Parallel Samples Research Articles

The effect of tocilizumab on patient reported outcomes and inflammatory biomarkers in hematopoietic cell transplantation

Inflammatory physiology has been linked to behavioral and emotional symptoms in a variety of contexts and experimental paradigms. Hematopoietic cell transplantation (HCT) represents an intersection of significant immune dysregulation and psychosocial stress, and this biobehavioral relationship can influence important clinical outcomes. For those undergoing HCT with inflammation-related neuropsychiatric symptoms, using targeted agents such as the IL-6 receptor antagonist tocilizumab may be an effective therapeutic approach. We conducted an observational cohort study to explore patient reported outcomes (PROs) and inflammatory biomarkers among allogeneic HCT recipients who received tocilizumab compared to those who did not. Individuals on a larger trial of tocilizumab for prevention of graft-versus-host disease received a single dose of tocilizumab 24 h prior to stem cell infusion. Measures of anxiety, depression, pain, fatigue, and sleep quality and parallel blood samples for inflammatory cytokines were collected from participants and an analogous comparison cohort at baseline and Day 28 after stem cell infusion. Demographic and medical characteristics were reported; an analysis of covariance regression model was fitted to evaluate differences in PROs and distance correlation t-tests assessed for associations between biomarkers and PRO measures. For n = 18 tocilizumab-treated and n = 22 comparison patients, there were no significant differences between patient demographics, but the tocilizumab cohort had a different distribution of primary diagnoses (p = 0.009) with more patients with leukemias and a higher proportion of patients in their first remission (64% vs 28%, p = 0.024). Depression was higher at Day 28 compared to baseline in both groups (comparison group: +5.1 [95% CI 0.14–10, p = 0.045], tocilizumab: +8.6 [95% CI 2.3–15, p = 0.011]), though the difference between groups did not reach statistical significance. The tocilizumab group had significantly increased circulating IL-6 and decreased CRP at Day 28 (all p < 0.05). There was an association between collective baseline biomarkers and PROs (distance correlation dCor = 0.110, p = 0.005), but this same association was not present at Day 28 (dCor = −0.001, p = 0.5). In univariate analyses, a 10-fold increase in plasma IL-6 was associated with a 3.6-point higher depression score (95% CI 1.0–6.2, p = 0.008). In this exploratory analysis of PROs and inflammatory biomarkers in patients undergoing HCT, tocilizumab was not associated with favorable patient-reported symptom profiles. This finding is aligned with our prior work in the HCT population but diverges from hypothesized therapeutic effects of tocilizumab on depressive symptoms, thus highlighting the need for larger prospective translational studies in biobehavioral HCT research.

In-situ comparison of interface instability of basal and edge planes during unidirectional growth of sea ice

The evolutions of water/ice interface with distinct ice orientations are one of the central problems in sea ice growth. Some misunderstandings prevailed in previous hypothesis on morphological evolution of sea ice, which need the validation with carefully designed experiments. Up to now, there is no in-situ comparison of unidirectional freezing behavior between distinct ice orientations, which makes the previous hypothesis on sea ice growth skeptical about its physical basis. The aim of this paper is to provide an in-situ comparison of unidirectional growth behavior of lamellar sea ice between basal and edge planes. Our experiment is realized by a delicate design of parallel freezing samples with two specified ice orientations in a modeled sea water under an imposed thermal gradient. The planar instability as well as the unidirectional cellular/dendritic growth patterns of water/ice interfaces of basal and edge plane ice are compared. It is found that the instability grows faster for edge plane ice, which is addressed by an incubation time coupled with the surface tension anisotropy. In addition, two types of tilted growth patterns of sea ice after planar instability are observed simultaneously, which are suggested to stem from distinct physical origins and provide a new insight into the tilted growth of cellular/dendritic ice. Collectively, these experimental results are suggested to promote our understanding of morphological evolution of unidirectional growth of sea ice, as well as its diverse relevance to many other areas involving ice growth.

Characterization of early phases of cardiomyopathy syndrome pathogenesis in Atlantic salmon (Salmo salar L.) through various diagnostic methods

Since the first description of cardiomyopathy syndrome (CMS) in Atlantic salmon, in 1985, the disease caused by piscine myocarditisvirus (PMCV) has become a common problem in Atlantic salmon farming, not only in Norway, but also in other salmon farming countries like Scotland and Ireland. In the last years, CMS has been ranked as the most important salmon viral disease in Norway regarding both mortality and economic losses. Detailed knowledge of infection and pathogenesis is still lacking, a decade after the causal agent was first described, and there is a need for a wider range of methods/tools for diagnostic and research purposes. In this study, we compared the detection of PMCV‐ and CMS‐related tissue lesions using previously used and well‐known methods like histopathology and real‐time RT‐PCR to immunohistochemistry (IHC), a less used method, and a new method, RNAscope in situ hybridization. Tissue samples of three different cardiac compartments, mid‐kidney and skin/muscle tissue were compared with non‐lethal parallel samplings of blood and mucus. The development of pathological cardiac lesions observed in this experiment was in accordance with previous descriptions of CMS. Our results indicate a viremic phase 10‐ to 20‐day post‐challenge (dpc) preceding the cardiac lesions. In this early phase, virus could also be detected in relatively high amount in mid‐kidney by real‐time RT‐PCR. Plasma and/or mid‐kidney samples may, therefore, be candidates to screen for early‐phase PMCV infection. The RNAscope in situ hybridization method showed higher sensitivity and robustness compared with the immunohistochemistry and may be a valuable support to histopathology in CMS diagnostics, especially in cases of untypical lesions or mixed infections.

In situ observation of the effect of the twin boundary orientation on the mechanical properties of single crystalline Ni

The construction of twin boundaries (TBs) in materials is a remarkable way of promoting their strength and ductility. However, the effects of TB orientation on the mechanical properties have not been reported experimentally so far. Using a state-of-the-art in situ tensile stage equipped in a transmission electron microscope, uniaxial tensile tests were performed on three single-crystalline Ni samples with TB parallel and perpendicular to the tensile direction and no TB. The results showed that the uniform tensile elongation strongly depends on TB, 120% for the perpendicular TB sample, 99% for the parallel TB sample, and only 55% for the no TB sample. In addition, dislocation interaction before reaching the perpendicular CTB contribute to cross-slip and dynamic formation of dislocation jogs, thereby improving strain hardening and resulting in a large uniform tensile elongation.

Mobile dust sampling device for dust filter generation at a Ni refinery

To study the distribution of Ni emission to air from the myriad of point and diffuse sources within a plant site is a complex sampling and analysis problem. However, it provides important underlying information for source abatement. At a Ni refinery in Southern Norway such sampling of Ni in air in close proximity to sources with subsequent analysis of content or particle structures by various methods has always been a complicated endeavour with no or inconclusive results. The main difficulty lies in obtaining both a representative and a large enough sample size to achieve quality results within a reasonable cost budget. Normally a filter sample of dust used for the chemical analysis of Ni in air is collected with fairly expensive reference instrumentation. If more than one filter sample is needed, e.g. several copies of a specific sampling period and location, several co-located instruments should be used, or one filter is cut into several pieces for post-analysis. Cutting a filter in pieces will compromise the sample and chemical analysis and most reference PM samplers are not easily or cheaply operated and transportable. Thus, a novel in-house sampling device that delivers 3 independent and parallel filters simultaneously was constructed. The goal was to obtain triplet sample sets from many locations inside the plant area. The sample sets could be screened for Ni levels and provide filter copies for advanced chemical analysis when needed. Comparisons of individual samples in sets of varying Ni content showed satisfactory equivalence. The sampling device is continuously used in a pilot Ni ambient distribution study within the plant site. The triplet sampler has been rotated at more than 10 sites since 2015. The sites varied between being on the ground and on roof tops of buildings. Some locations were near potential sources that give diffuse emissions of nickel dust. Results have been used to understand the Ni variation spatially and to identify important contributing sources to the total Ni emissions that potentially is emitted to the surrounding airshed. Parallel samples have been sent for more advanced post-analysis for periods with known elevated nickel concentration. The results have yielded more defensible abatement plans and more effective abatement measures.

