Calibration of Temperature in the Lower Stratosphere from Microwave Measurements Using COSMIC Radio Occultation Data: Preliminary Results

Accurate, consistent, and stable observations from different satellite missions are crucial for climate change detection. In this study, we use Global Positioning System (GPS) Radio Occultation (RO) data from the early phase of the FORMOSAT-3/Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) mission, which was successfully launched on 15 April 2006, to inter-calibrate Temperature in the Lower Stratosphere (TLS) taken from Advanced Microwave Sounding Unit (AMSU) microwave measurements from different satellites for potential improvements of stratospheric temperature trend analysis. Because of the limited number of COSMIC soundings in the early phase of the mission, these results are considered preliminary. In this study, we use COSMIC RO data to simulate microwave brightness temperatures for comparison with AMSU Ch9 measurements (e.g., TLS) on board NOAA15, 16, and 18. Excellent correlation was found between synthetic COSMIC brightness temperatures (Tbs) and Tbs from NOAA15, NOAA16, and NOAA18, respectively. However, systematic differences on the order of 0.7 to 2 K were found between COSMIC and AMSU observations over Antarctica. Our results demonstrate that synthetic COSMIC Tbs are very useful in identifying inter-satellite offsets among AMSU measurements from different satellites. To demonstrate the long-term stability of GPS RO data, we compare COSMIC dry temperature profiles to those from collocated CHAMP profiles, where CHAMP was launched in 2001. The fact that the CHAMPand COSMIC dry temperature difference between 500 and 10 hPa ranges from -0.35 K (at 10 hPa) to 0.25 K (at 30 hPa) and their mean difference is about -0.034 K demonstrates the long-term stability of GPS RO signals. In order to demonstrate the potential usage of the GPS RO calibrated AMSU Tbs to inter-calibrate other overlapping AMSU Tbs, we examine the uncertainty of the calibration coefficients derived from AMSU-GPS RO pairs. We found the difference between COSMIC calibrated AMSU Tbs and those from CHAMP to be in the range of __0.07 K with a 0.1 K standard deviation. This demonstrates the robustness of the calibration coefficients found from AMSU-GPS RO pairs and shows the potential to use the calibrated AMSU Tbs to calibrate other overlapping AMSU Tbs where no coincident GPS RO data are available

Glioblastoma cellular cross-talk converges on NF-κB to attenuate EGFR inhibitor sensitivity

Funding Information: We thank Dr. David James, Dr. Frederick Lang, Dr. Cameron Brennan, and Dr. Harley Kornblum for GBM-PDX neurospheres. We thank Dr. Karen Arden for continuous support and critical evaluation of the results. We thank Dr. Robert Davis, Dr. German Gomez, Dr. Tiffany Taylor, Dr. Rachel Reed, Dr. Melissa Mcalonis, and Dr. Sora Lee for technical support. In memory of Rosa Lupo. This work was supported by the Defeat GBM Research Collaborative, a subsidiary of the National Brain Tumor Society (F.B.F. and P.S.M.), R01-NS080939 (F.B.F.), the James S. McDonnell Foundation (F.B.F.), the National Cancer Institute (2T32CA009523-29A1) (A.H.T), and 1RO1NS097649-01 (C.C.C.). C.Z. was partially supported by an American-Italian Cancer Foundation post-doctoral research fellowship. F.L. received a Gao Feng Gao Yuan Scholarship Award. T.C.G., A.K.S., P.S.M., W.K.C., and F.B.F. receive salary and additional support from the Ludwig Institute for Cancer Research. Publisher Copyright: © 2017 Zanca et al.In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs). NF-κB and survivin are coordinately up-regulated in GBM patient tumors, and functional inhibition of either protein or BRD4 in in vitro and in vivo models restores sensitivity to EGFR TKIs. These results provide a rationale for improving anti-EGFR therapeutic efficacy through pharmacological uncoupling of a convergence point of NF-κB-mediated survival that is leveraged by an interclonal circuitry mechanism established by intratumoral mutational heterogeneity.publishersversionPeer reviewe

Stochastic Delay Accelerates Signaling in Gene Networks

The creation of protein from DNA is a dynamic process consisting of numerous reactions, such as transcription, translation and protein folding. Each of these reactions is further comprised of hundreds or thousands of sub-steps that must be completed before a protein is fully mature. Consequently, the time it takes to create a single protein depends on the number of steps in the reaction chain and the nature of each step. One way to account for these reactions in models of gene regulatory networks is to incorporate dynamical delay. However, the stochastic nature of the reactions necessary to produce protein leads to a waiting time that is randomly distributed. Here, we use queueing theory to examine the effects of such distributed delay on the propagation of information through transcriptionally regulated genetic networks. In an analytically tractable model we find that increasing the randomness in protein production delay can increase signaling speed in transcriptional networks. The effect is confirmed in stochastic simulations, and we demonstrate its impact in several common transcriptional motifs. In particular, we show that in feedforward loops signaling time and magnitude are significantly affected by distributed delay. In addition, delay has previously been shown to cause stable oscillations in circuits with negative feedback. We show that the period and the amplitude of the oscillations monotonically decrease as the variability of the delay time increases

