TINGKAT PARTISIPASI PENGELOLAAN DAN ANALISIS FINANSIAL HUTAN RAKYAT DENGAN SISTEM TUNDA TEBANG DI KABUPATEN KONAWE SELATAN

This study aims to determine the mechanism, level of participation, financial analysis in following the delayed logging program in community forests. The research was located in the community forests of Watudemba and Ulu Lakara villages, Konawe Selatan District from April to May 2018. Data collection techniques were carried out by observation, direct communication with 16 respondents and bibliographical studies. n addition, measurements were made by making 17 sample plots of teak stands (Tectona grandis L.f). The data analysis uses quantitative and qualitative methods. The results showed that: 1) The delay logging program mechanism consists of three stages, namely agreeing and signing a pending felling program agreement, distribution and loan repayment. 2) While the level of community participation in participating in the delayed cutting program at the planning stage (moderate-high, 81.25%), organizing (moderate-high, 68, 75%), implementation (moderate-high, 81.25%), as well as supervision and evaluation (moderate-high, 56.25%). 3) NPV value obtained is Rp. 266,811,200,-; BCR value obtained was 5.29; and the IRR value obtained by 37% over the age of the analysis of twenty years.

Spectral optical monitoring of 3C390.3 in 1995-2007: I. Light curves and flux variation of the continuum and broad lines

Here we present the results of the long-term (1995-2007) spectral monitoring of the broad line radio galaxy \object{3C~390.3}, a well known AGN with the double peaked broad emission lines, usually assumed to be emitted from an accretion disk. To explore dimensions and structure of the BLR, we analyze the light curves of the broad H$\alpha$ and H$\beta$ line fluxes and the continuum flux. In order to find changes in the BLR, we analyze the H$\alpha$ and H$\beta$ line profiles, as well as the change in the line profiles during the monitoring period. First we try to find a periodicity in the continuum and H$\beta$ light curves, finding that there is a good chance for quasi-periodical oscillations. Using the line shapes and their characteristics (as e.g. peaks separation and their intensity ratio, or FWHM) of broad H$\beta$ and H$\alpha$ lines, we discuss the structure of the BLR. Also, we cross-correlate the continuum flux with H$\beta$ and H$\alpha$ lines to find dimensions of the BLR. We found that during the monitoring period the broad emission component of the H$\alpha$ and H$\beta$ lines, and the continuum flux varied by a factor of $\approx$4-5. Also, we detected different structure in the line profiles of H$\alpha$ and H$\beta$. It seems that an additional central component is present and superposed to the disk emission. In the period of high activity (after 2002), H$\beta$ became broader than H$\alpha$ and red wing of H$\beta$ was higher than the one of H$\alpha$. We found time lags of $\sim$95 days between the continuum and H$\beta$ flux, and about 120 days between the continuum and H$\alpha$ flux. Variation in the line profiles, as well as correlation between the line and continuum flux during the monitoring period is in the favor of the disk origin of the broad lines with the possible contribution of some additional region and/or some kind of perturbation in the disk.Comment: 32 pages, accepted to A&A, typos correcte

HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy

Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial.W In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G − cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer.Fil: Palma, Maria Belen. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Tronik Le Roux, Diana. Saint-Louis Hospital; Francia. Universite de Paris 1 - Pantheon Sorbonne.; FranciaFil: Amin, Guadalupe. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castañeda, Sheila Lucia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Möbbs, Alan Miqueas. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scarafia, Maria Agustina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: la Greca, Alejandro Damián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Daouya, Marina. Hôpital Saint-louis; Francia. Universite de Paris 1 - Pantheon Sorbonne.; FranciaFil: Poras, Isabelle. Hôpital Saint-louis; Francia. Universite de Paris 1 - Pantheon Sorbonne.; FranciaFil: Inda, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Moro, Lucía Natalia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carosella, Edgardo Delfino. Hôpital Saint-louis; Francia. Universite de Paris 1 - Pantheon Sorbonne.; FranciaFil: García, Marcela Nilda. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Departamento de Ciencias Morfológicas. Cátedra de Citología y Embriología A; ArgentinaFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Multiplicity: an organizing principle for cancers and somatic mutations

<p>Abstract</p> <p>Background</p> <p>With the advent of whole-genome analysis for profiling tumor tissue, a pressing need has emerged for principled methods of organizing the large amounts of resulting genomic information. We propose the concept of multiplicity measures on cancer and gene networks to organize the information in a clinically meaningful manner. Multiplicity applied in this context extends Fearon and Vogelstein's multi-hit genetic model of colorectal carcinoma across multiple cancers.</p> <p>Methods</p> <p>Using the Catalogue of Somatic Mutations in Cancer (COSMIC), we construct networks of interacting cancers and genes. Multiplicity is calculated by evaluating the number of cancers and genes linked by the measurement of a somatic mutation. The Kamada-Kawai algorithm is used to find a two-dimensional minimum energy solution with multiplicity as an input similarity measure. Cancers and genes are positioned in two dimensions according to this similarity. A third dimension is added to the network by assigning a maximal multiplicity to each cancer or gene. Hierarchical clustering within this three-dimensional network is used to identify similar clusters in somatic mutation patterns across cancer types.</p> <p>Results</p> <p>The clustering of genes in a three-dimensional network reveals a similarity in acquired mutations across different cancer types. Surprisingly, the clusters separate known causal mutations. The multiplicity clustering technique identifies a set of causal genes with an area under the ROC curve of 0.84 versus 0.57 when clustering on gene mutation rate alone. The cluster multiplicity value and number of causal genes are positively correlated via Spearman's Rank Order correlation (<it>r_s</it>(8) = 0.894, Spearman's <it>t </it>= 17.48, <it>p </it>< 0.05). A clustering analysis of cancer types segregates different types of cancer. All blood tumors cluster together, and the cluster multiplicity values differ significantly (Kruskal-Wallis, <it>H </it>= 16.98, <it>df </it>= 2, <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>We demonstrate the principle of multiplicity for organizing somatic mutations and cancers in clinically relevant clusters. These clusters of cancers and mutations provide representations that identify segregations of cancer and genes driving cancer progression.</p

A TNF-JNK-Axl-ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma.

Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in turn of c-Jun N-terminal kinase (JNK), the Axl receptor tyrosine kinase and extracellular signal-regulated kinases (ERK). Inhibition of this adaptive axis at multiple nodes rendered glioma cells with primary resistance sensitive to EGFR inhibition. Our findings provide a possible explanation for the failures of anti-EGFR therapy in GBM and suggest a new approach to the treatment of EGFR-expressing GBM using a combination of EGFR and TNF inhibition

Single-cell analysis tools for drug discovery and development

The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed