New strategies for treatment of infectious sepsis

In this mini review, we describe the molecular mechanisms in polymicrobial sepsis that lead to a series of adverse events including activation of inflammatory and prothrombotic pathways, a faulty innate immune system, and multiorgan dysfunction. Complement activation is a well‐established feature of sepsis, especially involving generation of C5a and C5b‐9, along with engagement of relevant receptors for C5a. Activation of neutrophils by C5a leads to extrusion of DNA, forming neutrophil extracellular traps that contain myeloperoxidase and oxidases, along with extracellular histones. Generation of the distal complement activation product, C5b‐9 (known as the membrane attack complex, MAC), also occurs in sepsis. C5b‐9 activates the NLRP3 inflammasome, which damages mitochondria, together with appearance in plasma of IL‐1β and IL‐18. Histones are strongly proinflammatory as well as being prothrombotic, leading to activation of platelets and development of venous thrombosis. Multiorgan dysfunction is also a feature of sepsis. It is well known that septic cardiomyopathy, which if severe, can lead to death. This complication in sepsis is linked to reduced levels in cardiomyocytes of three critical proteins (SERCA2, NCX, Na+/K+‐ATPase). The reductions in these three key proteins are complement‐ and histone‐dependent. Dysfunction of these ATPases is linked to the cardiomyopathy of sepsis. These data suggest novel targets in the setting of sepsis in humans.Review on infectious sepsis and new therapeutic targets that include complement activation products and receptors and histones.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149767/1/jlb10342_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149767/2/jlb10342.pd

The potential of small mountain river systems for paleoenvironmental reconstructions in drylands - an example from the Binaloud Mountains in Northeastern Iran

Fluvial sediments are valuable paleoenvironmental archives of the Quaternary. Since besides environmental factors they are also affected by local tectonics or intrinsic processes, large instead of small catchments should be studied. In drylands covering ca. 45% of the global terrestrial surface large river systems are generally missing, and most river systems are small rivers originating from mountain ranges. Their sediments are potentially interesting paleoenvironmental archives, but are often affected by intensive tectonics. During this study, to obtain a robust regional paleoenvironmental signal a small river system in the southwestern Binaloud Mountains in semi-arid NE Iran was exemplarily studied with a combined approach that encompassed both alluvial fan and catchment. By using geomorphological mapping and numerical dating, fluvial aggradation followed by incision was independently identified in larger areas or in different parts of the river system ca. 95–88 ka, 40 ka, 20 ka, around/after the Pleistocene/Holocene transition and possibly ca. 2.6 ka. These could be linked with regional and over-regional paleoenvironmental data. Furthermore, large boulders on the alluvial fan suggest anthropogenic destabilisation of the catchment during the last decades. Despite strong local tectonics the fluvial dynamics was mostly controlled by paleoenvironmental changes and human activity. This indicates that despite their small size, such river systems form valuable paleoenvironmental archives in drylands where other archive types are largely missing

Nonlinear Vibrational Analysis of Nanobeams Embedded in an Elastic Medium including Surface Stress Effects

Due to size-dependent behavior of nanostructures, the classical continuum models are not applicable for the analyses at this submicron size. Surface stress effect is one of the most important matters which make the nanoscale structures have different properties compared to the conventional structures due to high surface to volume ratio. In the present study, nonlinear free vibrational characteristics of embedded nanobeams are investigated including surface stress effects. To this end, a thin surface layer is assumed on the upper and lower surfaces of the cross section to separate the surface and bulk of nanobeams with their own different material properties. Based on harmonic balance method, closed-form analytical solution is conducted for nonlinear vibrations to obtain natural frequencies of embedded nanobeams with and without considerations of surface elasticity and residual surface tension effects corresponding to the various values of nondimensional amplitude, elastic foundation modulus, and geometrical variables of the system. Selected numerical results are given to indicate the influence of each one in detail

IMPACT OF WATER RADIOLYSIS ON URANIUM DIOXIDE CORROSION

International audienc

On the response of a lean-premixed hydrogen combustor to acoustic and dissipative-dispersive entropy waves

Combustion of hydrogen or hydrogen containing blends in gas turbines and industrial combustors can activate thermoacoustic combustion instabilities. Convective instabilities are an important and yet less investigated class of combustion instability that are caused by the so called “entropy waves”. As a major shortcoming, the partial decay of these convective-diffusive waves in the post-flame region of combustors is still largely unexplored. This paper, therefore, presents an investigation of the annihilating effects, due to hydrodynamics, heat transfer and flow stretch upon the nozzle response. The classical compact analysis is first extended to include the decay of entropy waves and heat transfer from the nozzle. Amplitudes and phase shifts of the responding acoustical waves are then calculated for subcritical and supercritical nozzles subject to acoustic and entropic forcing. A relation for the stretch of entropy wave in the nozzle is subsequently developed. It is shown that heat transfer and hydrodynamic decay can impart considerable effects on the entropic response of the nozzle. It is further shown that the flow stretching effects are strongly frequency dependent. The results indicate that dissipation and dispersion of entropy waves can significantly influence their conversion to sound and therefore should be included in the entropy wave models