The contradictory effect of the methoxy-substituent in palladium-catalyzed ethylene/methyl acrylate cooligomerization

Two new nonsymmetric bis(aryl-imino)acenaphthene ligands (Ar,Ar'-BIAN) and one symmetric Ar2-BIAN were studied. The three ligands share the presence of at least one methoxy group on one of the two aryl rings. These ligands were used for the synthesis of neutral and monocationic palladium(II) complexes of general formula [Pd(CH3)Cl(N-N)] and [Pd(CH3)(L)(N-N)][PF6] (N-N = Ar,Ar'-BIAN, Ar2-BIAN; L = CH3CN, dmso). Due to the nonsymmetric nature of the ligands and their coordination to palladium in a nonsymmetric chemical environment, cis and trans isomers are possible for the three series of complexes with Ar,Ar'-BIANs. Both a detailed NMR investigation in solution and the X-ray characterization in solid state point out that the trans isomer is the preferred species for the neutral derivatives, whereas for the cationic compounds a decrease in the stereoselectivity of the coordination is observed. One of the new Ar,Ar'-BIANs differs from an already reported nonsymmetric \uf061-diimine for the replacement, on one aryl ring, of a methyl group with a methoxy susbtituent, thus allowing a comparison of the structural features of the relevant complexes. The monocationic complexes were tested as precatalysts for the ethylene/methyl acrylate copolymerization under mild reaction conditions. Despite the structural similarities observed in solution with the already known precatalysts, the present compounds demonstrated a remarkable decrease in the productivity values associated to a higher affinity for the polar monomer

SARX Model Application for Industrial Power Demand Forecasting in Brazil

The objective of this paper is to propose the application of the SARX model to arrive at industrial power consumption forecasts in Brazil, which are critical to support decisionmaking in the energy sector, based on technical, economic and environmentally sustainable grounds. The proposed model has a seasonal component and considers the influence of exogenous variables on the projection of the dependent variable and utilizes an autoregressive process for residual modeling so as to improve its explanatory power. Five exogenous variables were included: industrial capacity utilization, industrial electricity tariff, industrial real revenues, exchange rate, and machinery and equipment inflation. In addition, the model assumed that power forecast was dependent on its own time lags and also on a dummy variable to reflect 2009 economic crisis. The study used 84 monthly observations, from January 2003 to December 2009. The backward method was used to select exogenous variables, assuming a 0.10 descriptive value. The results showed an adjusted coefficient of determination of 93.9% and all the estimated coefficients were statistically significant at a 0.10 descriptive level. Forecasts were also made from January to May 2010 at a 95% confidence interval, which included actual consumption values for this period. The SARX model has demonstrated an excellent performance for industrial power consumption forecasting in Brazil

Mechanisms involved in the promoting activity of fibroblasts in HTLV-1-mediated lymphomagenesis: Insights into the plasticity of lymphomatous cells

Among the mechanisms leading to progression to Adult T-cell Leukaemia/Lymphoma in Human T-cell Leukaemia Virus type 1 (HTLV-1)-infected subjects, the contribution of stromal components remains poorly understood. To dissect the role of fibroblasts in HTLV-1-mediated lymphomagenesis, transcriptome studies, cytofluorimetric and qRT-PCR analyses of surface and intracellular markers linked to plasticity and stemness in coculture, and in vivo experiments were performed. A transcriptomic comparison between a more lymphomagenic (C91/III) and the parental (C91/PL) cell line evidenced hyperactivation of the PI3K/Akt pathway, confirmed by phospho-ELISA and 2-DE and WB analyses. C91/III cells also showed higher expression of mesenchymal and stemness genes. Short-term coculture with human foreskin fibroblasts (HFF) induced these features in C91/PL cells, and significantly increased not only the cancer stem cells (CSCs)-supporting CD10+GPR77+ HFF subpopulation, but also the percentage of ALDH1bright C91/PL cells. A non-cytotoxic acetylsalicylic acid treatment decreased HFF-induced ALDH1bright C91/PL cells, downregulated mesenchymal and stemness genes in cocultured cells, and delayed lymphoma growth in immunosuppressed mice, thus hindering the supportive activity of HFF on CSCs. These data suggest that crosstalk with HFF significantly intensifies the aggressiveness and plasticity of C91/PL cells, leading to the enrichment in lymphoma-initiating cells. Additional research is needed to better characterize these preliminary findings

The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis

This article is available open access through the publisher’s website at the link below. Copyright @ 2013 The American Society of Gene & Cell Therapy.Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.Imperial College London, the Wellcome Trust, and Brunel University

Identification of a novel gene required for competitive growth at high temperature in the thermotolerant yeast Kluyveromyces marxianus

It is important to understand the basis of thermotolerance in yeasts to broaden their application in industrial biotechnology. The capacity to run bioprocesses at temperatures above 40 \ub0C is of great interest but this is beyond the growth range of most of the commonly used yeast species. In contrast, some industrial yeasts such as Kluyveromyces marxianus can grow at temperatures of 45 \ub0C or higher. Such species are valuable for direct use in industrial biotechnology and as a vehicle to study the genetic and physiological basis of yeast thermotolerance. In previous work, we reported that evolutionarily young genes disproportionately changed expression when yeast were growing under stressful conditions and postulated that such genes could be important for long-term adaptation to stress. Here, we tested this hypothesis in K. marxianus by identifying and studying species-specific genes that showed increased expression during high-temperature growth. Twelve such genes were identified and 11 were successfully inactivated using CRISPR-mediated mutagenesis. One gene, KLMX_70384, is required for competitive growth at high temperature, supporting the hypothesis that evolutionary young genes could play roles in adaptation to harsh environments. KLMX_70384 is predicted to encode an 83 aa peptide, and RNA sequencing and ribo-sequencing were used to confirm transcription and translation of the gene. The precise function of KLMX_70384 remains unknown but some features are suggestive of RNA-binding activity. The gene is located in what was previously considered an intergenic region of the genome, which lacks homologues in other yeasts or in databases. Overall, the data support the hypothesis that genes that arose de novo in K. marxianus after the speciation event that separated K. marxianus and K. lactis contribute to some of its unique traits

