Airborne Measurements of Gravity Wave Breaking at the Tropopause

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ATP prevents Woronin bodies from sealing septal pores in unwounded cells of the fungus Zymoseptoria tritici

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Septa of filamentous ascomycetes are perforated by septal pores that allow communication between individual hyphal compartments. Upon injury, septal pores are plugged rapidly by Woronin bodies (WBs), thereby preventing extensive cytoplasmic bleeding. The mechanism by which WBs translocate into the pore is not known, but it has been suggested that wound-induced cytoplasmic bleeding "flushes" WBs into the septal opening. Alternatively, contraction of septum-associated tethering proteins may pull WBs into the septal pore. Here, we investigate Woronin body dynamics in the wheat pathogen Zymoseptoria tritici. Ultrastructural studies showed that 3.4 ± 0.2 WBs reside on each side of a septum and that single WBs of 128.5 ± 3.6 nm in diameter seal the septal pore (41±1.5 nm). Live cell imaging of green-fluorescent ZtHex1, a major protein in WBs, and the integral plasma membrane protein ZtSso1 confirms WB translocation into the septal pore. This was associated with the occasional formation of a plasma membrane "balloon", extruding into the dead cell, suggesting that the plasma membrane rapidly seals the wounded septal pore wound. Minor amounts of fluorescent ZtHex1-eGFP appeared associated with the "ballooning" plasma membrane, indicating that cytoplasmic ZtHex1-eGFP is recruited to the extending plasma membrane. Surprisingly, in ~15% of all cases, WBs moved from the ruptured cell into the septal pore. This translocation against the cytoplasmic flow suggests that an active mechanism drives in WB plugging. Indeed, treatment of unwounded and intact cells with the respiration inhibitor CCCP induced WB translocation into the pores. Moreover, CCCP treatment recruited cytoplasmic ZtHex1-eGFP to the lateral plasma membrane of the cells. Thus, keeping the WBs out of the septal pores, in Z. tritici, is an ATP-dependent process

Lenvatinib Targets PDGFR-β Pericytes and Inhibits Synergy with Thyroid Carcinoma Cells: Novel Translational Insights

Context: Pericyte populations abundantly express tyrosine kinases (eg, platelet-derived growth factor receptor-β [PDGFR-β]) and impact therapeutic response. Lenvatinib is a clinically available tyrosine kinase inhibitor that also targets PDGFR-β. Duration of therapeutic response was shorter in patients with greater disease burden and metastasis. Patients may develop drug resistance and tumor progression. Objectives: Develop a gene signature of pericyte abundance to assess with tumor aggressiveness and determine both the response of thyroid-derived pericytes to lenvatinib and their synergies with thyroid carcinoma-derived cells. Design: Using a new gene signature, we estimated the relative abundance of pericytes in papillary thyroid carcinoma (PTC) and normal thyroid (NT) TCGA samples. We also cocultured CD90+;PAX8- thyroid-derived pericytes and BRAFWT/V600E-PTC-derived cells to determine effects of coculture on paracrine communications and lenvatinib response. Results: Pericyte abundance is significantly higher in BRAFV600E-PTC with hTERT mutations and copy number alterations compared with NT or BRAFWT-PTC samples, even when data are corrected for clinical-pathologic confounders. We have identified upregulated pathways important for tumor survival, immunomodulation, RNA transcription, cell-cycle regulation, and cholesterol metabolism. Pericyte growth is significantly increased by platelet-derived growth factor-BB, which activates phospho(p)-PDGFR-β, pERK1/2, and pAKT. Lenvatinib strongly inhibits pericyte viability by down-regulating MAPK, pAKT, and p-p70S6-kinase downstream PDGFR-β. Critically, lenvatinib significantly induces higher BRAFWT/V600E-PTC cell death when cocultured with pericytes, as a result of pericyte targeting via PDGFR-β. Conclusions: This is the first thyroid-specific model of lenvatinib therapeutic efficacy against pericyte viability, which disadvantages BRAFWT/V600E-PTC growth. Assessing pericyte abundance in patients with PTC could be essential to selection rationales for appropriate targeted therapy with lenvatinib

Abrupt vessel closure complicating coronary angioplasty: Clinical, angiographic and therapeutic profile

AbstractTo assess the clinical, angiographic and procedural correlates of outcome after abrupt vessel closure during coronary angioplasty, results were analyzed of 109 patients (8.3%) who had abrupt vessel closure during 1,319 consecutive coronary angioplasty procedures performed between July 1, 1988 and June 30, 1990. These 109 patients had a mean age of 59 ± 11 years; 63% were male, 57% had had a prior myocardial infarction and 61% had multivessel disease. Coronary angioplasty was performed in the settings of acute myocardial infarction (14%), recent myocardial infarction (36%), unstable angina (34%) and stable ischemia (29%).Abrupt vessel closure occurred at a median of 27 min (range 0 min to 5 days) from the first balloon inflation. By angiographic criteria, thrombus or coronary dissection was identified in 20% and 28% of cases, respectively; both thrombus and dissection were present in 7% of closures, and 45% were due to indeterminate mechanisms. Successful reversal of abrupt vessel closure, defined as restoration of normal Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow without resultant Q wave myocardial infarction, emergency bypass surgery or death, was achieved in 47 patients (43%). By hierarchal analysis, the incidence of death, emergency coronary bypass surgery, Q wave and non-Q wave myocardial infarction was 8%, 20%, 9% and 11%, respectively.Univariate analysis using 23 clinical, morphologic and procedural variables demonstrated that successful outcome after abrupt closure was associated with prolonged balloon inflations (>120 s) (odds ratio = 6.87, p < 0.001), unstable angina (odds ratio = 2.37, p = 0.034) and placement of an intracoronary stent (odds ratio = 5.33, p = 0.062). By multivariate analysis, independent correlates of successful outcome were prolonged balloon inflations (odds ratio = 5.11, p = 0.001) and intracoronary stenting (odds ratio = 4.37, p = 0.049).Thus, although prolonged balloon inflations and intracoronary stents may improve outcome after abrupt vessel closure, the cumulative risk of morbidity or mortality remains significant and mandates investigation into improved strategies for its prevention and treatment

