Efficacy versus abundancy: Comparing vaccination schemes.

We introduce a novel compartmental model accounting for the effects of vaccine efficacy, deployment rates and timing of initiation of deployment. We simulate different scenarios and initial conditions, and we find that higher abundancy and rate of deployment of low efficacy vaccines lowers the cumulative number of deaths in comparison to slower deployment of high efficacy vaccines. We also forecast that, at the same daily deployment rate, the earlier introduction of vaccination schemes with lower efficacy would also lower the number of deaths with respect to a delayed introduction of high efficacy vaccines, which can however, still achieve lower numbers of infections and better herd immunity.

Design and characterization of a 3D-printed axon-mimetic phantom for diffusion MRI.

PURPOSE: To introduce and characterize inexpensive and easily produced 3D-printed axon-mimetic diffusion MRI phantoms in terms of pore geometry and diffusion kurtosis imaging metrics. METHODS: Phantoms were 3D-printed with a composite printing material that, after the dissolution of the polyvinyl alcohol, exhibits microscopic fibrous pores. Confocal microscopy and synchrotron phase-contrast micro-CT imaging were performed to visualize and assess the pore sizes. Diffusion MRI scans of four identical phantoms and phantoms with varying print parameters in water were performed at 9.4 T. Diffusion kurtosis imaging was fit to both data sets and used to assess the reproducibility between phantoms and effects of print parameters on diffusion kurtosis imaging metrics. Identical scans were performed 25 and 76 days later, to test their stability. RESULTS: Segmentation of pores in three microscopy images yielded a mean, median, and SD of equivalent pore diameters of 7.57 µm, 3.51 µm, and 12.13 µm, respectively. Phantoms had T1 /T2 = 2 seconds/180 ms, and those with identical parameters showed a low coefficient of variation (~10%) in mean diffusivity (1.38 × 10-3 mm2 /s) and kurtosis (0.52) metrics and radial diffusivity (1.01 × 10-3 mm2 /s) and kurtosis (1.13) metrics. Printing temperature and speed had a small effect on diffusion kurtosis imaging metrics (< 16%), whereas infill density had a larger and more variable effect (> 16%). The stability analysis showed small changes over 2.5 months (< 7%). CONCLUSION: Three-dimension-printed axon-mimetic phantoms can mimic the fibrous structure of axon bundles on a microscopic scale, serving as complex, anisotropic diffusion MRI phantoms.

The dynamics of COVID-19 spread: evidence from Lebanon.

We explore the spread of the Coronavirus disease 2019 (COVID-19) in Lebanon by adopting two different approaches: the STEIR model, which is a modified SEIR model accounting for the effect of travel, and a repeated iterations model. We fit available daily data since the first diagnosed case until the end of June 2020 and we forecast possible scenarios of contagion associated with different levels of social distancing measures and travel inflows. We determine the initial reproductive transmission rate in Lebanon and all subsequent dynamics. In the repeated iterations (RI) model we iterate the available data of currently infected people to forecast future infections under several possible scenarios of contagion. In both models, our results suggest that tougher mitigation measures would slow down the spread of the disease. On the other hand, the current relaxation of measures and partial resumption of international flights, as the STEIR reveals, would trigger a second outbreak of infections, with severity depending on the extent of relaxation. We recommend strong institutional and public commitment to mitigation measures to avoid uncontrolled spread.

Exploring Multiple Sclerosis (MS) and Amyotrophic Lateral Scler osis (ALS) as Neurodegenerative Diseases and their Treatments: A Review Study.