Gas Seepage Model and Experiment Based on Bedding Effect of Fractured Coal Body

Gas drainage is of great significance for the efficient and safe mining in coal mine, in which the coal seam layer bedding has a great influence on it. For obtaining gas permeability characteristics of coal body with the parallel and vertical bedding in fractured coal under the action of stress loading and unloading, experimental research was carried out employing a three-stress-axis simulation device. Experimental results showed that in the stress loading process, the permeability decreased with increasing effective stress; the decrement was initially rapid albeit it slowed later. With the increase of effective stress, the coal sample underwent three stages, namely, crack compaction, elastic deformation, and plastic deformation. In the stress unloading process, the permeability of coal samples increased with decreasing of effective stress, and the increasing trend of permeability was consistent. The degree of fracture compaction of the parallel bedding coal samples after compression was much higher than that of vertical bedding. In the stress-relieved coal seam, gas drainage boreholes should be arranged vertically to the bedding fissure to maximise the gas drainage effect. A group of parallel and vertical bedding gas drainage holes were arranged in the test mine to investigate the drainage effect. Field engineering application also showed that the drilling direction should be perpendicular to the bedding direction as far as possible, so as to improve the gas drainage effect. The research results can provide a reference for the gas drainage borehole layout, thus maximising the gas extraction efficiency and ensuring the sustainability of mine safety production.

HIVE Single-Cell TCR Sequencing: Assay Principle and Applications

Abstract Biological resolution at the level of individual cells is powering the next phase of precision health. Honeycomb Biotechnologies currently offers an assay for single-cell RNA sequencing with the HIVE™ scRNAseq Solution. The HIVE is a portable, handheld, single-use device that enables gentle capture, robust storage, and easy processing for the analysis of single-cell samples. The HIVE scRNAseq assay integrates sample storage and single-cell profiling into a single workflow, facilitating decentralized collection and centralized processing of samples. The design of the HIVE is ideal for the recovery of fragile cells, loading of large sample volumes, and efficient processing of numerous samples in parallel, particularly valuable for clinical applications. Here, we extend the application of the HIVE by offering a single-cell T cell receptor enrichment and sequencing (scTCRseq) assay. Using the stable whole transcriptome amplification (WTA) product obtained from the scRNAseq assay as the sample input, the HIVE scTCRseq assay enriches TCR in a streamlined target-specific amplification workflow. The assay is compatible with all human tissues, and can accommodate a wide range of cell numbers. We typically achieve over 75% TCR molecule recovery from the WTA, and over 60% sequencing reads are mapped to TCR. Here we also present TCR profiling of several specimens, demonstrating its value in clinical applications. Honeycomb aims to expand single-cell opportunities across basic, translational, and clinical research throughout the world.

Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting

ObjectiveTo estimate scent dogs’ diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and...

Factor Structure of the Memory for Intentions Test (MIsT): A Conceptual Replication in Older Adults and People with HIV Disease

ABSTRACT Objective The Memory for Intentions Test (MIsT) is a clinical measure of prospective memory that has strong evidence for convergent, discriminative, and ecological validity. This study uses a conceptual replication design to evaluate the latent structure of the MIsT in two parallel samples who commonly experience prospective memory deficits: older adults and people living with HIV disease. Participants and Methods Study participants included 303 people with HIV disease (ages 18–67) and 267 community-dwelling older adults (ages 50–91). Confirmatory factor analyses of the MIsT were conducted separately in each sample. We evaluated a one-factor model, as well as three two-factor models with the MIsT items loading onto each factor based on cue type, delay interval, or response modality. Results The one-factor model provided the best (and most parsimonious) fit to the data in both study samples. All two-factor models also demonstrated good fit statistics, although correlations between the two factors in each model were high and none of the two-factor models provided a significantly better fit than the one-factor model. Conclusions Results of this conceptual replication study provide support for a robust factor structure of the MIsT across older adults and people with HIV disease. A total score for the MIsT provides the most parsimonious solution, although available evidence and theory also support the potential use of subscales (e.g., cue type). Future studies of the MIsT would be useful to determine its psychometrics in different clinical populations and across demographic factors (e.g., race/ethnicity).

