Conditional Residual Coding: A Remedy for Bottleneck Problems in Conditional Inter Frame Coding

Conditional coding is a new video coding paradigm enabled by neural-network-based compression. It can be shown that conditional coding is in theory better than the traditional residual coding, which is widely used in video compression standards like HEVC or VVC. However, on closer inspection, it becomes clear that conditional coders can suffer from information bottlenecks in the prediction path, i.e., that due to the data processing inequality not all information from the prediction signal can be passed to the reconstructed signal, thereby impairing the coder performance. In this paper we propose the conditional residual coding concept, which we derive from information theoretical properties of the conditional coder. This coder significantly reduces the influence of bottlenecks, while maintaining the theoretical performance of the conditional coder. We provide a theoretical analysis of the coding paradigm and demonstrate the performance of the conditional residual coder in a practical example. We show that conditional residual coders alleviate the disadvantages of conditional coders while being able to maintain their advantages over residual coders. In the spectrum of residual and conditional coding, we can therefore consider them as ``the best from both worlds''.Comment: 12 pages, 8 figure

On Benefits and Challenges of Conditional Interframe Video Coding in Light of Information Theory

The rise of variational autoencoders for image and video compression has opened the door to many elaborate coding techniques. One example here is the possibility of conditional interframe coding. Here, instead of transmitting the residual between the original frame and the predicted frame (often obtained by motion compensation), the current frame is transmitted under the condition of knowing the prediction signal. In practice, conditional coding can be straightforwardly implemented using a conditional autoencoder, which has also shown good results in recent works. In this paper, we provide an information theoretical analysis of conditional coding for inter frames and show in which cases gains compared to traditional residual coding can be expected. We also show the effect of information bottlenecks which can occur in practical video coders in the prediction signal path due to the network structure, as a consequence of the data-processing theorem or due to quantization. We demonstrate that conditional coding has theoretical benefits over residual coding but that there are cases in which the benefits are quickly canceled by small information bottlenecks of the prediction signal.Comment: 5 pages, 4 figures, accepted to be presented at PCS 2022. arXiv admin note: text overlap with arXiv:2112.08011 Update Note: Fixed notation in Eq. 10, no changes otherwis

Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens

<p>Abstract</p> <p>Background</p> <p>Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models.</p> <p>Results</p> <p>This study examined the suitability of a murine model (CT26/Balb/C) of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO)-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver), invasion (invasion front), and immune response (invasion front and liver). Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%.</p> <p>Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver) whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%). However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0%) despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments.</p> <p>Conclusion</p> <p>In summary, cross-species comparison on a global gene expression scale suggests the validity of an animal model representing the human situation. The actual yield of potential target genes depends on several variables including the animal model, choice of inclusion criteria, inherent species differences and histologic assessment.</p

IRGM variants and susceptibility to inflammatory bowel disease in the German population.

Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study. Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin) was analyzed for six IRGM single nucleotide polymorphisms (SNPs) (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058). In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05-1.65]), rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06-1.66]) and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01-1.61]) with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (p<0.05). Genotype-phenotype analysis revealed no significant associations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes IRGM and ATG16L1 (p<0.05), which, however, did not remain significant after Bonferroni correction. Our results confirm IRGM as susceptibility gene for CD in the German population, supporting a role for the autophagy genes IRGM and ATG16L1 in the pathogenesis of CD

PTPN2 gene variants are associated with susceptibility to both Crohn's disease and ulcerative colitis supporting a common genetic disease background.

Genome-wide association studies identified PTPN2 (protein tyrosine phosphatase, non-receptor type 2) as susceptibility gene for inflammatory bowel diseases (IBD). However, the exact role of PTPN2 in Crohn's disease (CD) and ulcerative colitis (UC) and its phenotypic effect are unclear. We therefore performed a detailed genotype-phenotype and epistasis analysis of PTPN2 gene variants. Genomic DNA from 2131 individuals of Caucasian origin (905 patients with CD, 318 patients with UC, and 908 healthy, unrelated controls) was analyzed for two SNPs in the PTPN2 region (rs2542151, rs7234029) for which associations with IBD were found in previous studies in other cohorts. Our analysis revealed a significant association of PTPN2 SNP rs2542151 with both susceptibility to CD (p = 1.95×10⁻⁵; OR 1.49 [1.34-1.79]) and UC (p = 3.87×10⁻², OR 1.31 [1.02-1.68]). Moreover, PTPN2 SNP rs7234029 demonstrated a significant association with susceptibility to CD (p = 1.30×10⁻³; OR 1.35 [1.13-1.62]) and a trend towards association with UC (p = 7.53×10⁻²; OR 1.26 [0.98-1.62]). Genotype-phenotype analysis revealed an association of PTPN2 SNP rs7234029 with a stricturing disease phenotype (B2) in CD patients (p = 6.62×10⁻³). Epistasis analysis showed weak epistasis between the ATG16L1 SNP rs2241879 and PTPN2 SNP rs2542151 (p = 0.024) in CD and between ATG16L1 SNP rs4663396 and PTPN2 SNP rs7234029 (p = 4.68×10⁻³) in UC. There was no evidence of epistasis between PTPN2 and NOD2 and PTPN2 and IL23R. In silico analysis revealed that the SNP rs7234029 modulates potentially the binding sites of several transcription factors involved in inflammation including GATA-3, NF-κB, C/EBP, and E4BP4. Our data confirm the association of PTPN2 variants with susceptibility to both CD and UC, suggesting a common disease pathomechanism for these diseases. Given recent evidence that PTPN2 regulates autophagosome formation in intestinal epithelial cells, the potential link between PTPN2 and ATG16L1 should be further investigated

PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohn's disease and affect NF-κB and XBP1 binding sites.

Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes. A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10⁻⁵; 0.76 [0.67-0.87]) and of rs7720838 (p = 6.91×10⁻⁴; 0.81 [0.71-0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10⁻⁷ for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD. We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if changes in PTGER4 expression modulate CD susceptibility

A SAMPLING STRATEGY FOR RECENT AND FOSSIL BRACHIOPODS: SELECTING THE OPTIMAL SHELL SEGMENT FOR GEOCHEMICAL ANALYSES

Recent and fossil brachiopod shells have a long record as biomineral archives for (palaeo)climatic and (palaeo)environmental reconstructions, as they lack or exhibit limited vital effects in their calcite shell and generally are quite resistant to diagenetic alteration. Despite this, only few studies address the issue of identifying the best or optimal part of the shell for geochemical analyses. We investigated the link between ontogeny and geochemical signatures recorded in different parts of the shell. To reach this aim, we analysed the elemental (Ca, Mg, Sr, Na) and stable isotope (δ18O, δ13C) compositions of five recent brachiopod species (Magellania venosa, Liothyrella uva, Aerothyris kerguelensis, Liothyrella neozelanica and Gyphus vitreus), spanning broad geographical and environmental ranges (Chile, Antarctica, Indian Ocean, New Zealand and Italy) and having different shell layer successions (two-layer and three-layer shells). We observed similar patterns in the ventral and dorsal valves of these two groups, but different ontogenetic trends by the two- and three-layer shells in their trace element and stable isotope records. Our investigation led us to conclude that the optimal region to sample for geochemical and isotope analyses is the middle part of the mid-section of the shell, avoiding the primary layer, posterior and anterior parts as well as the outermost part of the secondary layer in recent brachiopods. Also, the outermost and innermost rims of shells should be avoided due to diagenetic impacts on fossil brachiopods

Variation in brachiopod microstructure and isotope geochemistry under low-pH-ocean acidification conditions

This project was supported by the European Union's Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement no. 643084 (BASE–LiNE Earth).In the last few decades and in the near future CO2-induced ocean acidification is potentially a big threat to marine calcite-shelled animals (e.g. brachiopods, bivalves, corals and gastropods). Despite the great number of studies focusing on the effects of acidification on shell growth, metabolism, shell dissolution and shell repair, the consequences for biomineral formation remain poorly understood. Only a few studies have addressed the impact of ocean acidification on shell microstructure and geochemistry. In this study, a detailed microstructure and stable isotope geochemistry investigation was performed on nine adult brachiopod specimens of Magellania venosa (Dixon, 1789). These were grown in the natural environment as well as in controlled culturing experiments under different pH conditions (ranging from 7.35 to 8.15±0.05) over different time intervals (214 to 335 days). Details of shell microstructural features, such as thickness of the primary layer, density and size of endopunctae and morphology of the basic structural unit of the secondary layer were analysed using scanning electron microscopy. Stable isotope compositions (δ13C and δ18O) were tested from the secondary shell layer along shell ontogenetic increments in both dorsal and ventral valves. Based on our comprehensive dataset, we observed that, under low-pH conditions, M. venosa produced a more organic-rich shell with higher density of and larger endopunctae, and smaller secondary layer fibres. Also, increasingly negative δ13C and δ18O values are recorded by the shell produced during culturing and are related to the CO2 source in the culture set-up. Both the microstructural changes and the stable isotope results are similar to observations on brachiopods from the fossil record and strongly support the value of brachiopods as robust archives of proxies for studying ocean acidification events in the geologic past.Publisher PDFPeer reviewe

Intestinal DMBT1 Expression Is Modulated by Crohn’s Disease-Associated IL23R Variants and by a DMBT1 Variant Which Influences Binding of the Transcription Factors CREB1 and ATF-2

Objectives: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. Methods: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn’s disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. Results: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0×10−7, OR 1.42; 95% CI 1.24–1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1×10−18). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. Conclusion: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis