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Social units, such as households and schools, can play an important role in controlling epidemic outbreaks. In this work, we study an epidemic model with a prompt quarantine measure on networks with cliques (a clique is a fully connected subgraph representing a social unit). According to this strategy, newly infected individuals are detected and quarantined (along with their close contacts) with probability f. Numerical simulations reveal that epidemic outbreaks in networks with cliques are abruptly suppressed at a transition point f_{c}. However, small outbreaks show features of a second-order phase transition around f_{c}. Therefore, our model can exhibit properties of both discontinuous and continuous phase transitions. Next, we show analytically that the probability of small outbreaks goes continuously to 1 at f_{c} in the thermodynamic limit. Finally, we find that our model exhibits a backward bifurcation phenomenon.

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Streamlit is an open-source Python coding framework for building web-applications or "web-apps" and is now being used by researchers to share large data sets from published studies and other resources. Here we present Stmol, an easy-to-use component for rendering interactive 3D molecular visualizations of protein and ligand structures within Streamlit web-apps. Stmol can render protein and ligand structures with just a few lines of Python code by utilizing popular visualization libraries, currently Py3DMol and Speck. On the user-end, Stmol does not require expertise to interactively navigate. On the developer-end, Stmol can be easily integrated within structural bioinformatic and cheminformatic pipelines to provide a simple means for user-end researchers to advance biological studies and drug discovery efforts. In this paper, we highlight a few examples of how Stmol has already been utilized by scientific communities to share interactive molecular visualizations of protein and ligand structures from known open databases. We hope Stmol will be used by researchers to build additional open-sourced web-apps to benefit current and future generations of scientists.

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An important group of antiemetic drugs used in the treatment of nausea and vomiting after chemotherapy containing an indole moiety in their structures, working as 5- hydroxytryptamine type 3 serotonin receptor antagonist (5-HT3). This study focuses on compounds bearing an indole core that present a 5-HT3 receptor antagonist activity, which have been successfully used as antiemetic drugs for reducing chemotherapy adverse secondary effects during cancer treatment. Their synthesis, biological activities, and some outstanding characteristics are discussed, providing a general outlook towards the development of more efficient antiemetic drugs.

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To examine the growth of Candida norvegensis (strain Levazoot 15), four experiments were conducted with different sources of energy, nitrogen, vitamins, and microminerals. Optical density was used as an indirect measure of strain growth in a fully randomized factorial design, in which principal factor A was the source of energy, nitrogen, vitamins, or microminerals and principal factor B was the measurement time point (0, 20, or 40 h). The results showed that the yeast strain used glucose (primarily sucrose and lactose) as the energy source and tryptone as the nitrogen source. The addition of B-complex vitamins or microminerals was not necessary for strain growth. It is concluded that the strain Levazoot 15 preferentially utilizes glucose as a source of energy, tryptone as a source of nitrogen and manganese as a mineral source, and that no vitamin source was necessary for growth.

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BACKGROUND: In order to develop new larvicidal agents derived from phytochemicals, the larvicidal activity of fifty molecules that are constituent of essential oils was evaluated against Culex quinquefasciatus Say. Terpenes, terpenoids and phenylpropanoids molecules were included in the in vitro evaluation, and QSAR models using genetic algorithms were built to identify molecular and structural properties of biological interest. Further, to obtain structural details on the possible mechanism of action, selected compounds were submitted to docking studies on sterol carrier protein-2 (SCP-2) as possible target. RESULTS: Results showed high larvicidal activity of carvacrol and thymol on the third and fourth larval stage with a median lethal concentration (LC50) of 5.5 and 11.1 µg/mL respectively. Myrcene and carvacrol were highly toxic for pupae, with LC50 values of 31.8 and 53.2 µg/mL. Structure-activity models showed that the structural property π-bonds is the largest contributor of larvicidal activity while ketone groups should be avoided. Similarly, property-activity models attributed to the molecular descriptor LogP the most contribution to larvicidal activity, followed by the absolute total charge (Qtot) and molar refractivity (AMR). The models were statistically significant; thus the information contributes to the design of new larvicidal agents. Docking studies show that all molecules tested have the ability to interact with the SCP-2 protein, wherein α-humulene and ß-caryophyllene were the compounds with higher binding energy. CONCLUSIONS: The description of the molecular properties and the structural characteristics responsible for larvicidal activity of the tested compounds were used for the development of mathematical models of structure-activity relationship. The identification of molecular and structural descriptors, as well as studies of molecular docking on the SCP-2 protein, provide insight on the mechanism of action of the active molecules, and the information can be used for the design of new structures for synthesis as potential new larvicidal agents.