Blockchain Framework for Artificial Intelligence Computation

Blockchain is an essentially distributed database recording all transactions or digital events among participating parties. Each transaction in the records is approved and verified by consensus of the participants in the system that requires solving a hard mathematical puzzle, which is known as proof-of-work. To make the approved records immutable, the mathematical puzzle is not trivial to solve and therefore consumes substantial computing resources. However, it is energy-wasteful to have many computational nodes installed in the blockchain competing to approve the records by just solving a meaningless puzzle. Here, we pose proof-of-work as a reinforcementlearning problem by modeling the blockchain growing as a Markov decision process, in which a learning agent makes an optimal decision over the environment’s state, whereas a new block is added and verified. Specifically, we design the block verification and consensus mechanism as a deep reinforcement-learning iteration process. As a result, our method utilizes the determination of state transition and the randomness of action selection of a Markov decision process, as well as the computational complexity of a deep neural network, collectively to make the blocks not easy to recompute and to preserve the order of transactions, while the blockchain nodes are exploited to train the same deep neural network with different data samples (state-action pairs) in parallel, allowing the model to experience multiple episodes across computing nodes but at one time. Our method is used to design the next generation of public blockchain networks, which has the potential not only to spare computational resources for industrial applications but also to encourage data sharing and AI model design for common problems.

Smartphone multiplex microcapillary diagnostics using Cygnus: Development andevaluation of rapid serotype-specific NS1 detection with dengue patient samples.

Laboratory diagnosis of dengue virus (DENV) infection including DENV serotyping requires skilled labor and well-equipped settings. DENV NS1 lateral flow rapid test (LFT) provides simplicity but lacks ability to identify serotype. A simple, economical, point-of-care device for serotyping is still needed. We present a gravity driven, smartphone compatible, microfluidic device using microcapillary film (MCF) to perform multiplex serotype-specific immunoassay detection of dengue virus NS1. A novel device–termed Cygnus–with a stackable design allows analysis of 1 to 12 samples in parallel in 40 minutes. A sandwich enzyme immunoassay was developed to specifically detect NS1 of all four DENV serotypes in one 60-μl plasma sample. This test aims to bridge the gap between rapid LFT and laboratory microplate ELISAs in terms of sensitivity, usability, accessibility and speed. The Cygnus NS1 assay was evaluated with retrospective undiluted plasma samples from 205 DENV infected patients alongside 50 febrile illness negative controls. Against the gold standard RT-PCR, clinical sensitivity for Cygnus was 82% in overall (with 78, 78, 80 and 76% for DENV1-4, respectively), comparable to an in-house serotyping NS1 microplate ELISA (82% vs 83%) but superior to commercial NS1-LFT (82% vs 74%). Specificity of the Cygnus device was 86%, lower than that of NS1-microplate ELISA and NS1-LFT (100% and 98%, respectively). For Cygnus positive samples, identification of DENV serotypes DENV2-4 matched those by RT-PCR by 100%, but for DENV1 capillaries false positives were seen, suggesting an improved DENV1 capture antibody is needed to increase specificity. Overall performance of Cygnus showed substantial agreement to NS1-microplate ELISA (κ = 0.68, 95%CI 0.58–0.77) and NS1-LFT (κ = 0.71, 95%CI 0.63–0.80). Although further refinement for DENV-1 NS1 detection is needed, the advantages of multiplexing and rapid processing time, this Cygnus device could deliver point-of-care NS1 antigen testing including serotyping for timely DENV diagnosis for epidemic surveillance and outbreak prediction.

