Virtual screening (VS) techniques are well-established tools in the modern drug discovery process, mainly used for hit finding in drug discovery. The availability of knowledge of structural ...information, which includes an increasing number of 3D protein structures and the readiness of free databases of commercially available smallmolecules, provides a broad platform for VS. This review summarizes the current developments in VS regarding chemical databases and highlights the achievements as well as the challenges with an emphasis on a recent example of the successful application for the identification of new hits for sterol 14α-demethylase (CYP51) of Trypanosoma cruzi.
Abstract
This experiment evaluated the effects of supplementing three sources of trace minerals to late-gestating beef cows and its impact on offspring productivity. Seventy-two pregnant cows were ...sorted by BW and BCS in three treatments at Red Bluff Ranch (Norris, MT). Seventy-two non-lactating, pregnant Angus cows initial body weight (BW) = 637 ± 13 kg; body condition score (BCS) = 5.5 ± 0.07; and age = 6.1 ± 0.57; exposed to AI = 54 and Bull = 18 were selected and assigned to this experiment at the end of their second trimester of gestation. Before beginning treatment application (d-10), cows were ranked by BW and BCS and allocated (d 0) to 1,000 acres pasture. At this time, cows were assigned to receive supplements containing 1 of 3 treatments: 1) Cu, Mn, and Zn sulfate trace mineral source (INR; n = 24), 2) Cu, Mn, and Zn organic trace mineral source (ORG; n = 24), and 3) Cu, Mn, and Zn hydroxychloride trace mineral source (HXD; n= 24). Cows were fed individually three times a week, Monday, Wednesday, and Friday. Cow full BW and BCS were recorded before the beginning of the experiment (d -11 and -10). On d -10 and at birth, liver biopsies were performed in all cows and calves via needle biopsy. After calving, cow-calf pairs were assigned to the general herd management, including inorganic mineral supplementation. Calves were weaned at 6 months of age and backgrounded for 85 d. No differences were detected (P ≥ 0.17) among HDX, INR, and ORG cows for initial liver concentrations of trace minerals. At calving, no differences were observed (P ≥ 0.25) in liver concentrations of Se, Co, Cu, Mn, and Zn. There were no differences (P ≥ 0.81) in calf birth BW, crow to rump, and hearth girth measurements between treatments. No treatment effect was observed (P ≥ 0.35) on the liver concentration of calves born to cows receiving treatment. At weaning, no treatment differences were detected (P ≥ 0.25) weaning BW and ADG from birth to weaning. Supplementing different sources of trace minerals to beef cows during the last trimester of gestation yielded similar cow-calf productive responses until weaning and backgrounding program.
BACKGROUNDTreatment of mycoses is often ineffective, usually prolonged, and has some side effects. These facts highlight the importance of discovering new molecules to treat fungal infections. ...OBJECTIVESTo search the Medicines for Malaria Venture COVID Box for drugs with antifungal activity. METHODSFourteen human pathogenic fungi were tested against the 160 drugs of this collection at 1.0 µM concentration. We evaluated the ability of the drugs to impair fungal growth, their fungicidal nature, and morphological changes caused to cells. FINDINGSThirty-four molecules (21.25%) presented antifungal activity. Seven are antifungal drugs and one is the agricultural fungicide cycloheximide. The other drugs with antifungal activity included antibiotics (n = 3), antimalarials (n = 4), antivirals (n = 2), antiparasitcs (n = 3), antitumor agents (n = 5), nervous system agents (n = 3), immunosuppressants (n = 3), antivomiting (n = 1), antiasthmatic (n = 1), and a genetic disorder agent (n = 1). Several of these drugs inhibited Histoplasma capsulatum and Paracoccidioides brasiliensis growth (15 and 20, respectively), while Fusarium solani was not affected by the drugs tested. Most drugs were fungistatic, but niclosamide presented fungicidal activity against the three dimorphic fungi tested. Cyclosporine affected morphology of Cryptococcus neoformans. MAIN CONCLUSIONSThese drugs represent new alternatives to the development of more accessible and effective therapies to treat human fungal infections.
EFFECTS OF MULTIPLE STRUCTURES AND TORSIONAL ANHARMONICITY FOR THE HYDROGEN ABSTRACTION REACTIONS OF THE THMETHYL BUTANOATE BY H RADICAL. Thermal rate constants for the hydrogen abstraction reactions ...of the methyl butanoate (MB) by H radical were estimated by applying the multistructural canonical variational theory with small-curvature tunneling (CVT/SCT). The conformational search was performed at MPWB1K/6-31+G(d,p) level of theory and 68 distinguishable conformers for MB and transition state located. The multistructural and torsional anharmonicity effects were corrected through the rovibrational partition functions calculated with the multistructural method based on a coupled torsional potential, MS-T(C). The MS-CVT/SCT thermal rate constants are shown in good concordance with previous combustion models. After fitting the rate constants in a four-parameters equation, the activation energy showed a temperature dependence. The product branching ratios indicate a preference for (Rα) until 500 K. Above this temperature, the contribution of other reactions becomes relevant, especially for (Rβ).
