We calculate the up-, down-, strange-, charm-, and bottom-quark masses using the MILC highly improved staggered-quark ensembles with four flavors of dynamical quarks. We use ensembles at six lattice ...spacings ranging from a≈0.15 to 0.03 fm and with both physical and unphysical values of the two light and the strange sea-quark masses. We use a new method based on heavy-quark effective theory (HQET) to extract quark masses from heavy-light pseudoscalar meson masses. Combining our analysis with our separate determination of ratios of light-quark masses we present masses of the up, down, strange, charm, and bottom quarks. Our results for the MS¯-renormalized masses are mu(2 GeV)=2.130(41) MeV, md(2 GeV)=4.675(56) MeV, ms(2 GeV)=92.47(69) MeV, mc(3 GeV)=983.7(5.6) MeV, and mc(mc)=1273(10) MeV, with four active flavors; and mb(mb)=4195(14) MeV with five active flavors. We also obtain ratios of quark masses mc/ms=11.783(25), mb/ms=53.94(12), and mb/mc=4.578(8). The result for mc matches the precision of the most precise calculation to date, and the other masses and all quoted ratios are the most precise to date. Moreover, these results are the first with a perturbative accuracy of αs4. As byproducts of our method, we obtain the matrix elements of HQET operators with dimension 4 and 5: Λ¯MRS=555(31) MeV in the minimal renormalon-subtracted (MRS) scheme, μπ2=0.05(22) GeV2, and μG2(mb)=0.38(2) GeV2. The MRS scheme Phys. Rev. D 97, 034503 (2018) is the key new aspect of our method.
We calculate the leptonic decay constants of heavy-light pseudoscalar mesons with charm and bottom quarks in lattice quantum chromodynamics on four-flavor QCD gauge-field configurations with ...dynamical u, d, s, and c quarks. We analyze over twenty isospin-symmetric ensembles with six lattice spacings down to a≈0.03 fm and several values of the light-quark mass down to the physical value 12(mu+md). We employ the highly-improved staggered-quark (HISQ) action for the sea and valence quarks; on the finest lattice spacings, discretization errors are sufficiently small that we can calculate the B-meson decay constants with the HISQ action for the first time directly at the physical b-quark mass. We obtain the most precise determinations to-date of the D- and B-meson decay constants and their ratios, fD+=212.7(0.6) MeV, fDs=249.9(0.4) MeV, fDs/fD+=1.1749(16), fB+=189.4(1.4) MeV, fBs=230.7(1.3) MeV, fBs/fB+=1.2180(47), where the errors include statistical and all systematic uncertainties. Our results for the B-meson decay constants are three times more precise than the previous best lattice-QCD calculations, and bring the QCD errors in the standard model predictions for the rare leptonic decays B¯(Bs→μ+μ−)=3.64(11)×10−9, B¯(B0→μ+μ−)=1.00(3)×10−11, and B¯(B0→μ+μ−)/B¯(Bs→μ+μ−)=0.00264(8) to well below other sources of uncertainty. As a byproduct of our analysis, we also update our previously published results for the light-quark-mass ratios and the scale-setting quantities fp4s, Mp4s, and Rp4s. We obtain the most precise lattice-QCD determination to date of the ratio fK+/fπ+=1.1950( −23+16) MeV.
Not all tropical fruits are equally desired by rainforest foragers and some fruit trees get depleted more quickly and carry fruit for shorter periods than others. We investigated whether a ripe-fruit ...specialist the chimpanzee (Pan troglodytes verus). arrived earlier at breakfast sites with very ephemeral and highly sought-after fruit, like figs, than sites with less ephemeral fruit that can be more predictably obtained throughout the entire day. We recorded when and where five adult female chimpanzees spent the night and acquired food for a total of 275 full days during three fruit-scarce periods in a West African tropical rainforest. We found that chimpanzees left their sleeping nests earlier (often before sunrise when the forest is still dark) when breakfasting on very ephemeral fruits, especially when they were farther away. Moreover, the females positioned their sleeping nests more in the direction of the next day's breakfast sites with ephemeral fruit compared with breakfast sites with other fruit. By analyzing departure times and nest positioning as a function of fruit type and location, while controlling for more parsimonious explanations, such as temperature, we found evidence that wild chimpanzees flexibly plan their breakfast time, type, and location after weighing multiple disparate pieces of information. Our study reveals a cognitive mechanism by which largebrained primates can buffer the effects of seasonal declines in food availability and increased interspecific competition to facilitate first access to nutritious food. We discuss the implications for theories on hominoid brain-size evolution.
