Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic ...metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.
This research starts by distinguishing how different emotion components may be stimulated by different product types. Based on initial findings, a conceptual model is developed and tested that ...investigates a tourist's emotional arousal as a mediating variable between the tourism activity type and subsequent storytelling intentions. Based on social facilitation theory and self-expansion model, this research further investigates the potential moderating effect of having a travel companion and that companion's relative ability related to the tourism activity type on the impact of tourism activity type on emotional arousal. Four experiments are used to test the hypothesized relationships. Findings indicate that an experiential purchase has a greater effect on emotional arousal (not pleasure) than the purchase of a physical good. A more challenging(relaxing) tourist activity has a stronger(weaker) positive impact on emotional arousal and a tourist's storytelling intentions. Emotional arousal fully mediates the effect of tourism activity type on storytelling intentions. Having a travel companion, or not, was found to moderate the relationship of tourist activity type and emotional arousal. A challenging tourism activity has a stronger positive effect on a tourist's arousal when traveling with a companion. The arousal effect of engaging in a challenging tourism activity is attenuated when traveling alone. Moreover, based on the moderating effect of having a companion, or not, the perceived ability of a travel companion regarding the type of activity engaged in, was also found to moderate the link between activity type and emotional arousal. The greater the traveling companion's relative perceived ability, the greater the effect on emotional arousal for challenging tourism activities. This effect is attenuated when the ability of the traveling companion is perceived as less than that of the tourist. The paper closes with a discussion of theoretical contributions and managerial implications derived from the findings.
•Investigate how emotional components are stimulated by different product types.•Activity type, arousal, storytelling relationship tested.•Effect of travel companion and relative ability of companion examined.•Four studies are conducted to test hypotheses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The number of flat portions on the boundary of the numerical range of $5 \times 5$ companion matrices, both unitarily reducible and unitarily irreducible cases, is examined. The complete ...characterization on the number of flat portions of a $5 \times 5$ unitarily reducible companion matrix is given. Also under some suitable conditions, it is shown that a unitarily irreducible $5 \times 5$ companion matrix cannot have four flat portions on the boundary of its numerical range. This gives a partial affirmative answer to the conjecture given in 3 for $n = 5$. Numerical examples are provided to illustrate the results.
The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of ...harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples.
BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials.
The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient ICC = 0.86–0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18–0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78–0.85).
BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The present study evaluated the alterations of the oxidative stress markers in adult dogs fed with high levels of PUFA from the mixture of soybean oil enriched with docosahexaenoic acid ...(DHA) and supplemented with a natural algae-based antioxidant (AOX). Twelve healthy adult (2 years old) Beagle dogs (6 males and 6 females, 11.20 ± 1.92 kg BW), were distributed in 2 completely randomized blocks design and fed with 4 experimental diets coated with 2 lipid sources: saturated (13% bovine tallow) or unsaturated (13% soybean oil enriched with DHA), supplemented or not with 500 mg of AOX for 4 wk, intercalated with a 4-wk adaptation period. Blood samples were collected on days 0, 15, and 30 of each block. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), sulfhydryl group (SH), protein carbonylation, thiobarbituric acid reactive substances (TBARS), and total reactive antioxidant potential (TRAP) were evaluated in the serum, while GSH-Px, SOD, glutathione S-transferase (GST), catalase (CAT), SH, and TBARS were measured in erythrocytes. There was no significant difference in most of the oxidative markers evaluated. In contrast, GST activity in erythrocytes was greater in the animals that consumed the diets coated with bovine tallow compared to dogs that consumed diets coated with soybean oil enriched with DHA (P < 0.05). Serum from dogs fed on diets supplemented with AOX presented greater TRAP values (P < 0.05). These data demonstrate that the concentrations of unsaturated fatty acids (UNS) used in the diets for dogs were not sufficient to cause large changes in the oxidative status. It was not possible to evaluate the efficiency of the natural antioxidant in maintaining the oxidative balance of the animals as it appears that the oxidative status of the dogs was not challenged by the unsaturated diets. Our findings also suggest that dogs, as descendants from carrion carnivores, may have some natural protection against oxidation.
Abstract
We have previously determined phenylalanine (Phe) requirements in mature dogs; however, little information is available on differences of Phe minimum requirements on different breed sizes. ...The objective of this study was to determine Phe requirements in adult dogs of three different breed sizes using the direct AA oxidation (DAAO) technique. In total, 12 adult dogs were used, four Miniature Dachshunds (5.3 ± 0.6 Kg BW; 1.8 ± 0.1 years old; mean ± SD), four Beagles (8.3 ± 0.7 Kg BW; 6.7 ± 0.2 years old; mean ± SD), and four Labrador Retrievers (34.9 ± 2.2 Kg BW; 4.4 ± 1.4 years old; mean ± SD). A basal Phe-deficient diet with excess of tyrosine (Tyr) was formulated. Dogs were randomly fed the basal diet supplemented with increasing levels of Phe; the Phe content in the final experimental diets was 0.24, 0.29, 0.34, 0.44, 0.54, 0.64, and 0.74%. After 2 d of adaptation to the experimental diets, dogs underwent individual DAAO studies. During the DAAO studies, total daily feed was divided in 13 equal meals; at the sixth meal, dogs were fed a bolus of L-1-13C-Phe (9.40 mg/kg BW), and thereafter, L-1-13C-Phe (2.4 mg/kg BW) was supplied with every meal. Total production of 13CO2 (F13CO2) during isotopic steady state was determined by enrichment of 13CO2 in breath samples and total production of CO2 measured using indirect calorimetry. The mean requirement for Phe and the 95% confidence interval (CI) was determined using a two-phase linear regression model. To account for differences in feed intake, requirements were expressed in mg.kg BW−1.d−1. The mean requirement for Phe were 41.9, 41.3, and 42.6, and upper 95% CI of Phe requirements were 57.3, 58.4, and 64.8 mg.kg BW−1.d−1 for Miniature Dachshunds, Beagles, and Labrador Retrievers, respectively. The mean requirement and the upper 95% CI for the pooled data (all dogs) was 45.3 and 55.4 mg.kg BW−1.d−1, respectively. In conclusion, the Phe requirements for different breeds were similar among dog breeds studied. However, Phe recommendations proposed in this study are lower than those proposed by NRC and AAFCO (mg.kg BW−1.d−1).