Growing concern about neurodegenerative diseases is becoming a global issue. It is estimated that not only will their prevalence increase but also morbidity and health burden will be concerning. Scientists, researchers and clinicians share the responsibility of raising the awareness and knowledge about the restricting and handicapping health restrains related to these diseases. Multiple Sclerosis (MS), as one of the prevalent autoimmune diseases, is characterized by abnormal regulation of the immune system that periodically attacks parts of the nervous system; brain and spinal cord. Symptoms and impairments include weakness, numbness, visual problems, tingling pain that are quietly variable among patients. Amyotrophic Lateral Sclerosis (ALS) is another neurodegenerative disease that is characterized by the degeneration of motor neurons in the brain and spinal cord. Unlike MS, symptoms begin with muscle weakness and progress to affect speech, swallowing and finally breathing. Despite the major differences between MS and ALS, misdiagnosis is still influencing disease prognosis and patient's quality of life. Diagnosis depends on obtaining a careful history and neurological examination as well as the use of Magnetic Resonance Imaging (MRI), which are considered challenging and depend on the current disease status in individuals. Fortunately, a myriad of treatments is available now for MS. Most of the cases are steroid responsive. Disease modifying therapy is amongst the most important set of treatments. In ALS, few medications that slow down disease progression are present. The aim of this paper is to summarize what has been globally known and practiced about MS and ALS, as they are currently classified as important growing key players among autoimmune diseases. In terms of treatments, it is concluded that special efforts and input should be directed towards repurposing of older drugs and on stem cells trials. As for ALS, it is highlighted that supportive measurements and supplementary treatments remain essentially needed for ALS patients and their families. On the other hand, it is noteworthy to clarify that the patient-doctor communication is relatively a cornerstone in selecting the best treatment for each MS patient.

Digest: The evolutionary relationship between environment and size in Australian rodents.

Biome shifts are thought to be relatively rare, but some clades shift among starkly different environments with relative ease. What causes these shifts, and how do they shape phenotypic evolution? Roycroft et al. found that biome shifts in the Pseudomys Division of murid rodents were repeatedly accompanied by body size evolution in accordance with Bergmann's rule, suggesting adaptive evolution in response to changing climate conditions.

Digest: A clinal polymorphism and life-history adaptations in Drosophila.

Does genetic variation in the insulin/insulin-like growth factor signaling pathway (IIS) underlie latitudinal life-history clines in North American Drosophila melanogaster? Durmaz et al. investigated how a clinally varying polymorphism in the IIS gene foxo affects fitness-related traits by isolating the effects of alternative low and high latitude alleles. The phenotypic effects of the polymorphism-for example, on body size-matched those normally observed across the cline, suggesting that variation in IIS is important for clinal life-history adaptation.

Digest: Fitness costs of Spiroplasma infection in pea aphids.

Endosymbionts sometimes help their hosts resist parasites, but does infection of pea aphids (Acyrthosiphon pisum) with different strains of the endosymbiont Spiroplasma confer fitness benefits that offset the costs? Mathé-Hubert et al. found that across four life-history traits, Spiroplasma infection induced negative effects on host fitness when compared to controls. Only two of 12 strains of Spiroplasma showed a marginal protective effect against host parasitism by Aphidius ervi, implying Spiroplasma infection is almost entirely detrimental to pea aphid host fitness.

Ligand recognition properties of the vasopressin V2 receptor studied under QSAR and molecular modeling strategies.

The design of new drugs that target vasopressin 2 receptor (V2R) is of vital importance to develop new therapeutic alternatives to treat diseases such as heart failure, polycystic kidney disease. To get structural insights related to V2R-ligand recognition, we have used a combined approach of docking, molecular dynamics simulations (MD) and quantitative structure-activity relationship (QSAR) to elucidate the detailed interaction of the V2R with 119 of its antagonists. The three-dimensional model of V2R was built by threading methods refining its structure through MD simulations upon which the 119 ligands were subjected to docking studies. The theoretical results show that binding recognition of these ligands on V2R is diverse, but the main pharmacophore (electronic and π-π interactions) is maintained; thus, this information was validated under QSAR results. QSAR studies were performed using MLR analysis followed by ANN analysis to increase the model quality. The final equation was developed by choosing the optimal combination of descriptors after removing the outliers. The applicability domains of the constructed QSAR models were defined using the leverage and standardization approaches. The results suggest that the proposed QSAR models can reliably predict the reproductive toxicity potential of diverse chemicals, and they can be useful tools for screening new chemicals for safety assessment.

Crystal structures of 4-phenyl-piperazin-1-ium 6-chloro-5-ethyl-2,4-dioxopyrimidin-1-ide and 4-phenyl-piperazin-1-ium 6-chloro-5-isopropyl-2,4-dioxopyrimidin-1-ide.

