Previously we have encapsulated host-directed therapy AR-12 into acetalated dextran (Ace-DEX) microparticles (MPs) to mitigate drug toxicity and passively target phagocytic host cells. Herein, we ...have improved upon our initial emulsion-based formulation of Ace-DEX MPs encapsulating AR-12 (AR-12/MPs) by improving the drug encapsulation efficiency, evaluating sterilization processes for manufacturing, and understanding cellular and in vivo trafficking of the MPs. By using an alternative solvent system, ethyl acetate, we report an increased encapsulation efficiency of AR-12 while maintaining the pH-responsive degradation kinetics of Ace-DEX MPs. To better manufacture this novel antimicrobial formulation, we sterilized AR-12/MPs by gamma irradiation or ethylene oxide and evaluated their efficacy against intracellular Salmonella enterica serovar Typhi. Sterilized AR-12/MPs resulted in a significant reduction in intracellular bacterial burden compared to Blank/MPs. We also characterized intracellular trafficking of Ace-DEX MPs encapsulating fluorophores, which demonstrated internalization of MPs in endo/lysosomal compartments and time and degradation-rate dependent lysosomal escape into cytosolic compartments. Additionally, in vivo toxicity was mitigated following encapsulation of AR-12, where the maximum tolerated dose of AR-12 was increased compared to soluble treatment via intranasal, intravenous, and intraperitoneal administration routes. Following in vivo trafficking of Ace-DEX MPs via the same routes, intranasal administration demonstrated the highest accumulation in the lungs, liver, and kidneys, which persisted out to 240 h. Overall, we have advanced the formulation of this host-directed therapy and broadened the understanding of Ace-DEX MP delivery.
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IJS, KILJ, NUK, PNG, UL, UM
Context . The detection of NH 2 CH 2 CH 2 OH (ethanolamine) in molecular cloud G+0.693-0.027 adds an additional player to the pre-biotic molecules discovered so far in the interstellar medium (ISM). ...As this molecule might be formed through condensed-phase hydrogenation steps, detecting one or more of the molecules involved might help to elucidate the chemical pathway leading to its production. Aims . The chemical path involves the formation of four chemical species. In this work, we study the energies of the isomers involved, indicate the best candidates for detection purposes, and provide the distortion constants of the most energetically favoured isomers undetected so far. Methods . We used highly accurate CCSD(T)-F12/cc-pCVTZ-F12 computations to predict the lowest energy isomers as well as their spectroscopic constants, taking corrections for core electron correlation and scalar relativity into account. Results . We studied 14 isomers. We find that the lowest energy isomer proposed in previous studies is not the actual minimum. We provide a set of rotational and distortion constants of the two new most stable isomers together with their fundamental vibrational frequencies in order to guide the search for these important astrochemical precursors of prebiotic molecules in the ISM.
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FMFMET, NUK, UL, UM, UPUK
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While highly active antiretroviral therapy (HAART) has significantly reduced mortality rates in patients with human immunodeficiency virus type 1 (HIV-1), its efficacy may be impeded ...by emergence of drug resistance caused by lack of patient adherence. A therapeutic strategy that requires infrequent drug administration as a result of sustained release of antiretroviral drugs would put less burden on the patient. Long-acting antiretroviral prodrugs for HIV therapy were synthesized through modification of the active drugs, emtricitabine (FTC) and elvitegravir (EVG), with docosahexaenoic acid (DHA) in one-step, one-pot, high-yielding reactions. The in vitro drug release profiles of these synthetic conjugates demonstrated sustained and controlled release of the active drug over a period of 3–4 weeks attributable to the hydrolysis of the chemical linker in conjunction with the hydrophilicity of the parent drug. Both conjugates exhibited superior antiviral activities in tissue culture models of HIV replication as compared to those of the free drugs, strengthening their role as potent prodrugs for HIV therapy. Pharmacokinetic analysis in CD1 mice further confirmed the long-acting aspect of these conjugates with released drug concentrations in plasma detected at their respective IC90/IC95 values over a period of 2 weeks and discernable amounts of active drug even at 6 weeks. Our findings suggest that the injectable small molecule conjugates could be used as long-acting controlled release of FTC and EVG in attempts to mitigate adherence-related HIV resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We relocate the 1990–1991 Potenza (Southern Apennines belt, Italy) sequences and calculate focal mechanisms. This seismicity clusters along an E–W, dextral strike–slip structure. Second‐order ...clusters are also present and reflect the activation of minor shears. The depth distribution of earthquakes evidences a peak between 14 and 20 km, within the basement of the subducting Apulian plate. The analysed seismicity does not mirror that of Southern Apennines, which include NW–SE striking normal faults and earthquakes concentrated within the first 15 km of the crust. We suggest that the E–W faults affecting the foreland region of Apennine propagate up to 25 km of depth. The Potenza earthquakes reflect the reactivation of a deep, preexisting fault system. We conclude that the seismotectonic setting of Apennines is characterized by NW–SE normal faults affecting the upper 15 km of the crust, and by E–W deeper strike–slip faults cutting the crystalline basement of the chain.