The Neron-Severi group of a proper seminormal complex variety

We prove a Lefschetz (1,1)-Theorem for proper seminormal varieties over the complex numbers. The proof is a non-trivial geometric argument applied to the isogeny class of the Lefschetz 1-motive associated to the mixed Hodge structure on H^2.Comment: 16 pages; Mathematische Zeitschrift (2008

Differential Forms on Log Canonical Spaces

The present paper is concerned with differential forms on log canonical varieties. It is shown that any p-form defined on the smooth locus of a variety with canonical or klt singularities extends regularly to any resolution of singularities. In fact, a much more general theorem for log canonical pairs is established. The proof relies on vanishing theorems for log canonical varieties and on methods of the minimal model program. In addition, a theory of differential forms on dlt pairs is developed. It is shown that many of the fundamental theorems and techniques known for sheaves of logarithmic differentials on smooth varieties also hold in the dlt setting. Immediate applications include the existence of a pull-back map for reflexive differentials, generalisations of Bogomolov-Sommese type vanishing results, and a positive answer to the Lipman-Zariski conjecture for klt spaces.Comment: 72 pages, 6 figures. A shortened version of this paper has appeared in Publications math\'ematiques de l'IH\'ES. The final publication is available at http://www.springerlink.co

Hirzebruch-Milnor classes and Steenbrink spectra of certain projective hypersurfaces

We show that the Hirzebruch-Milnor class of a projective hypersurface, which gives the difference between the Hirzebruch class and the virtual one, can be calculated by using the Steenbrink spectra of local defining functions of the hypersurface if certain good conditions are satisfied, e.g. in the case of projective hyperplane arrangements, where we can give a more explicit formula. This is a natural continuation of our previous paper on the Hirzebruch-Milnor classes of complete intersections.Comment: 15 pages, Introduction is modifie

Regina Lectures on Fat Points

These notes are a record of lectures given in the Workshop on Connections Between Algebra and Geometry at the University of Regina, May 29--June 1, 2012. The lectures were meant as an introduction to current research problems related to fat points for an audience that was not expected to have much background in commutative algebra or algebraic geometry (although sections 8 and 9 of these notes demand somewhat more background than earlier sections).Comment: 32 pages, 3 figure

Surface-functionalization with NFL peptide of Lipid NanoCapsules LNC: preferential entry into human glioblastoma cells

Glioblastoma (GBM) is one of the most fatal brain cancers with median survival of only 14.6 months. Hence, more efficacious therapies are necessary. Ferrocifen (FcTriOH) is an organometallic antitumor compound, selectively active on cancer cells [1]. However, this metallocomplexe is highly insoluble in water, requiring a formulation stage before being in vivo administered. Lipid nanocapsules (LNC), prepared via a solvent free process of emulsion phase inversion, could be a suitable vehicle for FcTriOH [2]. Moreover, NFL peptide is able to enter massively into glioblastoma cells, and poorly in healthy neurons and astrocytes (NHA) [3]. Indeed, the aim of the study was to evaluate the effect of the surface-functionalizing NFL concentrations on LNC uptake in U87MG human GBM cells. Moreover, FcTriOH was encapsulated in LNC and their in vitro efficacy on U87MG cells was evaluated. Finally, in vivo antitumor effect was evaluated in ectopic and orthotopic murine U87MG tumor models. Fluorescent LNC (F1), LNC with 0.86% w/w and LNC with 2.58% w/w surface-adsorbed NFL (F2 and F3 respectively) were prepared and characterized. FACS analysis revealed that cellular uptake of F3 into U87MG cells was 31.5 and 1.6-folds higher after 6 h compared to F1 and F2 respectively. Moreover, uptake of F3 was significantly higher in the GBM cells compared to NHA, whereas F1 was internalized preferentially in NHA. Uptake of F3 in U87MG cells was energy dependent. Macropinocytosis was possibly the major uptake pathway, followed by clathrin-dependent endocytosis. Then, FcTriOH loaded LNCs have been successfully prepared with a drug loading of 2.4 % and an encapsulation efficacy of 99 %. MTS assay on U87MG cells revealed an IC50 of 0.46 µM for F3-FcTriOH (free FcTriOH: IC50 = 1.31 µM). Preliminary in vivo experiments on subcutaneous U87MG tumor bearing nude mice showed significantly reduced relative tumor volume after two intravenous injections of F1-FcTriOH and F3-FcTriOH compared to saline. Moreover, intracranial administration of F3/F3-FcTriOH in orthotopic U87MG tumor bearing mice revealed 2 to 3-folds higher apparent diffusion coefficients (ADC) near the injection site in diffusion tensor imaging, compared to F1/F1-FcTriOH. Although dose adjustment will be necessary to avoid toxic effects, the results are promising as therapy induced increased ADC values could indicate possible cell necrosis/lysis.   References [1] Laine A.L. et al. (2014), Nanomedicine, 10, pp.1667-1677. [2] Heurtault B. et al. (2003), EJPS, 8, pp. 55-61. [3] Balzeau J. et al. (2013), Biomaterials, 34, pp.3381-3389

Resource: A multi‐species multi‐timepoint transcriptome database and webpage for the pineal gland and retina

