Reverse logistics network design with stochastic lead times

This work is concerned with the efficient design of a reverse logistics network using an extended version of models currently found in the literature. Those traditional, basic models are formulated as mixed integer linear programs (MILP-model) and determine which facilities to open that minimize the investment, processing, transportation, disposal and penalty costs while supply, demand and capacity constraints are satisfied. However, we show that they can be improved when they are combined with a queueing model because it enables to account for (1) some dynamic aspects like lead time and inventory positions, and (2) the higher degree of uncertainty inherent to reverse logistics. Since this extension introduces nonlinear relationships, the problem is defined as a mixed integer nonlinear program (MINLP-model). Due to this additional complexity, the MINLP-model is presented for a single product-single-level network. Several examples are solved with a genetic algorithm based on the technique of differential evolution.     

Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.     

Characterizing the deformation of cold-rolled copper sheet

An advanced x-ray diffraction technique allows the development of texture components to be monitored and provides supplementary information about the cold work and residual stresses in cold-rolled copper sheet. The new technique confirms the results of an ultrasonic test, except for the ultrasonic test’s sensitivity to grain size. The new x-ray diffraction technique could be adapted to provide in-process, nondestructive evaluation of thin copper sheet, even for material moving at high speeds.     

Interface between electroless amorphous Ni–Cu–P coatings and Al substrate

The initial phase arising at the interface with aluminum substrate during electroless deposition of amorphous high phosphorus (16–19 at.%) Ni–Cu–P alloy with alloyed copper 1.7–3.4 at.% is studied. Stripped deposit foils are inspected by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy coupled with energy dispersive X-ray analysis (TEM-EDX). Depending on the plating conditions, various particles, some of them crystalline, are revealed at the foils sides formerly adhering to the substrate. EDX analysis of the crystallites shows diverse copper contents of about 34–64 at.%, without any phosphorus. Electron diffraction analysis indicates a lattice structure very close to that of Cu. The presence of a phase without phosphorus and enriched in copper at the interface with the Al substrate is also confirmed by Auger electron spectroscopy. This initially arising crystalline phase might exert a limited effect on the main properties of bulk Ni–Cu–P deposits: the composition uniformity through the thickness, amorphous structure and paramagnetic behavior. A modification of the plating process is recommended, which is decreasing the probability of inhomogeneities formation.     

An Intelligent Man-Machine Dialogue System Based on AI Planning

We describe the modular architecture of a generic dialogue system that assists a user/operator in performing a task with a tool. This coaching system is named CALLIOPE after the Greek goddess of eloquence. It aims at being an active partner in an intelligent man-machine dialogue. The intelligent dimension of the coaching system is reflected by its ability to adapt to the user and the situation at hand. The CALLIOPE system contains an explicit user model and world model to situate its dialogue actions. A plan library allows it to follow loosely predetermined dialogue scenarios.The heart of the coaching system is an AI planning module, which plans a series of dialogue actions. We present a coherent set of three dialogue or speech actions that will make up the physical form of the man-machine communication.The use of the AI planning paradigm as a basis for man-machine interaction is motivated by research in various disciplines, as e.g., AI, Cognitive Science and Social Sciences. Starting from the man-man communication metaphor, we can view the thinking before speaking of a human communication partner as constructing an underlying plan which is responsible for the purposiveness, the organisation and the relevance of the communication.CALLIOPE has been fully implemented and tested on theoretical examples. At present, also three tailored versions of CALLIOPE are in operational use in different industrial application domains: operator support for remedying tasks in chemical process industry, operator support for a combined task of planning, plan execution and process control in the area of chemical process development, and thirdly decision support in production scheduling.     

Robust M-estimation of multivariate GARCH models

The Gaussian quasi-maximum likelihood estimator of Multivariate GARCH models is shown to be very sensitive to outliers in the data. A class of robust M-estimators for MGARCH models is developed. To increase the robustness of the estimators, the use of volatility models with the property of bounded innovation propagation is recommended. The Monte Carlo study and an empirical application to stock returns document the good robustness properties of the M-estimator with a fat-tailed Student t loss function.     

The role of electronic pocket dictionaries as an English learning tool among Chinese students

This study addressed the role of electronic pocket dictionaries as a language learning tool among university students in Hong Kong and Taiwan. The target groups included engineering and humanities students at both undergraduate and graduate level. Speed of reference was found to be the main motivator for using an electronic pocket dictionary. Next, the functionality used was found to be connected to the language proficiency of the learner. Finally, multimedia content was ranked least important. The results of this study have implications for the design of electronic dictionaries and for the teaching of second languages with electronic dictionaries. In particular, device developers should focus on improving the accessing speed and pay less attention to multimedia functionality. Educators should ensure that the device functionality matches the language proficiency level of the students.     

A well-based reverse-phase protein array applicable to extracts from formalin-fixed paraffin-embedded tissue

Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue offers significant diagnostic utility but is complicated due to the high level of covalently crosslinked proteins arising from formalin fixation. To address these challenges, we developed a reliable protein extraction method for FFPE tissue, based on heat-induced antigen retrieval within a pressure cooker. The protein extraction yield from archival FFPE tissue section is approximately 90% of that recovered from frozen tissue. This method demonstrates preservation of immunoreactivity and recovery of full-length proteins by Western blotting. Additionally, we developed a well-based RP protein array platform utilizing an electrochemiluminescence detection system. Protein samples derived from FFPE tissue by means of laser capture dissection, with as few as 500 shots demonstrate measurable signal differences for different proteins. The lysates coated to the array plate, remain stable over 1?month at room temperature. Theses data suggest that this new protein-profiling platform coupled with the protein extraction method can be used for molecular profiling analysis in FFPE tissue, and contribute to the validation and development of biomarkers in clinical studies.     

Synthetic Modular Antibody Construction by Using the SpyTag/SpyCatcher Protein-Ligase System

Efforts to engineer recombinant antibodies for specific diagnostic and therapy applications are time consuming and expensive, as each new recombinant antibody needs to be optimized for expression, stability, bio-distribution, and pharmacokinetics. We have developed a new way to construct recombinant antibody-like “devices” by using a bottom-up approach to build them from well-behaved discrete recombinant antibody domains or “parts”. Studies on antibody structure and function have identified antibody constant and variable domains with specific functions that can be expressed in isolation. We used the SpyTag/SpyCatcher protein ligase to join these parts together, thereby creating devices with desired properties based on summed properties of parts and in configurations that cannot be obtained by using genetic engineering. This strategy will create optimized recombinant antibody devices at reduced costs and with shortened development times.