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The 28 December 1908 Messina Straits earthquake represents one of the worst seismic catastrophes in world history. In spite of the relatively large and various amount of data available and the ...geophysical investigations accomplished in the straits, the seismogenic structure is still elusive and intensely debated. Some models proposed for the causative fault rely considerably on the hypothesis of significant subsidence preceding the event. By driving results that differ critically from previously debated models, this assumption would have crucial repercussions on the seismic hazard assessment in the area. However, the critical analysis of this assumption in the light of the available data allows the rejection of this possibility.
Reaction channels and spectroscopic properties of a series of silicon-carbon-bearing isomers of SiC3H+ and SiC3H, which are suitable species for astrophysical detection in carbon-rich sources, are ...calculated with correlated ab initio CCSD(T) and density functional theory methods. We present four isomers of SiC3H+ for which the electronic ground states have closed-shell configurations. For SiC3H, we considered the same structures in order to present a complete study. The global minimum among the SiC3H+ isomers corresponds to the rhomboidal structure with a transannular bond in a 1A1 electronic state (rb3-SiC3H+ C2v X1A1). The next minima correspond to a second rhomboid 1A1 isomer and a linear isomer (X1...) with relative energies 0.86 and 0.93 eV, respectively at the CCSD(T)/cc-pvTZ level of theory. The most stable mono-hydrogenated silicon carbon isomer is linear, followed by two rhomboidal isomers, rb2-SiC3H and rb3-SiC3H (0.23 and 0.31 eV). For each structure, a set of spectroscopic parameters including their equilibrium structures, rotational constants, harmonic frequencies and dipole moment is presented. Furthermore, we discuss plausible formation pathways of SiC3H+ isomers which are classified as charge-exchange, ion-neutral and dissociative recombination reactions. These results show one favourable pathway to produce rb3-SiC3H+ from rb-SiC3-3s. The formation energy of the cation's isomers coming from neutral isomers as linear l1-SiC3H, rb3-SiC3H and rb2-SiC3H plus H+ as reactants (charge-exchange reaction) are 203.8 kcal mol... (8.84eV), 175.4 kcal mol... (7.60 eV) and 195.2 kcal mol... (8.46 eV), which provides us with evidence of the endergonic character of these reactions. As a consequence, it does not seem to be feasible to produce a cation from neutral reactant plus H+ by a charge-exchange reaction that was proposed by UMIST. (ProQuest: ... denotes formulae/symbols omitted.)
Reaction channels and spectroscopic properties of a series of silicon-carbon-bearing isomers of SiC3H+ and SiC3H, which are suitable species for astrophysical detection in carbon-rich sources, are ...calculated with correlated ab initio CCSD(T) and density functional theory methods. We present four isomers of SiC3H+ for which the electronic ground states have closed-shell configurations. For SiC3H, we considered the same structures in order to present a complete study. The global minimum among the SiC3H+ isomers corresponds to the rhomboidal structure with a transannular bond in a 1A1 electronic state (rb3-SiC3H+ C2v X1A1). The next minima correspond to a second rhomboid 1A1 isomer and a linear isomer (X1...) with relative energies 0.86 and 0.93 eV, respectively at the CCSD(T)/cc-pvTZ level of theory. The most stable mono-hydrogenated silicon carbon isomer is linear, followed by two rhomboidal isomers, rb2-SiC3H and rb3-SiC3H (0.23 and 0.31 eV). For each structure, a set of spectroscopic parameters including their equilibrium structures, rotational constants, harmonic frequencies and dipole moment is presented. Furthermore, we discuss plausible formation pathways of SiC3H+ isomers which are classified as charge-exchange, ion-neutral and dissociative recombination reactions. These results show one favourable pathway to produce rb3-SiC3H+ from rb-SiC3-3s. The formation energy of the cation's isomers coming from neutral isomers as linear l1-SiC3H, rb3-SiC3H and rb2-SiC3H plus H+ as reactants (charge-exchange reaction) are 203.8 kcal mol... (8.84eV), 175.4 kcal mol... (7.60 eV) and 195.2 kcal mol... (8.46 eV), which provides us with evidence of the endergonic character of these reactions. As a consequence, it does not seem to be feasible to produce a cation from neutral reactant plus H+ by a charge-exchange reaction that was proposed by UMIST. (ProQuest: ... denotes formulae/symbols omitted.)