The title mol-ecular salts, C10H15N2 (+)·C6H6ClN2O2 (-), (I), and C10H15N2 (+)·C7H8ClN2O2 (-), (II), consist of 4-phenyl-piperazin-1-ium cations with a 6-chloro-5-ethyl-2,4-dioxopyrimidin-1-ide anion in (I) and a 6-chloro-5-isopropyl-2,4-dioxopyrimidin-1-ide anion in (II). Salt (I) crystallizes with two independent cations and anions in the asymmetric unit. In the crystal structures of both salts, the ions are linked via N-H⋯O and N-H⋯N hydrogen bonds, forming sheets which are parallel to (100) in (I) and to (001) in (II). In (I), the sheets are linked via C-H⋯Cl hydrogen bonds, forming a three-dimensional framework.

Spectroscopic investigation (FT-IR and FT-Raman), vibrational assignments, HOMO-LUMO, NBO, MEP analysis and molecular docking study of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-(phenylsulfanyl)-pyrimidine-5-carbonitrile, a potential chemotherapeutic agent.

Vibrational spectral analysis of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-(phenylsulfanyl)-pyrimidine-5-carbonitrile was carried out using FT-IR and FT-Raman spectroscopic techniques. The equilibrium geometry and vibrational wave numbers have been computed using density functional B3LYP method with 6-311++G(d,p)(5D,7F) as basis set. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using NBO analysis. The nonlinear optical behavior of the title compound is also theoretically predicted. From the MEP, it is evident that the negative charge covers the C≡N group and the positive region is over the phenyl and the pyrimidine rings. From the potential energy scan it is clear that the lone pairs of the sulfur atom prefer to point away from the pyrimidine ring and the C≡N group resulting with two possible minimum conformations at the N4C8S1C25 angle equal nearly 0° or 150°. Molecular docking results suggest that the compound might exhibit inhibitory activity against GPb and may act as potential anti-diabetic compound.

Vibrational spectroscopic and molecular docking study of 2-Benzylsulfanyl-4-[(4-methylphenyl)-sulfanyl]-6-pentylpyrimidine-5-carbonitrile, a potential chemotherapeutic agent.

FT-IR and FT-Raman spectra of 2-Benzylsulfanyl-4-[(4-methylphenyl)-sulfanyl]-6-pentylpyrimidine-5-carbonitrile were recorded and analyzed. The structure of the molecule has been optimized and the structural characteristics have been determined by density functional theory. The geometrical parameters (DFT) are in agreement with the XRD results. HOMO and LUMO and other chemical properties are reported. Nonlinear optical properties are reported. A detailed molecular picture of the title compound and its interactions were obtained from NBO analysis. The negative (red and yellow) regions of the MEP are related to electrophilic reactivity and the positive (blue) regions to nucleophilic reactivity, as shown in the MEP plot and the title compound has several possible sites, CN, N atom of pyrimidine ring and sulfur atoms for electrophilic attack. From the molecular docking studies it is clear that the title compound binds at the catalytic site of the substrate by weak non-covalent interactions most prominent of which are H-bonding, π-π, alkyl-π, and amide-π interactions.

QSAR/QSPR as an application of artificial neural networks.

Quantitative Structure-Activity Relationships (QSARs) and Quantitative Structure-Property Relationships (QSPRs) are mathematical models used to describe and predict a particular activity/property of compounds. On the other hand, the Artificial Neural Network (ANN) is a tool that emulates the human brain to solve very complex problems. The exponential need for new compounds in the drug industry requires alternatives for experimental methods to decrease development time and costs. This is where chemical computational methods have a great relevance, especially QSAR/QSPR-ANN. This chapter shows the importance of QSAR/QSPR-ANN and provides examples of its use.

Vibrational spectra, NBO analysis, HOMO-LUMO and first hyperpolarizability of 2-{[(2-Methylprop-2-en-1-yl)oxy]methyl}-6-phenyl-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dione, a potential chemotherapeutic agent based on density functional theory calculations.