TGL

Many real world graphs contain time domain information. Temporal Graph Neural Networks capture temporal information as well as structural and contextual information in the generated dynamic node embeddings. Researchers have shown that these embeddings achieve state-of-the-art performance in many different tasks. In this work, we propose TGL, a unified framework for large-scale offline Temporal Graph Neural Network training where users can compose various Temporal Graph Neural Networks with simple configuration files. TGL comprises five main components, a temporal sampler, a mailbox, a node memory module, a memory updater, and a message passing engine. We design a Temporal-CSR data structure and a parallel sampler to efficiently sample temporal neighbors to form training mini-batches. We propose a novel random chunk scheduling technique that mitigates the problem of obsolete node memory when training with a large batch size. To address the limitations of current TGNNs only being evaluated on small-scale datasets, we introduce two large-scale real-world datasets with 0.2 and 1.3 billion temporal edges. We evaluate the performance of TGL on four small-scale datasets with a single GPU and the two large datasets with multiple GPUs for both link prediction and node classification tasks. We compare TGL with the open-sourced code of five methods and show that TGL achieves similar or better accuracy with an average of 13X speedup. Our temporal parallel sampler achieves an average of 173X speedup on a multi-core CPU compared with the baselines. On a 4-GPU machine, TGL can train one epoch of more than one billion temporal edges within 1-10 hours. To the best of our knowledge, this is the first work that proposes a general framework for large-scale Temporal Graph Neural Networks training on multiple GPUs.

High-Bandwidth Arbitrary Signal Detection Using Low-Speed Electronics

The growing demand for bandwidth and energy efficiency requires new solutions for signal detection and processing. We demonstrate a concept for high-bandwidth signal detection with low-speed photodetectors and electronics. The method is based on the parallel optical sampling of a high-bandwidth signal with sinc-pulse sequences provided by a Mach-Zehnder modulator. For the electronic detection and processing this parallel sampling enables to divide the high-bandwidth optical signal with the bandwidth <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$B$</tex-math></inline-formula> into <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$N$</tex-math></inline-formula> electrical signals with the baseband bandwidth of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$B/(\text{2}\,N)$</tex-math></inline-formula> . In proof-of-concept experiments with <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$N=3$</tex-math></inline-formula> , we present the detection of 24 GHz optical signals by detectors with a bandwidth of only 4 GHz. For ideal components, the sampling and bandwidth down-conversion does not add an excess error to the signals and even for the non-ideal components of our proof-of-concept setup, it is below 1%. Thus, the rms error for the measurement of the 24 GHz signal was reduced by a factor of about 3.4 and the effective number of bits were increased by 1.8.

Measuring Six Facets of Curiosity in Germany and the UK: A German-Language Adaptation of the 5DCR and Its Comparability with the English-Language Source Version

The five-dimensional curiosity-scale revised (5DCR) by Kashdan et al. (2020) is the most comprehensive curiosity inventory available to date. 5DCR measures six facets of curiosity with four items each. Here, we present a German-language adaptation of the 5DCR and comprehensively validate this adaptation in a diverse sample of adults from Germany (N = 486). Moreover, we provide new evidence on the original English-language 5DCR in a parallel sample from the UK (N = 483). In both countries, we investigate the six facets' reliability, factorial validity, and convergent and discriminant validity with a large set of individual-differences constructs. In addition, we analyze the measurement invariance of the curiosity facets across the UK and Germany and across socio-demographic subgroups defined by age, sex, and education. Findings demonstrate that the new German-language adaptation of 5DCR and its English-language source version show psychometric properties similar to the original studies by Kashdan et al. (2020) in the United States. All six curiosity facets reach at least partial scalar invariance across cultures, sex, education, and mostly also across age groups. The findings support the six-faceted theory of curiosity and show that 5DCR allows for a valid assessment of curiosity across cultures.

Grave Monuments in South–Eastern End of the South Caucasus: Late Bronze – Early Iron Age Kurgans

The article deals with the results of the Late Bronze – Early Iron Age kurgans built in the foothills of the Talysh Mountains at the south-eastern end of the South Caucasus. Saribulag kurgans are located in Alar village of Yardimly district, on the pasture of the same name at an altitude of 2000 m above sea level. These grave monuments are very important in terms of studying the burial customs of the Late Bronze – Early Iron Age communities. Comparative analysis shows that such archaeological patterns are well known from the monuments of contemporary archaeological culture sites of the South Caucasus. When comparing the findings revealed during the excavations and the typology of graves with parallel samples in different regions of Azerbaijan and outside the Caucasus, the Saribulag kurgans can be attributed to the Late Bronze-Early Iron Age.

