Biting midges (Diptera: Ceratopogonidae) from an urban forest fragment in Central Amazon (Brazil): Effects of opening areas on abundance, richness, and composition

We assessed the immature stages of Ceratopogonidae (Diptera) in artificial containers in an urban forest fragment in Manaus (Brazil), including their behavioral, biological and ecological information. In addition, we evaluated the effects of deforestation in an open and forested area on Ceratopogonidae communities. Immatures were sampled between August 2012 and July 2014 in artificial containers installed in both habitat types. We collected 685 immatures of seven morpho-species of Bezzia Kieffer, Culicoides Latreille, Dasyhelea Kieffer, Forcipomyia Meigen, and Palpomyia Meigen. In the open area, we recorded higher temperature and electrical conductivity values than in the forested area; however, these variables did not differ between seasons. Water volume was higher in open area and in rainy season, while pH was similar in both areas and seasons. Species richness was higher in forested area, but did not differ between seasons. We did not record differences in abundance between areas or seasons. Community composition differed between areas, but not between seasons. We provide the first records of Culicoides (Hoffmania) insignis Lutz and C. (Haematomyidium) quasiparaensis Clastrier in artificial containers from the state of Amazonas. Our results suggest that the preservation of forested areas in Amazonas is fundamental for the maintenance of the life cycle of some species of Ceratopogonidae.Centro de Estudios Parasitológicos y de VectoresFacultad de Ciencias Naturales y Muse

Another step toward DNA selective targeting: NiII and CuII complexes of a Schiff base ligand able to bind gene promoter G-quadruplexes

DNA G-rich sequences are able to form four-stranded structures organized in stacked guanine tetrads. These structures, called G-quadruplexes, were found to have an important role in the regulation of oncogenes expression and became, for such a reason, appealing targets for anticancer drugs. Aiming at finding selective G-quadruplex binders, we have designed, synthesized and characterized a new water soluble Salen-like Schiff base ligand and its NiII and CuII metal complexes. UV-Vis, circular dichroism and FRET measurements indicated that the nickel complex can stabilize oncogene promoter G-quadruplexes with high selectivity, presenting no interactions with duplex DNA at all. The same compound exhibited dose-dependent cytotoxic activity in MCF-7 breast cancer cells when combined with lipofectamine as lipophilic carrier

Controlled assembly of SNAP-PNA-fluorophore systems on DNA templates to produce fluorescence resonance energy transfer

The SNAP protein is a widely used self-labeling tag that can be used for tracking protein localization and trafficking in living systems. A model system providing controlled alignment of SNAP-tag units can provide a new way to study clustering of fusion proteins. In this work, fluorescent SNAP-PNA conjugates were controllably assembled on DNA frameworks forming dimers, trimers, and tetramers. Modification of peptide nucleic acid (PNA) with the O6-benzyl guanine (BG) group allowed the generation of site-selective covalent links between PNA and the SNAP protein. The modified BG-PNAs were labeled with fluorescent Atto dyes and subsequently chemo-selectively conjugated to SNAP protein. Efficient assembly into dimer and oligomer forms was verified via size exclusion chromatography (SEC), electrophoresis (SDS-PAGE), and fluorescence spectroscopy. DNA directed assembly of homo- and hetero-dimers of SNAP-PNA constructs induced homo- and hetero-FRET, respectively. Longer DNA scaffolds controllably aligned similar fluorescent SNAP-PNA constructs into higher oligomers exhibiting homo-FRET. The combined SEC and homo-FRET studies indicated the 1:1 and saturated assemblies of SNAP-PNA-fluorophore:DNA formed preferentially in this system. This suggested a kinetic/stoichiometric model of assembly rather than binomially distributed products. These BG-PNA-fluorophore building blocks allow facile introduction of fluorophores and/or assembly directing moieties onto any protein containing SNAP. Template directed assembly of PNA modified SNAP proteins may be used to investigate clustering behavior both with and without fluorescent labels which may find use in the study of assembly processes in cells

Biting midges (Diptera: Ceratopogonidae) from an urban forest fragment in Central Amazon (Brazil): Effects of opening areas on abundance, richness, and composition

