INDUCTIVE LEARNING FOR PARAMETER OPTIMIZATION

Optimization of simulation model output is one of the most important tasks in a simulation study of a complex system. Efficacy of an optimization approach is expressed in the accuracy of locating a global extremum, as well as in the number of investigated search points. The approach Machine Learning Optimization (ML-Opt), presented in this article, explores functional dependencies between search points in order to reduce the number of evaluations. Functional relations between search points are determined by an inductive learning algorithm, which generates a classifier used as a control structure in the optimization process. The classifier approximates the structure of the unknown goal function given by a simulation model and affects the generation of new search points. A discussion of a numerical example concludes the paper.     

Burial grounds’ impact on groundwater and public health: an overview

The most common practice for disposal of dead bodies is inhumation in soil, which favours interactions with the surrounding environment and returns nutrients to the life cycle. However, when the burial ground is located where hydrogeological, geological and climatic conditions are not favourable to the process, contamination of soils and groundwater may occur, and decomposition may be inhibited, leading to social, economic and political problems. The most critical parameters when assessing the pollution potential of a burial ground are inhumation depth, geological formation, depth of the water table, density of inhumations, soil type and climate. Considering that, this paper presents an overview of the potential threat that cemeteries can pose, analysing and discussing the influence of the main variables causing environmental impacts and public health risks.     

Defects in offsite construction: timber module prefabrication

The construction industry is based on craftsmanship. Quality control and assurance procedures applied in manufacturing cannot usually be readily applied in construction, where there are higher degrees of uniqueness in each project. One category of companies, industrialized housebuilders, is attempting to bridge some of the gaps between construction and manufacturing. These companies prefabricate building modules for later assembly at the building site. Since they are wholly responsible for large parts of the building process, these companies have greater opportunities to control and improve quality in a more consistent way than ordinary construction companies. Thus, it could be hypothesized that the frequency and severity of defects should be lower in industrialized housing than in ordinary construction. The aim of the study presented here is to examine this hypothesis by measuring and characterizing defects in industrialized housing. The design and manufacturing processes at two Swedish timber module prefabrication firms has been analysed through interviews, site visits and document reviews. Quality audits from three phases of the building process were compiled, analysed and categorized to provide statistical measures of defects in industrialized housing. The results show that the case study companies are better in terms of product quality than conventional housing.     

A study of a plan-do-check-act method used in less industrialized activities: two cases from industrialized housebuilding

In construction projects, a large number of deviations are usually found during inspections and adjusted in a reactive manner. For projects to become proactive, root causes need to be identified and eliminated as a part of a process of continuous improvement (CI). Plan-do-check-act (PDCA) methods are part of CI and have been used with success within the manufacturing industry for decades. Research studies of PDCA in construction are less common, which could be explained by the past dominance of the project-based nature of construction compared to the process-based nature of manufacture. Industrialized construction, however, has changed this picture somewhat, and it is of interest to find out how well it works for less industrialized activities in construction. A PDCA method was tested in two cases selected from one medium-sized Swedish industrialized housebuilder, which uses a building system based on offsite manufactured modules. Empirical results are based on systematic data gathered through interviews and participant observations. Results from the two cases show that the PDCA method worked even when processes were divided into industrialized parts within a factory and non-industrial parts at the construction site although this might lead to temporary corrective actions rather than permanent process actions.     

