Spi-1, Fli-1 and Fli-3 (miR-17-92) Oncogenes Contribute to a Single Oncogenic Network Controlling Cell Proliferation in Friend Erythroleukemia

Clonal erythroleukemia developing in susceptible mice infected by Friend virus complex are associated with highly recurrent proviral insertions at one of three loci called Spi-1, Fli-1 or Fli-3, leading to deregulated expression of oncogenic Spi-1 or Fli-1 transcription factors or miR-17-92 miRNA cluster, respectively. Deregulated expression of each of these three oncogenes has been independently shown to contribute to cell proliferation of erythroleukemic clones. Previous studies showed a close relationship between Spi-1 and Fli-1, which belong to the same ETS family, Spi-1 activating fli-1 gene, and both Spi-1 and Fli-1 activating multiple common target genes involved in ribosome biogenesis. In this study, we demonstrated that Spi-1 and Fli-1 are also involved in direct miR-17-92 transcriptional activation through their binding to a conserved ETS binding site in its promoter. Moreover, we demonstrated that physiological re-expression of exogenous miR-17 and miR-20a are able to partially rescue the proliferation loss induced by Fli-1 knock-down and identified HBP1 as a target of these miRNA in erythroleukemic cells. These results establish that three of the most recurrently activated oncogenes in Friend erythroleukemia are actually involved in a same oncogenic network controlling cell proliferation. The putative contribution of a similar ETS-miR-17-92 network module in other normal or pathological proliferative contexts is discussed

Electron-Phonon Interacation in Quantum Dots: A Solvable Model

The relaxation of electrons in quantum dots via phonon emission is hindered by the discrete nature of the dot levels (phonon bottleneck). In order to clarify the issue theoretically we consider a system of $N$ discrete fermionic states (dot levels) coupled to an unlimited number of bosonic modes with the same energy (dispersionless phonons). In analogy to the Gram-Schmidt orthogonalization procedure, we perform a unitary transformation into new bosonic modes. Since only $N(N+1)/2$ of them couple to the fermions, a numerically exact treatment is possible. The formalism is applied to a GaAs quantum dot with only two electronic levels. If close to resonance with the phonon energy, the electronic transition shows a splitting due to quantum mechanical level repulsion. This is driven mainly by one bosonic mode, whereas the other two provide further polaronic renormalizations. The numerically exact results for the electron spectral function compare favourably with an analytic solution based on degenerate perturbation theory in the basis of shifted oscillator states. In contrast, the widely used selfconsistent first-order Born approximation proves insufficient in describing the rich spectral features.Comment: 8 pages, 4 figure

Colloidal stability of tannins: astringency, wine tasting and beyond

Tannin-tannin and tannin-protein interactions in water-ethanol solvent mixtures are studied in the context of red wine tasting. While tannin self-aggregation is relevant for visual aspect of wine tasting (limpidity and related colloidal phenomena), tannin affinities for salivary proline-rich proteins is fundamental for a wide spectrum of organoleptic properties related to astringency. Tannin-tannin interactions are analyzed in water-ethanol wine-like solvents and the precipitation map is constructed for a typical grape tannin. The interaction between tannins and human salivary proline-rich proteins (PRP) are investigated in the framework of the shell model for micellization, known for describing tannin-induced aggregation of beta-casein. Tannin-assisted micellization and compaction of proteins observed by SAXS are described quantitatively and discussed in the case of astringency

Effect of the Surface on the Electron Quantum Size Levels and Electron g-Factor in Spherical Semiconductor Nanocrystals

The structure of the electron quantum size levels in spherical nanocrystals is studied in the framework of an eight--band effective mass model at zero and weak magnetic fields. The effect of the nanocrystal surface is modeled through the boundary condition imposed on the envelope wave function at the surface. We show that the spin--orbit splitting of the valence band leads to the surface--induced spin--orbit splitting of the excited conduction band states and to the additional surface--induced magnetic moment for electrons in bare nanocrystals. This additional magnetic moment manifests itself in a nonzero surface contribution to the linear Zeeman splitting of all quantum size energy levels including the ground 1S electron state. The fitting of the size dependence of the ground state electron g factor in CdSe nanocrystals has allowed us to determine the appropriate surface parameter of the boundary conditions. The structure of the excited electron states is considered in the limits of weak and strong magnetic fields.Comment: 11 pages, 4 figures, submitted to Phys. Rev.

First principles theory of inelastic currents in a scanning tunneling microscope

A first principles theory of inelastic tunneling between a model probe tip and an atom adsorbed on a surface is presented, extending the elastic tunneling theory of Tersoff and Hamann. The inelastic current is proportional to the change in the local density of states at the center of the tip due to the addition of the adsorbate. We use the theory to investigate the vibrational heating of an adsorbate below an STM tip. We calculate the desorption rate of H from Si(100)-H(2$\times$1) as function of the sample bias and tunnel current, and find excellent agreement with recent experimental data.Comment: 5 pages, RevTeX, epsf file

PERC rule to exclude the diagnosis of pulmonary embolism in emergency low-risk patients: study protocol for the PROPER randomized controlled study.