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Human immunodeficiency virus type-1 (HIV-1) has infected more than 40 million people around the world. HIV-1 treatment still has several side effects, and the development of a vaccine, which is another potential option for decreasing human infections, has faced challenges. This work presents a computational study that includes a quantitative structure activity relationship(QSAR) using density functional theory(DFT) for reported peptides to identify the principal quantum mechanics descriptors related to peptide activity. In addition, the molecular recognition properties of these peptides are explored on major histocompatibility complex I (MHC-I) through docking and molecular dynamics (MD) simulations accompanied by the Molecular Mechanics Generalized Born Surface Area (MMGBSA) approach for correlating peptide activity reported elsewhere vs. theoretical peptide affinity. The results show that the carboxylic acid and hydroxyl groups are chemical moieties that have an inverse relationship with biological activity. The number of sulfides, pyrroles and imidazoles from the peptide structure are directly related to biological activity. In addition, the HOMO orbital energy values of the total absolute charge and the Ghose-Crippen molar refractivity of peptides are descriptors directly related to the activity and affinity on MHC-I. Docking and MD simulation studies accompanied by an MMGBSA analysis show that the binding free energy without considering the entropic contribution is energetically favorable for all the complexes. Furthermore, good peptide interaction with the most affinity is evaluated experimentally for three proteins. Overall, this study shows that the combination of quantum mechanics descriptors and molecular modeling studies could help describe the immunogenic properties of peptides from HIV-1.

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Various social, financial, biological and technological systems can be modeled by interdependent networks. It has been assumed that in order to remain functional, nodes in one network must receive the support from nodes belonging to different networks. So far these models have been limited to the case in which the failure propagates across networks only if the nodes lose all their supply nodes. In this paper we develop a more realistic model for two interdependent networks in which each node has its own supply threshold, i.e., they need the support of a minimum number of supply nodes to remain functional. In addition, we analyze different conditions of internal node failure due to disconnection from nodes within its own network. We show that several local internal failure conditions lead to similar nontrivial results. When there are no internal failures the model is equivalent to a bipartite system, which can be useful to model a financial market. We explore the rich behaviors of these models that include discontinuous and continuous phase transitions. Using the generating functions formalism, we analytically solve all the models in the limit of infinitely large networks and find an excellent agreement with the stochastic simulations.

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BACKGROUND: Prevalence rates of obesity and related diseases are quickly reaching epidemic proportions among Hispanic males in the United States. Hispanic males suffer from the highest prevalence of obesity-related diseases when compared to all other racial/ethnic groups. Despite evidence showing that weight loss can significantly reduce the risk of obesity-related health implications, literature informing best practices to engage Hispanic males in weight management programs is scarce. PURPOSE: The purpose of the current study was to engage Spanish-speaking, Mexican-origin males with overweight or obesity to examine their perspectives of diet-related behaviors related to weight management. METHODS: Demographic and acculturation data were collected using questionnaires. Fourteen semistructured interviews were completed with an all-Spanish-speaking cohort of men (age: 45.0±9.8 years; BMI: 34.2±6.5 kg m-2) who were born outside of the United States. We conducted a thematic analysis using a hybrid deductive-inductive analysis strategy using a previously developed codebook that was updated during iterative analysis of interview transcripts. RESULTS: Participants reported that healthful eating habits were hindered, among other factors, by lack of knowledge, sociocultural norms and conceptualizations of masculinity. Viable diet-related intervention approaches also surfaced, including building consciousness, promotion of traditional knowledge and the integration of the family in interventions. CONCLUSION: Findings suggest that Spanish-speaking, Mexican-origin men have interest in actively engaging in behavior changes that improve their dietary habits and engage in weight management. Our findings yield valuable insights that can be used to formulate tailored intervention strategies to improve obesity prevention and treatment programs for this vulnerable subgroup.

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Novel chalcone derivatives with different substituents attached to A and B-rings: hydroxyl, methoxyl, geranyl, and prenyl groups were synthesized. The obtained compounds were characterized by NMR, HRMS, UV-Vis, IR, and MS. The theoretical analysis was carried out in all the compounds using density functional theory (DFT) with the B3LYP, PBE0, and M06-2X functionals in combination with the 6-311G(d,p) Pople-type basis set. The excited state properties were calculated by time dependent density functional theory (TD-DFT) using the same methodology applied for the ground state properties. The calculated vertical absorption wavelengths (λmax) in gas phase and in ethanol as a solvent are consistent with the experimental ones, being the TD-DFT:B3LYP/6-311G(d,p) and PCM-TD-DFT:PBE0/6-311G(d,p) the best methodologies for these calculations with good approximation to the experimental values. The calculated reorganization energies indicated that, the four chalcone derivatives present an electron transfer character due to the smaller registered values. From these parameters it is proposed that these show an n-type semiconductor character. The localization of the frontier orbitals (HOMO and LUMO) shows that only the compound containing a hydroxyl group on the A-ring displays a marked delocalization favoring the charge-transfer process in this system. The HOMO-LUMO gap energies indicate that the inclusion of different donor groups in the rings does not improve the obtained values for this property. Graphical Abstract Relationship between spectroscopic and geometrical properties of chalcones were carried out using quantum-chemical calculations and compared with experimental values.

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The Ebola virus is spreading throughout West Africa and is causing thousands of deaths. In order to quantify the effectiveness of different strategies for controlling the spread, we develop a mathematical model in which the propagation of the Ebola virus through Liberia is caused by travel between counties. For the initial months in which the Ebola virus spreads, we find that the arrival times of the disease into the counties predicted by our model are compatible with World Health Organization data, but we also find that reducing mobility is insufficient to contain the epidemic because it delays the arrival of Ebola virus in each county by only a few weeks. We study the effect of a strategy in which safe burials are increased and effective hospitalisation instituted under two scenarios: (i) one implemented in mid-July 2014 and (ii) one in mid-August--which was the actual time that strong interventions began in Liberia. We find that if scenario (i) had been pursued the lifetime of the epidemic would have been three months shorter and the total number of infected individuals 80% less than in scenario (ii). Our projection under scenario (ii) is that the spreading will stop by mid-spring 2015.

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Many real-world networks depend on other networks, often in nontrivial ways, to maintain their functionality. These interdependent "networks of networks" are often extremely fragile. When a fraction 1-p of nodes in one network randomly fails, the damage propagates to nodes in networks that are interdependent and a dynamic failure cascade occurs that affects the entire system. We present dynamic equations for two interdependent networks that allow us to reproduce the failure cascade for an arbitrary pattern of interdependency. We study the "rich club" effect found in many real interdependent network systems in which the high-degree nodes are extremely interdependent, correlating a fraction α of the higher-degree nodes on each network. We find a rich phase diagram in the plane p-α, with a triple point reminiscent of the triple point of liquids that separates a nonfunctional phase from two functional phases.

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We study the critical effect of an intermittent social distancing strategy on the propagation of epidemics in adaptive complex networks. We characterize the effect of our strategy in the framework of the susceptible-infected-recovered model. In our model, based on local information, a susceptible individual interrupts the contact with an infected individual with a probability σ and restores it after a fixed time t(b). We find that, depending on the network topology, in our social distancing strategy there exists a cutoff threshold σ(c) beyond which the epidemic phase disappears. Our results are supported by a theoretical framework and extensive simulations of the model. Furthermore we show that this strategy is very efficient because it leads to a "susceptible herd behavior" that protects a large fraction of susceptible individuals. We explain our results using percolation arguments.

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Fortification of foods is now widely used to prevent folate deficiency. Folic acid has been added to corn flour and its efficacy in the prevention of NTD has been proved. The aim of this study was to compare the effect of the intake of fortified corn-flour versus non fortified flour and to folic acid supplement, on blood folate levels in women of childbearing age. Forty-five women were randomized into three groups according to: (A) use of fortified flour (n=18), (B) non-fortified flour (n=17); (C) supplementation with 5 mg of oralfolic acid (n=10). All females answer a dietary and anthropometric questionnaire applied once a month during three months. Blood red cell (IE) and plasmatic (P) folate were measured at the beginning and at the end of the study; also the DNA analysis for the 677T mutation was performed. The corn flour was provided to groups A and B during three months, to be consumed as eight tortillas daily. Group C received 5.0 mg tablet of folic acid (Valdecasas®), once per week, during three months. IE and P folate and hematocrito were significantly increased in women from group C (p<0.05). Only plasmatic folic acid levels were significantly increased in women from groups A and B. Genotype distribution was: 15.6 percent homozygous TT, 42.2 percent C/C and 42.2 percent CT. Weekly administration of 5.0 mg of folic acid is an effective way to increase blood folate levels and shows to be more efficient than fortified corn flour.

La fortificación de alimentos con ácido fólico puede ser efectiva en la prevención de los defectos del tubo neural, aunque no existen estudios que demuestren la eficacia de esta medida en la harina de maíz. El objetivo del estudio fue evaluar el efecto del consumo de harina de maíz vitaminada sobre los niveles de folatos sanguíneos, en comparación con la suplementación oral. Se incluyeron 45 mujeres en edad fértil aleatorizadas en tres grupos; grupo A (n=18) harina vitaminada, grupo B (n=17) harina sin vitaminas, grupo C (n=10) suplemento oral 5.0 mg de ácido fólico una vez por semana, durante tres meses. A las participantes se les aplicó una encuesta nutricional y se les midió por radioinmunoensayo el folato intraeritrocitario (FIE) y plasmático (FP) al inicio y final del estudio y se determinó la presencia del polimorfismo C677T del gen MTHFR. En las mujeres con suplemento oral los niveles FIE y FP y el hematocrito se incrementaron significativamente (p< 0.05), mientras que en los grupos A y B se registró un incremento significativo en los valores de FP pero no IE ni hematocrito. La ingesta de otras fuentes de ácido fólico se incrementó significativamente en los grupos A y B. El 15.6 por ciento de las mujeres fueron homocigotas TT, 42.2 por ciento homocigotas CC y 42.2 por ciento heterocigotas CT. La administración de 5 mg de ácido fólico por semana es una medida más eficiente que la ingesta de harina de maíz vitaminada para elevar los niveles de folatos.

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The aim of this work was to quantify NO,O(2)(-) and ONOO(-) production during heparin-induced capacitation of cryopreserved bovine spermatozoa. A time dependent hyperbolic increase was observed for heparin-dependent capacitation, O(2) uptake, and NO production. Conversely, O(2)(-) production was increased during the first 15 min of incubation, showing a decrease from this time until 45 min. At 15 min of heparin incubation, a threefold increase in O(2) consumption (5.9 ± 0.6 nmol/min × 10(7) cells), an enhancement in NO release (1.1 ± 0.2 nmol/min × 10(7) cells), and a five-fold increase in O(2)(-) production (1.3 ± 0.07 nmol/min × 10(7) cells), were observed. Peroxynitrite production rate was estimated taking into account NO and O(2)(-) generation and the second-order rate constant of the reaction between these species. To conclude, heparin-induced capacitation of cryopreserved bovine spermatozoa activates (i) mitochondrial O(2) uptake by high ADP levels due to increased energy requirements, (ii) NO production by a constitutive NOS and (iii) O(2)(-) production by a membrane-bound NAD(P)H oxidase. The products of both enzymes are released to the extracellular space and could be involved in the process of sperm capacitation.

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Human mononuclear cells (90% lymphocytes, 9% monocytes, and 1% polymorphonuclear leukocytes) produced spontaneously in resting state 0.11+/-0.01 nmol of nitric oxide (NO)/min/10(6) cells and 0.25+/-0.02 nmol of superoxide anion (O2-)/min/10(6) cells, as primary products. When these cells were stimulated with phorbol 12-myristate 13-acetate (PMA), the NO and O2- production increased by 82% and 204% to 0.25+/-0.02 nmol of NO/min/10(6) cells and 0.76+/-0.12 nmol of O2-/min/10(6) cells, respectively. Oxygen uptake reasonably accounted for the sum of the rates of NO and hydrogen peroxide (H2O2), the latter calculated as 0.5 O2- production, in nonstimulated and in PMA-stimulated cells. H2O2 and peroxynitrite formation were detected and measured as secondary products of the primary products O2- and NO. An original assay to determine H2O2 steady-state concentration and production rates is described. The determined production rates of the involved reactive species are in good agreement with known chemical equations. It is apparent that NO and O2- production by human mononuclear cells may constitute the basis of intercellular signaling and cell toxicity.

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OBJECTIVE: To establish the profile of children who suffer abuse and of abuse perpetrators. METHODS: 225 cases of confirmed child-abuse in Curitiba, state of Paraná, were studied in 1998 based on information collected using a protocol. RESULTS: The following patterns were observed: 56% of the children were in school age; 59.6% were the first child of the couple; 84.4% were natural offspring; and 71.1% of the children had a satisfactory school record. Multiple injuries (38.2%) were found on the victims bodies, mostly bruises (37.8%). The main aggressor was the mother (42.2%); 25.8% of them said that the reason for the violence was disciplining the child; 72% of the mothers denied the use of alcohol. CONCLUSION: Our results reveal that the children who are most affected by physical abuse are the first-borns of married couples, with age between 5 and 11 years; their schooling level is compatible with their age. Most violent acts are performed by the mother, who hits the child leaving bruises on several parts of the victimacute;s body, with the objective of educating, or setting limits to the child.

