Search

Potential vorticity (PV) analysis plays a central role in studying atmospheric dynamics and in particular in studying the life cycle of weather systems. The three-dimensional (3-D) structure and temporal evolution of the associated PV features, however, are not yet fully understood. An automated technique to objectively identify 3-D PV features can help to shed light on 3-D atmospheric dynamics in specific case studies as well as facilitate statistical evaluations within climatological studies. Such a technique to identify PV features fully in 3-D, however, does not yet exist. This study presents a novel algorithm for the objective identification of PV anomalies along the dynamical tropopause in gridded data, as commonly output by numerical simulation models. The algorithm is inspired by morphological image processing techniques and can be applied to both two-dimensional (2-D) and 3-D fields on vertically isentropic levels. The method maps input data to a horizontally stereographic projection and relies on an efficient computation of horizontal distances within the projected field. Candidates for PV anomaly features are filtered according to heuristic criteria, and feature description vectors are obtained for further analysis. The generated feature descriptions are well suited for subsequent case studies of 3-D atmospheric dynamics as represented by the underlying numerical simulation. We evaluate our approach by comparison with an existing 2-D technique and demonstrate the full 3-D perspective by means of a case study of an extreme precipitation event that was dynamically linked to a prominent subtropical PV anomaly. The case study demonstrates variations in the 3-D structure of the detected PV anomalies that would not have been captured by a 2-D method. We discuss further advantages of using a 3-D approach, including elimination of temporal inconsistencies in the detected features due to 3-D structural variation and elimination of the need to manually select a specific isentropic level on which the anomalies are assumed to be best captured. These advantages, as well as the suitability of the implementation to process big data sets, also open applications for climatological analyses. The method is made available as open-source for straightforward use by the atmospheric community.

Cancer cells exert mastery over the local tumor-associated stroma (TAS) to configure protective immunity within the tumor microenvironment. The immunomodulatory character of pancreatic lysates of patients with cancer differs from those with pancreatitis. In this study, we evaluated the cross-talk between pancreatic cancer and its TAS in primary human cell culture models. Upon exposure of TAS to pancreatic cancer cell-conditioned media, we documented robust secretion of IL6 and IL8. This TAS response was MyD88-dependent and sufficient to directly suppress both CD4+ and CD8+ T-cell proliferation, inducing Th17 polarization at the expense of Th1. We found that patients possessed a similar shift in circulating effector memory Th17:Th1 ratios compared with healthy controls. The TAS response also directly suppressed CD8+ T-cell–mediated cytotoxicity. Overall, our results demonstrate how TAS contributes to the production of an immunosuppressive tumor microenvironment in pancreatic cancer. Cancer Res; 77(3); 672–83. ©2016 AACR.

During an esophagectomy, many factors influence the anastomosis. Surgical factors include anastomotic tension, location of the anastomosis, surgical technique, and perfusion of the conduit. The use of fluorescent angiography is a possible avenue for more objective evaluation of the gastric conduit. There is a lot of variability in the way this tool has been used and what the results indicate. This article will discuss the various methods of fluorescent angiography to determine intestinal perfusion using indocyanine green and fluorescent imaging and the data on the association with clinical outcomes.

Muscle paralysis induced with botulinum toxin (Botox) injection increases vascular porosity and reduces osteocyte lacunar density in the tibial cortical bone of skeletally mature rats. These morphological changes potentially affect interstitial fluid flow in the lacunar–canalicular porosity, which is thought to play a role in osteocyte mechanotransduction. The aim of this study was to investigate the effects of disuse-induced morphological changes on interstitial fluid velocity around osteocytes in the bone cortex. Micro-CT images from a previous study that quantified the effects of Botox-induced muscle paralysis on bone microarchitecture in skeletally mature rats were used to create high-resolution, animal-specific finite element models that included the vascular pores and osteocyte lacunae within the tibial metaphysis of Botox-injected (BTX, n = 8) and saline-injected control (CTRL, n = 8) groups. To quantify fluid flow, lacunar and canalicular porosities were modeled as fluid-saturated poroelastic materials, and boundary conditions were applied to simulate physiological loading. This modeling approach allowed a detailed quantification of the fluid flow velocities around osteocytes in a relatively large volume of bone tissue. The analysis demonstrated that interstitial fluid velocity at the vascular pore surfaces was significantly lower in BTX compared to CTRL because of the decreased vascular canal separation. No significant differences in average fluid velocity were observed at the osteocyte lacunae and no correlation was found between the fluid velocity and the lacunar density, which was significantly lower in BTX. Instead, the lacunar fluid velocity was dependent on the osteocyte’s specific position in the bone cortex and its proximity to a vascular pore.

Introduction: Therapeutic approaches to target mutant KRAS is in progress, and transcription regulator PRMT5 (Protein arginine methyltransferase) has been previously reported to be a viable, surrogate target. Mutation of oncogenic KRAS is prevalent in several cancer types often rendering aggressiveness to the disease. Herein we used extensive molecular dynamics simulations to understand the intermediate complexities of the cross-talk. Methodology: GROMACS is a Molecular Dynamics Simulation software that renders a topology regulated by Newton’s Laws that can be employed to simulate interactions between proteins. Utilizing the STRING database, multiple pathways from KRAS linked to PRMT5 were extrapolated. Confidence values were determined. Protein complexes were downloaded from RCSB archives. Protein pairs were submitted to HDOCK for docking. Proteins were separated by chain identities, using PYMOL. Proteins were solvated and paired in GROMACS, and charges were neutralized. Each complex underwent energy minimization to configure the proteins in the most energetically favorable conformation. The complex was equilibrated and simulated. XmGrace was used to graph radius gyration between both proteins and their stabilities. The data produced were used to analyze the favorable interaction of the various pathways. Results: Three pathways were analyzed, with high, intermediate, and low confidence values of interaction. The intermediate mediators were simulated in pairs and energy scoring was performed for each interaction. The radius of gyration (Rg) values was calculated for each protein in its respective pathway. A cutoff of 10 nanoseconds was used to confirm stability. A scale was constructed to predict the order of operations of each pathway. HRAS was determined to be actively involved in the crosstalk. Conclusion: The crosstalk between PRMT5 and KRAS can be achieved through three different biochemical pathways with varying levels of confidence. Potentially, if one pathway is affected, an alternative route could be activated to achieve signaling toward PRMT5. These pathways introduce a more targeted approach toward discovering therapeutic advances against KRAS. More simulations are underway to compare the interactions of wildtype and mutant KRAS with their respective pathway intermediates. Citation Format: Isaac V. Silverman, Yitzchak F. Stein, Michael Shawn Gerber, Radhashree Maitra, Sanjay Goel. Molecular dynamic simulation of intermediates connecting KRAS and PRMT5 insight for targeting KRAS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2040.

In pancreatic cancer clinical trials, Black patients are under-represented while having higher morbidity and mortality rates as compared to other racial groups. Multiple factors, including socioeconomic and lifestyle factors may contribute to this disparity, but genomic contributions remain unclear. In an exploratory project to identify genes that may contribute to differences in survival between Black (n = 8) and White (n = 20) patients with pancreatic cancer, transcriptomic sequencing of over 24,900 genes was performed in human pancreatic tumor and non-tumor tissue obtained from Black and White patients. Over 4,400 genes were differentially expressed in tumor and non-tumor tissue, irrespective of race. To validate these results, the expression of four genes (AGR2, POSTN, TFF1, and CP) reported to be up-regulated in pancreatic tumor tissue as compared to non-tumor tissue were confirmed using quantitative PCR. Transcriptomic analysis that compared pancreatic tumor tissue from Black and White patients revealed differential expression in 1,200 genes, while a comparison of the non-tumor and tumor gene expression differences within each race revealed over 1,500 tumor-specific differentially expressed genes in pancreatic tumor and non-tumor tissue from Black patients. We identified TSPAN8 as a potential tumor-specific gene significantly overexpressed in pancreatic tumor tissue in Black patients as compared to White patients. Using Ingenuity Pathway Analysis software to compare the race-associated gene expression profiles, over 40 canonical pathways were identified to be potentially impacted by the gene expression differences between the races. Heightened expression of TSPAN8 was associated with poor overall survival, suggesting TSPAN8 as one potential genetic factor contributing to the differential outcomes in Black patients with pancreatic cancer, supporting the potential utility of larger genomic studies to further explore the role of TSPAN8 in pancreatic cancer.

This article comments on contributions to this special issue of School Psychology Review that focus on using cost-effectiveness analysis (CEA) to support decision making about implementation of evi...

Potential vorticity (PV) analysis plays a central role in studying atmospheric dynamics and in particular in studying the life cycle of weather systems. The three-dimensional (3-D) structure and temporal evolution of the associated PV anomalies, however, are not yet fully understood. An automated technique to objectively identify 3-D PV anomalies can help to shed light on 3-D atmospheric dynamics in specific case studies, as well as facilitate statistical evaluations within climatological studies. Such a technique to identify PV anomalies fully in 3-D, however, does not yet exist.This study presents a novel algorithm for the objective identification of PV anomalies. The algorithm is inspired by morphological image processing techniques and can be applied to both two-dimensional (2-D) and 3-D fields on vertically isentropic levels.The method maps input data to a horizontally stereographic projection and relies on an efficient computation of horizontal distances within the projected field. Candidates for PV anomaly features are filtered according to heuristic criteria, and feature description vectors are obtained for further analysis. The generated feature descriptions are well suited for subsequent case studies of 3-D atmospheric dynamics, or for generation of climatologies of feature characteristics.We evaluate our approach by comparison with an existing 2-D technique, and demonstrate the full 3-D perspective by means of meteorological case studies comprising tropical cyclogenesis and a subtropical extreme rainfall event. These case studies demonstrate the complexity and variations in the 3-D structure of the detected PV anomalies. Such anomalies are often insufficiently captured by a 2-D method. We discuss further advantages of using a 3-D approach, including elimination of temporal inconsistencies in the detected features due to 3-D structural variation, and elimination of the need to manually select a specific isentropic level on which the anomalies are assumed to be best captured.

While previous research on sub-seasonal tropical cyclone (TC) occurrence has mostly focused on either the validation of numerical weather prediction (NWP) models, or the development of statistical models trained on past data, the present study combines both approaches to a statistical–dynamical model for probabilistic forecasts in the North Atlantic basin. Although state-of-the-art NWP models have been shown to lack predictive skill with respect to sub-seasonal weekly TC occurrence, they may predict the environmental conditions sufficiently well to generate predictors for a statistical model. Therefore, an extensive predictor set was generated, including predictor groups representing the climatological seasonal cycle (CSC), oceanic, and tropical conditions, tropical wave modes, as well as extratropical influences, respectively. The developed hybrid forecast model is systematically validated for the Gulf of Mexico and Central Main Development Region (MDR) for lead times up to five weeks. Moreover, its performance is compared against a statistical approach trained on past data, as well as against different climatological and NWP benchmarks. For sub-seasonal lead times, the CSC models are found to outperform the NWP models, which quickly loose skill within the first two forecast weeks, even in case of recalibration. The statistical models trained on past data increase skill over the CSC models, whereas even greater improvements in skill are gained by the hybrid approach out to week five. The vast majority of the additional sub-seasonal skill in the hybrid model, relative to the CSC model, could be attributed to the tropical (oceanic) conditions in the Gulf of Mexico (Central MDR).

A dearth of literature exists on first-year transfer student interventions, which makes it difficult to determine whether there are transfer student subgroups that struggle more than others...

Research with English monolinguals has identified key subskills of reading comprehension that can differentiate subgroups of readers. There remains a dearth of research examining these subs...

Reduced mechanical loading can lead to disuse osteoporosis, resulting in bone fragility. Disuse models report macroscopic bone loss due to muscle inactivity and immobilization, yet only recently has there been quantification of the effects of disuse on the vascular pores and osteocyte network, which are believed to play an important role in mechanotransduction via interstitial fluid flow. The goal of this study was to perform a high-resolution analysis of the effects of muscle inactivity on intracortical porosity and osteocyte lacunar density in skeletally mature rats. Muscle paralysis was induced in 20-week-old female Sprague Dawley rats by injection of botulinum neurotoxin. Rats were injected in the right hindlimb muscles with either Botox (BTX, n = 8) or saline solution (CTRL, n = 8), with a third group used as baseline controls (n = 8). Four weeks after injection, Botox caused a ∼60% reduction in hindlimb muscle mass. High-resolution micro-CT analysis showed that Botox-induced muscle paralysis increased vascular canal porosity and reduced osteocyte lacunar density within the tibial metaphysis cortex. Cortical thickness and other areal properties were diminished in the proximal tibial metaphysis, whereas no differences were found in the mid-diaphysis. Within the BTX group, the injected limbs showed a lower cancellous bone volume fraction relative to the contralateral limb. These results indicate that diminished muscle activity alters the vascular canal porosity and osteocyte lacunar density in cortical bone, which could alter interstitial fluid flow, affecting molecular transport and the transmission of mechanical signals to osteocytes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Potential vorticity streamers (PVSs) are elongated quasi-horizontal filaments of stratospheric air in the upper troposphere related to, for example, Rossby wave breaking events. They are known to be related to partly extreme weather events in the midlatitudes and subtropics and can also be involved in (sub-)tropical cyclogenesis. While several algorithms have been developed to identify and track PVSs on planar isentropic surfaces, less is known about the evolution of these streamers in 3D, both climatologically but also for a better understanding of individual weather events. Furthermore, characteristics of their 3D shape have barely been considered as a predictor for high impact weather events like (sub-)tropical cyclones.We introduce a novel algorithm for detection and identification of PVSs based on image processing techniques which can be applied to 2D and 3D gridded datasets. The potential vorticity was taken from high resolution isentropic analyses based on the ERA5 dataset. The algorithm uses the 2 PVU (Potential Vorticity Unit) threshold to identify and extract anomalies in the PV field using signed distance functions. This is accomplished by using a stereographic projection to eliminate singularities and keeping track of the reduced distortions by storing precomputed distance maps. This approach is computationally efficient and detects more interesting structures that exhibit the general behavior of PVSs compared to existing 2D techniques.For each identified object a feature vector is computed, containing the individual characteristics of the streamers. In the 3D case, the algorithm looks at the structure en bloc instead of operating individually on multiple 2D levels. This also makes the identification stable regarding the seasonal cycle. Feature vectors contain parameters about quality, intensity and shape. In the case of 2D datasets, best-fitting ellipses computed from the statistical moments are regarded as a description of their shape. For 3D datasets, recent visualizations show that the boundary of these structures could be approximated by quadric surfaces . The feature vectors are also amended by tracking information, for example splitting and merging events. This low-dimensional representation serves as base for ERA5 climatologies. The data will be correlated with (sub-)tropical cyclone occurrence to spot useful and novel predictors for cyclone activity and preceding Rossby Wave Breaking events.Overall, this new type of PVS identification algorithm, applicable in 2D or 3D, allows to diagnose the role of PVS in extreme weather events, including their predictability in ensemble forecasts.