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The nongenetic mechanisms required to control tumor phenotypic plasticity and shape drug‐resistance remain unclear. We show here that the Aryl hydrocarbon Receptor (AhR) transcription factor directly regulates the gene expression program associated with the acquisition of resistance to BRAF inhibitor (BRAFi) in melanoma. In addition, we show in melanoma cells that canonical activation of AhR mediates the activation of the SRC pathway and promotes the acquisition of an invasive and aggressive resistant phenotype to front‐line BRAFi treatment in melanoma. This nongenetic reprogramming identifies a clinically compatible approach to reverse BRAFi resistance in melanoma. Using a preclinical BRAFi‐resistant PDX melanoma model, we demonstrate that SRC inhibition with dasatinib significantly re‐sensitizes melanoma cells to BRAFi. Together we identify the AhR/SRC axis as a new therapeutic vulnerability to trigger resistance and warrant the introduction of SRC inhibitors during the course of the treatment in combination with front‐line therapeutics to delay BRAFi resistance. Synopsis: This study reports that the AhR/SRC axis constitutes a therapeutic vulnerability in BRAFi‐resistant melanoma. AhR transcription factor promotes transcriptional reprogramming associated with the acquisition of BRAFi resistance in melanoma cells.Canonical activation of AhR induces the activation of SRC kinase after phosphorylation participating in the acquisition of the aggressive phenotype of melanoma.Specific inhibition of SRC pathway significantly re‐sensitizes melanoma to BRAFi. [ABSTRACT FROM AUTHOR]

The use of patient-derived primary cell cultures in cancer preclinical assays, including drug screens and genotoxic studies, has increased in recent years. However, their translational value is constrained by several limitations, including variability that can be caused by the culture conditions. Here, we show that the medium composition commonly used to propagate primary melanoma cultures has limited their representability of their tumor of origin and their cellular plasticity, and modified their sensitivity to therapy. Indeed, we established and compared cultures from different melanoma patients propagated in parallel in low-tyrosine (Ham's F10) or in high-tyrosine (Ham's F10 supplemented with tyrosine or RPMI1640 or DMEM) media. Tyrosine is the precursor of melanin biosynthesis, a process particularly active in differentiated melanocytes and melanoma cells. Unexpectedly, we found that the high tyrosine concentrations promoted an early phenotypic drift towards either a mesenchymal-like or senescence-like phenotype, and prevented the establishment of cultures of melanoma cells harboring differentiated features, which we show are frequently present in human clinical biopsies. Moreover, the invasive phenotype emerging in these culture conditions appeared irreversible and, as expected, associated with intrinsic resistance to MAPKi. In sharp contrast, differentiated melanoma cell cultures retained their phenotypes upon propagation in low-tyrosine medium, and importantly their phenotypic plasticity, a key hallmark of melanoma cells. Altogether, our findings underline the importance of culturing melanoma cells in low-tyrosine-containing medium in order to preserve their phenotypic identity of origin and cellular plasticity. [ABSTRACT FROM AUTHOR]

Carbonate reservoirs worldwide are complex in structure, diverse in form, and highly heterogeneous. Based on these characteristics, the reservoir stimulation technologies and fluid flow characteristics of carbonate reservoirs are briefly described in this study. The development methods and EOR technologies of carbonate reservoirs are systematically summarized, the relevant mechanisms are analyzed, and the application status of oil fields is catalogued. The challenges in the development of carbonate reservoirs are discussed, and future research directions are explored. In the current development processes of carbonate reservoirs, water flooding and gas flooding remain the primary means but are often prone to channeling problems. Chemical flooding is an effective method of tertiary oil recovery, but the harsh formation conditions require high-performance chemical agents. The application of emerging technologies can enhance the oil recovery efficiency and environmental friendliness to a certain extent, which is welcome in hard-to-recover areas such as heavy oil reservoirs, but the economic cost is often high. In future research on EOR technologies, flow field control and flow channel plugging will be the potential directions of traditional development methods, and the application of nanoparticles will revolutionize the chemical EOR methods. On the basis of diversified reservoir stimulation, combined with a variety of modern data processing schemes, multichannel EOR technologies are being developed to realize the systematic, intelligent, and cost-effective development of carbonate reservoirs. [ABSTRACT FROM AUTHOR]

This study examined the relationships among ethnicity/race, lifestyle factors, phylloquinone (vitamin K1) intake, and arterial pulse pressure in a nationally representative sample of older adults from four ethnic/racial groups: non-Hispanic Whites, non-Hispanic Blacks, Mexican Americans, and other Hispanics. This was a cross-sectional study of U.S. representative sample with data from the National Health and Nutrition Examination Surveys, 2007–2008 and 2009–2010 of adults aged 50 years and older (N = 5296). Vitamin K intake was determined by 24-hour recall. Pulse pressure was calculated as the difference between the averages of systolic blood pressure and diastolic blood pressure. Compared to White non-Hispanics, the other ethnic/racial groups were more likely to have inadequate vitamin K1intake. Inadequate vitamin K1intake was an independent predictor of high arterial pulse pressure. This was the first study that compared vitamin K1inadequacy with arterial pulse pressure across ethnicities/races in U.S. older adults. These findings suggest that vitamin K screening may be a beneficial marker for the health of older adults. [ABSTRACT FROM AUTHOR]

The work introduces a generalized interpretation of a modulor as a scale of segment proportions of human anthropometrical modules (extremities and body). Aims of study: (1) to reason the new idea of a 'growth modulor'; (2) using the modern empirical data, to prove the validity of a principle of linear similarity for anthropometrical segments; (3) to specify a system of invariants for constitutional anthropometrics. [ABSTRACT FROM AUTHOR]

