BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1_NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4^th generation, are reported here for the first time.     

Unraveling the Lagged Effect of Hydro-meteorological Conditions On the Trophic State of a Reservoir By Applying Dynamic Regression

In this study we develop a novel approach to quantify the relative importance of hydro-meteorological (HM) conditions on the trophic state index (TSI) of a water reservoir (San Roque, Córdoba, Argentina). Seven HM variables measured at four reservoir sites and different depths over a time period of near 2 decades are used. We propose a dynamic regression model to predict the TSI from these variables aggregated over a range of time lags, which has not been applied in such a complex setting so far. By performing coefficient analysis, we quantify the relative importance of these variables on the TSI, as well as the time duration over which they have significant impact (lagged effect). Additionally, the analysis of the autoregressive and moving average (ARIMA) terms reveals the impact of the residual effects of previous trophic states on the current trophic state. We find that surface temperature and precipitation have the largest direct relationship to the TSI in the short-term, while the reservoir water level is inversely related to the TSI in the short- to mid-term. Also, the residual effects of the trophic state impact from 1 month (generally) up to 2 years (exceptionally). This approach can be applied to other water bodies affected by similar eutrophication phenomena.

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The link between countries’ economic and scientific wealth has a complex dependence on technological activity and research policy

Scientometrics - We studied the research performance of 69 countries by considering two different types of new knowledge: incremental (normal) and fundamental (radical). In principle, these two...     

Energy Recovery in Pressurized Hydraulic Networks

Water Resources Management - This paper aims to evaluate the possibility of using non-utilized hydraulic energy in urban water distribution systems. For this purpose, the viability and possible...     

Effects of Ce Doping on the Photocatalytic and Electrochemical Performance of Nickel Hydroxide Nanostructures

Topics in Catalysis - Ni(OH)2 doped with cerium cations was synthesized by a hydrothermal method and its electrochemical, photoelectrochemical and photocatalytic behavior was determined by the...     

7-Amidocoumarins as Multitarget Agents against Neurodegenerative Diseases: Substitution Pattern Modulation

This study explores the potential of 7-amidocoumarins as multitarget agents against Parkinson's and Alzheimer's diseases, by modulating the substitution patterns within the scaffold. Sixteen compounds were synthesized via 7-amino-4-methylcoumarin acylation, and in vitro evaluation of the molecules against hMAO-A, hMAO-B, hAChE, hBuChE and hBACE1 was performed. Five compounds turned out to be potent and selective hMAO-B inhibitors in the nanomolar range, six displayed inhibitory activity of hMAO-A in the low micromolar range, one showed hAChE inhibitory activity and another one hBACE1 inhibitory activity. MAO-B reversibility profile of 7-(4’-chlorobenzamido)-4-methylcoumarin ( 10 ) was investigated, with this compound being a reversible inhibitor. Neurotoxicity on motor cortex neurons and neuroprotection against H₂O₂ were also studied, corroborating the safety profile of these molecules. Finally, theoretical ADME properties were also calculated, showing these molecules as good candidates for the optimization of a lead compound. Results suggest that by modulating the substitution pattern at position 7 of the scaffold, selective or multitarget molecules can be achieved.     

Source time reversal (STR) method for linear elasticity

We study the problem of source reconstruction for a linear elasticity problem applied to seismicity induced by mining. We assume the source is written as a variable separable function $\mathit{f}\left(\mathit{x}\right)g\left(t\right)$. We first present a simple proof a local decay result for elasticity in the case of homogeneous media. We then extend the source time reversal method, originally developed for acoustic waves, to an elastic system of waves. Additionally, we present a fast reconstruction implementation for large data sets. This is especially useful in the elastic case, in which the numerical cost is higher than in fluid acoustics. We complement this work with several 2D and 3D numerical experiments and an analysis of the results.     

The generalized discrete ‐centroid problem

The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included.