We study a supplier selection and order quantity allocation problem in a two-stage supply chain, which is composed of a set of potential suppliers and a single buyer/retailer trading one product. The ...demand at the buyer's stage is price-sensitive and suppliers have finite production rates. Within this framework, the optimization of the supply chain is evaluated by considering the performance of both stages and guaranteeing their profitability through a coordination mechanism based on profit-sharing. Two mixed integer nonlinear programming models are presented under different lot-sizing policies to determine the optimal set of selected suppliers, retail price, and order quantity and number of orders per order cycle for each selected supplier. The structure of the models' solutions is examined by deriving properties of the optimal supplier selection and order quantity allocation scheme. Numerical examples are also provided to illustrate the applicability of the proposed models.
•We consider a two-stage decentralized supply chain with multiple suppliers and a buyer.•Suppliers have finite production rates, and the demand is price sensitive.•We propose mathematical models based on order frequency and profit-sharing structure.•Optimal solutions satisfy the zero-inventory ordering property and the nested property.
The dwell points for idle vehicles in an automated guided vehicle (AGV) system determine the response times for pick-up requests and thus affect the performance of automated manufacturing systems. In ...this paper, we address the problem of optimally locating dwell points for a given number of AGVs in a general guide-path layout. Based on an optimality property, we propose new mixed integer linear programming (MILP) formulations for three versions of the problem: (i) minimizing the mean response time in the system, (ii) minimizing the maximum response time in the system, and (iii) minimizing the maximum response time in the system considering time restrictions on vehicle availability. Given that the computational time required to solve the MILP models significantly increases with the size of the guide-path network and number of available AGVs, we also develop a generic genetic algorithm (GA) that can be applied to all three versions of the problem. A computational study is carried out on the single-loop layout and two special cases of two-dimensional grid networks with the objectives of minimizing mean response time and minimizing the maximum response time. The results show that the proposed GA procedure can yield optimal or near optimal solutions in reasonable time.
•In this paper we consider the optimal location of dwell points in AGV systems.•Mathematical models for three versions of the problem are formulated.•A genetic algorithm to solve all the three versions of the problem is developed.•A computational study is carried out on loop layouts and general grid networks.•Computational results show that the genetic algorithm is very efficient.
This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of docetaxel (DTX). Nanospheres were prepared by solvent ...displacement method using polylactic acids (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles ranged from 100 to 200
nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest molecular weight PLA showed a zeta potential value of −28
mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence of the polymeric carrier on the interaction of DTX with biological membranes, we performed an
in vitro study using lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of Δ
H value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form nanospheres is affected by the molecular weight of the employed polymers.
Given the prevalence of both supplier selection and inventory control problems in supply chain management, this article addresses these problems simultaneously by developing a mathematical model for ...a serial system. This model determines an optimal inventory policy that coordinates the transfer of items between consecutive stages of the system while properly allocating orders to selected suppliers in stage 1. In addition, a lower bound on the minimum total cost per time unit is obtained and a 98% effective power-of-two (POT) inventory policy is derived for the system under consideration. This POT algorithm is advantageous since it is simple to compute and yields near optimal solutions.
Synchrotron radiation can facilitate novel radiation therapy modalities such as microbeam radiation therapy (MRT) and high dose-rate synchrotron broad-beam radiation therapy (SBBR). Both of these ...modalities have unique physical properties that could be exploited for an improved therapeutic effect. While pre-clinical studies report promising normal tissue sparing phenomena, systematic toxicity data are still required. Our objective was to characterise the toxicity of SBBR and MRT and to calculate equivalent doses of conventional radiation therapy (CRT). A dose-escalation study was performed on C57BLJ/6 mice using total body and partial body irradiations. Dose-response curves and TD
values were subsequently calculated using PROBIT analysis. For SBBR at dose-rates of 37 to 41 Gy/s, we found no evidence of a normal tissue sparing effect relative to CRT. Our findings also show that the MRT valley dose, rather than the peak dose, best correlates with CRT doses for acute toxicity. Importantly, longer-term weight tracking of irradiated animals revealed more pronounced growth impairment following MRT compared to both SBBR and CRT. Overall, this study provides the first in vivo dose-equivalence data between MRT, SBBR and CRT and presents systematic toxicity data for a range of organs that can be used as a reference point for future pre-clinical work.