Role of Tyrosine Kinase Syk in Thrombus Stabilisation at High Shear

Understanding the pathways involved in the formation and stability of the core and shell regions of a platelet-rich arterial thrombus may result in new ways to treat arterial thrombosis. The distinguishing feature between these two regions is the absence of fibrin in the shell which indicates that in vitro flow-based assays over thrombogenic surfaces, in the absence of coagulation, can be used to resemble this region. In this study, we have investigated the contribution of Syk tyrosine kinase in the stability of platelet aggregates (or thrombi) formed on collagen or atherosclerotic plaque homogenate at arterial shear (1000 s⁻¹). We show that post-perfusion of the Syk inhibitor PRT-060318 over preformed thrombi on both surfaces enhances thrombus breakdown and platelet detachment. The resulting loss of thrombus stability led to a reduction in thrombus contractile score which could be detected as early as 3 min after perfusion of the Syk inhibitor. A similar loss of thrombus stability was observed with ticagrelor and indomethacin, inhibitors of platelet adenosine diphosphate (ADP) receptor and thromboxane A₂ (TxA₂), respectively, and in the presence of the Src inhibitor, dasatinib. In contrast, the Btk inhibitor, ibrutinib, causes only a minor decrease in thrombus contractile score. Weak thrombus breakdown is also seen with the blocking GPVI nanobody, Nb21, which indicates, at best, a minor contribution of collagen to the stability of the platelet aggregate. These results show that Syk regulates thrombus stability in the absence of fibrin in human platelets under flow and provide evidence that this involves pathways additional to activation of GPVI by collagen.     

Teriflunomide Preserves Neuronal Activity and Protects Mitochondria in Brain Slices Exposed to Oxidative Stress

Teriflunomide (TFN) limits relapses in relapsing–remitting multiple sclerosis (RRMS) by reducing lymphocytic proliferation through the inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and the subsequent modulation of de novo pyrimidine synthesis. Alterations of mitochondrial function as a consequence of oxidative stress have been reported during neuroinflammation. Previously, we showed that TFN prevents alterations of mitochondrial motility caused by oxidative stress in peripheral axons. Here, we aimed to validate TFN effects on mitochondria and neuronal activity in hippocampal brain slices, in which cellular distribution and synaptic circuits are largely preserved. TFN effects on metabolism and neuronal activity were investigated by assessing oxygen partial pressure and local field potential in acute slices. Additionally, we imaged mitochondria in brain slices from the transgenic Thy1-CFP/COX8A)S2Lich/J (mitoCFP) mice using two-photon microscopy. Although TFN could not prevent oxidative stress-related depletion of ATP, it preserved oxygen consumption and neuronal activity in CNS tissue during oxidative stress. Furthermore, TFN prevented mitochondrial shortening and fragmentation of puncta-shaped and network mitochondria during oxidative stress. Regarding motility, TFN accentuated the decrease in mitochondrial displacement and increase in speed observed during oxidative stress. Importantly, these effects were not associated with neuronal viability and did not lead to axonal damage. In conclusion, during conditions of oxidative stress, TFN preserves the functionality of neurons and prevents morphological and motility alterations of mitochondria.     

Measuring individual research productivity: A review and development of the integrated research productivity index.

The purpose of the present study was to investigate methods of measuring individual research productivity for counseling psychologists. Using the 60 members of the Journal of Counseling Psychology editorial board, the authors computed a comparison of 6 popular indices of productivity, revealing considerable levels of positive skewness, kurtosis, and overlap with each other. Combining the strengths of the 6 indices, the authors developed a new productivity index entitled the Integrated Research Productivity Index (IRPI). The IRPI measures individual productivity by statistically combining an individual's author-weighted publications, average times cited by other publications, and years since first publication into a comprehensive score. Productivity values and IRPI scores for 3 groups of counseling psychologists (Tyler Award recipients, Kuder Award recipients, and Division 17 Presidents) were computed to provide evidence of discriminant validity among the indices. In contrast to the other measures examined, the IRPI accounts for productivity per year and years in the field and assesses mean citation count per article as opposed to total citation count, thus yielding similar scores for Tyler (lifetime) and Kuder (early career) research award recipients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells

Melanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were treated with DOX for 24, 48, and 72 h and their viabilities were assessed. The effect of DOX IC10 and IC20 (combined at 43 °C for 30, 60, and 120 min) on cell viability was further analyzed. Interference on cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis upon treatment (with 30 min at 43 °C and DOX at the IC20 for 48 h) were analyzed by flow cytometry. Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration. Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels. Additionally, it induced early apoptosis in MNT-1 cells, while in A375 cells this effect was similar to the one caused by hyperthermia alone. These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.