coincide with market volatility indicating that behavioral biases may become more visible during crises.
Rectal douching before sexual intercourse and inappropriate douching tool use associated with increased HIV infection among men who have sex with men: a cross-sectional study from Shenyang, China

Background: Rectal douching (RD) is widely practiced by men who have sex with men (MSM), and is correlated with increased risk of HIV infection. However, the mechanism of how RD increases the risk of HIV infection is not well understood, and there is limited data on RD behavior in MSM practicing anal sex in China. We examine the purpose of RD, its timing in relation to anal sex, the types of RD products used, and risky sexual behaviors among MSM reporting anal sex.Methods: Between August 2017 and December 2018, a cross-sectional study was conducted among adult MSM in Shenyang, China. Data were collected on demographics, sexual behaviors, and RD for the most recent sexual intercourse by means of interviewer-administered face-to-face questionnaires. Blood samples were collected to test for antibodies to HIV and syphilis. Multivariable logistic regression models were used to assess the risk factors associated with HIV infection.Results: A total of 515 eligible MSM participated in this survey (median age: 31 years). During the most recent anal intercourse, 28.3% (146/515) had condomless receptive anal intercourse (CRAI), 21.4% (110/515) practiced serosorting, and more than half (61.6%, 317/515) reported RD before or after anal sex. Of those practicing RD, 96.8% (307/317) conducted RD before sex, while 62.5% (198/317) conducted RD after sex. The douching devices used were primarily shower hoses (85.3%, 262/307), and relatively few MSM used commercial RD products (8.1%). The prevalence of HIV-1 and syphilis was 11.7% and 13.2%, respectively. HIV infection was positively associated with RD (adjusted odds ratio (AOR), 2.8; 95% confidence interval (CI), 1.4-5.5), practicing RD before sex (AOR, 2.3; 95% CI, 1.2–4.3), practicing RD after sex (AOR, 1.8; 95% CI, 1.0–3.1), using a shower hose for RD (AOR, 3.5; 95% CI, 1.1–13.0), condomless receptive anal intercourse (CRAI) (AOR, 2.9; 95% CI, 1.6–5.5), and using nitrite inhalants (AOR, 2.8; 95 % CI, 1.6-5.1) in the most recent anal intercourse.Conclusions: RD is popular among Chinese MSM. Improper noncommercial RD tools increase the rates of HIV infection. Public health workers and the MSM community should publicize scientific knowledge and prevention approaches relating to RD and HIV transmission to MSM, and we recommend that better tools be offered to assist in RD in order to decrease the risk of acquiring HIV.
Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane

Significance The aggregation of the amyloid-β peptide (Aβ) into neurotoxic oligomers is central to the development of Alzheimer’s disease. One possible source of their toxicity results from interactions of the Aβ oligomers with the neuronal membrane, damaging membrane integrity and thus neurons. However, molecular details of these interactions are unclear. Here, we contrast the dimerization of Aβ in solution and at the neuronal membrane. Our results clearly indicate that the sugar moieties of GM1 sequester Aβ by forming key hydrogen bonds with the peptide, which diverts the configuration of the Aβ dimers away from damaging β-sheet–rich structures. These findings underline the importance of GM1 in Alzheimer’s disease progression and provide a nanoscopic basis for its reported neuroprotective effect. Mounting evidence suggests that the neuronal cell membrane is the main site of oligomer-mediated neuronal toxicity of amyloid-β peptides in Alzheimer’s disease. To gain a detailed understanding of the mutual interference of amyloid-β oligomers and the neuronal membrane, we carried out microseconds of all-atom molecular dynamics (MD) simulations on the dimerization of amyloid-β (Aβ)42 in the aqueous phase and in the presence of a lipid bilayer mimicking the in vivo composition of neuronal membranes. The dimerization in solution is characterized by a random coil to β-sheet transition that seems on pathway to amyloid aggregation, while the interactions with the neuronal membrane decrease the order of the Aβ42 dimer by attenuating its propensity to form a β-sheet structure. The main lipid interaction partners of Aβ42 are the surface-exposed sugar groups of the gangliosides GM1. As the neurotoxic activity of amyloid oligomers increases with oligomer order, these results suggest that GM1 is neuroprotective against Aβ-mediated toxicity.
Multi-Dimensional Transcriptome Analysis Reveals Modulation of Cholesterol Metabolism as Highly Integrated Response to Brain Injury

