Laboratory and theoretical studies of baroclinic processes

An understanding is being developed for processes which may be important in the atmosphere, and the definition and analysis of baroclinic experiments utilizing the geophysical fluid flow cells (GFFC) apparatus in microgravity space flights. Included are studies using numerical codes, theoretical models, and terrestrial laboratory experiments. The numerical modeling is performed in three stages: calculation of steady axisymmetric flow, calculation of fastest-growing linear eigenmodes, and nonlinear effects (first, wave-mean flow interactions, then wave-wave interactions). The code can accommodate cylindrical, spherical, or channel geometry. It uses finite differences in the vertical and meridional directions, and is spectral in the azimuthal. The theoretical work was mostly in the area of effects of topography upon the baroclinic instability problem. The laboratory experiments are performed in a cylindrical annulus which has a temperture gradient imposed upon the lower surface and an approximately isothermal outer wall, with the upper and inner surfaces being nominally thermally insulating

Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality

Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis and mirror adaptive CD4(+) T helper (Th) cell subtypes in both usage of effector molecules and transcription factors. To better understand the relationship between ILC subsets and their Th cell counterparts, we measured genome-wide chromatin accessibility. We find that chromatin in proximity to effector genes is selectively accessible in ILCs prior to high-level transcription upon activation. Accessibility of these regions is acquired in a stepwise manner during development and changes little after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurs in naive CD4(+) T cells during Th cell differentiation using a type-2-infection model. This alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our data indicate extensive sharing of regulatory circuitry across the innate and adaptive compartments of the immune system, in spite of their divergent developing pathways

A Highly Sensitive Underwater Video System for Use in Turbid Aquaculture Ponds

The turbid, low-light waters characteristic of aquaculture ponds have made it difficult or impossible for previous video cameras to provide clear imagery of the ponds\u27 benthic habitat. We developed a highly sensitive, underwater video system (UVS) for this particular application and tested it in shrimp ponds having turbidities typical of those in southern Taiwan. The system\u27s high-quality video stream and images, together with its camera capacity (up to nine cameras), permit in situ observations of shrimp feeding behavior, shrimp size and internal anatomy, and organic matter residues on pond sediments. The UVS can operate continuously and be focused remotely, a convenience to shrimp farmers. The observations possible with the UVS provide aquaculturists with information critical to provision of feed with minimal waste; determining whether the accumulation of organic-matter residues dictates exchange of pond water; and management decisions concerning shrimp health

A Highly Sensitive Underwater Video System For Use in Turbid Aquaculture Ponds

The turbid, low-light waters characteristic of aquaculture ponds have made it difficult or impossible for previous video cameras to provide clear imagery of the ponds\u27 benthic habitat. We developed a highly sensitive, underwater video system (UVS) for this particular application and tested it in shrimp ponds having turbidities typical of those in southern Taiwan. The system\u27s high-quality video stream and images, together with its camera capacity (up to nine cameras), permit in situ observations of shrimp feeding behavior, shrimp size and internal anatomy, and organic matter residues on pond sediments. The UVS can operate continuously and be focused remotely, a convenience to shrimp farmers. The observations possible with the UVS provide aquaculturists with information critical to provision of feed with minimal waste; determining whether the accumulation of organic-matter residues dictates exchange of pond water; and management decisions concerning shrimp health

Evaluation of Heat Generation in Unidirectional Versus Oscillatory Modes During K‐Wire Insertion in Bone

Heat generation during insertion of Kirschner wires (K‐wires) may lead to thermal osteonecrosis and can affect the construct fixation. Unidirectional and oscillatory drilling modes are options for K‐wire insertion, but understanding of the difference in heat generation between the two modes is lacking. The goal of this study was to compare the temperature rise during K‐wire insertion under these two modes and provide technical guidelines for K‐wire placement to minimize thermal injury. Ten orthopedic surgeons were instructed to drill holes on hydrated ex vivo bovine bones under two modes. The drilling trials were evaluated in terms of temperature, thrust force, torque, drilling time, and tool wear. The analysis of variance showed that the oscillatory mode generated significantly lowered peak bone temperature rise (13% lower mean value, p = 0.036) over significantly longer drilling time (46% higher mean time, p < 0.001) than the unidirectional mode. Drilling time had significant effect on peak bone temperature rise under both modes (p < 0.001) and impact of peak thrust force was significant under oscillatory mode (p < 0.001). These findings suggest that the drilling mode choice is a compromise between peak temperature and bone exposure time. Shortening the drilling time was the key under both modes to minimize temperature rise and thermal necrosis risk. To achieve faster drilling, technique analysis found that “shaky” and intermittent drilling with moderate thrust force are preferred techniques by small vibration of the drill about the K‐wire axis and slight lift‐up of the K‐wire once or twice during drilling. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1903–1909, 2019Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151349/1/jor24345_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151349/2/jor24345.pd

Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells

Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor (TF) STAT5 is critical for accumulation of all known ILC subsets in mice and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15. We also uncover surprising features of STAT5 behavior, most notably the wholesale redistribution that occurs when NK cells shift from tonic signaling to acute cytokine-driven signaling, and genome-wide coordination with T-bet, another key TF in ILC biology. Collectively, our data position STAT5 as a central node in the TF network that instructs ILC development, homeostasis, and function and provide mechanistic insights on how it works at cellular and molecular levels

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment