144 research outputs found
Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype.
Tumor-associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9 <sup>Hi</sup> TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM-specific therapeutics to exploit this new biological understanding. Here, the discovery and characterization of multiple small-molecule enhancers of chemokine ligand 9 (CXCL9) and their targeted delivery in a TAM-avid systemic nanoformulation is reported. With this strategy, it is efficient encapsulation and release of multiple drug loads that can efficiently induce CXCL9 expression in macrophages, both in vitro and in vivo in a mouse tumor model. These observations provide a window into the molecular features that define TAM-specific states, an insight a novel therapeutic anticancer approach is used to discover
Large Eddy simulation of a reacting kerosene spray in hot vitiated cross-flow
The evaporation and combustion characteristics of a kerosene spray injected perpendicularly into a cross-flow of high-temperature vitiated air is investigated. This fundamental flow configuration has wider implications for the future development of ultra-low emission aeronautical combustors, particularly with respect to technologies involving MILD combustion. Large eddy simulations with a Eulerian–Lagrangian framework are performed to investigate the spray evolution and the characteristics of the reaction zone for a range of conditions. For the closure of turbulence-chemistry interactions at the sub-grid scales, a transported probability density function approach solved by the Eulerian stochastic fields method is applied. A configuration based on the use of airblast atomisation is assessed first and compared with experimental observations. The effect of the atomiser air-to-liquid mass flow ratio is studied in greater detail, both in terms of the resulting gas-phase properties and the droplet evaporation process. Then, the effect of ambient pressure on the global spray flame behaviour is examined. For this part of the study, no atomising air is included in the simulation to separate the effects of ambient pressure on the spray from the interaction with the air jet. Analysis of the flame and spray properties at cross-flow operating pressures of 1 atm, 2 bar and 4 bar highlights the strong coupling between the reacting flow and droplet evaporation characteristics, which are highly affected by the penetration of the spray into a flow field characterised by relatively large gradients of temperature. The results reported in this work provide fundamental understanding for the development of novel low-emission combustion technologies and demonstrate the feasibility of applying large eddy simulation with detailed chemistry for the investigation of reacting aviation fuel sprays in hot vitiated cross-flow
Assessment of risk of introduction of Echinococcus multilocularis to mainland Norway
Source at https://vkm.no/In the light of the recent findings of the tapeworm Echinococcus multilocularis (EM) in four red foxes from three different locations in Sweden, the Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen; VKM), Panel of Biological Hazards (Faggruppe hygiene og smittestoffer) took the initiative to undertake a risk assessment regarding the probability of this parasite being introduced to mainland Norway and thus becoming a threat to public health in the country.Med bakgrunn i funnet av bendelorm Echinococcus multilocularis (EM) i fire rødrev fra tre forskjellige steder i Sverige, har VKM ved Faggruppe hygiene og smittestoffer tatt initiativ til å foreta en vurdering av sannsynligheten for at EM kan bli introdusert til fastlands Norge og sannsynligheten for at mennesker i så fall også kan bli smittet
Air-blast atomization and ignition of a kerosene spray in hot vitiated crossflow
Increasingly stringent regulations of pollutant emissions from aviation require rapid implementation of novel combustion technologies. Promising concepts based on moderate or intense low-oxygen dilution (MILD) combustion have been investigated in academia and industry. This MILD regime can be obtained from the recirculation of the hot vitiated combustion products to raise the temperature of the reactants, resulting in distributed reaction regions and lower flame temperatures. In the present work, we consider the air-blast atomization of a kerosene spray in crossflow, which enables efficient mixing between fuel and oxidizer. We investigate experimentally and numerically the effect of the spray air-to-liquid massflow ratio (ALR) variation on the reaction front and flame topology of a kerosene spray flame. The spray is injected transversely into a turbulent vitiated crossflow composed of the products of a lean CH4-H2 flame. The spray flame thermal power is varied between 2.5 and 5 kW, along with the atomizer ALR between 2 and 6. The experimental characterization of the reaction zone is performed using OH∗ chemiluminescence and OH and fuel planar laser-induced fluorescence (PLIF). The Large Eddy Simulations (LES) of the multiphase reactive flow provide good agreement with the experimental observations. Experiments and simulations show that the ALR governs mixing, resulting in different flame stabilization mechanisms and combustion regimes. Low ALR results in a relatively small jet-to-crossflow momentum ratio and a large spray Sauter mean diameter (SMD). A thick windward reaction region is formed due to inefficient shear layer mixing between the fuel spray and the crossflow. Meanwhile, the correspondingly large spray SMD leads to isolated penetration and localized combustion of fuel clusters. At high ALR, the higher penetration and the faster droplet evaporation due to the lower spray SMD result in an efficient entrainmentinduced mixing between the two streams, forming more distributed reaction regions
Intersectin associates with synapsin and regulates its nanoscale localization and function.