This work introduces a novel methodology for the quantification of uncertainties associated with potential energy surfaces (PESs) computed from first-principles quantum mechanical calculations. The ...methodology relies on Bayesian inference and machine learning techniques to construct a stochastic PES and to express the inadequacies associated with the ab initio data points and their fit. By combining high fidelity calculations and reduced-order modeling, the resulting stochastic surface is efficiently forward propagated via quasi-classical trajectory and master equation calculations. In this way, the PES contribution to the uncertainty on predefined quantities of interest (QoIs) is explicitly determined. This study is done at both microscopic (e.g., rovibrational-specific rate coefficients) and macroscopic (e.g., thermal and chemical relaxation properties) levels. A correlation analysis is finally applied to identify the PES regions that require further refinement, based on their effects on the QoI reliability. The methodology is applied to the study of singlet (11A′) and quintet (25A′) PESs describing the interaction between O2 molecules and O atoms in their ground electronic state. The investigation of the singlet surface reveals a negligible uncertainty on the kinetic properties and relaxation times, which are found to be in excellent agreement with the ones previously published in the literature. On the other hand, the methodology demonstrated significant uncertainty on the quintet surface, due to inaccuracies in the description of the exchange barrier and the repulsive wall. When forward propagated, this uncertainty is responsible for the variability of 1 order of magnitude in the vibrational relaxation time and of factor four in the exchange reaction rate coefficient, both at 2500 K.
Sporotrichosis is a neglected zoonosis caused by pathogenic fungi belonging to the Sporothrix schenckii complex. In Rio de Janeiro state, this disease reached an epidemic status with over 4700 ...domestic felines and around 4000 humans affected since the mid-90s. The present study evaluated clinical and epidemiological aspects and also the frequency of colonization and infection by these fungi in healthy cats and among those with suspicious cutaneous lesions, inhabiting four Rio de Janeiro state distinct areas.
Three hundred and seventy-one cats were included in two groups: 175 healthy cats CRG and 196 cats showing lesions suggesting sporotrichosis SSG. Mycological diagnosis allowed SSG animals to be divided in positive 104 cats; +SG and negative 92 cats; -SG groups. Nails, oral mucosa and lesions swabs were submitted to culture and potential colonies were subculture for micromorphologycal analysis, dimorphism and molecular tests. In the CRG, only one cat was colonized in the oral cavity 0.57%; in the -SG group, four animals showed colonization of the nail and/or oral cavity 4.3%; while the highest frequency of colonization 39.4% was observed in the +SG. All molecularly typed isolates were identified as S. brasiliensis.
The results obtained here indicate that healthy cats have a minor role in sporotrichosis transmission within the state of Rio de Janeiro. Conversely, a higher participation of diseased feline in sporotrichosis transmission was evidenced, especially by the colonization of their oral cavity. Sporothrix brasiliensis equally affects and colonizes animals from distinct Rio de Janeiro state areas. Thus, we hypothesize that sporotrichosis is a uniform endemic throughout the state, whose transmission depends mainly on the contact with cats with sporotrichosis. Since Rio de Janeiro displays a world unique epidemic model of the disease, not fully understood, data on the infected and non-infected animals can be of major importance for future strategies of sporotrichosis prevention and control. Finally, considering the importance of the current concept of "one health", the experience here observed can be helpful for distinct epizootias and/or zoonosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The importance of the cellular immune response against DENV has been increasingly highlighted in the past few years, in particular for vaccine development. We have previously constructed two ...plasmids, pE1D2, and pcTPANS1, encoding the envelope (E) ectodomain (domains I, II, and III) and the non-structural 1 (NS1) protein of dengue virus serotype 2 (DENV2), respectively. In the present work, we analyzed the induction of the cellular response in mice immunized with these DNA vaccines and identified the immunogenic peptides. Vaccinated BALB/c mice became protected against a lethal challenge of DENV2. Depletion of CD4
cells in vaccinated animals almost completely abolished protection elicited by both vaccines. In contrast, a significant number of pE1D2- and pcTPANS1-immunized mice survived virus challenge after depletion of CD8
cells, although some animals presented morbidity. To identify immunogenic peptides recognized by T cells, we stimulated splenocytes with overlapping peptide libraries covering the E and NS1 proteins and evaluated the production of IFN-γ by ELISPOT. We detected two and three immunodominant epitopes in the E and NS1 proteins, respectively, and four additional NS1-derived peptides after virus challenge. Characterization by intracellular cytokine staining (ICS) revealed that both CD4
and CD8
T cells were involved in IFN-γ and TNF-α production. The IFN-γ ICS confirmed reaction of almost all E-derived peptides before challenge and identified other epitopes after infection. All NS1-derived peptides were able to elicit IFN-γ production in CD4
cells, while only a few peptides induced expression of this cytokine in CD8
T lymphocytes. Interestingly, we observed an increase in the frequency of either CD4
or CD8
T cells producing TNF-α after immunization with the pE1D2 and challenge with DENV2, while lymphocytes from pcTPANS1-vaccinated animals maintained ordinary TNF-α production after virus infection. We also assessed the recognition of E and NS1 immunogenic peptides in C57BL/6 mice due to the difference in MHC haplotype expression. Two NS1-derived epitopes featured prominently in the IFN-γ response with cells from both animal strains. Overall, our results emphasize the importance of the T cell response involved in protection against dengue induced by E and NS1 based DNA vaccines.
