Replenishment policy for a purchase-to-order seller: a tradeoff between ordering cost and delay cost

We consider replenishment decisions on when and how many goods to purchase for a seller under a purchase-to-order mode where there is no inventory and the seller purchases goods to fulfil orders already placed. For each purchase, there is a constant ordering cost. For each order, delay cost will be incurred if it is not fulfilled timely. Generally, the more frequent the replenishment, the higher the ordering cost but the lower the delay cost. Consequently, there is a tradeoff between the ordering cost and the delay cost for the seller to make replenishment decisions minimising the total cost. In this paper, we study three cases of the problem and investigate both offline versions and online versions according to the seller's knowledge about information of future orders. For offline versions with perfect information, we either develop an optimal policy, or prove it is NP-hard and develop an approximation policy. For online versions without any information about future orders, from the perspective of competitive analysis we prove the lower bound of competitive ratio for any possible online policy and present a 10-competitive online policy for the general case and a 2-competitive online policy for each of two special cases.     

The generalized discrete ‐centroid problem

The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

A longitudinal observational study of the dynamics of Mycoplasma bovis antibodies in naturally exposed and diseased dairy cows

Mycoplasma bovis is an important pathogen causing disease and substantial economic losses in cattle. However, knowledge of the dynamics of antibody responses in individual cows in the face of an outbreak is currently extremely limited. The use of commercial antibody tests to support clinical decision-making and for surveillance purposes is therefore challenging. Our objective was to describe the dynamics of M. bovis antibody responses in 4 Danish dairy herds experiencing an acute outbreak of M. bovis-associated disease, and to compare the antibody dynamics between dairy cows with different disease manifestations. A total of 120 cows were examined using a standardized clinical protocol and categorized into 4 disease groups: “mastitis,” “systemic,” “nonspecific,” and “none.” Paired blood and milk samples were collected and tested using a commercial M. bovis antibody–detecting ELISA. Plots of raw data and generalized additive mixed models with cow and herd as random effects were used to describe serum and milk antibody dynamics relative to the estimated time of onset of clinical disease. Cows with mastitis had high optical density measurement (ODC%) of antibodies in both milk and serum at disease onset. The estimated mean ODC% in milk was below the manufacturer's cut-off for the other groups for the entire study period. The estimated mean serum ODC% in the “systemic” group was high at onset of disease and stayed above the cut-off until 65 d after disease onset. However, the lower 95% confidence interval (CI) for the mean ODC% was only above the manufacturer's cut-off between 7 and 17 d after onset of disease. The CI of the “systemic” and “none” groups did not overlap at any time between the day of disease onset and 65 d after disease onset, and the estimated mean ODC% for both the “nonspecific” and “none” groups were generally below the cut-off for the majority of the study period. In conclusion, the serum antibody responses were highly dynamic and showed a high level of variation between individual cows. This strongly suggests that serology is unlikely to be useful for individual diagnosis of M. bovis-associated disease in dairy cows. However, it might still be useful for herd- or group-level diagnosis. Antibodies in milk were only increased in cows with M. bovis mastitis, indicating that milk antibody measurements only have diagnostic utility for cows with mastitis.     

Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker’s efficiency can be improved by using antigenic mimicry to native antigens present in vivo.     

A role of sea buckthorn on Alzheimer’s disease

Evidence suggests that diets rich in antioxidants reduce the risk factors of Alzheimer’s disease (AD). Hippophae rhamnoides, commonly known as sea buckthorn (SB), is rich in antioxidants which could have direct effects on amyloid-beta (Aβ) levels and consequently influence AD pathogenesis. In this study, sea buckthorn powder (SBP) was administered at varying concentrations (0.6, 0.9, 1.2, 1.5 and 1.8 µg mL⁻¹) to cell cultures (BE(2)-M17) with 20 mm Aβ for 72 h. MTS test indicated that SB significantly increased cell viability in Aβ-induced cells up to 95%. Results of Western blot showed maximum 38% inhibition of Aβ compared to the control (Aβ only). ELISA demonstrated significantly lower amyloid-β level (6672 pg mL⁻¹) than the control (10189 pg mL⁻¹). Images of AFM further confirmed the presence of low quantity of amyloid beta in SBP-treated cells. These findings suggest that SB warrants further investigation as potential therapeutic agent in the treatment of AD.     

Empirical examination of critical failure factors of continuous improvement deployments: stage-wise results and a contingency theory perspective

Organisations implement various Continuous Improvement (CI) practices such as Total Quality Management, Lean, Six Sigma and Lean Six Sigma (LSS) for improving their processes. Drawing from the success and failure stories of these structured CI practices, scholars enumerated Critical Success Factors and Critical Failure Factors (CFFs). This study empirically examines the occurrence of various CFFs across different stages of CI deployment. Further, from a contingency theoretic perspective, this study investigates their associations with contextual variables by collecting survey data from 213 business units from the USA, the UK, China, and India. Principal Component Analysis is used to group CFFs across five CI deployment stages leading to an empirically refined framework for CI. Crosstab analysis using the chi-square likelihood ratio presented associations of CFFs with contextual variables. Findings reveal significant differences in the occurrence of CFFs across countries. There is evidence that LSS is less prone to failures when compared with TQM, Lean and Six Sigma. The occurrence of CFFs has been relatively lower in smaller and medium-sized enterprises operating in the service sector. Findings also reveal that lessons learned from each CI deployment cycle, contribute to organisational learning, and thence, leading to success at the strategic CI level of maturity.     

Occurrence of toxigenic fungi and ochratoxin A in Ethiopian coffee for local consumption

Information on the presence of ochratoxin A (OTA) in local Ethiopian coffee is scarce. Therefore, the objective of this study was to type the fungal and mycotoxin contamination levels in Ethiopian coffee consumed by the local community. Coffee samples were collected from six major coffee growing districts in Jimma zone of Oromiya regional state in Ethiopia. Total fungal incidence mounted up to 87% and Aspergillus (79%), Fusarium (8%) and Penicillium (5%) were the predominant toxigenic genera. OTA producing species A. westerdijkiae, Aspergillus ochraceus, and Aspergillus steynii were identified for the first time in Ethiopia and were shown to be the predominant species while aflatoxin (AF) producing Aspergillus species were scarce. Using an in vitro approach, the OTA production potential was assessed under standardized conditions. Based on this experiment, it was concluded that Aspergillus westerdijkiae isolates were clearly the most potent producers of OTA. The median OTA level in the locally sold Ethiopian coffee was 1.53 μg/kg. Notwithstanding this low median value, significant differences in fungal and toxin incidences were observed between the different coffee processing types, coffee sample types, and storage characteristics.     

Pore-scale modeling of competition and cooperation of multispecies biofilms for nutrients in changing environments

In this article, we developed a pore-scale model of integrated lattice Boltzmann method and cellular automata to investigate competitive growth of aerobic nitrite and ammonium oxidizers in a bioreactor. The results showed that inlet nutrient concentrations have significant effects on maximum biofilm concentration, ratio of microorganisms' concentrations, growth pattern, and time. The local availability of oxygen could control the competition, resulting in different growth patterns. The coexistence of ammonium and nitrite in same inlet zone increased not only the biofilm concentration (7%) but also the ratio of microorganisms' concentrations (36%). Although this coexistence decreased the total biofilm concentration in some cases, it increased the growth rate about 25%. Changes of the maximum biomass concentration could change biofilm concentration of about 40% and microorganisms' concentrations ratio of about 30%. This framework provides a powerful tool to improve our understanding of dynamic interdependency of many complex microbial consortia systems with environments.