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Wave Induced Pressures on Submerged Plates

The prediction of forces, or more precisely, the pressure distributions, experienced by submerged structures due to the passage of gravity waves has become important with the advent of large offshore structures. If the size of a structure is small compared to the wavelength then the forces can be evaluated by the assignment of suitable drag and inertia coefficients using an approach similar to that of Morison (6) in which case it is necessary to determine the coefficients experimentally for any given geometry (2). If the size of the structure is a significant fraction of the wavelength, the preceding method is invalid and a more complicated analysis such as the diffraction theory of Garrison and Rao (1) is needed. Unfortunately, the application of diffraction theory for a given geometry is exceedingly difficult unless one assumes that the structure size is small compared to the wavelength, which may not be realistic. In order to circumvent the evaluation problems of diffraction theory an approximate analysis based on thin airfoil theory was developed. The analysis to be presented is developed for a thin horizontal flat plate, although extension to other objects is not difficult. One applicable physical situation is that of a protective cap over a vertical water intake. Typically such a cap might be 50 ft (15 m) wide submerged approximately mid-depth in water 25 ft (8 m) deep. Also typically, wavelengths of the order of 200 ft (61 m) would be experienced making the plate width of the order of one-fourth the wavelength. The question of wave induced loadings on such structures associated with nuclear power stations prompted the investigation presented herein

An Anti-inflammatory NOD-like Receptor Is Required for Microglia Development

Microglia are phagocytic cells that form the basis of the brain’s immune system. They derive from primitive macrophages that migrate into the brain during embryogenesis, but the genetic control of microglial development remains elusive. Starting with a genetic screen in zebrafish, we show that the noncanonical NOD-like receptor (NLR) nlrc3-like is essential for microglial formation. Although most NLRs trigger inflammatory signaling, nlrc3-like acts cell autonomously in microglia precursor cells to suppress unwarranted inflammation in the absence of overt immune challenge. In nlrc3-like mutants, primitive macrophages initiate a systemic inflammatory response with increased proinflammatory cytokines and actively aggregate instead of migrating into the brain to form microglia. NLRC3-like requires both its pyrin and NACHT domains, and it can bind the inflammasome component apoptosis-associated speck-like protein. Our studies suggest that NLRC3-like may regulate the inflammasome and other inflammatory pathways. Together, these results demonstrate that NLRC3-like prevents inappropriate macrophage activation, thereby allowing normal microglial development

Codes for PDAC-SMI and co-culture data

<p>This record contains two parts:</p> <p>1) The source codes of SCOTIA, a Python package for inferring ligand–receptor interactions from spatial imaging data. Please check the README file for how to install and use it. A quick start tutorial was included in this package.</p> <p>2) The codes for analyzing the PDAC-SMI and co-culture datasets, including the glandular subtype and neighborhood analysis, ligand–receptor interaction analysis, and topological data and classification analysis.</p&gt

Codes for PDAC-SMI and co-culture data

<p>This record contains two parts:</p> <p>1) The source codes of SCOTIA, a Python package for inferring ligand–receptor interactions from spatial imaging data. Please check the README file for how to install and use it. A quick start tutorial was included in this package.</p> <p>2) The codes for analyzing the PDAC-SMI and co-culture datasets, including the glandular subtype and neighborhood analysis, ligand–receptor interaction analysis, and topological data and classification analysis.</p&gt

Differential requirement for irf8 in formation of embryonic and adult macrophages in zebrafish.

Interferon regulatory factor 8 (Irf8) is critical for mammalian macrophage development and innate immunity, but its role in teleost myelopoiesis remains incompletely understood. In particular, genetic tools to analyze the role of Irf8 in zebrafish macrophage development at larval and adult stages are lacking. We generated irf8 null mutants in zebrafish using TALEN-mediated targeting. Our analysis defines different requirements for irf8 at different stages. irf8 is required for formation of all macrophages during primitive and transient definitive hematopoiesis, but not during adult-phase definitive hematopoiesis starting at 5-6 days postfertilization. At early stages, irf8 mutants have excess neutrophils and excess cell death in pu.1-expressing myeloid cells. Macrophage fates were recovered in irf8 mutants after wildtype irf8 expression in neutrophil and macrophage lineages, suggesting that irf8 regulates macrophage specification and survival. In juvenile irf8 mutant fish, mature macrophages are present, but at numbers significantly reduced compared to wildtype, indicating an ongoing requirement for irf8 after embryogenesis. As development progresses, tissue macrophages become apparent in zebrafish irf8 mutants, with the possible exception of microglia. Our study defines distinct requirement for irf8 in myelopoiesis before and after transition to the adult hematopoietic system