The best chance to achieve a future disaster-resilient society is through risk education in School: it has a great potential to strengthen capacity of communities to mitigate risks. The KnowRISK ...(Know your city, Reduce seISmic risK through non-structural elements) project took this opportunity and implemented a risk communication campaign for schools in Portugal, Italy, and Iceland. The idea was that suitably changes in people’s knowledge and attitude can trigger best practices. Crucial to reach such target is the raise of awareness on meaningful issues. The main challenge of the campaign was how to effectively address the mitigation of the vulnerability to earthquakes of non-structural elements, which is an issue considered to be of low priority even in the building regulations of many countries around the world. The campaign stood on a communication strategy that was systematized within a protocol, for 13- 15 years old students, that specifies goals, contents, learning strategy, support material, and relies on face-to-face intervention of scientists in the classroom. This protocol had training sessions bounded by assessment sessions, ex-ante and ex-post, that allowed to validate its efficacy. The training made large use of flipped learning and Episode of Situated Learning (EAS) strategy to raise student’s motivation and increase achievements. To ensure its replicability, the protocol was tested in zones matching a wide range of seismic hazard in Italy. The assessment showed the protocol be effective and ready for a wide dissemination.
The textile industry is a generator of high volumes of waste water with a high content of pollutants such as azo dyes, which are recalcitrant and persistent in the environment, these ones have been ...of interest in the last decades for the entities in charge of the care of the environment. This study evaluated the ability to discolor of reactive black 5 (NR5) by a consortium and the microorganisms that constitute Rhodotorula mucilaginosa, Galactomyces pseudocandidum and Escherichia coli free and immobilized in calcium alginate, coffee husks and bagasse of sugar cane. The results show discoloration was evidenced, where the highest percentage corresponds to G. pseudocandidum (90,05%) and the lowest to R. mucilaginosa (79,31%). When comparing the percentages of discoloration between the free microorganisms and the immobilization matrices, it is observed that the former exhibit the highest percentages of discoloration. In addition, there are no significant differences between using cane bagasse or coffee husks as immobilization matrix.
PID and LQI control algorithms using WNCS applied to a levitator Wilson, Ordonez A.; Wellington, Pino N.; Carlos, Pillajo A.
2021 IEEE CHILEAN Conference on Electrical, Electronics Engineering, Information and Communication Technologies (CHILECON),
2021-Dec.-6
Conference Proceeding
This work shows the procedure carried out to implement the Linear Quadratic Integral (LQI) and Predictive Integrative Derivative (PID) controllers through Wireless Network Control Systems (WNCS) ...applied to a Pneumatic Levitator, and the comparison of the stabilization time between them, whose plant consists of a base made of wood with a hole in the middle, and in this a fan is located at the bottom part, which is responsible for sending air to a funnel placed in the upper part, which concentrates the air and expels it through a grill towards a plastic tube to raise a pressed paperboard piece located inside it to the height indicated by the user in an interface developed through an App of the Blynk platform, which has: a numerical text input to determine the desired setpoint; a percentage meter of the PWM value that controls the fan; value that is delivered by the selected controller type; and a histogram that reflects the entered setpoint and the variation in the height of the paperboard piece over time. The system is implemented on a Raspberry Pi 4, where to realize all the processing of: the control algorithms; the data flow established with a NodeMCU development card, with which the plant communicates, and with the Blynk application.
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