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Peak/off-peak spreads on European electricity forward and spot markets are eroding due to the ongoing nuclear phaseout in Germany and the steady growth in photovoltaic capacity. The reduced profitability of peak/off-peak arbitrage forces hydropower producers to recover part of their original profitability on the reserve markets. We propose a bi-layer stochastic programming framework for the optimal operation of a fleet of interconnected hydropower plants that sells energy on both the spot and the reserve markets. The outer layer (the planner's problem) optimizes end-of-day reservoir filling levels over one year, whereas the inner layer (the trader's problem) selects optimal hourly market bids within each day. Using an information restriction whereby the planner prescribes the end-of-day reservoir targets one day in advance, we prove that the trader's problem simplifies from an infinite-dimensional stochastic program with 25 stages to a finite two-stage stochastic program with only two scenarios. Substituting this reformulation back into the outer layer and approximating the reservoir targets by affine decision rules allows us to simplify the planner's problem from an infinite-dimensional stochastic program with 365 stages to a two-stage stochastic program that can conveniently be solved via the sample average approximation. Numerical experiments based on a cascade in the Salzburg region of Austria demonstrate the effectiveness of the suggested framework.

Image-based profiling has emerged as a powerful technology for various steps in basic biological and pharmaceutical discovery, but the community has lacked a large, public reference set of data from chemical and genetic perturbations. Here we present data generated by the Joint Undertaking for Morphological Profiling (JUMP)-Cell Painting Consortium, a collaboration between 10 pharmaceutical companies, six supporting technology companies, and two non-profit partners. When completed, the dataset will contain images and profiles from the Cell Painting assay for over 116,750 unique compounds, over-expression of 12,602 genes, and knockout of 7,975 genes using CRISPR-Cas9, all in human osteosarcoma cells (U2OS). The dataset is estimated to be 115 TB in size and capturing 1.6 billion cells and their single-cell profiles. File quality control and upload is underway and will be completed over the coming months at the Cell Painting Gallery:https://registry.opendata.aws/cellpainting-gallery. A portal to visualize a subset of the data is available athttps://phenaid.ardigen.com/jumpcpexplorer/.

We introduce a distributionally robust minimium mean square error estimation model with a Wasserstein ambiguity set to recover an unknown signal from a noisy observation. The proposed model can be viewed as a zero-sum game between a statistician choosing an estimator—that is, a measurable function of the observation—and a fictitious adversary choosing a prior—that is, a pair of signal and noise distributions ranging over independent Wasserstein balls—with the goal to minimize and maximize the expected squared estimation error, respectively. We show that, if the Wasserstein balls are centered at normal distributions, then the zero-sum game admits a Nash equilibrium, by which the players’ optimal strategies are given by an affine estimator and a normal prior, respectively. We further prove that this Nash equilibrium can be computed by solving a tractable convex program. Finally, we develop a Frank–Wolfe algorithm that can solve this convex program orders of magnitude faster than state-of-the-art general-purpose solvers. We show that this algorithm enjoys a linear convergence rate and that its direction-finding subproblems can be solved in quasi-closed form. Funding: This research was supported by the Swiss National Science Foundation [Grants BSCGI0_ 157733 and 51NF40_180545], an Early Postdoc.Mobility Fellowship [Grant P2ELP2_195149], and the European Research Council [Grant TRUST-949796].

To select the most promising screening hits from antibody and VHH display campaigns for subsequent in-depth profiling and optimization, it is highly desirable to assess and select sequences on properties beyond only their binding signals from the sorting process. In addition, developability risk criteria, sequence diversity and the anticipated complexity for sequence optimization are relevant attributes for hit selection and optimization. Here, we describe an approach for thein silicodevelopability assessment of antibody and VHH sequences. This method not only allows for ranking and filtering multiple sequences with regard to their predicted developability properties and diversity, but also visualizes relevant sequence and structural features of potentially problematic regions and thereby provides rationales and starting points for multi-parameter sequence optimization.

Emerging micro pollutants are substances that have recently been identified in environmental matrices, of which information on environmental permanence and toxicity is still scarce. Because of their chemical structure, antibiotics are more stable and require more complex processes for degradation. The present study aimed to elaborate a proposal for the degradation of the β-lactam antibiotic amoxicillin by photolysis, evaluating the formation of by-products. As a methodology, 100 μg /L amoxicillin solutions were submitted to different ultraviolet lamp irradiations, at different potencies and distances, by means of a 100 mL batch quartz reactor. For the evaluation of the degradation of amoxicillin and of the products generated, the technique of high performance liquid chromatography with mass spectrometry was used. As a result, the best degradation condition (greater than 90% reduction of the original molecule) was with a 95W lamp, at a distance of 5 to 10 cm from the sample at 10 min irradiation time. Two by-products originated under different pH conditions of the irradiated solution were identified. Based on the obtained results, it is concluded that this prototype and the applied method can be used in the future to reduce this pollutant.