This paper analyzes different lot-sizing policies for the supplier selection and order allocation problem in a two-stage supply chain. The supply chain consists of multiple candidate suppliers and a ...single buyer. In this system, selected suppliers produce a product in batches at finite production rates, ship it to the buyer, and the buyer sells it to the market at a constant demand rate. Our goal is to evaluate two lot-sizing policies and select the one that optimizes the supply chain by minimizing the total cost and maximizing supplier efficiency. A bi-objective mixed-integer nonlinear programming (BOMINLP) model is proposed. The first objective consists of the development of a coordination mechanism for supplier selection and order allocation that minimizes the entire supply chain cost, and the second objective comprises a data envelopment analysis (DEA) approach to evaluate the overall performance of suppliers to optimize supplier efficiency. Then, the lot-for-lot and order frequency policies are applied to the BOMINLP model separately to determine the set of selected suppliers as well as the corresponding order quantities and number of orders allocated to each selected supplier per replenishment cycle. Numerical examples that illustrate the solution approach and compare the two lot-sizing policies are provided.
Voriconazole (VCZ) exhibits great inter- and intrapatient variability. The latter variation cannot exclusively be explained by concomitant medications, liver disease or dysfunction, and genetic ...polymorphisms in cytochrome P450 2C19 (CYP2C19). We hypothesized that inflammatory response in patients under VCZ medication might also influence this fluctuation in concentrations. In this study, we explored the association between inflammation, reflected by the C-reactive protein (CRP) concentration, and VCZ trough concentrations over time. A retrospective analysis of data was performed for patients with more than one steady-state VCZ trough concentration and a CRP concentration measured on the same day. A longitudinal analysis was used for series of observations obtained from many study participants over time. The approach involved inclusion of random effects and autocorrelation in linear models to reflect within-person cross-time correlation. A total of 50 patients were eligible for the study, resulting in 139 observations (paired VCZ and CRP concentrations) for the analysis, ranging from 2 to 6 observations per study participant. Inflammation, marked by the CRP concentration, had a significant association with VCZ trough concentrations (P < 0.001). Covariates such as age and interacting comedication (esomeprazole), also showed a significant correlation between VCZ and CRP concentrations (P < 0.05). The intrapatient variation of trough concentrations of VCZ was 1.401 (confidence interval CI, 0.881 to 2.567), and the interpatient variation was 1.756 (CI, 0.934 to 4.440). The autocorrelation between VCZ trough concentrations at two sequential time points was calculated at 0.71 (CI, 0.51 to 0.92). The inflammatory response appears to play a significant role in the largely unpredictable pharmacokinetics of VCZ, especially in patients with high inflammatory response, as reflected by high CRP concentrations.
Increased levels of enhancer of zeste homolog 2 (EZH2), a critical regulator of cellular memory, are associated with negative estrogen receptor (ER) expression and disease progression in breast ...cancer. High levels of EZH2 signal the presence of metastasis and poor outcome in breast cancer patients. To test the hypothesis that deregulation of EZH2 contributes to ER-negative breast cancer progression, EZH2 expression was inhibited in ER-negative breast cancer cells MDA-MB-231 and CAL51 using a lentivirus system. EZH2 knockdown decreased proliferation and delayed the G(2)/M cell-cycle transition, although not affecting apoptosis. In vivo, EZH2 downregulation significantly decreased breast xenograft growth and improved survival. EZH2 knockdown upregulated BRCA1 protein. Of note, BRCA1 knockdown was sufficient to rescue the effects of EZH2 downregulation on proliferation, G(2)/M arrest, and on the levels of hyperphosphorylated mitotic Cdc25C and Cyclin B1 proteins, crucial for entry into mitosis. Invasive ER-negative breast carcinomas show significant overexpression of EZH2 and downregulation of BRCA1 proteins. Taken together, we show that EZH2 is important in ER-negative breast cancer growth in vivo and in vitro, and that BRCA1 is required for the proliferative effects of EZH2. Blockade of EZH2 may provide a prime target to prevent and/or halt ER-negative breast cancer progression.
•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.
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