Effects of Particle Size of Bulk Drug and food on the Bioavailability of U-78875 in Dogs

The effects of particle size and food on the absolute bioavailability of U-78875 in dogs after oral administration of either a suspension or tablet dosage form were investigated. A reduction of particle size caused a significant increase in bioavailability along with an increase in dissolution rate. Additionally, both suspension and tablet dosage forms administered after food caused an increase in bioavailability. Thus, to accelerate drug dissolution, a reduction of U-78875 particle size from the unmilled state is important for the optimization of formulation compositions. To increase the bioavailability of U-78875, postprandial dosing should be considered.     

Optimization of semiochemical-based trapping ofMetamasius hemipterus sericeus (Olivier) (Coleoptera: Curculionidae)

Response of adults of the West Indian sugarcane weevil,Metamasius hemipterus sericeus, to various semiochemical treatments and physical trap designs was studied in southern Florida in field-grown banana and Canary Island date palms. Ethyl acetate released alone at 860–1007 mg/day was as effective for the capture ofM. h. sericeus as a combination of ethyl acetate (844–919 mg/day), ethyl propionate (348–362 mg/day), and ethyl butyrate (117–137 mg/day) and in one trial was more effective than fermenting sugarcane (250 g), ethyl propionate alone (353–384 mg/day), ethyl butyrate alone (123–174 mg/day), or no treatment. Ethyl acetate released alone at 675–683 mg/day was as attractive as 250 g of fermenting sugarcane or the racemic blend of the male-produced aggregation pheromones [(±)-5-methyl-nonan-4-ol and (±)-2-methyl-heptan-4-ol (8:1 ratio) “metalure”] at 3 mg/day. Weevil counts increased with binary combinations of ethyl acetate, sugarcane, and/or metalure over these treatments alone and the ternary combination was two to three times more effective than any of the binary treatments. Attraction to ethyl acetate released alone at 777 mg/day with metalure was greater than to the hydrolysis products of ethyl acetate (ethanol and/or acetic acid each released at about 6–8 mg/day) with metalure. Weevil counts from traps baited with 250 g of sugarcane and metalure increased with increasing dose of ethyl acetate to about 400 mg/day and then appeared to plateau. Ethyl acetate (about 700 mg/day) and metalure increased weevil counts in traps with increasing amounts of sugarcane (0–2 kg). Molasses (45 g) + water (158 ml) substitutes for sugarcane were about as effective for capturingM. h. sericeus as 250 g of fermenting sugarcane [all treatments with ethyl acetate (847 mg/day) and metalure]. Early experiments used a lethal pitfall trap. We demonstrated that several alternative trap designs were more effective than the lethal pitfall trap for capturing weevils. Color and height (on ground vs. 1 m on pole) did not affect trap efficacy when baited with the ternary combination of ethyl acetate (672–825 mg/day), sugarcane (250 g), and metalure.     

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors.     

Polymerization of lactams, 95 Preparation of polyesteramides by the anionic polymerization of ε-caprolactam in the presence of poly(ε-caprolactone)

Preparation of polyesteramides-poly[(ε-caprolactam)-co-(ε-caprolactone)]s by anionic polymerization of ε-caprolactam in the presence of poly(ε-caprolactone) at 150 °C was studied in this paper. ε-Caprolactam magnesium bromide was used as an initiator of polymerization and polymeric materials containing 5-25 wt% ε-caprolactone units were obtained. Thermal methods (DSC and DMA) were employed for characterization of poly[(ε-caprolactam)-co-(ε-caprolactone)]s and their mechanical properties were also evaluated. By introducing the activator with N-acyllactam structure, the polymerization rate increased and it was possible to carry out the polymerization at 110 °C. Mechanical properties of polyesteramides were influenced by both the content of ε-caprolactone units incorporated into copolymer and polymerization temperature. The mechanism of incorporation of poly(ε-caprolactone) is discussed. The results show that it is not possible to restrict exchange transacylation reactions, progressing in the course of polymerization, by kinetic tools.     

Die antioxidativen Eigenschaften von Lecithin

Antioxidizing Properties of Lecithin In various storage trials with sunflower oil and lard the antioxidizing properties of crude soybean lecithin as well as of its alcohol soluble and alcohol insoluble fraction could be proved. The addition of a very small quantity of these phospholipids to the oil after the refining process (prior to this process crude oil contains approx. 2–3% lecithin) improves the stability of these oils. The antioxidizing properties of phospholipids depend on: 1. composition of phospholipids, 2. tocopherol content of the oil. In our trials the alcohol soluble fraction of soybean lecithin performed the best antioxidizing results in sunflower oil by adding not less than 1%. In lard the same effect could already be reached with 0.1% of this fraction. As shown before, lecithin with a special phospholipid composition has antioxidizing properties and its addition in small quantities is beneficial to increase the stability of oils and fats. In new Japanese literature soybean saponines are the most favoured antioxidizing agents. Our trials did not confirm the results of these publications.     