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Superoxide radical (O2-) and nitric oxide (NO) produced at the mitochondrial inner membrane react to form peroxynitrite (ONOO-) in the mitochondrial matrix. Intramitochondrial ONOO- effectively reacts with a few biomolecules according to reaction constants and intramitochondrial concentrations. The second-order reaction constants (in M(-1) s(-1)) of ONOO- with NADH (233 +/- 27), ubiquinol-0 (485 +/- 54) and GSH (183 +/- 12) were determined fluorometrically by a simple competition assay of product formation. The oxidation of the components of the mitochondrial matrix by ONOO- was also followed in the presence of CO2, to assess the reactivity of the nitrosoperoxocarboxylate adduct (ONOOCO2-) towards the same reductants. The ratio of product formation was about similar both in the presence of 2.5 mM CO2 and in air-equilibrated conditions. Liver submitochondrial particles supplemented with 0.25-2 microM ONOO- showed a O2- production that indicated ubisemiquinone formation and autooxidation. The nitration of mitochondrial proteins produced after addition of 200 microM ONOO- was observed by Western blot analysis. Protein nitration was prevented by the addition of 50-200 microM ubiquinol-0 or GSH. An intramitochondrial steady state concentration of about 2 nM ONOO- was calculated, taking into account the rate constants and concentrations of ONOO- coreactants.

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Hypersensitivity pneumonitis (HP) is characterized by a T-cell-mediated alveolitis, and the putative role of other inflammatory cells in its pathogenesis remains unclear. In this study we determined whether increased quantities of neutrophils were present in HP lungs, and if they were positive for gelatinase B and collagenase-2. Fifteen nonsmoking patients with subacute/chronic active HP were included. Lung samples were analyzed using myeloperoxidase antibody, and neutrophil/total cell ratio was evaluated by digital processing. All HP tissue samples exhibited variable quantities of neutrophils located inside vessels, and in the interstitial and alveolar spaces. Lung neutrophil percentage ranged from 0.7% to 4.8% (2.1 +/- 1.4%). There was a positive correlation between the percentage of lung neutrophils and the percentage of lung fibrosis (r = 0.6, p < 0.02). Tissue neutrophils showed intense immunoreactive collagenase-2 and gelatinase B staining. Additionally, gelatinolytic activities corresponding to progelatinases A and B and their activated forms, were several-fold increased in the bronchoalveolar lavage fluid (BALF) from patients with HP as compared with control subjects. These findings suggest that in HP lungs there is a persistent traffic of neutrophils loaded with gelatinase B and collagenase-2 that may play a role in the lung damage and in the fibrotic response.

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BACKGROUND: A central feature in the pathogenesis of COPD is the inflammation coexisting with an abnormal protease/antiprotease balance. However, the possible role of different serine and metalloproteinases remains controversial. PATIENTS AND MEASUREMENTS: We examined the expression of gelatinases A and B (matrix metalloproteinase [MMP]-2 and MMP-9); collagenases 1, 2, and 3 (MMP-1, MMP-8, and MMP-13); as well as the presence of apoptosis in lung tissues of 10 COPD patients and 5 control subjects. In addition, gelatinase-A and gelatinase-B activities were assessed in BAL obtained from eight COPD patients, and from six healthy nonsmokers and six healthy smoker control subjects. SETTING: Tertiary referral center and university laboratories of biochemistry, and lung cell kinetics. RESULTS: Immunohistochemical analysis of COPD lungs showed a markedly increased expression of collagenases 1 and 2, and gelatinases A and B, while collagenase 3 was not found. Neutrophils exhibited a positive signal for collagenase 2 and gelatinase B, whereas collagenase 1 and gelatinase A were revealed mainly in macrophages and epithelial cells. BAL gelatin zymography showed a moderate increase of progelatinase-A activity and intense bands corresponding to progelatinase B. In situ end labeling of fragmented DNA displayed foci of positive endothelial cells, although some alveolar epithelial, interstitial, and inflammatory cells also revealed intranuclear staining. CONCLUSION: These findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.

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