mTOR is a signaling pathway involved in cell survival, cell stress response, and protein synthesis that may be a key point in sepsis-induced cardiac dysfunction. Curcumin has been reported in vitro ...as an mTOR inhibitor compound; however, there are no studies demonstrating this effect in experimental sepsis. Thus, this study aimed to evaluate the action of curcumin on the mTOR pathway in the heart of septic mice. Free curcumin (FC) and nanocurcumin (NC) were used, and samples were obtained at 24 and 120 h after sepsis. Histopathological and ultrastructural analysis showed that treatments with FC and NC reduced cardiac lesions caused by sepsis. Our main results demonstrated that curcumin reduced mTORC1 and Raptor mRNA at 24 and 120 h compared with the septic group; in contrast, mTORC2 mRNA increased at 24 h. Additionally, the total mTOR mRNA expression was reduced at 24 h compared with the septic group. Our results indicate that treatment with curcumin and nanocurcumin promoted a cardioprotective response that could be related to the modulation of the mTOR pathway.
Carbon nanotubes (CNTs) are noteworthy, as they reinforce the metallic matrix, due to mechanical properties, such as the ~ 1.0 TPa Young module. To improve the maintenance of the commercially pure ...aluminum surface, multi-walled carbon nanotubes were incorporated into the aluminum surface with heat treatment by solid solubilization, in order to improve the surface properties of aluminum. The aluminum samples were chemically attacked for 30, 60 and 120 s and placed in a container with CNTs, being subjected to a temperature of 640 °C for 1 h. Then, the roughness was evaluated by a roughness meter for morphology in the scanning electron microscopy. An intensity of aggregation of CNTs was evaluated by XRD, and the Raman Spectra has evaluated the transfer of charge to the matrix. Microhardness was performed to evaluate the influence of the incorporation of CNTs in the matrix. The results obtained show that the incorporation of CNTs in the aluminum matrix increases the hardness in approximately 20% of the surface, in comparison with the control sample. The process of incorporating CNTs into the aluminum matrix by solubilization is a promising, simple and inexpensive alternative to improve the durability of the aluminum surface.
Graphic Abstract
To understand the evolutionary roots of human spatial cognition, researchers have compared spatial abilities of humans and one of our closest living relatives, the chimpanzee (Pan troglodytes). ...However, how humans and chimpanzees compare in solving spatial tasks during real-world foraging is unclear to date, as measuring such spatial abilities in natural habitats is challenging. Here we compared spatial movement patterns of the Mbendjele BaYaka people and the Taï chimpanzees during their daily search for food in rainforests. We measured linearity and speed during off-trail travels toward out-of-sight locations as proxies for spatial knowledge. We found similarly high levels of linearity in individuals of Mbendjele foragers and Taï chimpanzees. However, human foragers and chimpanzees clearly differed in their reactions to group size and familiarity with the foraging areas. Mbendjele foragers increased travel linearity with increasing familiarity and group size, without obvious changes in speed. This pattern was reversed in Taï chimpanzees. We suggest that these differences between Mbendjele foragers and Taï chimpanzees reflect their different ranging styles, such as life-time range size and trail use. This result highlights the impact of socio-ecological settings on comparing spatial movement patterns. Our study provides a first step toward comparing long-range spatial movement patterns of two closely-related species in their natural environments.
Membrane transport proteins are involved in the absorption, disposition, efficacy, and/or toxicity of many drugs. Numerous mechanisms (e.g., nuclear receptors, epigenetic gene regulation, microRNAs, ...alternative splicing, post‐translational modifications, and trafficking) regulate transport protein levels, localization, and function. Various factors associated with disease, medications, and dietary constituents, for example, may alter the regulation and activity of transport proteins in the intestine, liver, kidneys, brain, lungs, placenta, and other important sites, such as tumor tissue. This white paper reviews key mechanisms and regulatory factors that alter the function of clinically relevant transport proteins involved in drug disposition. Current considerations with in vitro and in vivo models that are used to investigate transporter regulation are discussed, including strengths, limitations, and the inherent challenges in predicting the impact of changes due to regulation of one transporter on compensatory pathways and overall drug disposition. In addition, translation and scaling of in vitro observations to in vivo outcomes are considered. The importance of incorporating altered transporter regulation in modeling and simulation approaches to predict the clinical impact on drug disposition is also discussed. Regulation of transporters is highly complex and, therefore, identification of knowledge gaps will aid in directing future research to expand our understanding of clinically relevant molecular mechanisms of transporter regulation. This information is critical to the development of tools and approaches to improve therapeutic outcomes by predicting more accurately the impact of regulation‐mediated changes in transporter function on drug disposition and response.
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