Design,Synthesis and Evaluation of 2,4-Diaminoquinazoline Derivatives as Potential Tubulin Polymerization Inhibitors

Microtubules are highly dynamic polymers composed of α- and β-tubulin proteins that have been shown to be potential therapeutic targets for the development of anticancer drugs. Currently, a wide variety of chemically diverse agents that bind to β-tubulin have been reported. Nocodazole (NZ) and colchicine (COL) are well-known tubulin-depolymerizing agents that have close binding sites in the β-tubulin. In this study, we designed and synthesized a set of nine 2,4-diaminoquinazoline derivatives that could occupy both NZ and COL binding sites. The synthesized compounds were evaluated for their antiproliferative activities against five cancer cell lines (PC-3, HCT-15, MCF-7, MDA-MB-231, and SK-LU-1), a noncancerous one (COS-7), and peripheral blood mononuclear cells (PBMC). The effect of compounds 4 e and 4 i on tubulin organization and polymerization was analyzed on the SK-LU-1 cell line by indirect immunofluorescence, western blotting, and tubulin polymerization assays. Our results demonstrated that both compounds exert their antiproliferative activity by inhibiting tubulin polymerization. Finally, a possible binding pose of 4 i in the NZ/COL binding site was determined by using molecular docking and molecular dynamics (MD) approaches. To our knowledge, this is the first report of non-N-substituted 2,4-diaminoquinazoline derivatives with the ability to inhibit tubulin polymerization.     

Precisely Controlled Microsphere Design via Visible‐Light Cross‐Linking of Functional Prepolymers

A new strategy for particle synthesis is enabled by utilizing modern synthetic, polymer, and photochemical techniques to facilitate the synthesis of highly narrow–disperse multifunctional microspheres from visible‐light induced crosslinking of prepolymers in both a single and dual polymer system. The approach requires no stabilizers, bases, or initiators, and proceeds at ambient temperature to yield microspheres with a tunable size range (0.25–5 µm) in less than 4 h, depending largely on solvent composition, but also polymer concentration (2–10 mg mL^?1), ratio, and irradiation intensity (3–20 W). Critically, the visible‐light induced dimerization reaction exploited herein enables simple functional particle syntheses via a single polymer system. Underpinned by an in‐depth kinetic analysis of the particle formation as well as a detailed small molecule study, the mechanism for particle formation is also elucidated. Importantly, inherent advantages of the system are exploited for surface functionalization of residual acrylate and hydroxyl groups (generating inherently fluorescent particles).     

Ultrastructural and developmental toxicity of potato and tomato leaf extracts to beet armyworm,Spodoptera exigua (lepidoptera: noctuidae)

Beet Armyworm, Spodoptera exigua is a herbivorous moth and a serious pest of many economically important plants, which are used as food sources. Because of rigorous standards of food quality, usage of synthetic insecticides in crop protection, against pests, is limited. Solanaceae plant extracts may be a relatively cheap source of efficient natural insecticides that can limit usage of synthetic substances. Their biological activity is not fully known. In particular, ultrastructural studies, using transmission electron microscopy, are not usual. In the present article we describe the effects of sublethal concentrations of tomato and potato leaf extracts against S. exigua. Acute lethal effects were not observed. Both extracts exerted similar effects within midgut and fat body cells. Midgut cells were not significantly altered while fat body cells showed prominent swelling of nuclear envelope and endoplasmic reticulum, vacuolization of mitochondria and fusion of fat droplets. These changes were much more intensive within groups exposed to potato than tomato extracts at highest concentration at least. Light microscopy was used to observe and document developmental alterations of S. exigua exposed to potato and tomato leaf extracts. Potato leaf extracts significantly decreased hatching success and caused morphological malformations of imagoes. Among them, malformations of wings were the most prominent. Interestingly, these effects were not observed within populations exposed to tomato extracts at highest concentration at least.     

Large lakes in climate models: A Great Lakes case study on the usability of CMIP5

Large lakes have an impact on regional weather. In addition, they can be both sensitive to and influence regional climate changes. In the climate models that are used to investigate future climate changes, lakes are greatly simplified and sometimes absent. At the regional scale, this can have strong implications for the quality of the model information about the future. Through our work with climate information users in the Laurentian Great Lakes region, we have found that basic credibility of the information requires the underlying climate models simulate lake-atmosphere-land interactions. We are not aware of efforts within the scientific community to make known how individual large lakes are represented in models and how those representations translate to the quality of the data for particular regions. We share our framework for identifying how the Laurentian Great Lakes are represented in the Coupled Model Intercomparison Project (CMIP) version 5 climate models. We found that most CMIP5 models do not simulate the Great Lakes in a way that captures their impact on the regional climate, which is a credibility issue for their projections. We provide a perspective on the usability of CMIP5 for practitioners in the Great Lakes region and offer recommendations for alternative options.     

