What mechanism of niche segregation allows the coexistence of sympatric sibling rhinolophid bats?

Introduction: Our purpose was to assess how pairs of sibling horseshoe bats coexists when their morphology and echolocation are almost identical. We collected data on echolocation, wing morphology, diet, and habitat use of sympatric Rhinolophus mehelyi and R. euryale. We compared our results with literature data collected in allopatry with similar protocols and at the same time of the year (breeding season). Results:Echolocation frequencies recorded in sympatry for R. mehelyi (mean = 106.8 kHz) and R. euryale (105.1 kHz) were similar to those reported in allopatry (R. mehelyi 105–111 kHz; R. euryale 101–109 kHz). Wing parameters were larger in R. mehelyi than R. euryale for both sympatric and allopatric conditions. Moths constitute the bulk of the diet of both species in sympatry and allopatry, with minor variation in the amounts of other prey. There were no inter-specific differences in the use of foraging habitats in allopatry in terms of structural complexity, however we found inter-specific differences between sympatric populations: R. mehelyi foraged in less complex habitats. The subtle inter-specific differences in echolocation frequency seems to be unlikely to facilitate dietary niche partitioning; overall divergences observed in diet may be explained as a consequence of differential prey availability among foraging habitats. Inter-specific differences in the use of foraging habitats in sympatry seems to be the main dimension for niche partitioning between R. mehelyi and R. euryale, probably due to letter differences in wing morphology. Conclusions: Coexistence between sympatric sibling horseshoe bats is likely allowed by a displacement in spatial niche dimension, presumably due to the wing morphology of each species, and shifts the niche domains that minimise competition. Effective measures for conservation of sibling/similar horseshoe bats should guarantee structural diversity of foraging habitats.

Mechanism of transport of saquinavir-loaded nanostructured lipid carriers across the intestinal barrier

[EN] The aims of this work were (i) to evaluate the potential of nanostructured lipid carriers (NLCs) as a tool to 24 enhance the oral bioavailability of poorly soluble compounds using saquinavir (SQV), a BCS class IV drug 25 and P-gp substrate as a model drug, and (ii) to study NLC transport mechanisms across the intestinal barrier. 26 Three different NLC formulations were evaluated. SQV transport across Caco-2 monolayers was enhanced up 27 to 3.5-fold by NLCs compared to SQV suspension. M cells did not enhance the transport of NLCs loaded with 28 SQV. The size and amount of surfactant in the NLCs influenced SQV's permeability, the transcytosis pathway 29 and the efflux of SQV by P-gp. An NLC of size 247 nm and 1.5% (w/v) surfactant content circumvented P-gp 30 efflux and used both caveolae- and clathrin-mediated transcytosis, in contrast to the other NLC formulations, 31 which used only caveolae-mediated transcytosis. By modifying critical physicochemical parameters of the 32 NLC formulation, we were thus able to overcome the P-gp drug efflux and alter the transcytosis mechanism 33 of the nanoparticles. These findings support the use of NLCs approaches for oral delivery of poorly 34 water-soluble P-gp substrates.

Calpain-Mediated Processing of Adenylate Cyclase Toxin Generates a Cytosolic Soluble Catalytically Active N-Terminal Domain

Bordetella pertussis, the whooping cough pathogen, secretes several virulence factors among which adenylate cyclase toxin (ACT) is essential for establishment of the disease in the respiratory tract. ACT weakens host defenses by suppressing important bactericidal activities of the phagocytic cells. Up to now, it was believed that cell intoxication by ACT was a consequence of the accumulation of abnormally high levels of cAMP, generated exclusively beneath the host plasma membrane by the toxin N-terminal catalytic adenylate cyclase (AC) domain, upon its direct translocation across the lipid bilayer. Here we show that host calpain, a calcium-dependent Cys-protease, is activated into the phagocytes by a toxin-triggered calcium rise, resulting in the proteolytic cleavage of the toxin N-terminal domain that releases a catalytically active "soluble AC''. The calpain-mediated ACT processing allows trafficking of the "soluble AC'' domain into subcellular organella. At least two strategic advantages arise from this singular toxin cleavage, enhancing the specificity of action, and simultaneously preventing an indiscriminate activation of cAMP effectors throughout the cell. The present study provides novel insights into the toxin mechanism of action, as the calpain-mediated toxin processing would confer ACT the capacity for a space- and time-coordinated production of different cAMP "pools'', which would play different roles in the cell pathophysiology.