Several dynamic projects and fault diagnosis of mechanical structures require the knowledge of the acting external forces. However, the measurement of such forces is often difficult or even ...impossible; in such cases, an inverse problem must be solved. This paper proposes a force identification method that uses the response surface methodology (RSM) based on central composite design (CCD) in conjunction with a random forest regression algorithm. The procedure initially required the finite element modal model of the forced structure. Harmonic analyses were then performed with varied parameters of forces, and RSM generated a dataset containing the values of amplitude, frequency, location of forces, and vibration acceleration at several points of the structure. The dataset was used for training and testing a random forest regression model for the prediction of any location, amplitude, and frequency of the force to be identified with information on only the vibration acquisition at certain points of the structure. Numerical results showed excellent accuracy in identifying the force applied to the structure.
The optimization of economic emission load dispatch is one of the most significant tasks in power plants. This article aims to analyze a new application of the computational optimization by simulated ...annealing technique including turning off the motors with greatest losses. The incremental cost of fuel consumption and the lambda iteration methods are combined to determine the best parameters of active power of each
i
th
generator unit, ensuring that the total losses and demand are equal to the total generated power but minimizing the total cost of fuel consumption and carbon emission. Many materials and methods have been elaborated to fix the economic emission load dispatch, among them are as follows: differential evolution method, gradient method and Newton’s method. The results found for this case study, with the new application of simulated annealing, were outstanding having a reduction of 20.14% in the total fuel cost, comparing to classical methods that distribute the generation of power among all motors, including the least efficient ones. This method helps the expert in the decision making of preventive maintenance of machines that are not working in the moment of multi-objective optimization, improving not only the yield of generation and carbon emission reduction but also of the power plant generation planning.
The aim of our study was to produce and characterize poly-ε-caprolactone (PCL) nanospheres containing essential oils from
fruit and to evaluate their stability gains as well as their insecticidal and ...deterrent activities against whitefly (
). The PCL nanospheres exhibited a homogeneous spherical morphology, with particle diameters between 106.7 nm and 129.2 nm, pH of approximately 6, zeta potential (ZP) lower than -19.0 mV and encapsulation efficiency higher than 98%. Only 43% of the nanoencapsulated essential oil (NSEO) was degraded in response to ultraviolet light, whereas the essential oil (EO) degraded by 76% over the same period. In a free-choice test, the NSEO and EO reduced the number of whitefly eggs by approximately 70%. NSEO and EO at 1.5% killed 82.87% and 91.23% of 2nd-instar nymphs of whitefly, respectively. Although NSEO displayed lower insecticidal activity, it offers a greater advantage over the free EO, due to protection conferred by polymer against photodegradation. Therefore, its usage may optimize the maintenance of essential oils in the field through photoprotection and controlled release. Our results suggest that the EO of
fruit can be used for
management strategy; nevertheless, the benefits of NSEO require further evaluation at the field level.
The aim of this manuscript is to introduce solutions to optimize economic dispatch of loads and combined emissions (CEED) in thermal generators. We use metaheuristics, such as particle swarm ...optimization (PSO), ant lion optimization (ALO), dragonfly algorithm (DA), and differential evolution (DE), which are normally used for comparative simulations, and evaluation of CEED optimization, generated in MATLAB. For this study, we used a hybrid model composed of six (06) thermal units and thirteen (13) photovoltaic solar plants (PSP), considering emissions of contaminants into the air and the reduction in the total cost of combustibles. The implementation of a new method that identifies and turns off the least efficient thermal generators allows metaheuristic techniques to determine the value of the optimal power of the other generators, thereby reducing the level of pollutants in the atmosphere. The results are presented in comparative charts of the methods, where the power, emissions, and costs of the thermal plants are analyzed. Finally, the comparative results of the methods were analyzed to characterize the efficiency of the proposed algorithm.
Realizing fundamental cryptographic primitives with unconditional security is a central topic in information-theoretic cryptography. These primitives can be realized based on physical assumptions, ...such as the existence of noisy channels, an upper bound on the storage capacity, or the laws of quantum mechanics. Palmieri and Pereira <xref ref-type="bibr" rid="ref1">1 demonstrated that delays in communication channels can be used as a reasonable and effective assumption to obtain an unconditionally secure oblivious transfer protocol against honest-but-curious adversaries. While any oblivious transfer protocol secure against malicious adversaries can be used to implement commitment, the reduction does not work if the oblivious transfer protocol is only secure against honest-but-curious adversaries. Thus, the question of obtaining a secure commitment protocol based on channel delays is still open. In this paper, we provide a concrete protocol for implementing string commitments based on packet reordering - a consequence of channel delays in packet networks.
This work uses the multipath canonical variational theory with small curvature tunneling (MP-CVT/SCT) to calculate the thermal rate constants for the hydrogen abstraction reaction on the α carbon of ...methyl hexanoate by H-atom. In the conformational search, 233 indistinguishable conformers for MHEX and TSα were located. In the MP-CVT/SCT approach, the recrossing and quantum tunneling effects were incorporated into the rate constants by constructing the individual reaction paths from the jth transition state. The efficiency of truncation on the multistructural rovibrational partition functions and reactive paths and their impact on the thermal rate constants were also evaluated. The torsion over the ▪ group (ϕ5) produces unstable structures, and the reactive paths associated with them do not contribute to the magnitude of MP-CVT/SCT rate coefficients. Additionally, we concluded that rate constants generated from small sets of conformations have a precision of up to 90%, compared to considering all paths.
Display omitted
•Thermal rate constants for methyl hexanoate + H reaction.•Torsional flexibility of the MHEX and TSα generates 233 distinguishable conformations.•Torsion over the ▪ group leads to unstable structures.•Small sets of conformations produce accurate rate constants.
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