Pasting,thermal, gel texture,resistant starch and colour properties of unripe banana flour from 10 desert banana varieties cultivated in South Africa

Unripe banana flour is a potential commercial ingredient in various food products for increased resistant starch and reduced gluten contents. In the present study, the pasting (rapid visco-analysis), gel texture (penetration test), thermal (differential scanning calorimetry), colour (tri-stimulus colour indices) and the resistant starch properties of unripe banana flour produced from different dessert banana varieties (n?=?10) cultivated in South Africa, were analysed and juxtaposed to wheat and maize flour. The functional properties varied significantly (p?≤?0.05) between banana varieties, and from wheat and maize flours, to various extents. Selected functional property ranges of unripe banana, wheat and maize flours, respectively included; flour colour index (63.16–76.42, 77.34 and 80.96), paste viscosity (405.5–556.6, 124.7 and 115.6 RVU), gelatinization temperature (64.67–71.21, 71.11 and 69.95?°C), gel firmness (7.24–11.44?×?10^??2 N, 3.49?×?10^??2 N and 6.56?×?10^??2 N) and resistant starch content (19.9–47.4, 2.8 and 2.2% w/w). Multivariate analysis (principle component analysis) showed that the unripe banana flours from different varieties were distinguished from each other based on the pasting temperature. The unripe banana flours were distinguished from both wheat and maize flour based on breakdown and peak paste viscosities. The breakdown viscosity was the most positively related measure to the resistant starch content with a linear regression R-squared value of 0.898, indicating a significant role played by granule structure in resistance to enzymatic hydrolysis. The present research demonstrates that selection of appropriate dessert banana variety is important when replacing staple flours (wheat and maize) with unripe dessert banana flour as a functional ingredient.     

Long-term viable bioaerosol sampling using a temperature- and humidity-controlled filtration apparatus,a laboratory investigation using culturable E. coli.

Sampling for culturable (e.g., viable) aerosolized microbes (bioaerosols) is a useful means to provide information for public health monitoring and studies. However, it is challenging to maintain microbe culturability when sampling at high flow rates (>12 L/min) and extended periods of time (≥4 h). We developed a first-generation, viable bioaerosol collection system (VBCS) utilizing temperature (T) and relative humidity (RH)–conditioned filtration at a flow rate of 25 L/min. A two-stage system of tube-in-shell Nafion? exchange units provides cooling to ≤10°C and RH conditioning to 80–95%. Aerosol particles are collected on a polyurethane nanofiber filter providing a physical collection efficiency of >95% for sizes 0.06–10 µm. The T and RH conditions at the collection filter are maintained, despite changes to ambient conditions. The initial testing of the VBCS was done under indoor, laboratory conditions with aerosolized, vegetative E. coli. A scenario of a 30-min challenge of bioaerosol followed by continued sampling of clean air for various times was used to judge culturability maintenance under extended-term sampling. An initial loss of culturability upon collection onto the filter was observed; 23 ± 13% relative to 4-mm all-glass impinger. However once collected, 98% of culturability was maintained for an additional 4.5 h of sampling. An exponential decay in culturability was observed from 8 h to 15 h of sampling. Also, 24-h cold storage of the filters collected was studied. The VBCS is based on the use of dry filter cassettes, needs minimal maintenance, and preserves culturability of vegetative bacteria for >4 h.

© 2017 RTI International and Aerosol Dynamics Inc.     

Ecological efficiency and thermoeconomic analysis of a cogeneration system at a hospital

This work aims with an approach for cogeneration plants evaluation based on thermoeconomic functional diagram analysis. The second law of thermodynamics is used to develop a methodology to analyse cogeneration systems, based on exergoeconomics evaluation. The thermoeconomic optimisation method developed is applied to allow a better configuration of the cogeneration plant associated to a university hospital. Also ecological efficiency is evaluated. The method was efficient and contributes for thermoeconomics modelling and analysis and can be applied to any sort of thermal system, especially those with combined heat and power in thermal parity.