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Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.  相似文献   
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Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed kcnk3fl/fl animals to hypoxia, metabolic diet and low dose lipopolysaccharide (LPS) and performed molecular characterization of their tissue. We also used tissue samples from KCNK3 patients (skin fibroblast derived inducible pluripotent stem cells, blood, lungs, peripheral blood mononuclear cells) and performed microarray, immunohistochemistry (IHC) and mass cytometry time of flight (CyTOF) experiments. Although a hypoxic insult did not alter vascular tone in kcnk3fl/fl mice, RNASeq study of these lungs implied that inflammatory and metabolic factors were altered, and the follow-up diet study demonstrated a dysregulation of bone marrow cells in kcnk3fl/fl mice. Finally, a low dose LPS study clearly showed that inflammation could be a possible second hit driving PAH in kcnk3fl/fl mice. Multiplex, IHC and CyTOF immunophenotyping studies on human samples confirmed the mouse data and strongly indicated that cell mediated, and innate immune responses may drive PAH susceptibility in these patients. In conclusion, loss of function KCNK3 mutation alters various physiological processes from vascular tone to metabolic diet through inflammation. Our data suggests that altered circulating immune cells may drive PAH susceptibility in patients with KCNK3 mutation.  相似文献   
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Industrial chemical plant diagnosis is the task of analyzing process data to sufficiently pinpoint the causes of abnormal events as fast and as accurately as possible so corrective action can be taken in a timely manner. The need to identify failures explicitly and support human centered decision making becomes pronounced for enterprises. Qualitative diagnostic models offer robustness in capturing diagnostic behaviors when there is little or no data on fault conditions. This article develops, analyzes, and demonstrates a qualitative diagnostic methodology called Causal Link Assessment (CLA). CLA avoids the drawbacks of other methodologies while leveraging several new concepts that include dynamic pattern generation, single time step modeling with multitime step interpretation, and discretized, low granularity dynamic modeling. CLA is demonstrated for an existing ethylene production facility. Model building, robustness, reusability, unaccounted for faults and failures and alignment with emerging Smart Manufacturing infrastructure concepts are discussed. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3420–3431, 2016  相似文献   
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Blueberries, a functional food, are rich in bioactive polyphenols and anthocyanins. However, the shelf life is short and requires cold storage. This study provides evidence that edible foxtail millet flour (FMF) efficiently sorbs only blueberry bioactive components (polyphenols and anthocyanins) but not sugars, improves their stability and retains the activity. The concentration of blueberry polyphenols and anthocyanins sorbed to FMF ranged from 6 to 113 and 4 to 41 mg g?1, respectively. The concentration of bioactive components in one serving of blueberries (73 g) is equivalent to those present in 1.2 g of blueberry‐enriched foxtail millet flour (BFMF). The blueberry bioactive sorbed onto FMF remained stable for at least 16 weeks at 40 °C. BFMF eluates inhibited α‐glucosidase enzyme activity and scavenged the free radicals conferring that blueberry bioactive components in BFMF retained the activity. The sorption process described here provides a practical way of creating low glycemic protein‐rich edible flour enriched with plant bioactive compounds without sugars.  相似文献   
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Wireless Networks - Recent technological advancements in miniaturization of sensor and wireless communication lead to development of Wireless Body Area Networks (WBAN). It is similar to Wireless...  相似文献   
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