We study the gravitational-wave (GW) signatures of clouds of ultralight bosons around black holes (BHs) in binary inspirals. These clouds, which are formed via superradiance instabilities for rapidly ...rotating BHs, produce distinct effects in the population of BH masses and spins, and a continuous monochromatic GW signal. We show that the presence of a binary companion greatly enriches the dynamical evolution of the system, most remarkably through the existence of resonant transitions between the growing and decaying modes of the cloud (analogous to Rabi oscillations in atomic physics). These resonances have rich phenomenological implications for current and future GW detectors. Notably, the amplitude of the GW signal from the clouds may be reduced, and in many cases terminated, much before the binary merger. The presence of a boson cloud can also be revealed in the GW signal from the binary through the imprint of finite-size effects, such as spin-induced multipole moments and tidal Love numbers. The time dependence of the cloud’s energy density during the resonance leads to a sharp feature, or at least attenuation, in the contribution from the finite-size terms to the waveforms. The observation of these effects would constrain the properties of putative ultralight bosons through precision GW data, offering new probes of physics beyond the Standard Model.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Abstract
We describe Keck-telescope spectrophotometry and imaging of the companion of the “black widow” pulsar PSR J0952−0607, the fastest known spinning neutron star (NS) in the disk of the Milky ...Way. The companion is very faint at minimum brightness, presenting observational challenges, but we have measured multicolor light curves and obtained radial velocities over the illuminated “day” half of the orbit. The model fits indicate system inclination
i
= 59.°8 ± 1.°9 and a pulsar mass
M
NS
= 2.35 ± 0.17
M
⊙
, the largest well-measured mass found to date. Modeling uncertainties are small, since the heating is not extreme; the companion lies well within its Roche lobe and a simple direct-heating model provides the best fit. If the NS started at a typical pulsar birth mass, nearly 1
M
⊙
has been accreted; this may be connected with the especially low intrinsic dipole surface field, estimated at 6 × 10
7
G. Joined with reanalysis of other black widow and redback pulsars, we find that the minimum value for the maximum NS mass is
M
max
>
2.19
M
⊙
(2.09
M
⊙
) at 1
σ
(3
σ
) confidence. This is ∼ 0.15
M
⊙
heavier than the lower limit on
M
max
implied by the white dwarf–pulsar binaries measured via radio Shapiro-delay techniques.
The trend of incorporating assistive conversational agents into people's lives has followed the unprecedented expansion in the usage of artificial intelligence (AI). Amazon, in particular, has been a ...key trendsetter in this area through its Alexa‐powered devices. Alexa is an intelligent personal assistant (IPA) that performs tasks, such as playing music, providing news and information, and controlling smart home appliances. While this IPA is widely utilized, it is especially gaining attention and growing usage by people with special needs. Even though the importance of the utilization of AI by people with special needs has been widely acknowledged in the extant literature, a sizeable gap exists in the marketing literature in relation to the assessment of the managerial and societal implications of IPAs when used by people with special needs. Accordingly, this study aims to examine (a) the stages of relationship development between Alexa and consumers with special needs, and (b) the potential opportunity of this relationship for Amazon in relation to their corporate image. The findings indicate that a relationship between Alexa and consumers with special needs is established as it helps them regain their independence and freedom. This relationship provides an opportunity for Amazon in enhancing its overall image for providing solutions to facilitate the lives of people with special needs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The LIGO/Virgo Collaboration has by now observed or constrained the gravitational merger rates of different classes of compact objects. We consider the possibility that the bulk of these mergers are ...primordial black hole (PBH) mergers of PBHs formed during the QCD epoch making up the entirety of the dark matter. Having shown in a companion paper that mergers due to the initial binary population formed in the early Universe are likely negligible, we compute current merger rates in PBH clusters in which the typical PBH resides. We consider two scenarios: (i) the PBH mass function dictated by the QCD equation of state and (ii) the PBH mass function dictated by the existence of a peak in the inflationary perturbation spectrum. In the first scenario, which is essentially parameter-free, we reproduce very well the merger rates for heavy BHs, the merger rate of mass-asymmetric BHs such as GW190814, a recently discovered merger of a 23 M_{⊙} black hole with a 2.6 M_{⊙} object, and can naturally explain why LIGO/Virgo has not yet observed mergers of two light PBHs from the dominant ∼1 M_{⊙} PBH population. In the second scenario, which has some parameter freedom, we match well the observed rate of heavy PBHs but can currently not explain the rate for mass-asymmetric events. In either case, it is tantalizing that in both scenarios PBH merger rates made with a minimum of assumptions match most LIGO/Virgo observed rates very well.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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