In-situ growth optimization in focused electron-beam induced deposition

We present the application of an evolutionary genetic algorithm for the in-situ optimization of nanostructures prepared by focused electron-beam-induced deposition. It allows us to tune the properties of the deposits towards highest conductivity by using the time gradient of the measured in-situ rate of change of conductance as fitness parameter for the algorithm. The effectiveness of the procedure is presented for the precursor W(CO)6 as well as for post-treatment of Pt-C deposits obtained by dissociation of MeCpPt(Me)3. For W(CO)6-based structures an increase of conductivity by one order of magnitude can be achieved, whereas the effect for MeCpPt(Me)3 is largely suppressed. The presented technique can be applied to all beam-induced deposition processes and has great potential for further optimization or tuning of parameters for nanostrucures prepared by FEBID or related techniques

Juvenile Hormone (JH) Esterase of the Mosquito Culex quinquefasciatus Is Not a Target of the JH Analog Insecticide Methoprene

Juvenile hormones (JHs) are essential sesquiterpenes that control insect development and reproduction. JH analog (JHA) insecticides such as methoprene are compounds that mimic the structure and/or biological activity of JH. In this study we obtained a full-length cDNA, cqjhe, from the southern house mosquito Culex quinquefasciatus that encodes CqJHE, an esterase that selectively metabolizes JH. Unlike other recombinant esterases that have been identified from dipteran insects, CqJHE hydrolyzed JH with specificity constant (kcat/KM ratio) and Vmax values that are common among JH esterases (JHEs). CqJHE showed picomolar sensitivity to OTFP, a JHE-selective inhibitor, but more than 1000-fold lower sensitivity to DFP, a general esterase inhibitor. To our surprise, CqJHE did not metabolize the isopropyl ester of methoprene even when 25 pmol of methoprene was incubated with an amount of CqJHE that was sufficient to hydrolyze 7,200 pmol of JH to JH acid under the same assay conditions. In competition assays in which both JH and methoprene were available to CqJHE, methoprene did not show any inhibitory effects on the JH hydrolysis rate even when methoprene was present in the assay at a 10-fold higher concentration relative to JH. Our findings indicated that JHE is not a molecular target of methoprene. Our findings also do not support the hypothesis that methoprene functions in part by inhibiting the action of JHE

Production Characteristics and Body Composition of Juvenile Cobia Fed Three Different Commercial Diets in Recirculating Aquaculture Systems

The effect of feeding three commercial diets on production characteristics and body composition of juvenile cobia Rachycentron canadum reared using recirculating aquaculture systems (RASs) was assessed in a 56-d growth trial. Juvenile cobia (mean weight ± SE, 29.2 ± 0.7 g) were stocked into three 8-m3 tanks in each of four RASs at an initial density of 1.2 kg/m3. After stocking, fish were fed one of three commercial diets: Hybrid Striped Bass diet (HSB; 44% protein, 12% lipid), Finfish Gold diet (GOLD; 42% protein, 16% lipid), or Marine Grower diet (MG; 50% protein, 15% lipid), all at a targeted feed rate of 3–5% of body weight per day. At 2-week intervals, 10% of the population of each tank was collected to determine mean weight, weight gain, specific growth rate (SGR), feed conversion efficiency (FCE), and biomass. At the end of the rearing trial, the entire population of each tank was harvested to determine production characteristics and survival. In addition, fish were sampled to determine whole-body composition, hepatosomatic index, intraperitoneal fat ratio, energy retention (ER), protein efficiency ratio (PER), and protein productive value (PPV). Final weight (311.0 g), weight gain (281.8 g), SGR (4.23% per day), FCE (85.7%), biomass (11.20 kg/m3), and ER (32.7%) of fish fed the MG diet were significantly greater than those of fish fed the HSB and GOLD diets. No differences in survival, gross energy, ash, or crude lipid content existed among fish fed the three diets. Lowest dry matter content, lowest PPV, and highest protein content were observed in fish fed the HSB diet. Highest PER was observed in fish fed the GOLD diet. Although the cost of production per kilogram for rearing juvenile cobia with the MG diet would be greater, this cost could be offset by the 15% reduction in rearing time required as compared with the HSB and GOLD diets

Izokibep for the treatment of moderate-to-severe plaque psoriasis : a phase II, randomized, placebo-controlled, double-blind, dose-finding multicentre study including long-term treatment

Background:  Monoclonal antibodies to interleukin (IL)-17 have shown strong efficacy in patients with psoriasis. Izokibep is a unique IL-17A inhibitor with a small molecular size and favourable distribution to sites of inflammation.Objectives To evaluate the dose response, efficacy and safety of izokibep in patients with plaque psoriasis. Methods: In this double-blind, randomized, phase II dose-finding study (AFFIRM-35) in adults with moderate-to-severe plaque psoriasis and inadequate response to two or more standard therapies, patients were randomized (1:1:1:1:1) to placebo or izokibep 2, 20, 80 or 160 mg every 2 weeks for 12 weeks. During the remainder of the 52-week core study, patients given placebo were switched to izokibep 80 mg, and dosing intervals were adapted based on Psoriasis Area and Severity Index (PASI) scores for all patients. The core study was followed by two optional consecutive 1-year extension periods for a total duration of 3 years. The primary endpoint was a 90% reduction in PASI score (PASI 90) at week 12. Additional efficacy outcomes and adverse event (AE) rates were evaluated.Results In total, 109 patients were randomized [safety set, n = 108 (one exclusion criteria failure); full analysis set, n = 106]. At week 12, PASI 90 response rates were 0%, 5%, 19%, 71% and 59% for the placebo, 2-, 20-, 80- and 160-mg izokibep groups, respectively. Rapid dose-dependent improvements were also observed across other efficacy outcomes. During the placebo-controlled period, AEs in the izokibep groups were similar to placebo except for mild injection site reactions. AEs were generally mild to moderate and the drug was well tolerated. Izokibep maintained efficacy at the higher dosage groups for up to 3 years, with no new safety signals. Conclusions: Data from this phase II study indicate that izokibep is well tolerated and efficacious in the treatment of plaque psoriasis. Higher doses or more frequent dosing could be explored to further enhance response rates. We conducted a randomized, placebo-controlled, dose-finding, phase II study of izokibep, a novel small-molecule triple-helical protein that inhibits the interleukin-17A homodimer, in patients with moderate-to-severe plaque psoriasis. Subcutaneous izokibep at 80 or 160 mg every 2 weeks showed a high level of efficacy in reducing psoriasis symptoms vs. placebo, and was safe and well-tolerated up to 3 years

Logic and Philosophy of Science in Nancy (II)

This issue collects a selection of contributed papers presented at the 14th International Congress of Logic, Methodology and Philosophy of Science in Nancy, July 2011. These papers were originally presented within two of the main sections of the Congress. They deal with general philosophy of science (including ethical and historical aspects of philosophy of science), and philosophy of biology, physics, chemistry and economics. A first volume of contributed papers, dedicated to logic, philosophy of mathematics and cognitive science, and philosophy of technology, appeared in the last issue of Philosophia Scientiæ (18-3), 2014