PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation

P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1β, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1–p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells

Development of Ground-testable Phase Fresnel Lenses in Silicon

Diffractive/refractive optics, such as Phase Fresnel Lenses (PFL's), offer the potential to achieve excellent imaging performance in the x-ray and gamma-ray photon regimes. In principle, the angular resolution obtained with these devices can be diffraction limited. Furthermore, improvements in signal sensitivity can be achieved as virtually the entire flux incident on a lens can be concentrated onto a small detector area. In order to verify experimentally the imaging performance, we have fabricated PFL's in silicon using gray-scale lithography to produce the required Fresnel profile. These devices are to be evaluated in the recently constructed 600-meter x-ray interferometry testbed at NASA/GSFC. Profile measurements of the Fresnel structures in fabricated PFL's have been performed and have been used to obtain initial characterization of the expected PFL imaging efficiencies.Comment: Presented at GammaWave05: "Focusing Telescopes in Nuclear Astrophysics", Bonifacio, Corsica, September 2005, to be published in Experimental Astronomy, 8 pages, 3 figure

THREE DIMENSIONAL MEASUREMENT OF THE GEOMETRY OF THE HUMAN MOTION APPARATUS

INTRODUCTION: This work is part of a project of the Department for Sports Medicine to calculate the internal stresses arising when jumping from a squat position. The goal of the project is to facilitate individual calculations by establishing a biomechanical model whose parameters are the major anatomical-geometrical and physiological quantities, gained by electromyogram (EMG) and radiological measurement. Procedures for acquiring the latter data are described here. METHODS: As the study did not involve pathologies, ionizing radiation was ruled out, and magnetic resonance imaging (MRI) was used. The biomechanical model required geometrical parameters from joint positions beyond those occurring during the squat-vault, so the Siemens Magnetom Open device was chosen. It has the disadvantage of relatively low magnetic field strength (0.2 T), but allows for almost unlimited movement in the table plane. Different measurement parameters were evaluated. As the length of the field of view was about 25 cm, the different joints had to be scanned separately. A positioning table was used to serve three purposes: 1. Positioning with defined joint angles, so the morphology could be related to the EMG measurements. 2. Exertion of force, to measure the geometry of muscles and tendons under strain. 3. Placement of markers with high MRI contrast, to relate the relative position of the scans of the different joints. [delete line space]. The evaluation of the images was done using the ‘Tübinger Medstation’ software developed by the Department of Computer Science at the University of Tübingen. RESULTS: Although the use of T2 weighted sequences resulted in better soft tissue contrast, the T1 weighted spin echo sequence was preferred because of shorter acquisition time, which was an important factor because measurements had to be made under strain. Bones and tendons, with their low hydrogen content, produce weak signals in MRI and thus contrast with the adjacent soft tissue. Even shorter acquisition times by use of a gradient sequence were ruled out because of their low signal/noise ratio, which rendered the fascies undetectable. Automatic segmentation of these fascies is extremely hard to achieve. The ‘Medstation’ software was used to extract coordinates of muscle and tendon insertions by hand and combine them in a common frame of reference. CONCLUSIONS: A procedure has been established to extract the geometrical data of muscles, tendons and osseous structures important for the biomechanical model. For this model, extended muscle and tendon insertions have to be reduced to a point by calculation of the center of mass of the insertion area. A table for the positioning of the probationer enabled positioning with reproducible joint angles under exertion of strain. To define the relative position of different scans a screen of markers was integrated into this plate

First observations of sea ice flexural–gravity waves with ground-based radar interferometry in Utqiaġvik, Alaska

We investigate the application of ground-based radar interferometry for measuring flexural–gravity waves in sea ice. We deployed a GAMMA Portable Radar Interferometer (GPRI) on top of a grounded iceberg surrounded by landfast sea ice near Utqiaġvik, Alaska. The GPRI collected 238 acquisitions in stare mode during a period of moderate lateral ice motion during 23–24 April 2021. Individual 30 s interferograms exhibit ∼ 20–50 s periodic motion indicative of propagating infragravity waves with ∼ 1 mm amplitudes. Results include examples of onshore wave propagation at the speed predicted by the water depth and a possible edge wave along an ice discontinuity. Findings are supported through comparison with on-ice Ice Wave Rider (IWR) accelerometers and modeled wave propagation. These results suggest that the GPRI can be a valuable tool to track wave propagation through sea ice and possibly detect changes in such properties across variable ice conditions.</p

Model based optimization of transflection near infrared spectroscopy as a process analytical tool in a continuous flash pasteurizer

