1,728 research outputs found
Ameliorating effect of Erxian decoction combined with Fructus Schisandrae chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat model
Additional file 3. The animal studies were performed following the ARRIVE guideline
Hybrid silicon nanostructures with conductive ligands and their microscopic conductivities
Silicon nanoparticles (SiNPs) functionalized with conjugated molecules promise a potential pathway to generate a new category of thermoelectric materials. While the thermoelectric performance of materials based on phenyl-acetylene capped SiNPs has been proven, their low conductivity is still a problem for their general application. A muon study of phenyl-acetylene capped SiNPs has been recently carried out using the HiFi spectrometer at the Rutherford Appleton Laboratory, measuring the ALC spectra as a function of temperature. The results show a reduction in the measured line width of the resonance above room temperature, suggesting an activated behaviour for this system. This study shows that the muon study could be a powerful method to investigate microscopic conductivity of hybrid thermoelectric materials
Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity
The Publisher's final version can be found by following the DOI link. open access articleWith the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited. In vivo models are unable to adequately discriminate between the specific modes of action associated with the onset of genotoxicity. Additionally, in line with the recent European directives, there is an inherent need to move away from invasive animal testing strategies. Thus, in vitro systems are an important tool for expanding our mechanistic insight into NP genotoxicity. Yet uncertainty remains concerning their validity and specificity for this purpose due to the unique challenges presented when correlating NP behaviour in vitro and in vivo This review therefore highlights the current state of the art in advanced in vitro systems and their specific advantages and disadvantages from a NP genotoxicity testing perspective. Key indicators will be given related to how these systems might be used or improved to enhance understanding of NP genotoxicity
Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding
We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics
Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict
Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated
Mechanisms controlling anaemia in Trypanosoma congolense infected mice.
Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection
Phase 1 study of ixazomib, an investigational proteasome inhibitor, in advanced non-hematologic malignancies
Explanatory machine learning for sequential human teaching
The topic of comprehensibility of machine-learned theories has recently drawn
increasing attention. Inductive Logic Programming (ILP) uses logic programming
to derive logic theories from small data based on abduction and induction
techniques. Learned theories are represented in the form of rules as
declarative descriptions of obtained knowledge. In earlier work, the authors
provided the first evidence of a measurable increase in human comprehension
based on machine-learned logic rules for simple classification tasks. In a
later study, it was found that the presentation of machine-learned explanations
to humans can produce both beneficial and harmful effects in the context of
game learning. We continue our investigation of comprehensibility by examining
the effects of the ordering of concept presentations on human comprehension. In
this work, we examine the explanatory effects of curriculum order and the
presence of machine-learned explanations for sequential problem-solving. We
show that 1) there exist tasks A and B such that learning A before B has a
better human comprehension with respect to learning B before A and 2) there
exist tasks A and B such that the presence of explanations when learning A
contributes to improved human comprehension when subsequently learning B. We
propose a framework for the effects of sequential teaching on comprehension
based on an existing definition of comprehensibility and provide evidence for
support from data collected in human trials. Empirical results show that
sequential teaching of concepts with increasing complexity a) has a beneficial
effect on human comprehension and b) leads to human re-discovery of
divide-and-conquer problem-solving strategies, and c) studying machine-learned
explanations allows adaptations of human problem-solving strategy with better
performance.Comment: Submitted to the International Joint Conference on Learning &
Reasoning (IJCLR) 202
Danger: Wolf Crossing! Meantone Tuning and Froberger’s Keyboard Music
This thesis is an exploration of how tuning practices can influence compositional practice, focusing on the way temperament can provide new insights to a close reading of keyboard music by Johann Jakob Froberger (1616–67), a transitional figure between a predominantly meantone-oriented musical environment of the 17th century and the well temperament of the 18th century. Many scholars have pointed to Froberger’s characteristic chromaticism and experimentation with novel keys as indicative of his desire to compose beyond the restrictions of meantone tuning and towards well temperament. In an effort to move away from this oft-cited teleological narrative from unequal to equal, my analyses attend to the ways that Froberger works with the boundaries of meantone, ultimately arguing that a meantone tuning is integral to Froberger’s musical language. Transgressions of these boundaries, as we shall soon see, involve mistunings that result in shocking discordances, a rough aural quality that Froberger exploits to craft structures of expectation in the dimension of discordance that operate independently of harmony
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