Neurotransmission is mediated by the exocytic release of neurotransmitters from readily releasable synaptic vesicles (SVs) at the active zone. To sustain neurotransmission during periods of elevated activity, release-ready vesicles need to be replenished from the reserve pool of SVs. The SV-associated synapsins are crucial for maintaining this reserve pool and regulate the mobilization of reserve pool SVs. How replenishment of release-ready SVs from the reserve pool is regulated and which other factors cooperate with synapsins in this process is unknown. Here we identify the endocytic multidomain scaffold protein intersectin as an important regulator of SV replenishment at hippocampal synapses. We found that intersectin directly associates with synapsin I through its Src-homology 3 A domain, and this association is regulated by an intramolecular switch within intersectin 1. Deletion of intersectin 1/2 in mice alters the presynaptic nanoscale distribution of synapsin I and causes defects in sustained neurotransmission due to defective SV replenishment. These phenotypes were rescued by wild-type intersectin 1 but not by a locked mutant of intersectin 1. Our data reveal intersectin as an autoinhibited scaffold that serves as a molecular linker between the synapsin-dependent reserve pool and the presynaptic endocytosis machinery
Geologically constrained evolutionary geomechanical modelling of diapir and basin evolution: a case study from the Tarfaya basin, West African coast
We systematically incorporate burial history, sea floor geometry and tectonic loads from a sequential kinematic restoration model into a 2D evolutionary geomechanical model that simulates the formation of the Sandia salt diapir, Tarfaya basin, NW African Coast. We use a poro-elastoplastic description for the sediment behaviour and a viscoplastic description for the salt. Sedimentation is coupled with salt flow and regional shortening to determine the sediment porosity and strength and to capture the interaction between salt and sediments. We find that temporal and spatial variation in sedimentation rate is a key control on the kinematic evolution of the salt system. Incorporation of sedimentation rates from the kinematic restoration at a location east of Sandia leads to a final geomechanical model geometry very similar to that observed in seismic reflection data. We also find that changes in the variation of shortening rates can significantly affect the present-day stress state above salt. Overall, incorporating kinematic restoration data into evolutionary models provides insights into the key parameters that control the evolution of geologic systems. Furthermore, it enables more realistic evolutionary geomechanical models, which, in turn, provide insights into sediment stress and porosity
Thermal-elastic stresses and the criticality of the continental crust
Heating or cooling can lead to high stresses in rocks due to the different thermal-elastic properties of minerals. In the upper 4 km of the crust, such internal stresses might cause fracturing. Yet it is unclear if thermal elasticity contributes significantly to critical stresses and failure deeper in Earth's continental crust, where ductile creep causes stress relaxation. We combined a heating experiment conducted in a Synchrotron microtomograph (Advanced Photon Source, USA) with numerical simulations to calculate the grain-scale stress field in granite generated by slow burial. We find that deviatoric stresses >100 MPa can be stored during burial, with relaxation times from 100's to 1000's ka, even in the ductile crust. Hence, grain-scale thermal-elastic stresses may serve as nuclei for instabilities, thus rendering the continental crust close to criticality
Ketahanan Sumberdaya Genetik Jagung Sulawesi Tenggara terhadap Cekaman Kekeringan pada Berbagai Fase Vegetatif
Maize crops experiencing water stress can experience cell damage, loss of turgor, closed stomata, plant leaf roll then wilt. Germination and vegetative growth are thought to be a very sensitive phases in relation to the availability of water, because it can influence subsequent growth processes. This study aimed to determine the potential tolerance of Southeast Sulawesi\u27s maize genotypes to drought stress at different vegetative growth phases. This study was based on completely randomized design (CRD) with factorial pattern consisting of two factors: the first factor composed of 9 local maize genotypes of Southeast Sulawesi and 1 national variety (cv. Arjuna), while the second factor was drought stress at different vegetative growth phases, consisting of four levels ie: C0 = plants irrigated with 100 % water availability during the growth phase, C1 = Stress for 5 days , at 21-26 days old (vegetative phase), C2 = Stress for 5 days starting at panicle emergence (early flowering stage), and C3 = Stress for 5 days starting 2 weeks after silking. Research results showed that Genotype (G) treatment significantly influenced all observed growth variables (at age 21 and 42 days after planting, DAP), except for the variable of number of leaf, age 21 DAP. However, water stress treatment (C) only significantly affected plant height variable, at the age of 42 DAP. In general, G6 and G7 genotypes tended to have a higher crop and trunk diameter than the other genotypes. Contrary, G3 genotype tended to have shorter crop and smaller stem diameter than the other genotypes. There are indications that the drought stress treatment (C) significantly inhibited the growth of maize crops
Morphological characterization of bushy cells and their inputs in the laboratory mouse (Mus musculus) anteroventral cochlear nucleus.
PMC3753269Spherical and globular bushy cells of the AVCN receive huge auditory nerve endings specialized for high fidelity neural transmission in response to acoustic events. Recent studies in mice and other rodent species suggest that the distinction between bushy cell subtypes is not always straightforward. We conducted a systematic investigation of mouse bushy cells along the rostral-caudal axis in an effort to understand the morphological variation that gives rise to reported response properties in mice. We combined quantitative light and electron microscopy to investigate variations in cell morphology, immunostaining, and the distribution of primary and non-primary synaptic inputs along the rostral-caudal axis. Overall, large regional differences in bushy cell characteristics were not found; however, rostral bushy cells received a different complement of axosomatic input compared to caudal bushy cells. The percentage of primary auditory nerve terminals was larger in caudal AVCN, whereas non-primary excitatory and inhibitory inputs were more common in rostral AVCN. Other ultrastructural characteristics of primary auditory nerve inputs were similar across the rostral and caudal AVCN. Cross sectional area, postsynaptic density length and curvature, and mitochondrial volume fraction were similar for axosomatic auditory nerve terminals, although rostral auditory nerve terminals contained a greater concentration of synaptic vesicles near the postsynaptic densities. These data demonstrate regional differences in synaptic organization of inputs to mouse bushy cells rather than the morphological characteristic of the cells themselves.JH Libraries Open Access Fun
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