The website and database https://snengs.nichd.nih.gov provides RNA sequencing data from multi-species analysis of the pineal glands from zebrafish (Danio rerio), chicken (White Leghorn), rat (Rattus novegicus), mouse (Mus musculus), rhesus macaque (Macaca mulatta), and human (Homo sapiens); in most cases, retinal data are also included along with results of the analysis of a mixture of RNA from tissues. Studies cover day and night conditions; in addition, a time series over multiple hours, a developmental time series and pharmacological experiments on rats are included. The data have been uniformly re-processed using the latest methods and assemblies to allow for comparisons between experiments and to reduce processing differences. The website presents search functionality, graphical representations, Excel tables, and track hubs of all data for detailed visualization in the UCSC Genome Browser. As more data are collected from investigators and improved genomes become available in the future, the website will be updated. This database is in the public domain and elements can be reproduced by citing the URL and this report. This effort makes the results of 21st century transcriptome profiling widely available in a user-friendly format that is expected to broadly influence pineal research.Fil: Chang, Eric. National Instituto of Child Health & Human Development; Estados UnidosFil: Fu, Cong. National Instituto of Child Health & Human Development; Estados UnidosFil: Coon, Steven L.. National Instituto of Child Health & Human Development; Estados UnidosFil: Alon, Shahar. No especifíca;Fil: Bozinoski, Marjan. No especifíca;Fil: Breymaier, Matthew. National Instituto of Child Health & Human Development; Estados UnidosFil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Clokie, Samuel J.. National Instituto of Child Health & Human Development; Estados UnidosFil: Gothilf, Yoav. No especifíca;Fil: Esnault, Caroline. National Instituto of Child Health & Human Development; Estados UnidosFil: Iuvone, P. Michael. Emory University School of Medicine; Estados UnidosFil: Mason, Christopher E.. No especifíca;Fil: Ochocinska, Margaret J.. National Instituto of Child Health & Human Development; Estados UnidosFil: Tovin, Adi. No especifíca;Fil: Wang, Charles. Loma Linda University; Estados UnidosFil: Xu, Pinxian. No especifíca;Fil: Zhu, Jinhang. No especifíca;Fil: Dale, Ryan. National Instituto of Child Health & Human Development; Estados UnidosFil: Klein, David C.. National Instituto of Child Health & Human Development; Estados Unido

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Nursing Care of Patients With Cirrhosis: The LiverHope Nursing Project

Cirrhosis is a complex disease that is associated with disturbances in different organs besides the liver, including kidneys, heart, arterial circulation, lungs, gut, and brain. As a consequence, patients develop a number of complications that result in frequent hospital admissions and high morbidity and mortality. Patients with cirrhosis require constant and rigorous monitoring both in and outside the hospital. In this context, the role of nurses in the care of patients with cirrhosis has not been sufficiently emphasized and there is very limited information about nursing care of patients with cirrhosis compared with other chronic diseases. The current article provides a review of nursing care for the different complications of patients with cirrhosis. Nurses with specific knowledge on liver diseases should be incorporated into multidisciplinary teams managing patients with cirrhosis, both inpatient and outpatient. Conclusion: Nurses play an important role in the management and prevention of complications of the disease and improvement in patients’ quality of life and bridge the gap between clinicians and families, between primary care and hospital care, and provide medical education to patients and caregivers

Lichenological exploration of Algeria: historical overview and annotated bibliography, 1799-2013

yesDespite more than two centuries of almost uninterrupted surveys and studies of Algerian lichenology, the history and lichen diversity of Algeria are still poorly understood. During the preparation of a forthcoming checklist of Algerian lichens it was considered necessary to provide the present historical overview of lichenological exploration of the country from 1799 to 2013, supported by a reasonably comprehensive annotated bibliography of 171 titles

Pin1 Modulates the Type 1 Immune Response

BACKGROUND/ABSTRACT: Immune responses initiated by T cell receptor (TCR) and costimulatory molecule mediated signaling culminate in maximal cytokine mRNA production and stability. The transcriptional responses to co-stimulatory T cell signalling involve calcineurin and NF-AT, which can be antagonized by interference with the cis-trans peptidyl-prolyl isomerases (PPIase), cyclophilin A and FKBP. Signalling molecules downstream of CD28 which are essential for the stabilization of cytokine mRNAs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We now show that Pin1, a third member of the PPIase family mediates the post-transcriptional regulation of Th1 cytokines by activated T cells. Blockade of Pin1 by pharmacologic or genetic means greatly attenuated IFN-γ, IL-2 and CXCL-10 mRNA stability, accumulation and protein expression after cell activation. In vivo, Pin1 blockade prevented both the acute and chronic rejection of MHC mismatched, orthotopic rat lung transplants by reducing the expression of IFN-γ and CXCL-10. Combined transcriptional and post-transcriptional blockade with cyclosporine A and the Pin1 inhibitor, juglone, was synergistic. CONCLUSIONS/SIGNIFICANCE: These data suggest Pin1 inhibitors should be explored for use as immunosuppressants and employed with available calcineurin inhibitors to reduce toxicity and enhance effectiveness