Controlled Synthesis and Photoelectrochemical Performance Enhancement of Cu2−xSe Decorated Porous Au/Bi2Se3 Z-Scheme Plasmonic Photoelectrocatalyst

In this paper, uniform Cu2−xSe-modified Au/Bi2Se3 hybrid nanoparticles with porous shells have been prepared through a cation exchange method. Bi2Se3/Cu2−xSe Z-scheme heterojunction is introduced onto Au nanocube by replacing Bi3+ with Cu2+. Owing to the effective coupling between Au core and semiconductor shells, Au/Bi2Se3/Cu2−xSe hybrids present a broad and strong plasmon resonance absorption in the visible band. More intriguingly, the carrier lifetime of Au/Bi2Se3/Cu2−xSe hybrid photoelectrodes can be further tailored with corresponding Cu2−xSe content. Through parameter optimization, 0.1-Au/Bi2Se3/Cu2−xSe electrode exhibits the longest electron lifetime (86.03 ms) among all the parallel samples, and corresponding photoelectrochemical performance enhancement is also observed in the tests. Compared with that of pure Bi2Se3 (0.016% at 0.90 V vs. RHE) and Au/Bi2Se3 (0.02% at 0.90 V vs. RHE) nanoparticles, the maximum photoconversion efficiency of porous Au/Bi2Se3/Cu2−xSe hybrid photoanodes increased by 5.87 and 4.50 times under simulated sunlight illumination, attributing to the cooperation of Z-scheme heterojunction and plasmon resonance enhancement effects. All the results indicate that Au/Bi2Se3/Cu2−xSe porous hybrids combine eco-friendliness with excellent sunlight harvesting capability and effectively inhibiting the charge recombination, which provide a new idea for efficient solar-driven water splitting.

Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer.

Microsatellite stable colorectal cancers (MSS-CRC) are resistant to anti-PD-1/PD-L1 therapy but the combination of immune checkpoints inhibitors (ICI) could be a clue to reverse resistance. Our aim was to evaluate ex vivo the capacity of the combination of atezolizumab (anti-PD-L1) and tiragolumab (anti-TIGIT) to reactivate the immune response of tumor infiltrating lymphocytes (TILs) in MSS-CRC. We analysed CRC tumor tissue and the associated blood sample in parallel. For each patient sample, extensive immunomonitoring and cytokine production were tested. We generated an ex vivo assay to study immune reactivity following immune stimulation with checkpoint inhibitors of tumor cell suspensions. Three microsatellite instable (MSI) and 13 MSS-CRC tumors were analysed. To generalize our observations, bioinformatics analyses were performed on public data of single cell RNA sequencing of CRC TILs and RNA sequencing data of TCGA. Atezolizumab alone could only reactivate T cells from MSI tumors. Atezolizumab and tiragolumab reactivated T cells in 46% of MSS-CRC samples. Reactivation by ICK was observed in patients with higher baseline frequency of Th1 and Tc1 cells, and was also associated with higher baseline T cell polyfunctionality and higher CD96 expression. We showed that a high frequency of CD96 expression on T cells could be a surrogate marker of atezolizumab and tiragolumab efficacy. Together these data suggest that the association of atezolizumab and tiragolumab could restore function of CD4 and CD8 TILs in MSS-CRC and could be tested in a clinical trial in colorectal cancer patients with MSS status.

Evidence of depot-specific regulation of all-trans-retinoic acid biosynthesis in human adipose tissue.

