A paradox of non-monotonicity in stability of pipes conveying fluid

The paradoxical result of the non-monotonous relationship between the critical speed of the fluid that is conveyed in the elastic pipe, and the mass ratio was reported first some four decades ago. Since then this result was reproduced in numerous books and articles. In this study the paradox is revisited. It appears that it is a numerical artifact; instead of non-monotonicity there are jumps

A particle model of rolling grain ripples under waves

A simple model is presented for the formation of rolling grain ripples on a flat sand bed by the oscillatory flow generated by a surface wave. An equation of motion is derived for the individual ripples, seen as "particles", on the otherwise flat bed. The model account for the initial apperance of the ripples, the subsequent coarsening of the ripples and the final equilibrium state. The model is related to physical parameters of the problem, and an analytical approximation for the equilibrium spacing of the ripples is developed. It is found that the spacing between the ripples scale with the square-root of the non-dimensional shear stress (the Shields parameter) on a flat bed. The results of the model are compared with measurements, and reasonable agreement between the model and the measurements is demonstrated.Comment: 9 pages incl. figures. Revised versio

Slip distributions on active normal faults measured from LiDAR and field mapping of geomorphic offsets: an example from L\u2019Aquila, Italy, and implications for modelling seismic moment release

Surface slip distributions for an active normal fault in central Italy have been measured using terrestrial laser scanning (TLS), in order to assess the impact of changes in fault orientation and kinematics when modelling subsurface slip distributions that control seismic moment release. The southeastern segment of the surface trace of the Campo Felice active normal fault near the city of L\u2019Aquila was mapped and surveyed using techniques from structural geology and using TLS to define the vertical and horizontal offsets of geomorphic slopes since the last glacial maximum (15 \ub13 ka). The fault geometry and kinematics measured from 43 sites and throw/heave measurements from geomorphic offsets seen on 250 scarp profiles were analysed using a modification of the Kostrov equations to calculate the magnitudes and directions of horizontal principal strain-rates. The map trace of the studied fault is linear, except where a prominent bend has formed to link across a former left-stepping relay-zone. The dip of the fault and slip direction is constant across the bend. Throw-rates since 15 \ub13 ka decrease linearly from the fault centre to the tip, except in the location of the prominent bend where higher throw rates are recorded. Vertical coseismic offsets for two palaeoearthquake ruptures seen as fresh strips of rock at the base of the bedrock scarp also increase within the prominent bend. The principal strain-rate, calculated by combining strike, dip, slip-direction and post 15 \ub13 ka throw, decreases linearly from the fault centre towards the tip; the strain-rate does not increase across the prominent fault bend. The above shows that changes in fault strike, whilst having no effect on the principal horizontal strain-rate, can produce local maxima in throw-rates during single earthquakes that persist over the timescale of multiple earthquakes (15 \ub13 ka). Detailed geomorphological and structural investigation of active faults is therefore a critical input in order to properly define fault activity for the purpose of accurate seismic hazard assessment. We discuss the implications of modelling subsurface slip distributions for earthquake ruptures through inversion of GPS, InSAR and strong motion data using planar fault approximations, referring to recent examples on the nearby Paganica fault that ruptured in the Mw 6.3 2009 L\u2019Aquila Earthquak

Sterol metabolism modulates susceptibility to HIV-1 Infection

Background: 25-hydroxylase (CH25H) is an Interferon stimulated gene (ISG), which catalyzes the synthesis of 25-Hydroxycholesterol (25HC). 25HC intervenes in metabolic and infectious processes as controls cholesterol homeostasis and influences viral entry into host cells.We verified whether natural resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) individuals is at least partially mediated by particularities in sterol biosynthesis. Methods: Peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) isolated from 15 sexually-exposed HESN and 15 healthy controls (HC) were in vitro HIV-1-infected and analyzed for: 1) percentage of IFN\u3b1-producing plasmacytoid Dendritic Cells (pDCs); 2) Cholesterol signaling and inflammatory response RNA expression; 3) resistance to HIV-1 infection. MDMs from 5 HC were in vitro HIV-1-infected in the absence/presence of exogenously added 25HC. Results: IFN\u3b1-producing pDCs were augmented in HESN compared to HCs both in unstimulated and in in vitro HIV-1-infected PBMCs (p<0.001). An increased expression of CH25H and of a number of genes involved in cholesterol metabolism (ABCA1, ABCG1, CYP7B1, LXR\u3b1, OSBP, PPAR\u3b3, SCARB1) was observed as well; this, was associated with a reduced susceptibility to in vitro HIV-1-infection of PBMCs and MDMs (p<0.01). Notably, addition of 25HC to MDMs resulted in increased cholesterol efflux and augmented resistance to in vitro HIV-1-infection. Conclusions: Results herein show that in HESN sterol metabolism might be particularly efficient. This could be related to the activation of the IFN\u3b1 pathway and results into a reduced susceptibility to in vitro HIV-1 infection. These results suggest a possible basis for therapeutic interventions to modulate HIV-1 infection

Endoplasmic Reticulum Associated Aminopeptidase 2 (ERAP2) is released in the secretome of activated MDMs and reduces in vitro HIV-1 infection

Background: Haplotype-specific alternative splicing of the endoplasmic reticulum (ER) aminopeptidase type 2 (ERAP2) gene results in either full-length (FL, haplotype A) or alternatively spliced (AS, haplotype B) mRNA. HapA/HapA homozygous (HomoA) subjects show a reduced susceptibility to HIV-1 infection, probably secondary to the modulation of the antigen processing/presenting machinery. ERAP1 was recently shown to be secreted from the plasma membrane in response to activation; we investigated whether ERAP2 can be released as well and if the secreted form of this enzyme retains its antiviral function. Methods: Human monocyte derived macrophages (MDMs) were differentiated from peripheral blood mononuclear cells (PBMCs) isolated from 6 HomoA healthy controls and stimulated with IFN\u3b3 and LPS. ERAP2-FL secretion was evaluated by mass spectrometry. PBMCs (14 HomoA and 16 HomoB) and CD8-depleted PBMCs (CD8-PBMCs) (4 HomoA and 4 HomoB) were in vitro HIV-infected in the absence/presence of recombinant human ERAP2-FL (rhERAP2) protein; p24 viral antigen quantification was used to assess viral replication. IFN\u3b3 and CD69 mRNA expression, as well as the percentage of perforin-producing CD8+ T Lymphocytes, were analyzed 3 and 7-days post in vitro HIV-1-infection, respectively. The effect of rhERAP2 addition in cell cultures on T cell apoptosis, proliferation, activation, and maturation was evaluated as well on 24 h-stimulated PBMCs. Results: ERAP2 can be secreted from human MDMs in response to IFN\u3b3/LPS stimulation. Notably, the addition of rhERAP2 to PBMC and CD8-PBMC cultures resulted in the reduction of viral replication, though these differences were statistically significant only in PBMCs (p < 0.05 in both HomoA and HomoB). This protective effect was associated with an increase in IFN\u3b3 and CD69 mRNA expression and in the percentage of perforin-expressing CD107+CD8+ cells. RhERAP2 addition also resulted in an increase in CD8+ activated lymphocyte (CD25+HLA-DRII+) and Effector Memory/Terminally differentiated CD8+ T cells ratio. Conclusions: This is the first report providing evidence for the release of ERAP2 in the secretome of immunocompetent cells. Data herein also indicate that exogenous ERAP2-FL exerts its protective function against HIV-1 infection, even in HomoB subjects who do not genetically produce it. Presumably, this defensive extracellular feature is only partially dependent on immune system modulation

Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy.

Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers. We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment