Med news

The Med News was a newsletter published from 1960-1962 by the Student American Medical Association (SAMA) at Boston University School of Medicine

Quantile regression analysis of visitor spending: An example of mainland Chinese tourists in Hong Kong: Working paper series--09-06

A common approach to market segmentation based on visitor expenditures is to use the least-squares regression analysis to determine statistically significant variables upon which key market segments are identified for marketing purposes. This was done by Wang (2004) for survey data based on expenditures by Mainland Chinese visitors to Hong Kong. We use this same dataset to demonstrate the benefits of using the quantile regression analysis approach to better identify tourist spending patterns and market segments. The quantile regression measures tourist spending in different categories against a fixed range of dependent variable, which distinguished between lower, medium, and higher spenders. The results show that quantile regression is less susceptible to influence by outlier values and is better able to target finer tourist spending market segments

A Study of Gaussianity in CMB band maps

The detection of non-Gaussianity in the CMB data would rule out a number of inflationary models. A null detection of non-Gaussianity, instead, would exclude alternative models for the early universe. Thus, a detection or non-detection of primordial non-Gaussianity in the CMB data is crucial to discriminate among inflationary models, and to test alternative scenarios. However, there are various non-cosmological sources of non-Gaussianity. This makes important to employ different indicators in order to detect distinct forms of non-Gaussianity in CMB data. Recently, we proposed two new indicators to measure deviation from Gaussianity on large angular scales, and used them to study the Gaussianity of the raw band WMAP maps with and without the KQ75 mask. Here we extend this work by using these indicators to perform similar analyses of deviation from Gaussianity of the foreground-reduced Q, V, and W band maps. We show that there is a significant deviation from Gaussianity in the considered full-sky maps, which is reduced to a level consistent with Gaussianity when the KQ75 mask is employed.Comment: 5 pages, 2 PS figures, uses ws-ijmpd.cls ; to be published in the International Journal of Modern Physics

The search for CDK4/6 inhibitor biomarkers has been hampered by inappropriate proliferation assays

CDK4/6 inhibitors are effective at treating advanced HR+ /HER2- breast cancer, however biomarkers that can predict response are urgently needed. We demonstrate here that previous large-scale screens designed to identify which tumour types or genotypes are most sensitive to CDK4/6 inhibitors have misrepresented the responsive cell lines because of a reliance on metabolic proliferation assays. CDK4/6-inhibited cells arrest in G1 but continue to grow in size, thereby producing more mitochondria. We show that this growth obscures the arrest using ATP-based proliferation assays but not if DNA-based assays are used instead. Furthermore, lymphoma lines, previously identified as the most sensitive, simply appear to respond the best using ATP-based assays because they fail to overgrow during the G1 arrest. Similarly, the CDK4/6 inhibitor abemaciclib appears to inhibit proliferation better than palbociclib because it also restricts cellular overgrowth through off-target effects. DepMap analysis of screening data using reliable assay types, demonstrates that palbociclib-sensitive cell types are also sensitive to Cyclin D1, CDK4 and CDK6 knockout/knockdown, whereas the palbociclib-resistant lines are sensitive to Cyclin E1, CDK2 and SKP2 knockout/knockdown. Potential biomarkers of palbociclib-sensitive cells are increased expression of CCND1 and RB1, and reduced expression of CCNE1 and CDKN2A. Probing DepMap with similar data from metabolic assays fails to reveal these associations. Together, this demonstrates why CDK4/6 inhibitors, and any other anti-cancer drugs that arrest the cell cycle but permit continued cell growth, must now be re-screened against a wide-range of cell types using an appropriate proliferation assay. This would help to better inform clinical trials and to identify much needed biomarkers of response.</p

Mechanistic mathematical model of polarity in yeast

The establishment of cell polarity involves positive-feedback mechanisms that concentrate polarity regulators, including the conserved GTPase Cdc42p, at the “front” of the polarized cell. Previous studies in yeast suggested the presence of two parallel positive-feedback loops, one operating as a diffusion-based system, and the other involving actin-directed trafficking of Cdc42p on vesicles. F-actin (and hence directed vesicle traffic) speeds fluorescence recovery of Cdc42p after photobleaching, suggesting that vesicle traffic of Cdc42p contributes to polarization. We present a mathematical modeling framework that combines previously developed mechanistic reaction-diffusion and vesicle-trafficking models. Surprisingly, the combined model recapitulated the observed effect of vesicle traffic on Cdc42p dynamics even when the vesicles did not carry significant amounts of Cdc42p. Vesicle traffic reduced the concentration of Cdc42p at the front, so that fluorescence recovery mediated by Cdc42p flux from the cytoplasm took less time to replenish the bleached pool. Simulations in which Cdc42p was concentrated into vesicles or depleted from vesicles yielded almost identical predictions, because Cdc42p flux from the cytoplasm was dominant. These findings indicate that vesicle-mediated delivery of Cdc42p is not required to explain the observed Cdc42p dynamics, and raise the question of whether such Cdc42p traffic actually contributes to polarity establishment

Variational Integrators for Almost-Integrable Systems

We construct several variational integrators--integrators based on a discrete variational principle--for systems with Lagrangians of the form L = L_A + epsilon L_B, with epsilon << 1, where L_A describes an integrable system. These integrators exploit that epsilon << 1 to increase their accuracy by constructing discrete Lagrangians based on the assumption that the integrator trajectory is close to that of the integrable system. Several of the integrators we present are equivalent to well-known symplectic integrators for the equivalent perturbed Hamiltonian systems, but their construction and error analysis is significantly simpler in the variational framework. One novel method we present, involving a weighted time-averaging of the perturbing terms, removes all errors from the integration at O(epsilon). This last method is implicit, and involves evaluating a potentially expensive time-integral, but for some systems and some error tolerances it can significantly outperform traditional simulation methods.Comment: 14 pages, 4 figures. Version 2: added informative example; as accepted by Celestial Mechanics and Dynamical Astronom