Modeling and solving a one-supplier multi-vehicle production-inventory-distribution problem with clustered retailers

This paper considers a supply chain management problem which integrates production, inventory, and distribution decisions. The supply chain is composed of one supplier production facility and several retailers located in a given geographic region. The supplier is responsible for the production and the replenishment of the inventory of retailers, in a vendor managed inventory (VMI) context. The distance between retailers is negligible compared to the distance between the supplier and the retailers’ region. Thus, for each vehicle, there is a major fixed cost for traveling to the cluster of retailers and a minor fixed cost for visiting each individual retailer. The problem consists of determining quantities to be produced, quantities to be delivered to retailers, vehicles to be used, and retailers to be serviced by each vehicle. This problem is an extension of the one warehouse multi-retailer problem with the consideration of production planning and storage and vehicle capacity limitations in addition to fixed vehicle utilization costs and retailer servicing costs. The objective is to minimize a total cost composed of production, transportation, and inventory holding costs at the supplier and at the retailers. Two mixed integer linear programming formulations are proposed and six families of valid inequalities are added to strengthen these formulations. Two of these families are new and the others are adapted from the literature. The numerical results show that the valid inequalities considerably improve the quality of the formulations. Moreover, the parameters that influence the most computational times are analyzed.     

Thermally stable antimicrobial polyvinylchloride/maleimido aromatic hydrazide composites

Antimicrobial novel substituted maleimido aromatic hydrazides were synthesized from N‐[4‐(chlorocarbonyl) phenyl] maleimide with salicylhydrazide, p‐aminobenzohydrazide, or p‐aminosalicylhydrazide. They were characterized by Fourier transform infrared (FTIR), hydrogen‐1 nuclear magnetic resonance (¹H‐NMR), mass spectra, elemental analyses, and antimicrobial activities. These derivatives were investigated as thermal stabilizers for rigid poly(vinyl chloride) (PVC) at 180°C in air by measuring the rate of dehydrochlorination, the extent of discoloration, and the changes that occurred in the molecular masses of the degraded PVC samples. The previously reported stabilizing efficiency data of a nonsubstituted derivative, which was synthesized from N‐[4‐(chlorocarbonyl) phenyl] maleimide with benzohydrazide, is also given for comparison. The results reveal the greater stabilizing efficiency of the investigated derivatives as shown by their longer thermal stability (Ts) periods and lower dehydrochlorination rates in relation to dibasic lead carbonate, cadmium‐barium‐zinc stearate, and n‐octyltin mercaptide industrial stabilizers. The stabilizing efficiency increases with the introduction of electron donating substituent groups in the aromatic ring of the stabilizer molecules. Moreover, the investigated stabilizers impart better color stability for the degraded samples as compared with the reference stabilizers. A synergistic effect is achieved when the materials under investigation were mixed in various weight ratios with any of the reference stabilizers, reaching its maximum at equivalent weight ratio of the investigated stabilizer to the reference one. J. VINYL ADDIT. TECHNOL., 22:247–258, 2016. © 2014 Society of Plastics Engineers     

In vitro evaluation of spray‐dried chitosan microspheres crosslinked with pyromellitic dianhydride for oral colon‐specific delivery of protein drugs

Chitosan microspheres have been prepared using a spray‐drying method, and crosslinked with pyromellitic dianhydride. The chemical structure of the modified chitosan was characterized by FTIR spectroscopy and solid state 13C NMR analysis. The particle size and morphology of the crosslinked chitosan were investigated. These microspheres were evaluated for colon‐specific delivery of bovine serum albumin (BSA) as a model protein drug. The results indicate that the drug was released as follows: 37.1 ± 2.8% after 2 h in SGF, 73.1 ± 4.8% after 8 h (2 h in SGF+ 6 h in SIF), and 80.9 ± 4.1% after 12 h in SCF. The effect of β‐glucosidase on the drug release was also examined. The encapsulation efficiency was decreased from 88.4 ± 3.1% to 62.8 ± 2.9%, with increasing BSA concentration. Loading capacity was significantly increased from 6.3 ± 0.3% to 41.8 ± 4.1% by increasing the initial BSA concentration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40514.     

Thermally stable antimicrobial PVC/maleimido phenyl urea composites

Four novel antimicro bial maleimido phenyl urea derivatives were synthesized from N-[4-(chlorocarbonyl) phenyl] maleimide with phenyl urea derivatives (p-methyl, o-chloro and p-carboxy). They were characterized by FTIR, ¹H-NMR, mass spectra, elemental analyses and antimicrobial activities. These derivatives were investigated as thermal stabilizers for rigid poly(vinyl chloride) at 180 °C in air by measuring the rate of dehydrochlorination and the extent of discoloration. The results reveal the greater stabilizing efficiency of the investigated derivatives as shown by their longer thermal stability periods (Ts) and lower dehydrochlorination rates in relation to dibasic lead carbonate, cadmium-barium-zinc stearate and n-octyltin mercaptide industrial stabilizers. The stabilizing efficiency increases with the introduction of electron donating substituent groups in the aromatic ring of the stabilizer molecules. Moreover, the investigated stabilizers impart better color stability for the degraded samples as compared with the reference stabilizers.     

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.     

In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU)

Phenylketonuria (PKU) is a rare autosomal recessive inborn error of metabolism where the mainstay of treatment is a Phe restricted diet consisting of a combination of limited amounts of natural protein with supplementation of Phe-free or low-Phe protein substitutes and special low protein foods. Suboptimal outcomes may be related to the different absorption kinetics of free AAs, which have lower biological efficacy than natural proteins. Physiomimic Technology^TM is a technology engineered to prolong AA (AA-PT) release allowing physiological absorption and masking the odor and taste of free AAs. The aim of these studies was to assess the impact of AA-PT formulation on selected functional and metabolic parameters both in acute and long-term experimental studies. Adult rats in fasting conditions were randomized in different groups and treated by oral gavage. Acute AA-PT administration resulted in significantly lower BUN at 90 min versus baseline. Both BUN and glycemia were modulated in the same direction as intact casein protein. Long-term treatment with AA-PT significantly reduces the protein expression of the muscle degradation marker Bnip3L (−46%) while significantly increasing the proliferation of market myostatin (+58%). Animals dosed for 15 days with AA-PT had significantly stronger grip strength (+30%) versus baseline. In conclusion, the results suggest that the AA-PT formulation may have beneficial effects on both AA oxidation and catabolism with a direct impact on muscle as well as on other metabolic pathways.