Evaluation of Standard Precautions Compliance Instruments: A Systematic Review Using COSMIN Methodology

Background: Standard precautions (SPs) are first-line strategies with a dual goal: to protect health care workers from occupational contamination while providing care to infected patients and to prevent/reduce health care-associated infections (HAIs). This study aimed at (1) identifying the instruments currently available for measuring healthcare professionals’ compliance with standard precautions; (2) evaluating their measurement properties; and (3) providing sound evidence for instrument selection for use by researchers, teachers, staff trainers, and clinical tutors. Methods: We carried out a systematic review to examine the psychometric properties of standard precautions self-assessment instruments in conformity with the COSMIN guidelines. The search was conducted on the databases PubMed, CINAHL, and APA PsycInfo. Results: Thirteen instruments were identified. These were classified into four categories of tools assessing: compliance with universal precautions, adherence to standard precautions, compliance with hand hygiene, and adherence to transmission-based guidelines and precautions. The psychometric properties of instruments and methodological approaches of the included studies were often not satisfactory. Only four instruments were classified as high-quality measurements. Conclusions: The available instruments that measure healthcare professionals’ compliance with standard precautions are of low-moderate quality. It is necessary that future research completes the validation processes undertaken for long-established and newly developed instruments, using higher-quality methods and estimating all psychometric properties

Stress-induced expression is enriched for evolutionarily young genes in diverse budding yeasts

The Saccharomycotina subphylum (budding yeasts) spans 400 million years of evolution and includes species that thrive in diverse environments. To study niche-adaptation, we identify changes in gene expression in three divergent yeasts grown in the presence of various stressors. Duplicated and non-conserved genes are significantly more likely to respond to stress than genes that are conserved as single-copy orthologs. Next, we develop a sorting method that considers evolutionary origin and duplication timing to assign an evolutionary age to each gene. Subsequent analysis reveals that genes that emerged in recent evolutionary time are enriched amongst stress-responsive genes for each species. This gene expression pattern suggests that budding yeasts share a stress adaptation mechanism, whereby selective pressure leads to functionalization of young genes to improve growth in adverse conditions. Further characterization of young genes from species that thrive in harsh environments can inform the design of more robust strains for biotechnology

miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia

MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden

4.5 years multi-wavelength observations of Mrk 421 during the ARGO-YBJ and Fermi common operation time

We report on the extensive multi-wavelength observations of the blazar Markarian 421 (Mrk 421) covering radio to gamma-rays, during the 4.5 year period of ARGO-YBJ and Fermi common operation time, from August 2008 to February 2013. In particular, thanks to the ARGO-YBJ and Fermi data, the whole energy range from 100 MeV to 10 TeV is covered without any gap. In the observation period, Mrk 421 showed both low and high activity states at all wavebands. The correlations among flux variations in different wavebands were analyzed. Seven large flares, including five X-ray flares and two GeV gamma-ray flares with variable durations (3-58 days), and one X-ray outburst phase were identified and used to investigate the variation of the spectral energy distribution with respect to a relative quiescent phase. During the outburst phase and the seven flaring episodes, the peak energy in X-rays is observed to increase from sub-keV to few keV. The TeV gamma-ray flux increases up to 0.9-7.2 times the flux of the Crab Nebula. The behavior of GeV gamma-rays is found to vary depending on the flare, a feature that leads us to classify flares into three groups according to the GeV flux variation. Finally, the one-zone synchrotron self-Compton model was adopted to describe the emission spectra. Two out of three groups can be satisfactorily described using injected electrons with a power-law spectral index around 2.2, as expected from relativistic diffuse shock acceleration, whereas the remaining group requires a harder injected spectrum. The underlying physical mechanisms responsible for different groups may be related to the acceleration process or to the environment properties.Comment: 17 pages, 9 figures, 5 tables, Accepted for publication in ApJ

The cosmic ray proton plus helium energy spectrum measured by the ARGO-YBJ experiment in the energy range 3-300 TeV

The ARGO-YBJ experiment is a full-coverage air shower detector located at the Yangbajing Cosmic Ray Observatory (Tibet, People's Republic of China, 4300 m a.s.l.). The high altitude, combined with the full-coverage technique, allows the detection of extensive air showers in a wide energy range and offer the possibility of measuring the cosmic ray proton plus helium spectrum down to the TeV region, where direct balloon/space-borne measurements are available. The detector has been in stable data taking in its full configuration from November 2007 to February 2013. In this paper the measurement of the cosmic ray proton plus helium energy spectrum is presented in the region 3-300 TeV by analyzing the full collected data sample. The resulting spectral index is $\gamma = -2.64 \pm 0.01$. These results demonstrate the possibility of performing an accurate measurement of the spectrum of light elements with a ground based air shower detector.Comment: 18 pages, 8 figures, preprint submitted to Phys. Rev.