Synthesis and Stochastic Assessment of Cost-Optimal Schedules

We present a novel approach to synthesize good schedules for a class of scheduling problems that is slightly more general than the scheduling problem FJm,a|gpr,r_j,d_j|early/tardy. The idea is to prime the schedule synthesizer with stochastic information more meaningful than performance factors with the objective to minimize the expected cost caused by storage or delay. The priming information is obtained by stochastic simulation of the system environment. The generated schedules are assessed again by simulation. The approach is demonstrated by means of a non-trivial scheduling problem from lacquer production. The experimental results show that our approach achieves in all considered scenarios better results than the extended processing times approach

Groundwater modelling to assess the effect of interceptor drainage and lining; hydrological and modelling concepts

Recharge to the aquifer through seepage from irrigation canals is often quoted as one of the main causes for waterlogging in Pakistan. In the design of drainage systems to control this waterlogging, rules-of-thumb are often used to quantify the seepage from canals. This paper presents the option to use a groundwater model for a more detailed assessment. Groundwater models can assist in evaluating the effect of recharge reducing measures such as interceptor drains along irrigation canals and lining. These measures are commonly aimed at reducing the drainage requirement of adjacent agricultural lands. In this paper the hydrological concepts with respect to leakage from irrigation canals and interception by interceptor drains are presented. A good understanding of these concepts is critical for the proper application of numerical groundwater models and for the correct quantification of model parameters. Key hydraulic parameters are the infiltration resistance of the bed and slopes of irrigation canals, the drain entry resistance of interceptor drains, hydraulic conductivity and hydraulic resistance of soil layers and equivalent depth of groundwater flow. The paper shows how the hydrological concepts can be transferred into model parameters for the widely used groundwater modelling package MODFLOW. Most concepts, however, can also be applied in other modelling packages. The presented hydrological and modelling concepts have been applied in a numerical model for the Fordwah Eastern Sadiqia project, Pakistan. This model application is reported in a separate paper

Controlled drainage for integrated water management

Controlled drainage is an essential component of Integrated Water Resource Management (IWRM) and Water Demand Management (WDM). Controlled drainage can play an important role to save water and nutrients and to improve and optimise downstream water availability and quality. Examples of controlled drainage practices in the Netherlands, USA, Egypt and brief references to work in other countries are given. Shifts in priorities of different aspects of water management take place. These shifts in paradigms to ¿do not drain unless absolutely necessary¿, controlled drainage, and ¿give room to flood waters¿ (controlled flooding) are described. In the Netherlands, the new water management tool Waternood emphasises the relation between land functions and water management and aims at managing conflicting objectives. The impact of agricultural water management on nature and the use of Best Management Principles (BMP) to control downstream impacts are described. In the USA, sub-irrigation is also a component of BMP and controlled drainage. The options, advantages and constraints of controlled drainage are given, while on-going activities in the field are presented

Groundwater modelling to assess the effect of interceptor drainage and lining; example of model application in the Fordwah Eastern Sadiqia projedct, Pakistan

Recharge to the aquifer through seepage from irrigation canals is often quoted as one of the main causes for waterlogging in Pakistan. In the design of drainage systems to control this waterlogging, rules-of-thumb are often used to quantify the seepage from canals. This paper presents the option to use a groundwater model for a more detailed assessment. Groundwater models may assist in evaluating the effect of recharge reducing measures such as interceptor drains along irrigation canals and lining. These measures are commonly aimed at reducing the drainage requirement of adjacent agricultural lands

Patient-derived oral mucosa organoids as an in vitro model for methotrexate induced toxicity in pediatric acute lymphoblastic leukemia

We have recently established a protocol to grow wildtype human oral mucosa organoids. These three-dimensional structures can be maintained in culture long-term, do not require immortalization, and recapitulate the multilayered composition of the epithelial lining of the oral mucosa. Here, we validate the use of this model to study the effect of Leucovorin (LV) on Methotrexate (MTX)-induced toxicity. MTX is a chemotherapeutic agent used in the treatment of pediatric acute lymphoblastic leukemia. Although effective, the use of MTX often results in s

TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer

The aim of this study was to determine an optimal workflow to detect TP53 mutations in baseline and longitudinal serum cell free DNA (cfDNA) from high-grade serous ovarian carcinomas (HGSOC) patients and to define whether TP53 mutations are suitable as biomarker for disease. TP53 was investigated in tissue and archived serum from 20 HGSOC patients by a next-generation sequencing (NGS) workflow alone or combined with digital PCR (dPCR). AmpliSeq™-focused NGS panels and customized dPCR assays were used for tissue DNA and longitudinal cfDNAs, and Oncomine NGS panel with molecular barcoding was used for baseline cfDNAs. TP53 missense mutations were observed in 17 tissue specimens and in baseline cfDNA for 4/8 patients by AmpliSeq, 6/9 patients by Oncomine, and 4/6 patients by dPCR. Mutations in cfDNA were detected in 4/6 patients with residual disease and 3/4 patients with disease progression within six months, compared to 5/11 patients with no residual disease and 6/13 patients with progression after six months. Finally, mutations were detected at progression in 5/6 patients, but not during chemotherapy. NGS with molecular barcoding and dPCR were most optimal workflows to detect TP53 mutations in baseline and longitudinal serum cfDNA, respectively. TP53 mutations were undetectable in cfDNA during treatment but re-appeared at disease progression, illustrating its promise as a biomarker for disease monitoring

Neurobiological correlates of antisociality across adolescence and young adulthood: a multi-sample, multi-method study

Pathways through Adolescenc