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This study proposes a machine learning based methodology for estimating Arctic thin sea ice thickness (up to 1 m) from brightness temperature measurements of SMOS. The approach involves employing the so-called Burke model for sea ice emission modeling, integrating a suitable permittivity model and a radiative transfer equation. The training dataset is generated through a model-based simulation, and is then used to train and evaluate two machine learning regression algorithms: Random Forest and Gradient Boosting. Overall, this machine learning methodology results in great agreement with the ESA's official sea ice thickness product. Additionally, a validation performed by using data from mooring measurements shows a subtle improvement by the machine learning algorithms with respect to the ESA's official product. These results indicate their potential to surpass the performance of the current SMOS thin sea ice thickness retrievals.

IntroductionNonalcoholic fatty liver disease (NAFLD) affects a quarter of the world’s population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis.Material and methodsThis cross-sectional study aimed to explore the relationship between NAFLD severity, assessed via liver biopsy, and early atherosclerosis using adventitial vasa vasorum (VV) density. It included 44 patients with obesity (33 with steatosis, 11 with NASH) undergoing bariatric surgery.ResultsResults revealed no significant differences in adventitial VV density between steatosis and NASH groups, neither in the mean values [0.759 ± 0.104 vs. 0.780 ± 0.043, P=0.702] nor left-right sides. Similarly, carotid intima-media thickness (cIMT) did not vary between these groups. Additionally, no linear correlation existed between VV density and cIMT. Only gender showed an association with VV density.ConclusionThese findings suggest that NASH severity doesn’t independently drive early atherosclerosis or affects cIMT. Gender might play a role in early atherosclerotic disease in NAFLD, impacting VV density and cIMT. This highlights the need to consider other risk factors when evaluating cardiovascular risk in NAFLD patients.

Goal: We hypothesized that COVID-19 subjects, especially including asymptomatics, could be accurately discriminated only from a forced-cough cell phone recording using Artificial Intelligence. To train our MIT Open Voice model we built a data collection pipeline of COVID-19 cough recordings through our website (opensigma.mit.edu) between April and May 2020 and created the largest audio COVID-19 cough balanced dataset reported to date with 5,320 subjects. Methods: We developed an AI speech processing framework that leverages acoustic biomarker feature extractors to pre-screen for COVID-19 from cough recordings, and provide a personalized patient saliency map to longitudinally monitor patients in real-time, non-invasively, and at essentially zero variable cost. Cough recordings are transformed with Mel Frequency Cepstral Coefficient and inputted into a Convolutional Neural Network (CNN) based architecture made up of one Poisson biomarker layer and 3 pre-trained ResNet50's in parallel, outputting a binary pre-screening diagnostic. Our CNN-based models have been trained on 4256 subjects and tested on the remaining 1064 subjects of our dataset. Transfer learning was used to learn biomarker features on larger datasets, previously successfully tested in our Lab on Alzheimer's, which significantly improves the COVID-19 discrimination accuracy of our architecture. Results: When validated with subjects diagnosed using an official test, the model achieves COVID-19 sensitivity of 98.5% with a specificity of 94.2% (AUC: 0.97). For asymptomatic subjects it achieves sensitivity of 100% with a specificity of 83.2%. Conclusions: AI techniques can produce a free, non-invasive, real-time, any-time, instantly distributable, large-scale COVID-19 asymptomatic screening tool to augment current approaches in containing the spread of COVID-19. Practical use cases could be for daily screening of students, workers, and public as schools, jobs, and transport reopen, or for pool testing to quickly alert of outbreaks in groups. General speech biomarkers may exist that cover several disease categories, as we demonstrated using the same ones for COVID-19 and Alzheimer's.

Combinatorics

Combinatorics

A combined atomic force microscope (AFM) and scanning electron microscope (SEM) experiment examining the first steps in limestone weathering and erosion is presented. The experiment deals with the exposure of polished limestone rock tablets to a Western Mediterranean coastal environment and with the rate and patterns of weathering addressed by roughness quantification and qualitative assessment of nanoforms. Observations show how rock surface roughness increases at high rates after four and six months of exposure, passing from initial roughness RMS values between 14 and 32 mm to values between 396 to 492 mm. From the qualitative SEM approach, it can be concluded that the roughness increase relates with the widening of the space between rock grains and results in the isolation and detaching of rock grains.