Background Zebrafish is an attractive model to investigate regeneration of the nervous system. Despite major progress in our understanding of the underlying processes, the transcriptomic changes are largely unknown. We analysed the transcriptome of the regenerating telencephalon for changes in the expression of mRNAs, their splice variants and investigated the putative role of regulatory RNAs in the modulation of these transcriptional changes. Results Profound changes in the expression of genes and their splice variants engaged in many distinct processes were observed. As exemplified by the coordinated regulation of the cholesterol synthesizing enzymes and transporters, the genome responded to injury of the telencephalon in a multi-tiered manner with distinct and interwoven changes in expression of enzymes, transporters and their regulatory molecules. This coordinated genomic response involved a decrease of the mRNA of the key transcription factor SREBF2, induction of microRNAs (miR- 182, miR-155, miR-146, miR-31) targeting cholesterol genes, shifts in abundance of splice variants as well as regulation of long non-coding RNAs. Conclusions Differential transcription and splicing are important processes in response to injury of the telencephalon. Cholesterol metabolism is switched from synthesis to relocation of cholesterol. Based on our in silico analysis, this switch involves complementary and synergistic inputs by different regulatory principles. Our studies suggest that adaptation of cholesterol metabolism appears to be a key process involved in regeneration of the injured zebrafish brain.
Multiple Adjoining Word- and Face-Selective Regions in Ventral Temporal Cortex Exhibit Distinct Dynamics

The map of category-selectivity in human ventral temporal cortex (VTC) provides organizational constraints to models of object recognition. One important principle is lateral-medial response biases to stimuli that are typically viewed in the center or periphery of the visual field. However, little is known about the relative temporal dynamics and location of regions that respond preferentially to stimulus classes that are centrally viewed, such as the face- and word-processing networks. Here, word- and face-selective regions within VTC were mapped using intracranial recordings from 36 patients. Partially overlapping, but also anatomically dissociable patches of face- and word-selectivity, were found in VTC. In addition to canonical word-selective regions along the left posterior occipitotemporal sulcus, selectivity was also located medial and anterior to face-selective regions on the fusiform gyrus at the group level and within individual male and female subjects. These regions were replicated using 7 Tesla fMRI in healthy subjects. Left hemisphere word-selective regions preceded right hemisphere responses by 125 ms, potentially reflecting the left hemisphere bias for language, with no hemispheric difference in face-selective response latency. Word-selective regions along the posterior fusiform responded first, then spread medially and laterally, then anteriorally. Face-selective responses were first seen in posterior fusiform regions bilaterally, then proceeded anteriorally from there. For both words and faces, the relative delay between regions was longer than would be predicted by purely feedforward models of visual processing. The distinct time courses of responses across these regions, and between hemispheres, suggest that a complex and dynamic functional circuit supports face and word perception. SIGNIFICANCE STATEMENT Representations of visual objects in the human brain have been shown to be organized by several principles, including whether those objects tend to be viewed centrally or peripherally in the visual field. However, it remains unclear how regions that process objects that are viewed centrally, such as words and faces, are organized relative to one another. Here, invasive and noninvasive neuroimaging suggests that there is a mosaic of regions in ventral temporal cortex that respond selectively to either words or faces. These regions display differences in the strength and timing of their responses, both within and between brain hemispheres, suggesting that they play different roles in perception. These results illuminate extended, bilateral, and dynamic brain pathways that support face perception and reading.
Mapping the Inhospitable Landscapes of the Orkney Islands using RPAS

This paper reports the outcome of the RPAS‐based prospection of four prehistoric and early historic sites on Mainland, Rousay and South Ronaldsay Islands of the Orkney archipelago (Northern Scotland). Application of RPAS (Remotely Piloted Aircraft System) improved the effectiveness and accuracy of the mapping of the archaeological landscape, comparing to the ground‐base survey. The paper presents the workflow used to obtain the low altitude images using RPAS and photogrammetric pipeline applied to create ortophotomaps and digital elevation models. Then the interpretation of mapped remnants at the sites of Brough of Deerness, Burrian, Hashwick and Burwick is discussed. Beside reporting the new datasets for the Orkney the author is clarifying the problem of surveying “the inhospitable” landscapes ‐ the areas that for different reasons might be difficult to access by survey using ground‐based methods. Therefore Remotely Piloted Aircraft Systems are advocated as a solution in such challenging conditions.
Distribution of Huntington’s disease Haplogroups in Indian population

