Asymptotic Conditional Distribution of Exceedance Counts: Fragility Index with Different Margins

Let $\bm X=(X_1,...,X_d)$ be a random vector, whose components are not necessarily independent nor are they required to have identical distribution functions $F_1,...,F_d$. Denote by $N_s$ the number of exceedances among $X_1,...,X_d$ above a high threshold $s$. The fragility index, defined by $FI=\lim_{s\nearrow}E(N_s\mid N_s>0)$ if this limit exists, measures the asymptotic stability of the stochastic system $\bm X$ as the threshold increases. The system is called stable if $FI=1$ and fragile otherwise. In this paper we show that the asymptotic conditional distribution of exceedance counts (ACDEC) $p_k=\lim_{s\nearrow}P(N_s=k\mid N_s>0)$, $1\le k\le d$, exists, if the copula of $\bm X$ is in the domain of attraction of a multivariate extreme value distribution, and if $\lim_{s\nearrow}(1-F_i(s))/(1-F_\kappa(s))=\gamma_i\in[0,\infty)$ exists for $1\le i\le d$ and some $\kappa\in{1,...,d}$. This enables the computation of the FI corresponding to $\bm X$ and of the extended FI as well as of the asymptotic distribution of the exceedance cluster length also in that case, where the components of $\bm X$ are not identically distributed

Exactly solvable Ising--Heisenberg chain with triangular XXZ-Heisenberg plaquettes

A mixed Ising-Heisenberg spin system consisting of triangular XXZ-Heisenberg spin clusters assembled into a chain by alternating with Ising spins interacting to all three spins in the triangle is considered. The exact solution of the model is given in terms of the generalized decoration--iteration map and within the transfer-matrix technique. Exact expressions for thermodynamic functions are derived. Ground state phase diagrams, thermodynamic and magnetic properties of the system are examined.Comment: 16 pages, 12 figure

World caf\ue9 method to engage smart energy-district project partners in assessing urban co-benefits

Urban energy-district projects introduce outstanding technological innovation in buildings and energy systems increasing sustainability in city neighborhoods. Such projects generate additional co-benefits for the city beyond changes in physical elements and development of social and institutional relationships (e.g. local employment, environmental quality, public health, property values, innovation attitude, etc.). Since exceeding main declared goals or not always clearly foreseen in the early project phase, these co-benefits are often not properly understood and considered. However, only their explicit recognition will make possible their inclusion in the assessment of the whole project\u2019s performance. From these considerations, this study faces the issue of engaging project partners in assessing co-benefits in order to consider a broad spectrum of relevant, positive effects in the evaluation process. Group knowledge and group thinking of this complex topic are investigated through the world caf\ue9 method, providing an atmosphere of trust and open discussions among participants. This empirical work lays the foundations to go beyond the mere economic measure as the sole criterion for assessing project effects, also including changes in end-user behavior and intangible asset

Sorting live stem cells based on Sox2 mRNA expression.

PMCID: PMC3507951This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs) offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES) and neural stem cells (NSC). One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+)SSEA1(+) cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+) cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(-) cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner

The direct drivers of recent global anthropogenic biodiversity loss

Effective policies to halt biodiversity loss require knowing which anthropogenic drivers are the most important direct causes. Whereas previous knowledge has been limited in scope and rigor, here we statistically synthesize empirical comparisons of recent driver impacts found through a wide-ranging review. We show that land/sea use change has been the dominant direct driver of recent biodiversity loss worldwide. Direct exploitation of natural resources ranks second and pollution third; climate change and invasive alien species have been significantly less important than the top two drivers. The oceans, where direct exploitation and climate change dominate, have a different driver hierarchy from land and fresh water. It also varies among types of biodiversity indicators. For example, climate change is a more important driver of community composition change than of changes in species populations. Stopping global biodiversity loss requires policies and actions to tackle all the major drivers and their interactions, not some of them in isolation.Fil: Jaureguiberry, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Titeux, Nicolas. German Centre For Integrative Biodiversity Research (idiv) Halle-Jena-Leipzig; Alemania. Luxembourg Institute Of Science And Technology; Luxemburgo. Helmholtz Zentrum Für Umweltforschung; AlemaniaFil: Wiemers, Martin. Helmholtz Zentrum Für Umweltforschung; Alemania. Senckenberg Gesellschaft Für Naturforschung; AlemaniaFil: Bowler, Diana E.. German Centre For Integrative Biodiversity Research (idiv) Halle-Jena-Leipzig; Alemania. Universitat Jena; Alemania. Helmholtz Zentrum Für Umweltforschung; AlemaniaFil: Coscieme, Luca. Hot Or Cool Institute; AlemaniaFil: Golden, Abigail S.. University of Washington; Estados Unidos. German Centre For Integrative Biodiversity Research (idiv) Halle-Jena-Leipzig; Alemania. Department Of Marine And Coastal Sciences; Estados UnidosFil: Guerra, Carlos A.. German Centre For Integrative Biodiversity Research (idiv) Halle-Jena-Leipzig; Alemania. Martin Luther University Halle Wittenberg; AlemaniaFil: Jacob, Ute. Universität Oldenburg; Alemania. Alfred-Wegener-Institut Helmholtz-Zentrum Für Polar- Und Meeresforschung; AlemaniaFil: Takahashi, Yasuo. Institute For Global Environmental Strategies; JapónFil: Settele, Josef. German Centre For Integrative Biodiversity Research (idiv) Halle-Jena-Leipzig; Alemania. University Of The Philippines, Los Baños; Filipinas. Helmholtz Zentrum Für Umweltforschung; AlemaniaFil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Molnár, Zsolt. Institute Of Ecology And Botany; HungríaFil: Purvis, Andy. Imperial College London; Reino Unido. Natural History Museum; Reino Unid

Targeting Sinonasal Undifferentiated Carcinoma With a Combinatory Immunotherapy Approach

PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal cavity with poor prognosis and limited treatment options. To investigate the potential for SNUC sensitivity to combinatory immunotherapy, we performed in vitro studies with SNUC cell lines and used multi-spectral immunofluorescence to characterize the in vivo patient SNUC tumor immune microenvironment (TIME). EXPERIMENTAL DESIGN: Human-derived SNUC cell lines were used for in vitro studies of tumor cell susceptibility to natural killer (NK) cell-based immunotherapeutic strategies. Tumor samples from 14 treatment naïve SNUC patients were examined via multi-spectral immunofluorescence and clinical correlations assessed. RESULTS: Anti-PD-L1 blockade enhanced NK cell lysis of SNUC cell lines ∼5.4 fold (P ≤ 0.0001). This effect was blocked by a CD16 neutralizing antibody demonstrating activity through an antibody-dependent cellular cytotoxicity (ADCC) mediated pathway. ADCC-dependent lysis of SNUC cells was further enhanced by upregulation of PD-L1 on tumor cells by exogenous interferon-gamma (IFN-γ) administration or interleukin-15 (IL-15) stimulated IFN-γ release from NK cells. Combination treatment with anti-PD-L1 blockade and IL-15 superagonism enhanced NK-cell killing of SNUC cells 9.6-fold (P ≤ 0.0001). Untreated SNUC patient tumor samples were found to have an NK cell infiltrate and PD-L1 CONCLUSION: These data provide the pre-clinical rationale for ongoing investigation into combinatory immunotherapy approaches for SNUC

Inhibition of Acetylcholinesterase and Fatty Acid Composition in Theobroma grandiflorum Seeds

Theobroma grandiflorum is an important fruit tree from Sterculiaceae family, native to the Brazilian Amazon, known in the region as cupuaçu. The seeds have a high fat content (24%) with characteristics that resemble those of cocoa (Theobroma cacao) butter with potential applications in the cosmetic, pharmaceutical and food industries. The main objective of this work was to explore the seed fats from T. grandiflorum that were analyzed for fatty acid composition by Gas Chromatography with Flame Ionization Detector (GC-FID) and to analyze their activity for acetylcholinesterase inhibition. Chromatographic analysis provided detection of nine fatty acids. The major fatty acids found in the species were oleic (40.0%), stearic (32.7%), arachidic (10.4%) and palmitic (8.0%). The acetylcholinesterase inhibition by fats from seeds was over 40.48%. DOI: http://dx.doi.org/10.17807/orbital.v0i0.89

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations

SummaryAccumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly “drug-tolerant” cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.PaperCli