Global Self-Organization of the Cellular Metabolic Structure

Background: Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using "metabolic networks models'' are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used "dissipative metabolic networks'' (DMNs) to show that enzymes can present a self-organized global functional structure, in which several sets of enzymes are always in an active state, whereas the rest of molecular catalytic sets exhibit dynamics of on-off changing states. We suggested that this kind of global metabolic dynamics might be a genuine and universal functional configuration of the cellular metabolic structure, common to all living cells. Later, a different group has shown experimentally that this kind of functional structure does, indeed, exist in several microorganisms. Methodology/Principal Findings: Here we have analyzed around 2.500.000 different DMNs in order to investigate the underlying mechanism of this dynamic global configuration. The numerical analyses that we have performed show that this global configuration is an emergent property inherent to the cellular metabolic dynamics. Concretely, we have found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state. Conclusions/Significance: This self-organized dynamic structure seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. To better understand cellular functionality, it will be crucial to structurally characterize these enzymatic self-organized global structures.

Formation Mechanism Of Lamellar Chips During Machining Of Bulk Metallic Glass

The uniqThe unique lamellar chips formed in turning–machining of a Vit 1 bulk metallic glass (BMG) are found to be due to repeated shearband formation in the primary shear zone (PSZ). A coupled thermomechanical orthogonal cutting model, taking into account force, free volume and energy balance in the PSZ, is developed to quantitatively characterize lamellar chip formation. Its onset criterion is revealed through a linear perturbation analysis. Lamellar chip formation is understood as a self-sustained limit-cycle phenomenon: there is autonomous feedback in stress, free volume and temperature in the PSZ. The underlying mechanism is the symmetry breaking of free volume flow and source, rather than thermal instability. These results are fundamentally useful for machining BMGs and even for understanding the physical nature of inhomogeneous flow in BMGs.ue lamellar chips formed in turning–machining of a Vit 1 bulk metallic glass (BMG) are found to be due to repeated shearband.

Catalytic Cracking and Heat Sink Capacity of Aviation Kerosene Under Supercritical Conditions

Catalytic cracking of China no. 3 aviation kerosene using a zeolite catalyst was investigated under supercritical conditions. A three-stage heating/cracking system was specially designed to be capable of heating 0.8 kg kerosene to a temperature of 1050 K and pressure of 7.0 MPa with maximum mass flow rate of 80 g/s. Sonic nozzles of different diameters were used to calibrate and monitor the mass flow rate of the cracked fuel mixture. With proper experiment arrangements, the mass flow rate per unit throat area of the cracked fuel mixture was found to well correlate with the extent of fuel conversion. The gaseous products obtained from fuel cracking under different conditions were also analyzed using gas chromatography. Composition analysis showed that the average molecular weight of the resulting gaseous products and the fuel mass conversion percentage were a strong function of the fuel temperature and were only slightly affected by the fuel pressure. The fuel conversion was also shown to depend on the fuel residence time in the reactor, as expected. Furthermore, the heat sink levels due to sensible heating and endothermic cracking were determined and compared at varying test conditions. It was found that at a fuel temperature of similar to 1050 K, the total heat sink reached similar to 3.4 MJ/kg, in which chemical heat sink accounted for similar to 1.5 MJ/kg.

Investigation on mechanism of critical cavitating flow in liquid jet pumps under operating limits

The critical cavitating flow in liquid jet pumps under operating limits is investigated in this paper. Measurements on the axial pressure distribution along the wall of jet pumps indicate that two-phase critical flow occurs in the throat pipe under operating limits. The entrained flow rate and the distribution of the wall pressure upstream lowest pressure section does not change when the outlet pressure is lower than a critical value. A liquid-vapor mixing shockwave is also observed under operating limits. The wave front moves back and forth in low frequency around the position of the lowest pressure. With the measured axial wall pressures, the Mach number of the two-phase cavitating flow is calculated. It's found that the maximum Mach number is very close to I under operating limits. Further analysis infers a cross-section where Mach number approaches to I near the wave front. Thus, the liquid-vapor mixture velocity should reach the local sound velocity and resulting in the occurrence of operating limits.

Development of catalytic methane reforming systems integrating hydrogen selective PdCu membrane modules

En la presente tesis doctoral se ha estudiado la integración del proceso de producción de hidrógeno con su purificación mediante el empleo de membranas selectivas de hidrógeno. La producción de hidrógeno se realiza empleando catalizadores no convencionales de níquel soportado sobre magnesia y alúmina en un reactor catalítico. Se analiza la actividad de los catalizadores y la producción de hidrógeno mediante distintos procesos con metano como son la oxidación parcial catalítica (OPC), OPC húmeda y reformadoLa purificación de hidrógeno se realiza en un módulo provisto de una membrana selectiva de hidrógeno de PdCu depositado en un soporte poroso cerámico. Una vez optimizada su preparación mediante deposición no electrolítica se caracterizan. Para ello se determina su permeabilidad a distintas temperaturas y realizando ciclos térmicos en atmósferas inerte y de hidrógeno, que puede fragilizar el metal. Una vez preparados los catalizadores y las membranas se integran los dos sistemas y se determinan los parámetros de operación óptimos como la presión de la línea de alimentación y el caudal de gas de arrastre en el módulo de membrana. Ambos parámetros se optimizan para lograr la máxima recuperación de hidrógeno en el módulo de membrana. Por últimos se realizan ensayos completos de producción y purificación, que permiten observar el rendimiento del sistema y también el efecto que los compuestos de la mezcla compleja alimentada a las membranas tienen en su comportamiento. Para concluir la integración de procesos se realizan ensayos añadiendo azufre de forma que el sistema sea más similar al proceso real. Esto permite también analizar el efecto del azufre tanto en los catalizadores como en las membranas.

The mechanism of PEO process on Al–Si alloys with the bulk primary silicon

This study focuses on mechanism of ceramic coating on Al-Si alloys with bulk primary Si using plasma electrolytic oxidation (PEO) technology. Al-Si alloys with 27-32% Si in weight were used as substrates. The morphologies, composition and microstructure of PEO coatings were investigated by scanning electron microscopy (SEM) with energy dispersive X-ray system (EDX). Results showed that the PEO process had four different stages. The effect of bulk Si is greatly on the morphology and composition of coatings at first three stages. Anodic oxide films formed on Al and Si phases, respectively. When the voltage exceeded 40 V, glow appeared and concentrated on the localized zone of interface of Al and Si phase. Al-Si-O compounds formed and covered on the dendrite Si phase surface, and the coating on bulk Si, which was silicon oxide, was rougher than that on other phase. If the treatment time was long enough, the coatings with uniform surface morphologies and elements distribution will be obtained but the microstructure of inner layer is looser due to the bulk Si.

Single cell proteomics microchip to profile immune function, with applications in stem cell biology, translational disease mechanism study and clinical therapeutics monitoring

In response to infection or tissue dysfunction, immune cells develop into highly heterogeneous repertoires with diverse functions. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. However, currently only 3-5 functional proteins can be measured from single cells. We developed a single cell functional proteomics approach that integrates a microchip platform with multiplex cell purification. This approach can quantitate 20 proteins from >5,000 phenotypically pure single cells simultaneously. With a 1-million fold miniaturization, the system can detect down to ~100 molecules and requires only ~104 cells. Single cell functional proteomic analysis finds broad applications in basic, translational and clinical studies. In the three studies conducted, it yielded critical insights for understanding clinical cancer immunotherapy, inflammatory bowel disease (IBD) mechanism and hematopoietic stem cell (HSC) biology.

To study phenotypically defined cell populations, single cell barcode microchips were coupled with upstream multiplex cell purification based on up to 11 parameters. Statistical algorithms were developed to process and model the high dimensional readouts. This analysis evaluates rare cells and is versatile for various cells and proteins. (1) We conducted an immune monitoring study of a phase 2 cancer cellular immunotherapy clinical trial that used T-cell receptor (TCR) transgenic T cells as major therapeutics to treat metastatic melanoma. We evaluated the functional proteome of 4 antigen-specific, phenotypically defined T cell populations from peripheral blood of 3 patients across 8 time points. (2) Natural killer (NK) cells can play a protective role in chronic inflammation and their surface receptor – killer immunoglobulin-like receptor (KIR) – has been identified as a risk factor of IBD. We compared the functional behavior of NK cells that had differential KIR expressions. These NK cells were retrieved from the blood of 12 patients with different genetic backgrounds. (3) HSCs are the progenitors of immune cells and are thought to have no immediate functional capacity against pathogen. However, recent studies identified expression of Toll-like receptors (TLRs) on HSCs. We studied the functional capacity of HSCs upon TLR activation. The comparison of HSCs from wild-type mice against those from genetics knock-out mouse models elucidates the responding signaling pathway.