Huntington’s disease (HD), a rare neurodegenerative disorder, is inherited in an autosomal dominant manner, and caused by a pathological trinucleotide expansion at exon1 of the HTT locus. Previous studies have described the haplogroups at the HTT locus that can explain the differences in prevalence of HD. We have selected three informative SNPs (rs762855, rs3856973 and rs4690073) to study these haplogroups in an Indian sample. Our results show that the genotype frequencies are significantly different between cases and controls for these SNPs. More than 90% of both cases and controls belong to Haplogroup A which is the predominant European haplogroup.
Colour Ambiguity in Real Scenes and the Role of Perceptual Organisation

In this study we show a reproduction of the dress-ambiguity phenomenon in a real scene and we report quantitative measurements of the corresponding colour perceptions. The original, real dress, known from #thedress-illusion, was illuminated by combined short- and longwavelength broadband lights from two slide projectors. Test subjects viewing the dress reported to perceive the dress’ fabric and lace colours as blue & black, white & gold or light blue & brown; their corresponding perceptual matches were distributed along the blue/yellow cardinal axis, and exhibited a variability comparable to the ambiguity of the dress photograph. It is particularly noteworthy that the colour ambiguity emerged despite explicit knowledge of the observers about the direction of the light source. Manipulating the background of the real dress (change in chromaticity and luminance, or masking) revealed significant differences between the perceptual groups regarding lightness and colour of the dress. Our findings suggest that observer specific differences in the perceptual organisation of the visual scene are responsible for the colour ambiguity observed for the real dress; in particular, we conclude that colour computations of white & gold viewers focused onto the local region of the dress, whereas the colour processes of blue & black and light-blue & brown viewers were strongly influenced by contextual computations including the background. Our segmentation hypothesis extends existing explanations for the dress’ ambiguity and proposes image based (in the case of the real scene) and high level (in the case of the photograph) neural processes which control the spatial reach of contextual colour computations. The relation between the ambiguity in our real scene and the dress photograph is discussed.
Priming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), is predominantly mediated by pro-inflammatory CD4+ T cell responses to CNS antigens, including myelin proteolipid protein (PLP). Dendritic cells (DCs) are considered critical for inducing T cell responses against infectious agents, but the importance of DCs in priming self-reactive CD4+ T cells in autoimmune disease such as MS has been unclear. To determine the requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE.
Time-dependent pleiotropic phenotypes are caused by progressive DNA polymerase α 1 deficiency in zebrafish 2

30 The mechanisms underlying variation in celland tissue-specific phenotypes caused by mutations 31 are poorly understood. For example, why some cancers show cellular atypia more than others is 32 unclear. As an illustration of phylogenetic variation in phenotype, mutations in a subunit of DNA 33 polymerase α (Pol α), one of the primary eukaryotic replicative DNA polymerases, result in 34 immediate cell cycle arrest in yeast and Arabidopsis; a null mutation in the same subunit results in 35 lethality in 5 to 7 days in zebrafish, in association with striking tissue-specific, time-dependent 36 pleiotropic cellular phenotypes. Here, we describe a zebrafish null mutant in the gene encoding 37 the B subunit of Pol α, huli hutu (hht), in which cell death with nuclear fragmentation is found in 38 the central nervous system where the largest number of cells arise, while cells present in smaller 39 numbers, such as the gastrointestinal epithelial cells, instead show cellular atypia that is associated 40 with hepatic dysgenesis and pancreatic and air bladder agenesis. Wild-type maternal mRNA in 41 genotypically mutant eggs becomes undetectable by 24 hours post-fertilization (hpf). Furthermore, 42 the treatment of wild-type larvae with DNA synthesis inhibitors aphidicolin or hydroxyurea from 43 24 hpf phenocopies hht. Taken together, the data are consistent with a model in which reduced 44 capacity for cell proliferation caused by either genetic or chemical mechanisms of DNA synthesis 45 beginning at about 24 hpf results in cell death in tissues with large cell number, and abnormal 46 nuclear morphology in tissues with fewer cells, including the gastrointestinal tract. 47
Zebrafish Polycomb repressive complex-2 critical roles are largely Ezh2- over Ezh1-driven and concentrate during early embryogenesis

