Rejoinder: Bayesian Checking of the Second Levels of Hierarchical Models

Rejoinder: Bayesian Checking of the Second Levels of Hierarchical Models [arXiv:0802.0743]Comment: Published in at http://dx.doi.org/10.1214/07-STS235REJ the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Ripples in Tapped or Blown Powder

We observe ripples forming on the surface of a granular powder in a container submitted from below to a series of brief and distinct shocks. After a few taps, the pattern turns out to be stable against any further shock of the same amplitude. We find experimentally that the characteristic wavelength of the pattern is proportional to the amplitude of the shocks. Starting from consideration involving Darcy's law for air flow through the porous granulate and avalanche properties, we build up a semi-quantitative model which fits satisfactorily the set of experimental observations as well as a couple of additional experiments.Comment: 7 pages, four postscript figures, submitted PRL 11/19/9

A comprehensive study of high-metallicity giant extragalactic H II regions: ionizing populations

This is an electronic version of an article published in Revista Mexicana de Astronomía y Astrofísica. Castellanos, M., Díaz, A.I., and E. Terlevich. A comprehensive study of high-metallicity giant extragalactic H II regions: ionizing populations. Revista Mexicana de Astronomía y Astrofísica 12 (2002): 25

Food drugs as drivers of therapeutic knowledge and the role of chemosensory qualities

Ethnopharmacological relevance: Chemosensory qualities of botanical drugs are important cues for anticipating physiologic consequences. Whether a botanical drug is used for both, food and medicine, or only as medicine depends on taste preferences, nutritional content, cultural background, and the individual and overall epidemiological context. Material and methods: We subjected 540 botanical drugs described in De Materia Medica having at least one oral medical application to a tasting panel. The 540 drugs were grouped into those only used for medicine (388) and those also used for food (152). The associations with chemosensory qualities and therapeutic indications were compared across the two groups. We considered 22 experimentally assessed chemosensory qualities and 39 categories of therapeutic use groups. We wanted to know, 1): which chemosensory qualities increase the probability of an orally applied botanical drug to be also used for food ? 2): which chemosensory qualities augment the probability of an orally applied botanical drug to be only used for medicine? and 3): whether there are differences in therapeutic indications between orally applied botanical drugs also used for food (food drugs) and botanical drugs applied exclusively for medicinal purposes (non-food drugs) and, if yes, how the differences can be explained. Results: Chemosensory qualities augmenting the probability of an orally applied botanical drug to be also used for food were sweet, starchy, salty, burning/hot, fruity, nutty, and cooling. Therapeutics used for diarrhoea, as libido modulators, purgatives, laxatives, for expelling parasites, breast and lactation and increasing diuresis, were preferentially sourced from food drugs while drugs used for liver and jaundice, vaginal discharge and humoral management showed significant negative associations with food dugs in ancient Greek-Roman materia medica. Conclusion: Therapeutics used for ailments of body organs involved in the digestion of food and the excretion of waste products showed a tendency to be sourced from food drugs. Arguably, the daily consumption of food offered the possibility for observing post-prandial physiologic and pharmacologic effects which led to a high therapeutic versatility of food drugs and the possibility to understand benefits of taste and flavour qualities. The difference in chemosensory qualities between food drugs and non-food drugs is demarcating the organoleptic requirements of food rather than that of medicine

Adaptive resistance is not responsible for long-term drug resistance in a cellular model of triple negative breast cancer

Resistance to cancer therapeutics represents a leading cause of mortality and is particularly important in cancers, such as triple negative breast cancer, for which no targeted therapy is available, as these are only treated with traditional chemotherapeutics. Cancer, as well as bacterial, drug resistance can be intrinsic, acquired or adaptive. Adaptive cancer drug resistance is gaining attention as a mechanism for the generation of long-term drug resistance as is the case with bacterial antibiotic resistance. We have used a cellular model of triple negative breast cancer (CAL51) and its drug resistance derivative (CALDOX) to gain insight into genome-wide expression changes associated with long-term doxorubicin (a widely used anthracycline for cancer treatment) resistance and doxorubicin-induced stress. Previous work indicates that both naïve and resistance cells have a functional p53-p21 axis controlling cell cycle at G1, although this is not a driver for drug resistance, but down-regulation of TOP2A (topoisomerase IIα). As expected, CALDOX cells have a signature characterized, in addition to down-regulation of TOP2A, by genes and pathways associated with drug resistance, metastasis and stemness. Both CAL51 and CALDOX stress signatures share 12 common genes (TRIM22, FAS, SPATA18, SULF2, CDKN1A, GDF15, MYO6, CXCL5, CROT, EPPK1, ZMAT3 and CD44), with roles in the above-mentioned pathways, indicating that these cells have similar functional responses to doxorubicin relaying on the p53 control of apoptosis. Eight genes are shared by both drug stress signatures (in CAL51 and CALDOX cells) and CALDOX resistant cells (FAS, SULF2, CDKN1A, CXCL5, CD44, SPATA18, TRIM22 and CROT), many of them targets of p53. This corroborates experimental data indicating that CALDOX cells, even in the absence of drug, have activated, at least partially, the p53-p21 axis and DNA damage response. Although this eight-gene signature might be an indicator of adaptive resistance, as this transient phenomenon due to short-term stress may not revert to its original state upon withdrawal of the stressor, previous experimental data indicates that the p53-p21 axis is not responsible for doxorubicin resistance. Importantly, TOP2A is not responsive to doxorubicin treatment and thus absent in both drug stress signatures. This indicates that during the generation of doxorubicin resistance, cells acquire genetic changes likely to be random, leading to down regulation of TOP2A, but selected during the generation of cells due to the presence of drug in the culture medium. This poses a considerable constraint for the development of strategies aimed at avoiding the emergence of drug resistance in the clinic