Computing the Ramsey number R(4,3,3) using abstraction and symmetry breaking

The number R(4, 3, 3) is often presented as the unknown Ramsey number with the best chances of being found “soon”. Yet, its precise value has remained unknown for almost 50 years. This paper presents a methodology based on abstraction and symmetry breaking that applies to solve hard graph edge-coloring problems. The utility of this methodology is demonstrated by using it to compute the value R(4, 3, 3) = 30. Along the way it is required to first compute the previously unknown set \(\mathcal {R}(3,3,3;13)\) consisting of 78,892 Ramsey colorings.     

Multimodal focus attention and stress detection and feedback in an augmented driver simulator

This paper presents a driver simulator, which takes into account the information about the user’s state of mind (level of attention, fatigue state, stress state). The user’s state of mind analysis is based on video data and biological signals. Facial movements such as eyes blinking, yawning, head rotations, etc., are detected on video data: they are used in order to evaluate the fatigue and the attention level of the driver. The user’s electrocardiogram and galvanic skin response are recorded and analyzed in order to evaluate the stress level of the driver. A driver simulator software is modified so that the system is able to appropriately react to these critical situations of fatigue and stress: some audio and visual messages are sent to the driver, wheel vibrations are generated and the driver is supposed to react to the alert messages. A multi-threaded system is proposed to support multi-messages sent by the different modalities. Strategies for data fusion and fission are also provided. Some of these components are integrated within the first prototype of OpenInterface: the multimodal similar platform.     

Formal Specification and Quantitative Analysis of a Constellation of Navigation Satellites

Navigation satellites are a core component of navigation satellite‐based systems such as Global Positioning System, Global Navigation Satellite System and Galileo, which provide location and timing information for a variety of uses. Such satellites are designed for operating on orbit to perform tasks and have lifetimes of 10 years or more. Reliability, availability and maintainability analysis of systems has been indispensable in the design phase of satellites in order to achieve minimum failures or to increase mean time between failures and thus to plan maintenance strategies, optimise reliability and maximise availability. In this paper, we present formal models of both a single satellite and a navigation satellite constellation and logical specification of their reliability, availability and maintainability properties, respectively. The probabilistic model checker PRISM has been used to perform automated analysis of these quantitative properties. Copyright © 2014 John Wiley & Sons, Ltd.     

Hybridized electronic states between CdSe nanoparticles and conjugated organic ligands: A theoretical and ultrafast photo-excited carrier dynamics study

Formation of densely packed thin films of semiconductor nanocrystals is advantageous for the exploitation of their unique optoelectronic properties for real-world applications. Here we investigate the fundamental role of the structure of the bridging ligand on the optoelectronic properties of the resulting hybrid film. In particular, we considered hybrid films formed using the same CdSe nanocrystals and two organic ligands that have the same bidentate dithiocarbamate binding moiety, but differ in their bridging structures, one bridged by ethylene, the other by phenylene that exhibits conjugation. Based on the results of photo-excited carrier dynamics experiments combined with theoretical calculations on the electronic states of bridged CdSe layers, we show that only the phenylene-based ligand presents a strong hybridization of the molecular HOMO state with CdSe layers, that is a marker of formation of an effective bridge. We argue that this hybridization spread favors the hopping of photo-excited carriers between nanocrystals, which may explain the reported larger photo-currents in phenylene-based hybrid films than those observed in ethylene-based ones.

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Comparison of paper-and-pencil versus Web administration of the Youth Risk Behavior Survey (YRBS): Participation,data quality,and perceived privacy and anonymity

The Youth Risk Behavior Surveillance System (YRBSS) monitors priority health-risk behaviors among US high school students. To better understand the ramifications of changing the YRBSS from paper-and-pencil to Web administration, in 2008 the Centers for Disease Control and Prevention conducted a study comparing these two modes of administration. Eighty-five schools in 15 states agreed to participate in the study. Within each participating school, four classrooms of students in grades 9 or 10 were randomly assigned to complete the Youth Risk Behavior Survey questionnaire in one of four conditions (in-class paper-and-pencil, in-class Web without programmed skip patterns, in-class Web with programmed skip patterns, and “on your own” Web without programmed skip patterns). Findings included less missing data for the paper-and-pencil condition (1.5% vs. 5.3%, 4.4%, 6.4%; p < .001), less perceived privacy and anonymity among respondents for the in-class Web conditions, and a lower response rate for the “on your own” Web condition than for in-class administration by either mode (28.0% vs. 91.2%, 90.1%, 91.4%; p < .001). Although Web administration might be useful for some surveys, these findings do not favor the use of a Web survey for the YRBSS.