Practical Bayesian optimization in the presence of outliers

Inference in the presence of outliers is an important field of research as outliers are ubiquitous and may arise across a variety of problems and domains. Bayesian optimization is method that heavily relies on probabilistic inference. This allows outstanding sample efficiency because the probabilistic machinery provides a memory of the whole optimization process. However, that virtue becomes a disadvantage when the memory is populated with outliers, inducing bias in the estimation. In this paper, we present an empirical evaluation of Bayesian optimization methods in the presence of outliers. The empirical evidence shows that Bayesian optimization with robust regression often produces suboptimal results. We then propose a new algorithm which combines robust regression (a Gaussian process with Student-t likelihood) with outlier diagnostics to classify data points as outliers or inliers. By using an scheduler for the classification of outliers, our method is more efficient and has better convergence over the standard robust regression. Furthermore, we show that even in controlled situations with no expected outliers, our method is able to produce better results.Comment: 10 pages (2 of references), 6 figures, 1 algorith

Editorial: HIV-1 genetic diversity, volume II

EditorialS

An evaluation of the fast-mixed spectrum reactor

"February 1980."Also issued as an M.S. thesis written by the first author and supervised by the second and third authors, MIT Dept. of Nuclear Engineering, 1980Includes bibliographical references (pages 145-147)An independent evaluation of the neutronic characteristics of a gas-cooled fast-mixed spectrum reactor (FMSR) core design has been performed. A benchmark core configuration for an early FMSR design was provided by Brookhaven National Laboratory, the originators of the concept. The results of the evaluation were compared with those of BNL. Points of comparison included system reactivity and breeding ratio, and region-wise power densities and isotopic compositions as a function of burnup. The results are in sufficiently good agreement to conclude that the neutronic feasibility of the FMSR concept has been independently validated. Significant differences, primarily in higher plutonium isotope concentrations, occur only in regions of low neutronic importance, and plausible reasons for the differences are advanced based on sensitivity studies and comparison of spectral indices. While both M.I.T. and BNL calculations tend to predict that the benchmark design is slightly subcritical, at the beginning of equilibrium cycle, the margin to k = 1.0 is close enough (Ak < 0.03) that the situation can be remedied. Establishment of a consensus fission product cross section set was identified as an objective of merit, since non-negligible differences were found in results computed using various extant sets (BNL, LIB-IV, Japanese). Non-fission heating by gamma and neutron interactions was evaluated for the reference core design using a coupled neutron/gamma cross section set and SN calculations. In the unfueled regions of the core, moderator elements in particular, the non-fission heating rate was found to be significant (averaging about 6 kw/liter), but posed no obvious problems. In fueled regions the common assumption of local deposition of all energy at the point of fission was verified to be a good approximation for most engineering purposes.Engineering and Advanced Reactor Safety Division of the U.S. Department of Energy at Brookhaven National Laboratory contract 472241-

Modelling the mitigation of the negative effects on human resource management

Human resource professionals are often overlooked in the study of frontline workers and the negative effects of burnout, compassion fatigue, stress and vicarious trauma even though exposure to these negative workplace conditions is intrinsic to their job description. Understanding how these negative workplace conditions affect human resources professionals will lead to reduced employee absenteeism and higher staff turnover and mitigate the effects of presenteeism, such as reduced productivity and loss of general work satisfaction. In this paper, the literature is explored to examine the impact of negative workplace conditions on an organisation\u27s operations in the context of workplace programmes and compassion satisfaction. A model is presented to explain how individual and organisational interventions mitigate the negative workplace conditions of burnout, compassion fatigue, stress and vicarious trauma on workplace performance and compassion satisfaction. This model will form the basis for further research into the negative effects of employment conditions impacting human resource managers

Business competitiveness: building and applying the 3Cs and the Strategic Change Matrix across COVID-19

This India-wide, empirical, point-in-time, global literature-supported, quantitative study involves 232 leading management consulting firm (MCF) consultants and contracting client firm (CF) perspectives. It relationally builds a structural MCF-CF 3Cs model that links MCF competencies into MCF-CF capabilities systems and then into CF business competitiveness. The 3Cs model can be visually and numerically presented as a CF three-dimensional positioning within the strategic change matrix. Future pathways towards a new optimal strategic future CF position can then be strategic change matrix mapped. A contribution towards Management-Consulting-Theory is presented as one that likely follows and embodies the MCF-CF 3Cs model processes

