English-speakers sometimes say that they feel moved to tears, emotionally touched, stirred, or that something warmed their heart; other languages use similar passive contact metaphors to refer to an affective state. We propose and measure the concept of kama muta to understand experiences often given these and other labels. Do the same experiences evoke the same kama muta emotion across nations and languages? We conducted studies in 19 different countries, five continents, 15 languages, with a total of 3542 participants. We tested the construct while validating a comprehensive scale to measure the appraisals, valence, bodily sensations, motivation, and lexical labels posited to characterize kama muta. Our results are congruent with theory and previous findings showing that kama muta is a distinct positive social relational emotion that is evoked by experiencing or observing a sudden intensification of communal sharing. It is commonly accompanied by a warm feeling in the chest, moist eyes or tears, chills or piloerection, feeling choked up or having a lump in the throat, buoyancy and exhilaration. It motivates affective devotion and moral commitment to communal sharing. While we observed some variations across cultures, these five facets of kama muta are highly correlated in every sample, supporting the validity of the construct and the measure.
A series of 3,6-diaryl-2,5-dihydroxybenzoquinones were synthesized and evaluated for their abilities to selectively activate human insulin receptor tyrosine kinase (IRTK). 2, 5-Dihydroxy-6-(1-methylindol-3-yl)-3-phenyl-1,4-benzoquinone (2h) was identified as a potent, highly selective, and orally active small-molecule insulin receptor activator. It activated IRTK with an EC(50) of 300 nM and did not induce the activation of closely related receptors (IGFIR, EGFR, and PDGFR) at concentrations up to 30 000 nM. Oral administration of the compound to hyperglycemic db/db mice (0.1-10 mg/kg/day) elicited substantial to nearly complete correction of hyperglycemia in a dose-dependent manner. In ob/ob mice, the compound (10 mg/kg) caused significant reduction in hyperinsulinemia. A structurally related compound 2c, inactive in IRTK assay, failed to affect blood glucose level in db/db mice at equivalent exposure levels. Results from additional studies with compound 2h, aimed at evaluating classical quinone-related phenomena, provided sufficient grounds for optimism to allow more extensive toxicologic evaluation.
The small crack effect was investigated in two high‐strength aluminium alloys: 7075‐T6 bare and LC9cs clad alloy. Both experimental and analytical investigations were conducted to study crack initiation and growth of small cracks. In the experimental program, fatigue tests, small crack and large crack tests were conducted under constant amplitude and Mini‐TWIST spectrum loading conditions. A pronounced small crack effect was observed in both materials, especially for the negative stress ratios. For all loading conditions, most of the fatigue life of the SENT specimens was shown to be crack propagation from initial material defects or from the cladding layer. In the analysis program, three‐dimensional finite element and weight function methods were used to determine stress intensity factors and to develop SIF equations for surface and corner cracks at the notch in the SENT specimens. A plasticity‐induced crack‐closure model was used to correlate small and large crack data, and to make fatigue life predictions. Predicted crack‐growth rates and fatigue lives agreed well with experiments. A total fatigue life prediction method for the aluminium alloys was developed and demonstrated using the crack‐closure model.
Abstract. Quercitrin, glycosylated form of flavonoid compounds, is widely distributed in nature. Extensive studies have demonstrated that quercitrin exhibits strong antioxidant and anti-carcinogenic activities. However, the molecular mechanism is poorly understood. The present study examines the effects of quercitrin on tumor promotion in mouse JB6 cells, a validated model for screening cancer chemopreventive agents and elucidating the molecular mechanisms. Quercitrin blocked TPA-induced neoplastic transformation in JB6 P + cells. Pretreatment of JB6 cells with quercitrin down-regulated transactivation of AP-1 and NF-κB induced by UVB or TPA. In the skin of AP-1-luciferase transgenic mice, topical treatment of the mouse with quercitrin markedly blocked the TPA-induced AP-1 transactivation. Further studies indicated that these inhibitory actions appear to be mediated through the inhibition of MAPKs phosphorylation, including ERKs, p38 kinase, and JNKs. In addition, quercitrin stimulated the activation of NF-E2-related factor (Nrf2) and GST AREluciferase activity. Comet assays showed that quercitrin could block DNA damage induced by UVB. To our knowledge, these results provide the first evidence that quercitrin contributes to the inhibition of neoplastic transformation by blocking activation of the MAPK pathway and stimulation of cellular protection signaling. Moreover, to our knowledge, these findings provide the first molecular basis for the anticarcinogenic action of quercitrin. IntroductionPrevious studies have indicated that reactive oxidative species (ROS) function as second messengers in numerous signaling pathways involved in a diverse array of biological responses ranging from transcriptional regulation, differentiation and proliferation to oncogenic transformation (1,2). Increased formation of ROS can promote the development of malignancy, and the 'normal' rates of ROS generation may account for the increased risk of cancer development and neurodegenerative disorders (3,4). Therefore, interventions favoring the scavenging of ROS (dietary and pharmacological antioxidants) to attenuate the oxidative stress may prevent oxidant stressassociated diseases. A report published by the American Institute for Cancer Research regarding dietary prevention of cancer indicates that 7-31% of all cancers worldwide could be reduced by diets high in fruits and vegetables (5). Thus, searching for novel natural agents and defining novel targets for chemoprevention have become an important area of investigation.Flavonoids are components of the human diet and are widely found in vegetables and fruits (4). Flavonoids exert various biological activities, which are mainly related to their abilities to inhibit enzymes, to their antioxidant properties, and to their effects on immune responses (6). These activities may explain the beneficial effects that flavonoid intake exerts in different human pathologies, including hypertension, inflammatory conditions, and cancer (7). Quercetin is the most abundant bioflavonoid compound, which ...
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