•The chemical profile of mango at four maturation stages was determined using ESI-MS.•Primary and secondary metabolites were identified at the third maturation stage.•The third stage of maturation is ...the best stage for the harvest and consumption.•The potential cancer chemoprevention of the secondary metabolites was evaluated.
Mangifera indica L., mango fruit, is consumed as a dietary supplement with purported health benefits; it is widely used in the food industry. Herein, the chemical profile of the Ubá mango at four distinct maturation stages was evaluated during the process of growth and maturity using negative-ion mode electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI(−)FT-ICR MS) and physicochemical characterisation analysis (total titratable acidity (TA), total soluble solids (TSS), TSS/TA ratio, and total polyphenolic content). Primary (organic acids and sugars) and secondary metabolites (polyphenolic compounds) were mostly identified in the third maturation stage, thus indicating the best stage for harvesting and consuming the fruit. In addition, the potential cancer chemoprevention of the secondary metabolites (phenolic extracts obtained from mango samples) was evaluated using the induction of quinone reductase activity, concluding that fruit polyphenols have the potential for cancer chemoprevention.
Lot-streaming is the process of splitting a job (lot) into a number of smaller sublots to allow the overlapping of operations between successive machines in a multi-stage production system. The use ...of sublots usually results in substantially shorter job completion times for the corresponding schedule. A new genetic algorithm (NGA) is proposed for an
n
-job,
m
-machine, lot-streaming flow shop scheduling problem with equal size sublots and limited capacity buffers with blocking in which the objective is to minimize total earliness and tardiness penalties. NGA replaces the selection and mating operators of genetic algorithms (GAs), which often lead to premature convergence, by new operators (marriage and pregnancy operators) and also adopts the idea of inter-chromosomal dominance and individuals’ similarities. Extensive computational experiments have been conducted to compare the performance of NGA with that of GA. The results show that, on the average, NGA outperforms GA by 9.86 % in terms of objective function value for medium to large-scale lot-streaming flow-shop scheduling problems.
Summary
The palatable, energy‐dense foods that characterize modern environments can promote unhealthy eating habits, along with humans' predispositions to accept sweet tastes and reject those that ...are sour or bitter. Yet food preferences are malleable, and examining food preference learning during early life can highlight ways to promote acceptance of healthier foods. This narrative review describes research from the past 10 years focused on food preference learning from the prenatal period through early childhood (ages 2–5 years).
Exposure to a variety of healthy foods from the start, including during the prenatal period, early milk‐feeding and the introduction to complementary foods and beverages, can support subsequent acceptance of those foods. Yet development is plastic, and healthier food preferences can still be promoted after infancy. In early childhood, research supports starting with the simplest strategies, such as repeated exposure and modelling, reserving other strategies for use when needed to motivate the initial tasting necessary for repeated exposure effects to begin.
This review can help caregivers and practitioners to promote the development of healthy food preferences early in life. Specific implementation recommendations, the role of individual differences and next steps for research in this area are also discussed.
Room temperature tensile properties and microhardness of a laser welded Ti–6Al–2Sn–4Zr–2Mo (Ti6242) titanium alloy sheet were examined and correlated to the microstructure evolution across the weld. ...Tensile testing integrated with the optical image correlation Instron® system indicated that the average yield strength (YS), ultimate tensile strength (UTS), and total elongation of the weldment were respectively 88%, 87%, and 69% of the corresponding base material (BM) values. Electron probe microanalysis (EPMA) demonstrated a uniform distribution of the main alloying elements across the weld. The hardness raised increasingly from the BM toward the heat affected zone (HAZ) and the fusion zone (FZ) due to mainly a higher α volume fraction in HAZ and acicular α′ martensite formation in the FZ. Because of the higher hardness of the HAZ and FZ, a higher YS for the weldment relative to the BM would be expected. However, the lower YS as well as the lower UTS of the weldment can be explained by presence of some porosity and underfill in the FZ. The lower total elongation of the weldment compared to the BM can be related to the higher hardness of the HAZ and FZ.
•We consider a serial supply chain with multiple suppliers and price sensitive demand.•The objective is to maximize profit and determine order quantities for selected suppliers.•This integrated ...process is modelled as a mixed integer nonlinear program.•A different multiplicative factor is assigned to each supplier.•We propose a power-of-two heuristic algorithm that generates near optimal solutions.