In all three cases, we observed profound functional heterogeneity within phenotypically defined cells. Polyfunctional cells that conduct multiple functions also produce those proteins in large amounts. They dominate the immune response. In the cancer immunotherapy, the strong cytotoxic and antitumor functions from transgenic TCR T cells contributed to a ~30% tumor reduction immediately after the therapy. However, this infused immune response disappeared within 2-3 weeks. Later on, some patients gained a second antitumor response, consisted of the emergence of endogenous antitumor cytotoxic T cells and their production of multiple antitumor functions. These patients showed more effective long-term tumor control. In the IBD mechanism study, we noticed that, compared with others, NK cells expressing KIR2DL3 receptor secreted a large array of effector proteins, such as TNF-α, CCLs and CXCLs. The functions from these cells regulated disease-contributing cells and protected host tissues. Their existence correlated with IBD disease susceptibility. In the HSC study, the HSCs exhibited functional capacity by producing TNF-α, IL-6 and GM-CSF. TLR stimulation activated the NF-κB signaling in HSCs. Single cell functional proteome contains rich information that is independent from the genome and transcriptome. In all three cases, functional proteomic evaluation uncovered critical biological insights that would not be resolved otherwise. The integrated single cell functional proteomic analysis constructed a detail kinetic picture of the immune response that took place during the clinical cancer immunotherapy. It revealed concrete functional evidence that connected genetics to IBD disease susceptibility. Further, it provided predictors that correlated with clinical responses and pathogenic outcomes.

The formation mechanism of low leaching glassy slag during plasma arc vitrification treatment of fly ash

In this paper, the glass formation theory is applied to study the formation mechanism of the low leaching glassy slag during the process of plasma waste treatment. The research shows that SiO2 acts as network former to form a 3-dimensional Si-O tetrahedral network in which heavy metals are bonded or encapsulated, so the Si-O tetrahedron protect heavy metals against leaching from the vitrified slag or acid corrosion. For given chemical compositions of waste, the formation ability of the vitrified slag can be represented by the ratio of the whole oxygen ions to the whole network former ions in glass (O/Si) which is appropriate in the range of 2~3. A plasma arc reactor is used to conduct the vitrification experiments of two kinds of fly ashes with additives in which effects of various parameters including arc power, cooling speed, treatment temperature are studied. The chemical compositions of fly ashes are analyzed by X-ray fluorescence (XRF) spectrometry. The experimental results show that both cooling speed and O/Si have important influence on the formation of the vitrified slag, which is qualitatively in accordance with the predictions of the glass formation theory.

THE FORMATION MECHANISM OF THE VITRIFIED SLAG IN A PLASMA ARC REACTOR FOR HAZARDOUS WASTE TREATMENT

Various hazardous wastes with additives have been vitrified to investigate the formation mechanism of the glassy slag by a 30 kW DC plasma-arc reactor developed by the Institute of Mechanics, Chinese Academy of Sciences. The average temperature in the reaction area is controlled at 1500°C. The chemical compositions of three sorts of fly ashes are analyzed by XRF (X-Ray Fluorescence). Fly ashes with vitrifying additives can be vitrified to form glassy slag, which show that the ratio of the whole oxygen ions to the whole network former ions in glass (R) is appropriate in the range of 2~3 to form durable vitrified slag. In this experiment, the arc power is controlled below 5 kW to inhibit waste evaporation. To enhance the effects of heat transfer to wastes, ferrous powder has been added into the graphite crucible, which aggregates as ingot below the molten silicate after vitrification. The slag fails to form glass if the quenching rate is less than 1 K/min. Therefore, the slag will break into small chips due to the sharp quenching rate, which is more than 100 K/sec.