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A method for optimizing the net present value of a full field development by varying the placement and sequence of production wells is presented. This approach is automated and combines an economics package and Mobil's in-house simulator, PEGASUS, within a simulated annealing optimization engine. A novel framing of the well placement and scheduling problem as a classic "travelling salesman problem" is required before optimization via simulated annealing can be applied practically. Ah example of a full field development using this technique shows that non-uniform well spacings are optimal (from an NPV standpoint) when the effects of well interference and variable reservoir properties are considered. Examples of optimizing field NPV with variable well costs also show that non-uniform wells spacings are optimal. Project NPV increases of 25 to 30 million dollars were shown using the optimal, non-uniform development versus reasonable, uniform developments. The ability of this technology to deduce these non-uniform well spacings opens up many potential applications that should materially impact the economic performance of field developments. Introduction Optimal field-scale production of hydrocarbons must consider many reservoir, operational, and economic inputs and constraints. These inputs and constraints include, among many others, effects on well productivity from well interference, areal variations in reservoir quality, nonuniform well costs and variable oil price projections. These effects on optimal reservoir producibility are spatial and temporal. Drill and complete times place an temporal operational constraint on the availability of hydrocarbon production. Variable cost structures for different well trajectories within a field must be balanced against improved or accelerated production from more expensive wells. Well scheduling constraints may occur if phased development due to capital restrictions is required. Facility throughput limitations may also place operational limits on the number and scheduling of development wells. These multiple competing effects mean that developing an optimum well plan for field development is challenging and that development on uniform spacing may not be optimum when viewed from an economic point of view. In this paper we show how optimization techniques, specifically simulated annealing, can be successfully used to produce economically optimal well placements and schedules. Development scenarios that maximize the entire project NPV show nonuniform well spacings are required when variable well costs and variable reservoir properties are considered. Methodology The well scheduling and placement for optimal field development can be expressed generically as the classical "travelling salesman problem". For this work we define "optimal field development" as the placement and scheduling of wells that maximize a measure of field NPV. Such a realization is a fundamental to the successful application of optimization methods, such as simulated annealing', genetic algorithms or other methods suitable to the travelling salesman problem. P. 209

A fundamental prerequisite for the micromechanical simulation of fatigue is the appropriate modelling of the effective cyclic properties of the considered material. Therefore, kinematic hardening formulations on the slip system level are of crucial importance due to their fundamental relevance in cyclic material modelling. The focus of this study is the comparison of three different kinematic hardening models (Armstrong Frederick, Chaboche, and Ohno–Wang). In this work, investigations are performed on the modelling and prediction of the cyclic stress-strain behavior of the martensitic high-strength steel SAE 4150 for two different total strain ratios (R ε = −1 and R ε = 0). In the first step, a three-dimensional martensitic microstructure model is developed by using multiscale Voronoi tessellations. Based on this martensitic representative volume element, micromechanical simulations are performed by a crystal plasticity finite element model. For the constitutive model calibration, a new multi-objective calibration procedure incorporating a sensitivity analysis as well as an evolutionary algorithm is presented. The numerical results of different kinematic hardening models are compared to experimental data with respect to the appropriate modelling of the Bauschinger effect and the mean stress relaxation behavior at R ε = 0. It is concluded that the Ohno–Wang model is superior to the Armstrong Frederick and Chaboche kinematic hardening model at R ε = −1 as well as at R ε = 0.

The EtOAc-soluble fraction of a 90% MeOH extract of the fibrous roots of Polygonatum odoratum was found to potentiate insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. Bioassay-guided fractionation yielded nine homoisoflavonoids (1-9), four of which were new (1-4), together with an isoflavone glycoside (10) and a flavanone glycoside (11). The structures of new compounds were elucidated on the basis of extensive 1D and 2D NMR spectroscopy, and the absolute configurations were deduced by CD spectra. All 11 compounds showed effects of sensitizing adipocytes for insulin in a cell-based glucose uptake assay using 3T3-L1 adipocytes. The results indicate that homoisoflavonoids may be potential insulin sensitizers.

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ObjectiveThe selection of individualized treatment for recurrent cervical cancer is challenging. This study aimed to investigate the impact of various therapies on survival outcomes after recurrence.MethodsEligible patients were diagnosed with recurrent cervical cancer between March 2012 and April 2018. Postrecurrence progression-free survival (PFS) and overall survival (OS) were investigated in the whole cohort and in subgroups, categorized by recurrence site and prior radiotherapy history, using a multivariate model that incorporated treatment for primary and recurrent tumors, histological pathology, and FIGO staging.ResultsTwo hundred and sixty recurrent cervical cancer patients were included. As of March 1, 2020, the median postrecurrence PFS and OS were 7.0 (range 0-94) and 24.0 (1.8-149.1) months, respectively. In a multivariate model measured by PFS, radiotherapy was superior to other therapies for the whole cohort (p=0.029) and recurrence only within the pelvic cavity (p=0.005), but the advantages of radiotherapy disappeared in patients with a history of radiotherapy (p values >0.05). For recurrence only beyond the pelvic cavity, combination therapy resulted in improved PFS (p=0.028). For recurrence both within and beyond the pelvic cavity, no therapy regimen provided additional PFS benefits (p values >0.05). Radiotherapy and combination therapy were also associated with improved postrecurrence OS for recurrence within the pelvic cavity (p=0.034) and only beyond the pelvic cavity (p=0.017), respectively.ConclusionsIn cervical cancer patients, postrecurrence radiotherapy can improve PFS and OS for patients with recurrence within the pelvic cavity and without prior radiotherapy. For recurrence beyond the pelvic cavity or cases with a history of radiotherapy, combination or individualized therapy may provide potential survival benefits.

The ring pessary with support was successfully fitted in patients with advanced POP with a high success rate and few complications. Older patients were more likely to prefer the ring pessary with support due to its convenient use.