In this article, we consider a serial supply chain controlled by a decision-maker who is responsible for deciding the amount of raw material to order from the selected suppliers, the amount of product to transfer between consecutive stages in order to avoid any inventory shortages, and the final product's selling price so that the profit per time unit is maximized. Coordinating all these decisions simultaneously is a topic that has been neglected in literature. This integrated process is modeled as a mixed-integer nonlinear programming model. In addition, the model requires the order quantity received from each selected supplier to be an integer multiple of the order quantity delivered to the following stage, which means that a different multiplicative factor can be assigned to each supplier. This coordination mechanism shows an improvement in the objective function compared to existing models that assign the same multiplicative factor to each selected supplier. Moreover, we develop a heuristic algorithm that generates near optimal solutions in a timely manner. Two numerical examples are presented to illustrate the proposed model and the heuristic algorithm.
•We consider a single retailer, multiple suppliers, and price sensitive demand.•The objective is to maximize profit and determine order quantities for selected supplier.•A mixed integer nonlinear ...programming formulation of the problem is provided.•We determine sufficient conditions for the optimal selection of a single supplier.•We also investigate the impact of supplier's capacity on the optimal sourcing strategy.
This article presents a mixed integer nonlinear programming model to find the optimal selling price and replenishment policy for a particular type of product in a supply chain defined by a single retailer and multiple potential suppliers. Each supplier offers all-unit quantity discounts as an incentive mechanism. Multiple orders are allowed to be submitted to the selected suppliers during a repeating order cycle. The demand rate is considered to be not constant but dependent upon the selling price. The model provides the optimal number of orders and corresponding order quantities for the selected suppliers, and the optimal demand rate and selling price that maximize the total profit per time unit under suppliers’ capacity and quality constraints. In addition, we provide sufficient conditions under which there exists an optimal solution where the retailer only orders from one supplier. We also apply the Karush–Kuhn–Tucker conditions to investigate the impact of supplier's capacity on the optimal sourcing strategy. The results show that, there may exist a range of capacity values for the dominating supplier, where the retailer's optimal sourcing strategy is to consider multiple suppliers without fully utilizing the dominating supplier's capacity. A numerical example is presented to illustrate the proposed model.
Aims
To develop and validate a self‐report measure designed to assess perceived and experienced stigma for adults with Type 1 diabetes: the Type 1 Diabetes Stigma Assessment Scale (DSAS‐1).
Methods
A ...large item‐pool (64 items) was drafted based on qualitative data from interviews with 27 adults with Type 1 diabetes. Eleven adults with Type 1 diabetes completed the draft questionnaire (responding to items using a five‐point Likert scale), and participated in cognitive debriefing interviews. Based on their feedback, the item‐pool was reduced and refined. Adults with Type 1 diabetes (N=898) completed an online survey including the draft stigma questionnaire (41 items) and other validated measures. Psychometric validation included principal components analysis and confirmatory factor analysis (split samples), internal consistency reliability assessment and Spearman's rho correlations.
Results
Scale reduction techniques resulted in 19 items (α=0.93). An unforced three‐factor solution suggested three subscales: Treated Differently (six items, α=0.89); Blame and Judgement (six items, α=0.88); and Identity Concerns (seven items, α=0.89). This was corroborated with a confirmatory factor analysis, which demonstrated reasonable model fit with the three factors; less so for a single‐factor model. Satisfactory concurrent, convergent and discriminant validity were demonstrated.
Conclusions
The 19‐item DSAS‐1 is a valid and reliable measure of the perceptions and experiences of Type 1 diabetes stigma. This novel, relatively brief measure has satisfactory psychometric properties. The DSAS‐1 is now available for investigations into the nature and magnitude of the relationships between diabetes stigma and diabetes self‐care behaviours and outcomes.
What's new?
This paper reports on the rigorous development and validation of the first self‐report measure of perceived and experienced stigma specific to Type 1 diabetes: the novel Type 1 Diabetes Stigma Assessment Scale (DSAS‐1).
Questionnaire design was informed by exploratory qualitative research and items were confirmed after cognitive debriefing with people with Type 1 diabetes.
Psychometric validation showed that this 19‐item measure was acceptable, had a three‐factor structure, high internal consistency reliability, and satisfactory concurrent, convergent and discriminant validity.