The prevalence of obesity continues to rise, underscoring the need to better understand the pathways mediating adipose tissue (AT) expansion. All‐trans‐retinoic acid (atRA), a bioactive vitamin A metabolite, regulates adipogenesis and energy metabolism, and, in rodent studies, aberrant vitamin A metabolism appears a key facet of metabolic dysregulation. The relevance of these findings to human disease is unknown, as are the specific enzymes implicated in vitamin A metabolism within human AT. We hypothesized that in human AT, family 1A aldehyde dehydrogenase (ALDH1A) enzymes contribute to atRA biosynthesis in a depot‐specific manner. To test this hypothesis, parallel samples of subcutaneous and omental AT from participants (n = 15) were collected during elective abdominal surgeries to quantify atRA biosynthesis and key atRA synthesizing enzymes. ALDH1A1 was the most abundant ALDH1A isoform in both AT depots with expression approximately twofold higher in omental than subcutaneous AT. ALDH1A2 was detected only in omental AT. Formation velocity of atRA was approximately threefold higher (p = 0.0001) in omental AT (9.8 [7.6, 11.2]) pmol/min/mg) than subcutaneous AT (3.2 [2.1, 4.0] pmol/min/mg) and correlated with ALDH1A2 expression in omental AT (β‐coefficient = 3.07, p = 0.0007) and with ALDH1A1 expression in subcutaneous AT (β‐coefficient = 0.13, p = 0.003). Despite a positive correlation between body mass index (BMI) and omental ALDH1A1 protein expression (Spearman r = 0.65, p = 0.01), BMI did not correlate with atRA formation. Our findings suggest that ALDH1A2 is the primary mediator of atRA formation in omental AT, whereas ALDH1A1 is the principal atRA‐synthesizing enzyme in subcutaneous AT. These data highlight AT depot as a critical variable for defining the roles of retinoids in human AT biology.

A parallel sampling algorithm for some nonlinear inverse problems

AbstractWe derive a parallel sampling algorithm for computational inverse problems that present an unknown linear forcing term and a vector of nonlinear parameters to be recovered. It is assumed that the data are noisy and that the linear part of the problem is ill-posed. The vector of nonlinear parameters ${m} $ is modeled as a random variable. A dilation parameter $\alpha $ is used to scale the regularity of the linear unknown and is also modeled as a random variable. A posterior probability distribution for $({m}, \alpha )$ is derived following an approach related to the maximum likelihood (ML) regularization parameter selection (Galatsanos, N. P. &amp; Katsaggelos, A. K. (1992). Methods for choosing the regularization parameter and estimating the noise variance in image restoration and their relation. IEEE Trans. Image Process., 1, 322–336). A major difference in our approach is that, unlike in Galatsanos, N. P. &amp; Katsaggelos, A. K. (1992, Methods for choosing the regularization parameter and estimating the noise variance in image restoration and their relation. IEEE Trans. Image Process., 1, 322–336), we do not limit ourselves to the maximum likelihood value of $\alpha $. We then derive a parallel sampling algorithm where we alternate computing proposals in parallel and combining proposals to accept or reject them as in Calderhead, B. (2014, A general construction for parallelizing metropolis- hastings algorithms. Proc. Natl Acad Sci, 111, 17408–17413). This algorithm is well suited to problems where proposals are expensive to compute. We then apply it to an inverse problem in seismology. We show how our results compare favorably to those obtained from the ML, the Generalized Cross Validation and the Constrained Least Squares algorithms.

Submicron-scale aerosol above the city canopy in Beijing in spring based on in-situ meteorological tower measurements

Non-refractory submicron-scale aerosol (NR-PM1) chemical species above the city canopy in Beijing in spring were studied based on observations at the Beijing 325-m meteorological tower in combination with analyses of the meteorological field and mixing layer height (MLH). The parallel sampling showed that the NR-PM1 at 260 m (60 μg/m3) was ~70% of that at ground level. Organic aerosol (Org) was the species with the most significant vertical difference, as its average mass concentration at 260 m was half of that at ground level. In 91% of cases, the Org at ground level was higher than that at 260 m. Sulfate (SO4) and chloride had more regional transport characteristics. Nitrate (NO3) and Org were more enriched at ground level, as the online molar ratio of NO3 to SO4 and the mass ratio of Org to SNA (sulfate–nitrate–ammonium) were higher at ground level. Among all the five NR-PM1 chemical species, ammonium nitrate was the species with the most uniform vertical distribution. Pollution events in spring in urban Beijing were accompanied by a gradual increase in ground RH from 10% to more than 35%. Strong winds from the southwest polluted region could also maintain the NR-PM1 at a high level. The polluted air masses transported from the south accounted for 39%, which was about four times that of the clean air masses from the northwest (11%). Thus, atmospheric circulation in spring is generally conducive to the formation of pollution. The estimated dilution efficiency on NR-PM1 chemical species influenced by boundary layer variation in spring showed that, when the mix layer was elevated the dilution effect at higher altitude was stronger than that at ground level.