Polycomb repressive complex-2 (PRC2) methylation of histone H3 lysine-27 (H3K27me) is associated with stable transcriptional repression. PRC2 famously silences Hox genes to maintain anterior-posterior segment identities but also enables early cell fate specification, restrains progenitor cell differentiation, and canalizes cell identities. Zebrafish PRC2 genetic studies have focused on ezh2, which, with its paralog ezh1, encodes the H3K27 methyltransferase component. ezh2 loss-of-function mutants reinforce essential vertebrate PRC2 functions during early embryogenesis albeit with limited contributions to body plan establishment. However, redundancy with ezh1 and the lethality of maternal-zygotic homozygous ezh2 nulls could obscure additional early developmental and organogenesis roles of PRC2. Here, we combine new and existing zebrafish ezh1 and ezh2 alleles to show collective maternal/zygotic ezh2 exclusively provides earliest embryonic PRC2 H3K27me3 activity. Zygotic ezh1, which becomes progressively expressed as ezh2 levels dissipate, has minor redundant and noncompensatory larval roles but itself is not required for viability or fertility. Zygotic Ezh2/PRC2 promotes correct craniofacial bone shape and size by maintaining proliferative pre-osteoblast pools. An ezh2 allelic series including disrupted maternal ezh2 uncovers axial skeleton homeotic transformations and pleiotropic organogenesis defects. Further, once past a critical early window, we show zebrafish can develop near normally with minimal bulk H3K27me3. Our results suggest Ezh2-containing PRC2 stabilizes rather than instructs early developmental decisions while broadly contributing to organ size and embellishment.
Genome-Wide Binding Analyses of HOXB1 Revealed a Novel DNA Binding Motif Associated with Gene Repression

Knowledge of the diverse DNA binding specificities of transcription factors is important for understanding their specific regulatory functions in animal development and evolution. We have examined the genome-wide binding properties of the mouse HOXB1 protein in ES cells differentiated into neural fates. Unexpectedly, only a small number of HOXB1 bound regions (7%) correlate with binding of the known HOX cofactors PBX and MEIS. In contrast, 22% of the HOXB1 binding peaks display co-occupancy with the transcriptional repressor REST. Analyses revealed that co-binding of HOXB1 with PBX correlates with active histone marks and high levels of expression, while co-occupancy with REST correlates with repressive histone marks and repression of the target genes. Analysis of HOXB1 bound regions uncovered enrichment of a novel 15 base pair HOXB1 binding motif HB1RE (HOXB1 response element). In vitro template binding assays showed that HOXB1, PBX1 and MEIS can bind to this motif. In vivo, this motif is sufficient to direct expression of a reporter gene and over-expression of HOXB1 selectively represses this activity. Our analyses suggest that HOXB1 has evolved an association with REST in gene regulation and the novel HB1RE motif contributes to HOXB1 function in part through a repressive role in gene expression.
Designing novel biochemical pathways to commodity chemicals using ReactPRED and RetroPath2.0

Commodity chemicals are high-demand chemicals, used by chemical industries to synthesise cocountless chemical products of daily use. For many of these chemicals, the main production process uses petroleum-based feedstocks. Concerns over these limited resources and their associated environmental problems, as well as mounting global pressure to reduce CO2 emissions have motivated efforts to find biochemical pathways capable of producing these chemicals. Advances in metabolic engineering have led to the development of technologies capable of designing novel biochemical pathways to commodity chemicals. Computational software tools, ReactPRED and RetroPath2.0 were utilised to design 49 novel pathways to produce benzene, phenol, and 1,2-propanediol — all industrially important chemicals with limited biochemical knowledge. A pragmatic methodology for pathway curation was developed to analyse thousands and millions of pathways that were generated using the software. This method utilises publicly accessible biological databases, including MetaNetX, PubChem, and MetaCyc to analyse the generated outputs and assign EC numbers to the predicted reactions. The workflow described here for pathway generation and curation can be used to develop novel biochemical pathways to commodity chemicals from numerous starting compounds.