The experimental FT-IR and FT-Raman spectra of 2-{[(2-Methylprop-2-en-1-yl)oxy]methyl}-6-phenyl-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dione were recorded. The optimized geometric parameters, normal mode frequencies and corresponding vibrational assignments of the compound have been examined by means of density functional theory. Reliable vibrational assignments and molecular orbital have been investigated by the potential energy distribution and natural bonding orbital analyses, respectively. The calculated first hyperpolarizability of the title compound is 2.82×10(-30) esu which is 21.69 times that of the standard NLO material urea. MEP was performed by the B3LYP level and the predicted infrared intensities and Raman activities have also been reported. Quantum chemical parameters were arrived from the frontier molecular orbital theory. The calculated geometrical parameters are in agreement with experimental results. From the MEP it is evident that the negative charge covers the CO groups and the positive region is over the rings and NH group.

The biomolecule, 2-[(2-methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile: FT-IR, Laser-Raman spectra and DFT.

In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential chemotherapeutic agent namely, 2-[(2-methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile have been investigated. The experimental FT-IR (4000-400cm(-1)) and Laser-Raman spectra (4000-100cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated using the same theoretical calculations.

Structural and spectroscopic characterization of a novel potential anti-inflammatory agent 3-(adamantan-1-yl)-4-ethyl-1H-1,2,4-triazole-5(4H)thione by first principle calculations.

A comprehensive investigation on the molecular structure, electronic properties and vibrational spectra of the 3-(adamantan-1-yl)-4-ethyl-1H-1,2,4-triazole-5(4H)thione, a novel potential anti-inflammatory agent has been done with the hope that the results of present study may be helpful in the prediction of its mechanism of biological activity. The experimentally observed spectral data (FT-IR and FT-Raman) of the title compound was compared with the spectral data obtained by DFT/B3LYP method. The (1)H nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the Gauge Including Atomic Orbital method and compared with experimental results. The molecular properties like dipole moment, polarizability, first static hyperpolarizability, the molecular electrostatic potential surface, contour map have been calculated to get a better insight of the properties of the title molecule. Natural bond orbital (NBO) analysis has been applied to study stability of the molecule arising from charge delocalization. UV-Vis spectrum of the title compound was also recorded and the electronic properties, such as Frontier orbitals and band gap energies were calculated by TD-DFT approach. Global and local reactivity descriptors have been computed to predict reactivity and reactive sites on the molecule.

Exploring QSARs of the interaction of flavonoids with GABA (A) receptor using MLR, ANN and SVM techniques.

Quantitative Structure-Activity Relationship (QSAR) models for binding affinity constants (log Ki) of 78 flavonoid ligands towards the benzodiazepine site of GABA (A) receptor complex were calculated using the machine learning methods: artificial neural network (ANN) and support vector machine (SVM) techniques. The models obtained were compared with those obtained using multiple linear regression (MLR) analysis. The descriptor selection and model building were performed with 10-fold cross-validation using the training data set. The SVM and MLR coefficient of determination values are 0.944 and 0.879, respectively, for the training set and are higher than those of ANN models. Though the SVM model shows improvement of training set fitting, the ANN model was superior to SVM and MLR in predicting the test set. Randomization test is employed to check the suitability of the models.

Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of a potential chemotherapeutic agent 6-(2-methylpropyl)-4-oxo-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile.

In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential chemotherapeutic agent namely, 6-(2-methylpropyl)-4-oxo-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile have been investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09 W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and depicted.

Exploring the ligand recognition properties of the human vasopressin V1a receptor using QSAR and molecular modeling studies.

Vaptans are compounds that act as non-peptide vasopressin receptor antagonists. These compounds have diverse chemical structures. In this study, we used a combined approach of protein folding, molecular dynamics simulations, docking, and quantitative structure-activity relationship (QSAR) to elucidate the detailed interaction of the vasopressin receptor V1a (V1aR) with some of its blockers (134). QSAR studies were performed using MLR analysis and were gathered into one group to perform an artificial neural network (ANN) analysis. For each molecule, 1481 molecular descriptors were calculated. Additionally, 15 quantum chemical descriptors were calculated. The final equation was developed by choosing the optimal combination of descriptors after removing the outliers. Molecular modeling enabled us to obtain a reliable tridimensional model of V1aR. The docking results indicated that the great majority of ligands reach the binding site under π-π, π-cation, and hydrophobic interactions. The QSAR studies demonstrated that the heteroatoms N and O are important for ligand recognition, which could explain the structural diversity of ligands that reach V1aR.