BACKGROUND: The diagnosis of Pulmonary Embolism (PE) in the emergency department (ED) is crucial. As emergency physicians fear missing this potential life-threatening condition, PE tends to be over-investigated, exposing patients to unnecessary risks and uncertain benefit in terms of outcome. The Pulmonary Embolism Rule-out Criteria (PERC) is an eight-item block of clinical criteria that can identify patients who can safely be discharged from the ED without further investigation for PE. The endorsement of this rule could markedly reduce the number of irradiative imaging studies, ED length of stay, and rate of adverse events resulting from both diagnostic and therapeutic interventions. Several retrospective and prospective studies have shown the safety and benefits of the PERC rule for PE diagnosis in low-risk patients, but the validity of this rule is still controversial. We hypothesize that in European patients with a low gestalt clinical probability and who are PERC-negative, PE can be safely ruled out and the patient discharged without further testing. METHODS/DESIGN: This is a controlled, cluster randomized trial, in 15 centers in France. Each center will be randomized for the sequence of intervention periods: a 6-month intervention period (PERC-based strategy) followed by a 6-month control period (usual care), or in reverse order, with 2 months of "wash-out" between the 2 periods. Adult patients presenting to the ED with a suspicion of PE and a low pre test probability estimated by clinical gestalt will be eligible. The primary outcome is the percentage of failure resulting from the diagnostic strategy, defined as diagnosed venous thromboembolic events at 3-month follow-up, among patients for whom PE has been initially ruled out. DISCUSSION: The PERC rule has the potential to decrease the number of irradiative imaging studies in the ED, and is reported to be safe. However, no randomized study has ever validated the safety of PERC. Furthermore, some studies have challenged the safety of a PERC-based strategy to rule-out PE, especially in Europe where the prevalence of PE diagnosed in the ED is high. The PROPER study should provide high-quality evidence to settle this issue. If it confirms the safety of the PERC rule, physicians will be able to reduce the number of investigations, associated subsequent adverse events, costs, and ED length of stay for patients with a low clinical probability of PE. TRIAL REGISTRATION: NCT02375919

The Beginning and Evolution of the Universe

We review the current standard model for the evolution of the Universe from an early inflationary epoch to the complex hierarchy of structure seen today. We summarize and provide key references for the following topics: observations of the expanding Universe; the hot early Universe and nucleosynthesis; theory and observations of the cosmic microwave background; Big Bang cosmology; inflation; dark matter and dark energy; theory of structure formation; the cold dark matter model; galaxy formation; cosmological simulations; observations of galaxies, clusters, and quasars; statistical measures of large-scale structure; and measurement of cosmological parameters. We conclude with discussion of some open questions in cosmology. This review is designed to provide a graduate student or other new worker in the field an introduction to the cosmological literature.Comment: 69 pages. Invited review article for Publications of the Astronomical Society of the Pacific. Supplementary references, tables, and more concise PDF file at http://www.physics.drexel.edu/univers

Projected increases in the annual flood pulse of the Western Amazon

The impact of a changing climate on the Amazon basin is a subject of intensive research because of its rich biodiversity and the significant role of rainforests in carbon cycling. Climate change has also a direct hydrological impact, and increasing efforts have focused on understanding the hydrological dynamics at continental and subregional scales, such as the Western Amazon. New projections from the Coupled Model Inter-comparison Project Phase 5 ensemble indicate consistent climatic warming and increasing seasonality of precipitation in the Peruvian Amazon basin. Here we use a distributed land surface model to quantify the potential impact of this change in the climate on the hydrological regime of the upper Amazon river. Using extreme value analysis, historical and future projections of the annual minimum, mean, and maximum river flows are produced for a range of return periods between 1 and 100 yr. We show that the RCP 4.5 and 8.5 scenarios of climate change project an increased severity of the wet season flood pulse (7.5% and 12% increases respectively for the 100 yr return floods). These findings agree with previously projected increases in high extremes under the Special Report on Emissions Scenarios climate projections, and are important to highlight due to the potential consequences on reproductive processes of in-stream species, swamp forest ecology, and socio-economy in the floodplain, amidst a growing literature that more strongly emphasises future droughts and their impact on the viability of the rainforest system over greater Amazonia

Effects of shade on the development and sugar metabolism of coffee (Coffea arabica L.) fruits.

Coffee fruits grown in shade are characterized by larger bean size than those grown under full-sun conditions. The present study assessed the effects of shade on bean characteristics and sugar metabolism by analyzing tissue development, sugar contents, activities of sucrose metabolizing enzymes and expression of sucrose synthase-encoding genes in fruits of coffee (Coffea arabica L.) plants submitted to full-sun (FS) and shade (SH) conditions. Evolution of tissue fresh weights measured in fruits collected regularly from flowering to maturation indicated that this increase is due to greater development of the perisperm tissue in the shade. The effects of light regime on sucrose and reducing sugar (glucose and fructose) contents were studied in fresh and dry coffee beans. Shade led to a significant reduction in sucrose content and to an increase in reducing sugars. In pericarp and perisperm tissues, higher activities of sucrose synthase (EC 2.4.1.13) and sucrose-phosphate synthase (SPS: EC 2.4.1.14) were detected at maturation in the shade compared with full sun. These two enzymes also had higher peaks of activities in developing endosperm under shade than in full sun. It was also noted that shade modified the expression of SUS-encoding genes in coffee beans; CaSUS2 gene transcripts levels were higher in SH than in FS. As no sucrose increase accompanied these changes, this suggests that sucrose metabolism was redirected to other metabolic pathways that need to be identified

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al