A critical evaluation of the status and trends in high speed fluid film lubrication

High speed fluid film lubricatio

Rhubarb A Play and Two Halves

Rhubarb is a collection of two one-act comedies written in the absurdist tradition, with a critical statement that offers the project\u27s framework. Both plays engage the discord between the human inclination to search for inherent meaning and the ultimate inability to find any. Case #6,037,492,801 concerns two of Hell\u27s recently deceased as they determine the confines of their afterlife. Fishbowl focuses on a new recruit as she ascends a corporate system. The characters in these plays are atypical, either being flat or extremely exaggerated, working as parts of the larger metaphor. These plays are satirical, being saturated with nonsense and meaningless dialogue. The conventional well-made play structure is subverted so time is unstable and largely irrelevant, and the plot is circular but also intermittent

Marked recent declines in boron in Baltic Sea cod otoliths – a bellwether of incipient acidification in a vast hypoxic system?

Ocean acidification is spreading globally as a result of anthropogenic CO2 emissions, but the Baltic Sea has until recently been thought to be relatively well-buffered by terrigenous inputs of alkalinity from its watershed. We discovered a 3- to 5-fold decline in boron (as B : Ca) in otoliths of eastern Baltic cod (EBC) between the late 1990s and 2021. Examining a time series of EBC otoliths, we found varying levels of B : Ca starting in the 1980s, with the most recent years showing an all-time low for this period. This trend correlates with declines in pH and dissolved oxygen but not with changes in salinity. We examined possible physiological influences on B : Ca by including a collection of Icelandic cod as an “out-group”. Icelandic cod otoliths showed strongly positive correlations of B : Ca with physiologically regulated P : Ca; this was not the case for EBC. Finally, B : Ca in EBC otoliths is negatively correlated, to some extent, with Mn : Mg, a proposed proxy for hypoxia exposure. This negative relationship is hypothesized to reflect the dual phenomena of hypoxia and acidification as a result of decomposition of large algal blooms. Taken together, the otolith biomarkers Mn : Mg and B : Ca in cod suggest a general increase in both hypoxia and acidification within the Baltic intermediate and deep waters in the last decade

Regulation of Reactive Oxygen Species and the Antioxidant Protein DJ-1 in Mastocytosis

Neoplastic accumulation of mast cells in systemic mastocytosis (SM) associates with activating mutations in the receptor tyrosine kinase KIT. Constitutive activation of tyrosine kinase oncogenes has been linked to imbalances in oxidant/antioxidant mechanisms in other myeloproliferative disorders. However, the impact of KIT mutations on the redox status in SM and the potential therapeutic implications are not well understood. Here, we examined the regulation of reactive oxygen species (ROS) and of the antioxidant protein DJ-1 (PARK-7), which increases with cancer progression and acts to lessen oxidative damage to malignant cells, in relationship with SM severity. ROS levels were increased in both indolent (ISM) and aggressive variants of the disease (ASM). However, while DJ-1 levels were reduced in ISM with lower mast cell burden, they rose in ISM with higher mast cell burden and were significantly elevated in patients with ASM. Studies on mast cell lines revealed that activating KIT mutations induced constant ROS production and consequent DJ-1 oxidation and degradation that could explain the reduced levels of DJ-1 in the ISM population, while IL-6, a cytokine that increases with disease severity, caused a counteracting transcriptional induction of DJ-1 which would protect malignant mast cells from oxidative damage. A mouse model of mastocytosis recapitulated the biphasic changes in DJ-1 and the escalating IL-6, ROS and DJ-1 levels as mast cells accumulate, findings which were reversed with anti-IL-6 receptor blocking antibody. Our findings provide evidence of increased ROS and a biphasic regulation of the antioxidant DJ-1 in variants of SM and implicate IL-6 in DJ-1 induction and expansion of mast cells with KIT mutations. We propose consideration of IL-6 blockade as a potential adjunctive therapy in the treatment of patients with advanced mastocytosis, as it would reduce DJ-1 levels making mutation-positive mast cells vulnerable to oxidative damage

Towards Characterizing Domain Counterfactuals For Invertible Latent Causal Models

Answering counterfactual queries has many important applications such as knowledge discovery and explainability, but is challenging when causal variables are unobserved and we only see a projection onto an observation space, for instance, image pixels. One approach is to recover the latent Structural Causal Model (SCM), but this typically needs unrealistic assumptions, such as linearity of the causal mechanisms. Another approach is to use na\"ive ML approximations, such as generative models, to generate counterfactual samples; however, these lack guarantees of accuracy. In this work, we strive to strike a balance between practicality and theoretical guarantees by focusing on a specific type of causal query called domain counterfactuals, which hypothesizes what a sample would have looked like if it had been generated in a different domain (or environment). Concretely, by only assuming invertibility, sparse domain interventions and access to observational data from different domains, we aim to improve domain counterfactual estimation both theoretically and practically with less restrictive assumptions. We define domain counterfactually equivalent models and prove necessary and sufficient properties for equivalent models that provide a tight characterization of the domain counterfactual equivalence classes. Building upon this result, we prove that every equivalence class contains a model where all intervened variables are at the end when topologically sorted by the causal DAG. This surprising result suggests that a model design that only allows intervention in the last $k$ latent variables may improve model estimation for counterfactuals. We then test this model design on extensive simulated and image-based experiments which show the sparse canonical model indeed improves counterfactual estimation over baseline non-sparse models

Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data

Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide

Protein expression profiling identifies key proteins and pathways involved in growth inhibitory effects exerted by guggulsterone in human colorectal cancer cells

Colorectal cancer (CRC) is a leading killer cancer worldwide and one of the most common malignancies with increasing incidences of mortality. Guggulsterone (GS) is a plant sterol used for treatment of various ailments such as obesity, hyperlipidemia, diabetes, and arthritis. In the current study, anti-cancer effects of GS in human colorectal cancer cell line HCT 116 was tested, potential targets identified using mass spectrometry-based label-free shotgun proteomics approach and key pathways validated by proteome profiler antibody arrays. Comprehensive proteomic profiling identified 14 proteins as significantly dysregulated. Proteins involved in cell proliferation/migration, tumorigenesis, cell growth, metabolism, and DNA replication were downregulated while the protein with functional role in exocytosis/tumor suppression was found to be upregulated. Our study evidenced that GS treatment altered expression of Bcl-2 mediated the mitochondrial release of cytochrome c which triggered the formation of apoptosome as well as activation of caspase-3/7 leading to death of HCT 116 cells via intrinsic apoptosis pathway. GS treatment also induced expression of p53 protein while p21 expression was unaltered with no cell cycle arrest. In addition, GS was found to inhibit NF-kB signaling in colon cancer cells by quelling the expression of its regulated gene products Bcl-2, cIAP-1, and survivin. - 2019 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This study was funded by MEDICAL RESEARCH CENTER (MRC) at HAMAD MEDICAL CORPORATION, Doha, State of Qatar with grant number MRC#15264/15.Scopu