Capability assessment for application of clay mixture as barrier material for irradiated zirconium alloy structure elements long-term processing for storage during decommissioning of uranium-graphite nuclear reactors

The radionuclide composition and the activity level of the irradiated zirconium alloy E110, the radionuclide immobilization strength and the retention properties of the mixed clay barrier material with respect to the radionuclides identified in the alloy were investigated to perform the safety assessment of handling structural units of zirconium alloy used for the technological channels in uranium-graphite reactors. The irradiated zirconium alloy waste contained the following activation products:{93m}Nb and the long-lived {94}Nb, {93}Zr radionuclides. Radionuclides of {60}Co, {137}Cs, {90}Sr, and actinides were also present in the alloy. In the course of the runs no leaching of niobium and zirconium isotopes from the E110 alloy was detected. Leach rates were observed merely for {60}Co and {137}Cs present in the deposits formed on the internal surface of technological channels. The radionuclides present were effectively adsorbed by the barrier material. To ensure the localization of radionuclides in case of the radionuclide migration from the irradiated zirconium alloy into the barrier material, the sorption properties were determined of the barrier material used for creating the long-term storage point for the graphite stack from uranium-graphite reactors

Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to represent stimuli and task states, and that information capacity measured through whole brain models is a theory-driven measure of processing capacity that could be used as a biomarker of injury for outcome prediction or target for rehabilitation intervention

Inverse kinematics of redundant systems driver IKORv1.0-2.0 (full space parameterization with orientation control, platform mobility, and portability)

Few optimization methods exist for path planning of kinematically redundant manipulators. Among these, a universal method is lacking that takes advantage of a manipulator`s redundancy while satisfying possibly varying constraints and task requirements. Full Space Parameterization (FSP) is a new method that generates the entire solution space of underspecified systems of algebraic equations and then calculates the unique solution satisfying specific constraints and optimization criteria. The FSP method has been previously tested on several configurations of the redundant manipulator HERMIES-III. This report deals with the extension of the FSP driver, Inverse Kinematics On Redundant systems (IKOR), to include three-dimensional manipulation systems, possibly incorporating a mobile platform, with and without orientation control. The driver was also extended by integrating two optimized versions of the FSP solution generator as well as the ability to easily port to any manipulator. IKOR was first altered to include the ability to handle orientation control and to integrate an optimized solution generator. The resulting system was tested on a 4 degrees-of-redundancy manipulator arm and was found to successfully perform trajectories with least norm criteria while avoiding obstacles and joint limits. Next, the system was adapted and tested on a manipulator arm placed on a mobile platform yielding 7 degrees of redundancy. After successful testing on least norm trajectories while avoiding obstacles and joint limits, IKORv1.0 was developed. The system was successfully verified using comparisons with a current industry standard, the Moore Penrose Pseudo-Inverse. Finally, IKORv2.0 was created, which includes both the one shot and two step methods, manipulator portability, integration of a second optimized solution generator, and finally a more robust and usable code design

PAR1- and PAR2-induced innate immune markers are negatively regulated by PI3K/Akt signaling pathway in oral keratinocytes

<p>Abstract</p> <p>Background</p> <p>Protease-Activated Receptors (PARs), members of G-protein-coupled receptors, are activated by proteolytic activity of various proteases. Activation of PAR1 and PAR2 triggers innate immune responses in human oral keratinocytes (HOKs), but the signaling pathways downstream of PAR activation in HOKs have not been clearly defined. In this study, we aimed to determine if PAR1- and PAR2-mediated signaling differs in the induction of innate immune markers CXCL3, CXCL5 and CCL20 via ERK, p38 and PI3K/Akt.</p> <p>Results</p> <p>Our data show the induction of innate immunity by PAR1 requires both p38 and ERK MAP kinases, while PAR2 prominently signals via p38. However, inhibition of PI3K enhances expression of innate immune markers predominantly via suppressing p38 phosphorylation signaled by PAR activation.</p> <p>Conclusion</p> <p>Our data indicate that proteases mediating PAR1 and PAR2 activation differentially signal via MAP kinase cascades. In addition, the production of chemokines induced by PAR1 and PAR2 is suppressed by PI3K/Akt, thus keeping the innate immune responses of HOK in balance. The results of our study provide a novel insight into signaling pathways involved in PAR activation.</p