Clonal hematopoiesis of indeterminate potential (CHIP) describes a widespread expansion of genetically variant hematopoietic cells that increases exponentially with age and is associated with ...increased risks of cancers, cardiovascular disease, and other maladies. Here, we discuss how environmental contexts associated with CHIP, such as old age, infections, chemotherapy, or cigarette smoking, alter tissue microenvironments to facilitate the selection and expansion of specific CHIP mutant clones. Further, we consider major remaining gaps in knowledge, including intrinsic effects, clone size thresholds, and factors affecting clonal competition, that will determine future application of this field in transplant and preventive medicine.
Double seismic zones are ubiquitous features of subduction zones, where seismicity is distributed along two layers separated by a region with significantly less seismic activity. Dehydration ...embrittlement is thought to be responsible for earthquakes in the subducting crust (upper layer), but the case for it in the lithospheric mantle (lower layer) is less clear. We apply a recently developed relative relocation technique to characterize seismicity in 32 slab segments. The high‐precision hypocentral depths allow us to assign events to either the upper or lower layer and to separately estimate frequency size distributions for each plane. We find consistently larger b values, correlating with slab age, for the upper layer and roughly constant values for the lower. We also show that thermal parameter and plate age are the key controls on double seismic zone geometry. Our results point to a relatively dry lower layer and suggest a fundamentally different mechanism for lithospheric mantle earthquakes.
Plain Language Summary
Despite being a common feature of global seismicity, intermediate‐depth earthquakes (70–350 km in depth approximately) and their physical mechanism are not well understood. These earthquakes occur at pressures and temperatures incompatible with our current models of brittle failure. At those depths, most subducting slabs feature two separate layers of seismicity, with little activity in‐between. It is commonly believed that the release of high‐pressure fluids enables the brittle‐like behavior; however, it is not yet clear whether this mechanism can operate on both layers. We have applied a recently developed earthquake location technique to construct a new global catalog of intermediate‐depth seismicity. We use this data set to study the geometrical structure of the two layers and their statistical characteristics. Our results point to a relatively dry lithospheric mantle—lower layer—regardless of plate age, convergence velocity, or composition and suggest that the physical mechanism enabling rupture in the lower layer is fundamentally different from the one in the upper.
Key Points
Double seismic zone geometrical structure is controlled by plate age and the slab's thermal parameter
We find consistently larger b values for the upper seismicity layer, correlating with slab age, and roughly constant values for the lower
Our results are consistent with dehydration embrittlement operating in the upper layer but point to a relatively dry lithospheric mantle
White-box models are detailed models for the investigation of the internal behavior of transformers during dielectric design. A new model of this type with significantly improved characteristics is ...presented in this paper. The model has been developed in state-space form, which is more flexible than an equivalent circuit and also makes it possible to optionally hide proprietary information on internal voltages. The proposed parameter determination methodology is very robust and allows the adequate representation of the damping. The methodology for determining inductive impedances and capacitances as a function of frequency using the Finite Element Method is described first. Then the fitting of the impedances obtained in the frequency domain by means of rational approximation functions is presented, which is based on the Vector Fitting algorithm in combination with Particle Swarm Optimization. The state-space model is obtained next, which is then used to perform time and frequency domain calculations. This new model has been successfully validated by comparison with measurements on a large power transformer used as case study during the activities of the JWG CIGRE A2/C4.52.
Small-strain stiffness properties of unsaturated soils, particularly shear-wave velocity, shear modulus, and material damping, play a fundamental role in the analysis and design of geotechnical ...infrastructure resting on unsaturated ground, or made of compacted unsaturated soils, as they are subjected to static or dynamic loading. Most conventional soil testing devices, however, are not able to adequately capture this small-strain behavior and hence vastly underestimate the true soil stiffness. This paper introduces a suction-controlled, proximitor-based resonant column device also featuring an independent set of self-contained bender elements for simultaneous testing of soils using both techniques. The work is partly aimed at assessing the suitability of bender elements for soil testing under controlled suction states, as compared to more reliable and fully-standardized procedures such as resonant column or simple shear test methods. A series of resonant column and bender element tests were simultaneously conducted on statically compacted specimens of silty sand for suction states ranging from 50 to 400kPa attained via the axis-translation technique. Particular attention was devoted to the influence of suction over the frequency response curves, damped free-vibration cycles, and cyclic hysteretic stress–strain loops. Results show the critical influence of matric suction on small-strain stiffness properties of compacted silty sand, as well as reasonably good agreement between resonant column and bender element test results.
•Results from suction-controlled resonant column/bender element tests on SM soil•Results show critical effect of suction on small-strain shear modulus and damping.•Good agreement between resonant column and bender element tests for all suctions
In the post-genomic era, most components of a cell are known and they can be quantified by large-scale functional genomics approaches. However, genome annotation is the bottleneck that hampers our ...understanding of living cells and organisms. Up-to-date functional annotation is of special importance for model organisms that provide a frame of reference for studies with other relevant organisms. We have generated a Wiki-type database for the Gram-positive model bacterium Bacillus subtilis, SubtiWiki (http://subtiwiki.uni-goettingen.de/). This Wiki is centered around the individual genes and gene products of B. subtilis and provides information on each aspect of gene function and expression as well as protein activity and its control. SubtiWiki is accompanied by two companion databases SubtiPathways and SubtInteract that provide graphical representations of B. subtilis metabolism and its regulation and of protein-protein interactions, respectively. The diagrams of both databases are easily navigatable using the popular Google maps API, and they are extensively linked with the SubtiWiki gene pages. Moreover, each gene/gene product was assigned to one or more functional categories and transcription factor regulons. Pages for the specific categories and regulons provide a rapid overview of functionally related genes/proteins. Today, SubtiWiki can be regarded as one of the most complete inventories of knowledge on a living organism in one single resource.