The DSAS‐1 could facilitate research to quantify the extent and impact of stigma associated with Type 1 diabetes.
Voriconazole pharmacokinetics shows a large inter- and intrapatient variability. Inflammation is associated with changes in the expression of CYP isoenzymes. Here, we evaluated the influence of ...inflammation, marked by C-reactive protein (CRP) levels in blood, on the metabolism of voriconazole. Observational data showed an association between CRP level and the ratio of voriconazole N-oxide to voriconazole.
To assess the gross motor development of children with presumed congenital Zika virus (ZIKV) infection over the first 2 years of their lives.
Seventy-seven children were assessed at the median ages ...of 11, 18, and 24 months, using the evaluative instrument Gross Motor Function Measure (GMFM-66). At the third assessment, the children with diagnoses of cerebral palsy (CP) were classified by severity through the Gross Motor Function Classification System (GMFCS) and stratified by topography indicating the predominantly affected limbs. With these instruments in combination and using the motor development curves as reference, the rate of development and functional ability were estimated.
At 2 years of age, all children had the diagnosis of CP. Seventy-four (96.1%) presented gross motor skills similar to those of children aged 4 months or younger, according to the World Health Organization's standard. The GMFM-66 median score among the 73 (94.8%) children with quadriplegia and GMFCS level V showed significant change between 11 and 18 months (p < 0.001) and between 11 and 24 months (p < 0.001). No significant difference (p = 0.076) was found between 18 and 24 months.
Despite showing some gross motor progress during the initial 18 months of life, these children with presumed congenital ZIKV infection and CP experienced severe motor impairment by 2 years of age. According to the motor development curves, these children with quadriplegia have probably already reached about 90% of their motor development potential.
In this work, we carried out the design and synthesis of new chimeric compounds from the natural cytotoxic chalcone 2',4'-dihydroxychalcone (2',4'-DHC,
) in combination with cinnamic acids. For this ...purpose, a descriptive and predictive quantitative structure-activity relationship (QSAR) model was developed to study the chimeric compounds' anti-cancer activities against human breast cancer MCF-7, relying on the presence or absence of structural motifs in the chalcone structure, like in a Free-Wilson approach. For this, we used 207 chalcone derivatives with a great variety of structural modifications over the α and β rings, such as halogens (F, Cl, and Br), heterocyclic rings (piperazine, piperidine, pyridine, etc.), and hydroxyl and methoxy groups. The multilinear equation was obtained by the genetic algorithm technique, using logIC
as a dependent variable and molecular descriptors (constitutional, topological, functional group count, atom-centered fragments, and molecular properties) as independent variables, with acceptable statistical parameter values (R2 = 86.93, Q2
= 82.578, Q2
= 80.436, and Q2
= 80.226), which supports the predictive ability of the model. Considering the aromatic and planar nature of the chalcone and cinnamic acid cores, a structural-specific QSAR model was developed by incorporating geometrical descriptors into the previous general QSAR model, again, with acceptable parameters (R2 = 85.554, Q2
= 80.534, Q2
= 78.186, and Q2
= 79.41). Employing this new QSAR model over the natural parent chalcone 2',4'-DHC (
) and the chimeric compound 2'-hydroxy,4'-cinnamate chalcone (
), the predicted cytotoxic activity was achieved with values of 55.95 and 17.86 µM, respectively. Therefore, to corroborate the predicted cytotoxic activity compounds
and
were synthesized by two- and three-step reactions. The structures were confirmed by
H and
C NMR and ESI+MS analysis and further evaluated in vitro against HepG2, Hep3B (liver), A-549 (lung), MCF-7 (breast), and CasKi (cervical) human cancer cell lines. The results showed IC
values of 11.89, 10.27, 56.75, 14.86, and 29.72 µM, respectively, for the chimeric cinnamate chalcone
. Finally, we employed
as a molecular scaffold for the generation of cinnamate candidates (
-
), which incorporated structural motifs that enhance the cytotoxic activity (pyridine ring, halogens, and methoxy groups) according to our QSAR model. ADME/tox in silico analysis showed that the synthesized compounds
and
, as well as the proposed chalcones
and
, are the best candidates with adequate drug-likeness properties. From all these results, we propose
(as a molecular scaffold) and our two QSAR models as reliable tools for the generation of anti-cancer compounds over the MCF-7 cell line.
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