Socioecological models assume that primates adapt their social behavior to ecological conditions, and predict that food availability and distribution, predation risk and risk of infanticide by males affect patterns of social organization, social structure and mating system of primates. However, adaptability and variation of social behavior may be constrained by conservative adaptations and by phylogenetic inertia. The comparative study of closely related species can help to identify the relative contribution of ecological and of genetic determinants to primate social systems. We compared ecological features and social behavior of two species of the genus Sapajus, S. nigritus in Carlos Botelho State Park, an area of Atlantic Forest in São Paulo state, and S. libidinosus in Fazenda Boa Vista, a semi-arid habitat in Piauí state, Brazil. S. libidinosus perceived higher predation risk and fed on clumped, high quality, and usurpable resources (fruits) all year round, whereas S. nigritus perceived lower predation risk and relied on evenly distributed, low-quality food sources (leaves) during periods of fruit shortage. As predicted by socioecology models, S. libidinosus females were philopatric and established linear and stable dominance hierarchies, coalitions, and grooming relationships. S. nigritus females competed less often, and could transfer between groups, which might explain the lack of coalitions and grooming bonds among them. Both populations presented similar group size and composition and the same polygynous mating system. The species differed from each other in accordance with differences in the characteristics of their main food sources, as predicted by socioecological models, suggesting that phylogenetic inertia does not constrain social relationships established among female Sapajus. The similarity in mating systems indicates that this element of the social system is not affected by ecological variables and thus, is a more conservative behavioral feature of the genus Sapajus. Am. J. Primatol. 74:315-331, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Electrodermal activity (EDA) is a sensitive index of sympathetic nervous system activity. Due to the lack of sensors that can be worn comfortably during normal daily activity and over extensive periods of time, research in this area is limited to laboratory settings or artificial clinical environments. We developed a novel, unobtrusive, nonstigmatizing, wrist-worn integrated sensor, and present, for the very first time, a demonstration of long-term, continuous assessment of EDA outside of a laboratory setting. We evaluated the performance of our device against a Food and Drug Administration (FDA) approved system for the measurement of EDA during physical, cognitive, as well as emotional stressors at both palmar and distal forearm sites, and found high correlations across all the tests. We also evaluated the choice of electrode material by comparing conductive fabric with Ag/AgCl electrodes and discuss the limitations found. An important result presented in this paper is evidence that the distal forearm is a viable alternative to the traditional palmar sites for EDA measurements. Our device offers the unprecedented ability to perform comfortable, long-term, and in situ assessment of EDA. This paper opens up opportunities for future investigations that were previously not feasible, and could have far-reaching implications for diagnosis and understanding of psychological or neurological conditions. [ABSTRACT FROM AUTHOR]

AbstractThe classes in Valiant's theory are classes of polynomials defined by arithmetic circuits. We characterize them by different notions of tensor calculus, in the vein of Damm, Holzer and McKenzie. This characterization underlines in particular the role played by properties of parallelization in these classes. We also give a first natural complete sequence for the class VPnb, the analogue of the class P in this context. [ABSTRACT FROM AUTHOR]

An additional investigation has been carried out of the rational model (Aslanov, 2000) of the separation of drops from the tops of the unstable wave formation on the molten surface of a meteoroid. The ratio of the wavelength of unstable hydrodynamic disturbances to the diameter of drops has been calculated in a mathematically closed form. Particular theoretical estimates of the size of the region of spraying of molten drops agree with prevailing sizes given in the known classification of the forms of meteoroid fragmentation. [ABSTRACT FROM AUTHOR]

Presents a method on proving boundedness of singular Radon transforms. Definition of singular Radon transforms; Consideration on local properties of Schwarz function; Use of lifting to nilpotent Lie groups theory.

The photoplethysmographic (PPG) signal, which is a measure of the systolic oscillations in the tissue blood volume, spontaneously fluctuates in the respiration rate and in lower frequencies similar to the heart rate fluctuations. In the current study, the low frequency fluctuations, which are attributed to the sympathetic nervous system activity, were obtained from PPG examinations simultaneously performed on the right and the left hands of healthy subjects and hemiplegic patients. For normal subjects, the fluctuations in the two hands were found to be correlated, demonstrating their central origin. For some of the hemiplegic patients, the coefficient of correlation between the right and the left hands was significantly lower than the normal range. The simultaneous measurement of the PPG signal fluctuations in both hands provides information on the adequate function of the autonomic nervous system. [ABSTRACT FROM AUTHOR]

We experienced a rare case of intestinal Behçet's disease simulating Crohn's colitis. A 70-yr-old female presented oral and genital ulcers, erythema nodosum, arthralgias, and abdominal pain. Regardless of our efforts, she died of septic shock. Autopsy showed punched-out ulcers in the terminal ileum and multiple longitudinal ulcers with inflammatory polyposis spreading from the ascending to the descending colon. The differential diagnosis of intestinal Behçet's disease versus Crohn's disease was difficult. However, microscopic findings showed nonspecific ulceration, and no evidence of Crohn's disease could be found. Clinically, the patient met the criteria of Behçet's disease, and punched-out ulcers in the ileocecal region, which is characteristic of intestinal Behçet's disease, confirmed the diagnosis of Behçet's colitis. Although rarely encountered, multiple longitudinal ulcers can involve all of the colon in Behçet's disease, like Crohn's disease. [ABSTRACT FROM AUTHOR]