Graphs and Algorithms

General

Graphs and Algorithms

The retrieval of sea ice thickness using L-band passive remote sensing requires robust models for emission from sea ice. In this work, measurements obtained from surface-based radiometers during the MOSAiC expedition are assessed with the Burke, Wilheit and SMRT radiative transfer models. These models encompass distinct methodologies: radiative transfer with/without wave coherence effects, and with/without scattering. Before running these emission models, the sea ice growth is simulated using the Cumulative Freezing Degree Days (CFDD) model to further compute the evolution of the ice structure during each period. Ice coring profiles done near the instruments are used to obtain the initial state of the computation, along with Digital Thermistor Chain (DTC) data to derive the sea ice temperature during the analyzed periods. The results suggest that the coherent approach used in the Wilheit model results in a better agreement with the horizontal polarization of the in situ measured brightness temperature. The Burke and SMRT incoherent models offer a more robust fit for the vertical component. These models are almost equivalent since the scattering considered in SMRT can be safely neglected at this low frequency, but the Burke model misses an important contribution from the snow layer above sea ice. The results also suggest that a more realistic permittivity falls between the spheres and random needles formulations, with potential for refinement, particularly for L-band applications, through future field measurements.

Engagement of the receptor programmed cell death molecule 1 (PD-1) by its ligands PD-L1 and PD-L2 inhibits T cell-mediated immune responses. Blocking such signaling provides the clinical effects of PD-1-targeted immunotherapy. Here, we investigated the mechanisms underlying PD-1-mediated inhibition. Because dynamic actin remodeling is crucial for T cell functions, we characterized the effects of PD-1 engagement on actin remodeling at the immunological synapse, the interface between a T cell and an antigen-presenting cell (APC) or target cell. We used microscopy to analyze the formation of immunological synapses between PD-1 + Jurkat cells or primary human CD8 + cytotoxic T cells and APCs that presented T cell-activating antibodies and were either positive or negative for PD-L1. PD-1 binding to PD-L1 inhibited T cell spreading induced by antibody-mediated activation, which was characterized by the absence of the F-actin-dense distal lamellipodial network at the immunological synapse and the Arp2/3 complex, which mediates branched actin formation. PD-1-induced inhibition of actin remodeling also prevented the characteristic deformation of T cells that contact APCs and the release of cytotoxic granules. We showed that the effects of PD-1 on actin remodeling did not require its tyrosine-based signaling motifs, which are thought to mediate the co-inhibitory effects of PD-1. Our study highlights a previously unappreciated mechanism of PD-1-mediated suppression of T cell activity, which depends on the regulation of actin cytoskeleton dynamics in a signaling motif-independent manner.

In innate immune cells, intracellular sensors such as cGAS-STING stimulate type I/III interferon (IFN) expression, which promotes antiviral defense and immune activation. However, how IFN-I/III expression is controlled in adaptive cells is poorly understood. Here, we identify a transcriptional rheostat orchestrated by RELA that confers human T cells with innate-like abilities to produce IFN-I/III. Despite intact cGAS-STING signaling, IFN-I/III responses are stunted in CD4+ T cells compared with dendritic cells or macrophages. We find that lysine residues in RELA tune the IFN-I/III response at baseline and in response to STING stimulation in CD4+ T cells. This response requires positive feedback driven by cGAS and IRF7 expression. By combining RELA with IRF3 and DNA demethylation, IFN-I/III production in CD4+ T cells reaches levels observed in dendritic cells. IFN-I/III production provides self-protection of CD4+ T cells against HIV infection and enhances the elimination of tumor cells by CAR T cells. Therefore, innate-like functions can be tuned and leveraged in human T cells., (© 2023 Jeremiah et al.)

We propose a freely accessible web-based pipeline, which processes raw microarray scan data to obtain experimentally consolidated gene expression values. The tool MADSCAN, which stands for MicroArray Data Suites of Computed ANalysis, makes a practical choice among the numerous methods available for filtering, normalizing and scaling of raw microarray expression data in a dynamic and automatic way. Different statistical methods have been adapted to extract reliable information from replicate gene spots as well as from replicate microarrays for each biological situation under study. A carefully constructed experimental design thus allows to detect outlying expression values and to identify statistically significant expression values, together with a list of quality controls with proposed threshold values. The integrated processing procedure described here, based on multiple measurements per gene, is decisive for reliably monitoring subtle gene expression changes typical for most biological events.

