Applying the Moment Generating Functions to the Study of Probability Distributions

In this paper, we describe a tool to aid in proving theorems about random variables, called the moment generating function, which converts problems about probabilities and expectations into problems from calculus about function values and derivates. We show how the moment generating function determinates the moments and how the moments can be used to recover the moment generating function. Using of moment generating functions to find distributions of functions of random variables is presented. A standard form of the central limit theorem is also stated and proved.probability distribution, probability density function, moment generating function, central limit theorem

Simvastatin Rapidly and Reversibly Inhibits Insulin Secretion in Intact Single-Islet Cultures

open10Epidemiological studies suggest that statins may promote the development or exacerbation of diabetes, but whether this occurs through inhibition of insulin secretion is unclear. This lack of understanding is partly due to the cellular models used to explore this phenomenon (cell lines or pooled islets), which are non-physiologic and have limited clinical transferability.openScattolini, Valentina; Luni, Camilla; Zambon, Alessandro; Galvanin, Silvia; Gagliano, Onelia; Ciubotaru, Catalin Dacian; Avogaro, Angelo; Mammano, Fabio; Elvassore, Nicola; Fadini, Gian PaoloScattolini, Valentina; Luni, Camilla; Zambon, Alessandro; Galvanin, Silvia; Gagliano, Onelia; Ciubotaru, CATALIN DACIAN; Avogaro, Angelo; Mammano, Fabio; Elvassore, Nicola; Fadini, GIAN PAOL

Short-term inhibition of TERT induces telomere length-independent cell cycle arrest and apoptotic response in EBV-immortalized and transformed B cells

open7siBesides its canonical role in stabilizing telomeres, telomerase reverse transcriptase (TERT) may promote tumorigenesis through extra-telomeric functions. The possible therapeutic effects of BIBR1532 (BIBR), a powerful TERT inhibitor, have been evaluated in different cellular backgrounds, but no data are currently available regarding Epstein-Barr virus (EBV)-driven B-cell malignancies. Our aim was to characterize the biological effects of TERT inhibition by BIBR on EBV-immortalized lymphoblastoid cell lines (LCLs) and fully transformed Burkitt's lymphoma (BL) cell lines. We found that BIBR selectively inhibits telomerase activity in TERT-positive 4134/Late and 4134/TERT+ LCLs and EBV-negative BL41 and EBV-positive BL41/B95.8 BL cell lines. TERT inhibition led to decreased cell proliferation, accumulation of cells in the S-phase and ultimately to increased apoptosis, compared with mock-treated control cells. All these effects occurred within 72 h and were not observed in BIBR-treated TERT-negative 4134/TERT- and U2OS cells. The cell cycle arrest and apoptosis, consequent upon short-term TERT inhibition, were associated with and likely dependent on the activation of the DNA damage response (DDR), highlighted by the increased levels of γH2AX and activation of ATM and ATR pathways. Analyses of the mean and range of telomere lengths and telomere dysfunction-induced foci indicated that DDR after short-term TERT inhibition was not related to telomere dysfunction, thus suggesting that TERT, besides stabilizing telomere, may protect DNA via telomere-independent mechanisms. Notably, TERT-positive LCLs treated with BIBR in combination with fludarabine or cyclophosphamide showed a significant increase in the number of apoptotic cells with respect to those treated with chemotherapeutic agents alone. In conclusion, TERT inhibition impairs cell cycle progression and enhances the pro-apoptotic effects of chemotherapeutic agents in TERT-positive cells. These results support new therapeutic applications of TERT inhibitors in EBV-driven B-cell malignancies.openCeleghin, Andrea; Giunco, Silvia; Freguja, Riccardo; Zangrossi, Manuela; Nalio, Silvia; Dolcetti, Riccardo; De Rossi, AnitaCeleghin, Andrea; Giunco, Silvia; Freguja, Riccardo; Zangrossi, Manuela; Nalio, Silvia; Dolcetti, Riccardo; DE ROSSI, Anit

The Role of Dust in the Early Universe I : Protogalaxy Evolution

We develop one-zone galaxy formation models in the early Universe, taking into account dust formation and evolution by supernova (SN) explosions. Especially we focus on the time evolution of dust size distribution, because ${\rm H}_{2}$ formation on the dust surface plays a critical role in the star formation process in the early Universe. In the model we assume that star formation rate (SFR) is proportional to the total amount of ${\rm H}_{2}$. We consistently treat (i) the formation and size evolution of dust, (ii) the chemical reaction networks including ${\rm H}_{2}$ formation both on the surface of dust and in gas phase, and (iii) the SFR in the model. First, we find that, because of dust destruction due to both reverse and forward shocks driven by SNe, H$_{2}$ formation is more suppressed than that without dust destruction. At the galaxy age of $sim0.8 {\rm Gyr}$, for galaxy models with virial mass $M_{\rm vir}=10^{9} M_{\odot}$ and formation redshift $z_{\rm vir}=10$, the molecular fraction is 2.5 orders of magnitude less in the model with dust destruction by both shocks than that in the model without dust destruction. Second, we show that the H$_{2}$ formation rate strongly depends on the ISM density around SN progenitors. The SFR in higher ISM density is lower, since dust destruction by reverse shocks is more effective in higher ISM density. We conclude that not only the amount but also the size distribution of dust being related with the star formation activity strongly affects the evolution of galaxies in the early Universe.Comment: 23 pages, 12 figures, 3 tables, Accepted for publication in Ap

Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study

open32Regorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection.openKhan, Khurum; Rata, Mihaela; Cunningham, David; Koh, Dow-Mu; Tunariu, Nina; Hahne, Jens C; Vlachogiannis, George; Hedayat, Somaieh; Marchetti, Silvia; Lampis, Andrea; Damavandi, Mahnaz Darvish; Lote, Hazel; Rana, Isma; Williams, Anja; Eccles, Suzanne A; Fontana, Elisa; Collins, David; Eltahir, Zakaria; Rao, Sheela; Watkins, David; Starling, Naureen; Thomas, Jan; Kalaitzaki, Eleftheria; Fotiadis, Nicos; Begum, Ruwaida; Bali, Maria; Rugge, Massimo; Temple, Eleanor; Fassan, Matteo; Chau, Ian; Braconi, Chiara; Valeri, NicolaKhan, Khurum; Rata, Mihaela; Cunningham, David; Koh, Dow-Mu; Tunariu, Nina; Hahne, Jens C; Vlachogiannis, George; Hedayat, Somaieh; Marchetti, Silvia; Lampis, Andrea; Damavandi, Mahnaz Darvish; Lote, Hazel; Rana, Isma; Williams, Anja; Eccles, Suzanne A; Fontana, Elisa; Collins, David; Eltahir, Zakaria; Rao, Sheela; Watkins, David; Starling, Naureen; Thomas, Jan; Kalaitzaki, Eleftheria; Fotiadis, Nicos; Begum, Ruwaida; Bali, Maria; Rugge, Massimo; Temple, Eleanor; Fassan, Matteo; Chau, Ian; Braconi, Chiara; Valeri, Nicol

The Light Curve of the Weakly-Accreting T Tauri Binary KH 15D from 2005-10: Insights into the Nature of its Protoplanetary Disk

Photometry of the unique pre-main sequence binary system KH 15D is presented, spanning the years 2005-2010. This system has exhibited photometric variations and eclipses over the last 50 years caused by a precessing circumbinary disk. Advancement of the occulting edge across the binary orbit has continued and the photospheres of both stars are now completely obscured at all times. The system is now visible only by scattered light, and yet it continues to show a periodic variation on the orbital cycle with an amplitude exceeding two magnitudes. This variation, which depends only on the binary phase, has likely been present in the data since at least 1995. It can, by itself, account for shoulders on the light curve prior to ingress and following egress, obviating the need for components of extant models such as a scattering halo around star A or forward scattering from a fuzzy disk edge. A plausible source for the variable scattering component is reflected light from the far side of a warped occulting disk. We have detected color changes in V-I of several tenths of a magnitude to both the blue and red that occur during times of minima. These may indicate the presence of a third source of light (faint star) within the system, or a change in the reflectance properties of the disk as the portion being illuminated varies with the orbital motion of the stars. The data support a picture of the circumbinary disk as a geometrically thin, optically thick layer of perhaps mm or cm-sized particles that has been sculpted by the binary stars and possibly other components into a decidedly nonplanar configuration. A simple (infinitely sharp) knife-edge model does a good job of accounting for all of the recent (2005-2010) occultation data.Comment: To appear in The Astronomical Journa

Westminster can learn a lot about gender equality by looking at Welsh and Scottish levels of political representation

Discrimination and under-representation of women is still overt and visible in politics. Diana Silvia Stirbu argues that progress on the gender equality agenda doesn’t come easily, but it is possible through a combination of structural, political and cultural factors. Westminster can learn a lot from the successes in the Welsh National Assembly and Scottish Parliament

Curated Issue: Cultural Works—Transitions and Dislocations, Introduction

Introduction to the curated issue of PORTAL Journal of Multidisciplinary International Studies, Cultural Works—Transitions and Dislocations. Some parts of this introduction contain material previously published in my review of Silvia Spitta's Misplaced Objects: Migrating Collections and Recollections in Europe and the Americas (Austin: University of Texas Press, 2009), in The Comparatist, 34 (May 2010), pp. 201–7

Neutron Skins and Halo Orbits in the sd and pf Shells

open3siThe strong dependence of Coulomb energies on nuclear radii makes it possible to extract the latter from calculations of the former. The resulting estimates of neutron skins indicate that two mechanisms are involved. The first one --isovector monopole polarizability—amounts to noting that when a particle is added to a system it drives the radii of neutrons and protons in different directions, tending to equalize the radii of both fluids independently of the neutron excess. This mechanism is well understood and the Duflo- Zuker (small) neutron skin values derived 14 years ago are consistent with recent measures and estimates. The alternative mechanism involves halo orbits whose huge sizes tend to make the neutron skins larger and have a subtle influence on the radial behavior of sd and f shell nuclei. In particular, they account for the sudden rise in the isotope shifts of nuclei beyond N=28 and the near constancy of radii in the A=40–56 region. This mechanism, detected here for the first time, is not well understood and may well go beyond the Efimov physics usually associated with halo orbits.openBonnard, JEREMY CHRISTIAN FREDERIC; Lenzi, SILVIA MONICA; Zuker, A. P.Bonnard, JEREMY CHRISTIAN FREDERIC; Lenzi, SILVIA MONICA; Zuker, A. P

Faculty Profile: Philip Silvia

Profile of professor Philip Silvia of the History Department