Pulling the Strings: Exploiting Metabolic Dependencies in Pediatric Cancer

Cancer is highly complex and variable, encompassing hundreds of diseases that share key features called "hallmarks,” which help explain how cancer develops, grows, and spreads. This thesis highlights one of these hallmarks, reprogrammed cancer metabolism, and explores the importance of understanding cancer metabolism and how to exploit metabolic vulnerabilities to develop targeted therapies in pediatric cancers. Pediatric cancers challenge the idea of cancer as a disease of aging. Unlike adult cancers, childhood cancers typically involve fewer mutations and are driven by specific genetic changes in driver genes. These mutations can directly alter cellular metabolism, or reprogrammed cancer metabolism itself can drive cancer through mutations in metabolic enzymes or the accumulation of harmful oncometabolites. Part of this thesis explores the relationship between cancer metabolism and epigenetics. We explored the use of novel drug, ARV-825, which targets BRD4 protein, and identified several new combination therapy strategies that effectively target T-cell acute lymphoblastic leukemia (T-ALL). We found that ARV-825 indirectly reduces MYC activity, a gene with broad functions in metabolic regulation, and that combining ARV-825 with other drugs targeting metabolism-related genes induces cell death by converging on the MYC pathway. Another focus of this thesis was on methionine metabolism. Cancer cells possess altered nutrient processing to fuel their uninhibited growth. One of the most well-known examples of this, known as the "Warburg effect," describes tumor cells’ preference for glycolysis, a less efficient but faster way to metabolize glucose. Cancer cells can also manipulate their use of certain nutrients, like amino acids, becoming more or less dependent on them as needed. In turn, these metabolic changes or dependencies create vulnerabilities that can be targeted for treatment. Methionine, an essential amino acid vital for various bodily functions, plays a crucial role in several cancers. We found in neuroblastoma, that dietary methionine restriction slowed cancer growth, and that targeting autophagy further amplified this MR-effect. Similarly, we also found that KMT2A-rearranged leukemia, an aggressive pediatric cancer, was highly sensitive to methionine restriction. These leukemia cells depend on excessive methylation, which requires methionine-derived S-adenosylmethionine, or SAM. By limiting methionine, methylation is disrupted, thereby inducing cell death and inhibiting cancer growth. We highlighted in our research several effective methods for targeting the methionine cycle, including a methionine-restricted diet, the enzyme methionine-γ-lyase (MGL), which breaks down circulating methionine, and the small molecule inhibitor FIDAS-5, which reduces SAM production. These approaches present promising new options for treating methionine-dependent cancers, and demonstrate how understanding reprogrammed metabolism can be leveraged for therapeutic advantage

Characterization of Organic Carbon in Sediments from Old Rifle, CO, a Former Uranium Mill

Characterization of sediments from Old Rifle, CO, a former uranium mill More than 34 million gallons (~129 million liters) of groundwater are contaminated with uranium at Old Rifle, Colorado – a former uranium-processing site that operated until 1958. The original Department of Energy strategy for remediation, involving natural flushing of U from the groundwater through mixing with surface water, has not been as successful as predicted. The uranium plume is replenished when insoluble U(IV) is oxidized to the more mobile U(VI). Relatively thin pockets of silt-, clay-, and organic-rich sediments contain reduced uranium, iron and sulfur and are referred to as naturally reduced zones (NRZs). There is a correlation between organic carbon (OC) and U concentrations; thus it can be inferred that OC is controlling U distribution and speciation. Sediment samples representing five different depths from the JB-02 well at Old Rifle were collected; two depths are above the NRZ, two are within the NRZ and one is below the NRZ. Sub-samples were then extracted using deionized water, NaCl and NaOH. The extractions were analyzed for non-purgeable organic carbon (NPOC) concentrations. Base extractions produced the highest concentrations of dissolved organic carbon (DOC) at all depths. Sediments within the NRZ produced more DOC than sediments above or below the NRZ. Further analysis by X-ray absorption spectroscopy (XAS) is expected to give key information on which organic functional groups are present within the sediments and their extractable carbon fractions, which will inform uranium management strategies. Additionally the amount of permanganate oxidizable carbon will be determined to further compare the carbon pools in and out of the NRZ