We assessed the immature stages of Ceratopogonidae (Diptera) in artificial containers in an urban forest fragment in Manaus (Brazil), including their behavioral, biological and ecological information. In addition, we evaluated the effects of deforestation in an open and forested area on Ceratopogonidae communities. Immatures were sampled between August 2012 and July 2014 in artificial containers installed in both habitat types. We collected 685 immatures of seven morpho-species of Bezzia Kieffer, Culicoides Latreille, Dasyhelea Kieffer, Forcipomyia Meigen, and Palpomyia Meigen. In the open area, we recorded higher temperature and electrical conductivity values than in the forested area; however, these variables did not differ between seasons. Water volume was higher in open area and in rainy season, while pH was similar in both areas and seasons. Species richness was higher in forested area, but did not differ between seasons. We did not record differences in abundance between areas or seasons. Community composition differed between areas, but not between seasons. We provide the first records of Culicoides (Hoffmania) insignis Lutz and C. (Haematomyidium) quasiparaensis Clastrier in artificial containers from the state of Amazonas. Our results suggest that the preservation of forested areas in Amazonas is fundamental for the maintenance of the life cycle of some species of Ceratopogonidae.Centro de Estudios Parasitológicos y de VectoresFacultad de Ciencias Naturales y Muse

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial

Background: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-naïve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m2 (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m2, all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. Patients and methods: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. Results: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m2. The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. Conclusions: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment optio

Experimental Determination of the Characteristics of a Positron Source Using Channeling

Numerical simulations and `proof of principle' experiments showed clearly the interest of using crystals as photon generators dedicated to intense positron sources for linear colliders. An experimental investigation, using a 10 GeV secondary electron beam, of the SPS-CERN, impinging on an axially oriented thick tungsten crystal, has been prepared and operated between May and August 2000. After a short recall on the main features of positron sources using channeling in oriented crystals, the experimental set-up is described. A particular emphasis is put on the positron detector made of a drift chamber, partially immersed in a magnetic field. The enhancement in photon and positron production in the aligned crystal have been observed in the energy range 5 to 40 GeV, for the incident electrons, in crystals of 4 and 8 mm as in an hybrid target. The first results concerning this experiment are presented hereafter.Comment: 3 pages, 6 figures, submitted to Linac200

Post conjunction detection of β\beta Pictoris b with VLT/SPHERE

With an orbital distance comparable to that of Saturn in the solar system, \bpic b is the closest (semi-major axis $\simeq$\,9\,au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to \bpic have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters. We aimed at further constraining \bpic b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit. We used SPHERE at the VLT to precisely monitor the orbital motion of beta \bpic b since first light of the instrument in 2014. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6\,au) and prevented further detection. We redetected \bpic b on the northeast side of the disk at a separation of 139\,mas and a PA of 30$^{\circ}$ in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of $a = 9.0 \pm 0.5$ au (1 $\sigma$), it definitely excludes previously reported possible long orbital periods, and excludes \bpic b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.Comment: accepted by A&

Emerging transporters of clinical importance: an update from the International Transporter Consortium

The International Transporter Consortium (ITC) has recently described seven transporters of particular relevance to drug development. Based on the second ITC transporter workshop in 2012, we have identified additional transporters of emerging importance in pharmacokinetics, interference of drugs with transport of endogenous compounds, and drug-drug interactions (DDIs) in humans. The multidrug and toxin extrusion proteins (MATEs, gene symbol SLC47A) mediate excretion of organic cations into bile and urine. MATEs are important in renal DDIs. Multidrug resistance proteins (MRPs or ABCCs) are drug and conjugate efflux pumps, and impaired activity of MRP2 results in conjugated hyperbilirubinemia. The bile salt export pump (BSEP or ABCB11) prevents accumulation of toxic bile salt concentrations in hepatocytes, and BSEP inhibition or deficiency may cause cholestasis and liver injury. In addition, examples are presented on the roles of nucleoside and peptide transporters in drug targeting and disposition

Random Tilings: Concepts and Examples

We introduce a concept for random tilings which, comprising the conventional one, is also applicable to tiling ensembles without height representation. In particular, we focus on the random tiling entropy as a function of the tile densities. In this context, and under rather mild assumptions, we prove a generalization of the first random tiling hypothesis which connects the maximum of the entropy with the symmetry of the ensemble. Explicit examples are obtained through the re-interpretation of several exactly solvable models. This also leads to a counterexample to the analogue of the second random tiling hypothesis about the form of the entropy function near its maximum.Comment: 32 pages, 42 eps-figures, Latex2e updated version, minor grammatical change