Complete clinical expression of the HFE1 hemochromatosis is very likely modulated by genes linked to duodenal iron absorption, whose level is conditioned by unknown processes taking place during enterocyte differentiation. We carried out a transcriptomic study on CaCo-2 cells used as a model of enterocyte differentiation in vitro. Of the 720 genes on the microarrays, 80, 50, and 56 were significantly down-regulated up-regulated, and invariant during differentiation. With regard to iron metabolism, we showed that HEPH, SLC11A2, SLC11A3, and TF are significantly up-regulated, while ATP7B and SLC39A1 (and SFT) are down-regulated and ACO1, dCYTb, FECH, and FTH1 show constant expression. Ontological annotations highlight the decrease in the expression of cell cycle and DNA metabolism associated genes as well as transcription, protein metabolism, signal transduction, and nucleocytoplasmic transport associated genes, whereas there are increases in the expression of genes linked to cell adhesion, lipid and xenobiotic metabolism, iron transport and homeostasis, and immune response.

Single nucleotide polymorphisms (SNPs) can significantly contribute to the characterization of the genes predisposing to iron overloads or deficiencies. We report an SNP survey of coding and non-coding regions of eight genes involved in iron metabolism, by two successive methods. First, we made use of the public domain sequence data, by using assembled expressed sequence tags, non-redundant sequences, and SNP database screening. We extracted 77 potential SNPs of which only 31 could be further validated by sequencing DNA from 44 unrelated multi-ethnic individuals. Our results indicate that a bioinformatic approach may be effective only in those cases where candidate SNPs are extracted from two different data sources or in cases of experimentally confirmed SNPs. Second, additional systematic sequencing of DNA from 24 unrelated Breton subjects increased the number of SNPs over a total length of 86 kb to 96. The average distance between the SNPs and minor allele frequencies were higher than reported by others authors; this discrepancy may reflect the nature of the genes studied and the ethnic homogeneity of our test population.

Hereditary haemochromatosis is an autosomal recessive disease which results in iron overload, and it is the most frequently inherited disorder in Caucasian populations. The gene involved (HFE) has recently been identified, and it encodes an MHC class I-like molecule. A 2.7 kb cDNA has been isolated, whereas the HFE gene expression is characterized by an almost ubiquitous mRNA of 4.1 kb in size. The difference between this transcript and the isolated cDNA has not yet been explained. Thus, the 5' end of the HFE gene is still undefined and very little is known about the regulation of its expression. By searching this end, we isolated an antisense transcript originating from the same gene locus. Further investigations (rapid amplification of cDNA ends, RT-PCR experiments and dbEST screening) indicated that this RNA spans exon 1, exon 2, part of intron 1 of the HFE gene and approximately 1 kb upstream of it. This HFE antisense transcript is polyadenylated but displays no open reading frame. A ribonuclease A protection assay definitively demonstrated the biological existence of the HFE antisense RNA, which appears to be expressed in all of the tissues and cell lines tested. Furthermore, in vitro coupled transcription-translation experiments revealed that the HFE expression is decreased by this antisense RNA, indicating that it may play a critical role in the regulation of the HFE gene expression.

The standard assay for lipid peroxidation is the measurement of the pink, 532 nm absorbing chromogen which is formed upon reaction of 2-thiobarbituric acid (TBA) with the lipid peroxidation product malonaldehyde (MDA). The present studies indicate that the toxic lipid peroxidation product trans-4-hydroxynonenal and its dehydration product trans,trans-nonadienal react with TBA to form chromogens which absorb maximally at 530 and 532 nm, respectively. Other biologically active alpha,beta-unsaturated aldehydes, such as acrolein and crotonaldehyde, short-chain homologs of alkenals formed during lipid peroxidation, and trans,trans-muconaldehyde, a novel diene dialdehyde, react with TBA to form products which absorb maximally at 495 nm. The molar extinction coefficients of the aldehyde:TBA chromogens formed were found to vary widely, suggesting that only small contributions to the 532 nm absorption by TBA adducts of reactive aldehydes other than MDA may be encountered during the use of the TBA assay.