Near infrared spectroscopy in combination with a transflection probe was investigated as inline measurement in a continuous flash pasteurizer system with a sugar–water model solution. Robustness and reproducibility of fluctuations of recorded spectra as well as trueness of the chemometric analysis were compared under different process parameter settings. Variable parameters were the flow rate (from laminar flow at 30 L/h to turbulent flow at 90 L/h), temperature (20 to 100 °C) and the path length of the transflection probe (2 and 4 mm) while the pressure was kept constant at 2.5 bar. Temperature and path length were identified as the most affecting parameters, in case of homogenous test medium. In case of particle containing systems, the flow rate could have an impact as well. However, the application of a PLS model, which includes a broad temperature range, and the correction of prediction results by applying a polynomial regression function for prediction errors, was able to compensate these effects. Also, a path length of 2 mm leads to a higher accuracy. The applied strategy shows that by the identification of relevant process parameters and settings as well as the establishment of a compensation strategy, near infrared spectroscopy is a powerful process analytical tool for continuous flash pasteurization systems.BMBF, 13FH024IX6, IngenieurNachwuchs 2016: Cyber-Physisches System (CPS) zur thermischen Entkeimung von Getränken unter Nutzung der NIR-Sensorik als Schlüsseltechnologi

Dynamical Scaling from Multi-Scale Measurements

We present a new measure of the Dynamical Critical behavior: the "Multi-scale Dynamical Exponent (MDE)"Comment: 9 pages,Latex, Request figures from [email protected]

Cerebral palsy and placental infection: a case-cohort study

BACKGROUND: The association between cerebral palsy in very preterm infants and clinical, histopathologic and microbiological indicators of chorioamnionitis, including the identification of specific micro-organisms in the placenta, was evaluated in a case-cohort study. METHODS: Children with a diagnosis of cerebral palsy at five years of age were identified from amongst participants in a long-term follow-up program of preterm infants. The comparison group was a subcohort of infants randomly selected from all infants enrolled in the program. The placentas were examined histopathologically for chorioamnionitis and funisitis, and the chorioamnionic interface was aseptically swabbed and comprehensively cultured for aerobic and anaerobic bacteria, yeast and genital mycoplasmas. Associations between obstetric and demographic variables, indicators of chorioamnionitis and cerebral palsy status were examined by univariate analysis. RESULTS: Eighty-two infants with cerebral palsy were compared with the subcohort of 207 infants. Threatened preterm labor was nearly twice as common among the cases as in the subcohort (p < 0.01). Recorded clinical choroamnionitis was similar in the two groups and there was no difference in histopathologic evidence of infection between the two groups. E. coli was cultured from the placenta in 6/30 (20%) of cases as compared with 4/85 (5%) of subcohort (p = 0.01). Group B Streptococcus was more frequent among the cases, but the difference was not statistically significant. CONCLUSIONS: The association between E. coli in the chorioamnion and cerebral palsy in preterm infants identified in this study requires confirmation in larger multicenter studies which include microbiological study of placentas

Nonequilibrium relaxation of the two-dimensional Ising model: Series-expansion and Monte Carlo studies

We study the critical relaxation of the two-dimensional Ising model from a fully ordered configuration by series expansion in time t and by Monte Carlo simulation. Both the magnetization (m) and energy series are obtained up to 12-th order. An accurate estimate from series analysis for the dynamical critical exponent z is difficult but compatible with 2.2. We also use Monte Carlo simulation to determine an effective exponent, z_eff(t) = - {1/8} d ln t /d ln m, directly from a ratio of three-spin correlation to m. Extrapolation to t = infinity leads to an estimate z = 2.169 +/- 0.003.Comment: 9 pages including 2 figure

The Dynamic Exponent of the Two-Dimensional Ising Model and Monte Carlo Computation of the Sub-Dominant Eigenvalue of the Stochastic Matrix

We introduce a novel variance-reducing Monte Carlo algorithm for accurate determination of autocorrelation times. We apply this method to two-dimensional Ising systems with sizes up to $15 \times 15$, using single-spin flip dynamics, random site selection and transition probabilities according to the heat-bath method. From a finite-size scaling analysis of these autocorrelation times, the dynamical critical exponent $z$ is determined as $z=2.1665$ (12)

Heuristic derivation of continuum kinetic equations from microscopic dynamics

We present an approximate and heuristic scheme for the derivation of continuum kinetic equations from microscopic dynamics for stochastic, interacting systems. The method consists of a mean-field type, decoupled approximation of the master equation followed by the `naive' continuum limit. The Ising model and driven diffusive systems are used as illustrations. The equations derived are in agreement with other approaches, and consequences of the microscopic dependences of coarse-grained parameters compare favorably with exact or high-temperature expansions. The method is valuable when more systematic and rigorous approaches fail, and when microscopic inputs in the continuum theory are desirable.Comment: 7 pages, RevTeX, two-column, 4 PS figures include