Synthetic pharmaceutical effluents loaded with the β-lactam antibiotic oxacillin were treated using advanced oxidation processes (the photo-Fenton system and TiO2 photocatalysis) and chloride ...mediated electrochemical oxidation (with Ti/IrO2 anodes). Combinations of the antibiotic with excipients (mannitol or tartaric acid), an active ingredient (calcium carbonate, i.e. bicarbonate ions due to the pH) and a cleaning agent (sodium lauryl ether sulfate) were considered. Additionally, urban wastewater that had undergone biological treatment was doped with oxacillin and treated with the tested systems. The evolution of antimicrobial activity was monitored as a parameter of processes efficiency. Although the two advanced oxidation processes (AOPs) differ only in the way they produce OH, marked differences were observed between them. There were also differences between the AOPs and the electrochemical system. Interestingly, each additive had a different effect on each treatment. For water loaded with mannitol, electrochemical treatment was the most suitable option because the additive did not significantly affect the efficiency of the system. Due to the formation of a complex with Fe3+, tartaric acid accelerated the elimination of antibiotic activity during the photo-Fenton process. For TiO2 photocatalysis, the presence of bicarbonate ions contributed to antibiotic activity elimination through the possible formation of carbonate and bicarbonate radicals. Sodium lauryl ether sulfate negatively affected all of the processes. However, due to the higher selectivity of HOCl compared with OH, electrochemical oxidation showed the least inhibited efficiency. For the urban wastewater doped with oxacillin, TiO2 photocatalysis was the most efficient process. These results will help select the most suitable technology for the treatment of water polluted with β-lactam antibiotics.
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•Effect of additives on oxacillin removal was evaluated by three oxidation systems.•Tartaric acid favored the efficiency of the photo-Fenton processes.•Calcium carbonate did not affect the TiO2 photocatalytic system.•In the presence of mannitol and laureth sulfate, electrochemical process is efficient.•TiO2 photocatalysis removes the antibiotic activity from an urban wastewater.
During chronic infection, the inflammatory cytokine interferon gamma (IFNγ) damages hematopoietic stem cells (HSCs) by disrupting quiescence and promoting excessive terminal differentiation. However, ...the mechanism by which IFNγ hinders HSC quiescence remains undefined. Using intravital 3-dimensional microscopy, we find that IFNγ disrupts the normally close interaction between HSCs and CXCL12-abundant reticular (CAR) cells in the HSC niche. IFNγ stimulation increases expression of the cell surface protein BST2, which we find is required for IFNγ-dependent HSC relocalization and activation. IFNγ stimulation of HSCs increases their E-selectin binding by BST2 and homing to the bone marrow, which depends on E-selectin binding. Upon chronic infection, HSCs from mice lacking BST2 are more quiescent and more resistant to depletion than HSCs from wild-type mice. Overall, this study defines a critical mechanism by which IFNγ promotes niche relocalization and activation in response to inflammatory stimulation and identifies BST2 as a key regulator of HSC quiescence.
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•Interferon gamma displaces hematopoietic stem cells in the bone marrow niche•Stem cell relocalization is mediated by BST2, an E-selectin ligand•Bst2−/− stem cells are hyperquiescent and resist depletion upon chronic infection
Florez et al. identify BST2 as a surface protein, induced by interferon gamma on hematopoietic stem cells, that is required for their relocalization and cell cycle activation in response to infection. BST2 may become an important target for enhancing stem cell homing and persistence in the face of inflammatory stress.
Chagas disease is an endemic disease of the American continent caused by Trypanosoma cruzi and divided into six discrete typing units (TcI – TcVI). Nearly 10 million people harbour the infection ...representing a serious issue in public health. Epidemiological surveillance allowed us to detect a bat‐related T. cruzi genotype (henceforth named TcBat) in a 5‐year‐old female living in a forest area in northwestern Colombia. Molecular tools determined a mixed infection of T. cruzi I and TcBat genotypes. This represents the first report of TcBat infection in humans; the epidemiological consequences of this finding are discussed herein.
The relationship between vitamin D deficiency and the risk of suffering from a plethora of health disorders, ranging from autoimmune processes to infectious diseases has been widely described. ...Nonetheless, the potential role of vitamin D in visceral leishmaniasis remains uncharacterized. In the Mediterranean basin, where the dog is leishmania's main peri-domestic reservoir, control measures against the canine disease have shown beneficial effects on the incidence of human leishmaniasis. In this study, we measured the vitamin D levels in serum samples from a cohort of 68 healthy and disease dogs from a highly endemic area and we have also studied the relationship of these levels with parasitological and immunological parameters. The sick dogs presented significantly lower (P < 0.001) vitamin D levels (19.6 ng/mL) than their non-infected (31.8 ng/mL) and the asymptomatic counterparts (29.6 ng/mL). In addition, vitamin D deficiency correlated with several parameters linked to leishmaniasis progression. However, there was no correlation between vitamin D levels and the Leishmania-specific cellular immune response. Moreover, both the leishmanin skin test and the IFN-γ levels displayed negative correlations with serological, parasitological and clinical signs. Further studies to determine the functional role of vitamin D on the progression and control of canine leishmaniasis are needed.
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