Explainable and accurate predictions of bioactivity values are indispensable to accelerate drug design and reduce attrition during drug development. To enhance the accuracy of predictions, a new algorithmic approach was designed, which unites the advantages of matched molecular series and supervised machine learning (ML) techniques. This approach named Network Balance Scaling (NBS) employs convex optimization on matched molecular series networks enriched with ML data. By applying NBS, the performance of supervised ML methods can be improved, and predictions can be rationalized following the network of similar compounds. The approach was validated on the freely available MoleculeNet benchmark with respective ML models as well as on real-world targets and corresponding ML models provided by Merck KGaA. In all cases, when combining NBS with supervised ML models, we observe a substantial improvement in the different activity and physicochemical data sets and bioactivity-related application scenarios. The open-source code of NBS can be found freely available at https://github.com/rareylab/NetworkBalanceScaling.

Wasserstein balls, which contain all probability measures within a pre-specified Wasserstein distance to a reference measure, have recently enjoyed wide popularity in the distributionally robust optimization and machine learning communities to formulate and solve data-driven optimization problems with rigorous statistical guarantees. In this technical note we prove that the Wasserstein ball is weakly compact under mild conditions, and we offer necessary and sufficient conditions for the existence of optimal solutions. We also characterize the sparsity of solutions if the Wasserstein ball is centred at a discrete reference measure. In comparison with the existing literature, which has proved similar results under different conditions, our proofs are self-contained and shorter, yet mathematically rigorous, and our necessary and sufficient conditions for the existence of optimal solutions are easily verifiable in practice.

Cephalexin (CEX) is an antibiotic commonly used to treat bacterial infections in humans and animals. However, it is also a micropollutant. Thus, this study evaluated the degradation of CEX using ultraviolet irradiation (UV-C) and analyzed the by-products as well as their residual antimicrobial activity. A reactor with a mercury vapor lamp was used for the degradation. Irradiated CEX solutions were collected over a period of 4 hours and analyzed using high-performance liquid chromatography coupled with mass spectrometry. For the residual antimicrobial activity the susceptibility test was performed using Staphylococcus aureus and Escherichia coli microorganisms by broth microdilution. It was found that CEX, after treatment, generated a metabolite with a mass of 150 m/z in 15 min. A four- and eightfold increase in the minimum inhibitory concentration of the drug against S. aureus and E. coli could be observed, respectively, after 20 min. Therefore, this treatment proved to be effective in the degradation of CEX, being able to degrade 81% of the initial molecule of the drug in 20 min. Furthermore, the antimicrobial activity of the CEX solution decreased as the irradiation time increased, indicating loss of antimicrobial function of the initial CEX molecule and the resulting by-products. HIGHLIGHTS Degradation of micropollutant cephalexin.; Metabolites analyzed and residual antimicrobial activity.; Water treatment with irradiation.; Antimicrobial activity using susceptibility test.

We develop a two-stage stochastic program for energy and reserve dispatch of a joint power and gas system with a high penetration of renewables. Data-driven distributionally robust chance constraints ensure that there is no load shedding and renewable spillage with high probability. We solve this problem efficiently using conditional value-at-risk approximations and linear decision rules. Out-of-sample experiments show that this model dominates the corresponding stochastic program without chance constraints that models the effects of load shedding and renewable spillage explicitly.

Wolfgang Mährle (Hg.), Württemberg und die Deutsche Frage 1866 – 1870. Politik – Diskurs – Historiografie (Geschichte Württembergs, Impulse der Forschung, Bd. 5). Stuttgart: Kohlhammer 2019. 293 S. mit 25 Abb. ISBN 978-3-17-037530-7. Geb. € 25,–

Identifying genetic and chemical perturbations with similar impacts on cell morphology can reveal compounds’ mechanisms of action or novel regulators of genetic pathways. Research on methods for identifying such similarities has lagged due to a lack of carefully designed and well-annotated image sets of cells treated with chemical and genetic perturbations. Here, we create such a Resource dataset, CPJUMP1, where each perturbed gene is a known target of at least two chemical compounds in the dataset. We systematically explore the directionality of correlations among perturbations that target the same gene, and we find that identifying matches between chemical perturbations and genetic perturbations is a challenging task. Our dataset and baseline analyses provide a benchmark for evaluating methods that measure perturbation similarities and impact, and more generally, learn effective representations of cellular state from microscopy images. Such advancements would accelerate the applications of image-based profiling, such as functional genomics and drug discovery.

Distributionally robust chance constrained programs minimize a deterministic cost function subject to the satisfaction of one or more safety conditions with high probability, given that the probability distribution of the uncertain problem parameters affecting the safety condition(s) is only known to belong to some ambiguity set. We study three popular approximation schemes for distributionally robust chance constrained programs over Wasserstein balls, where the ambiguity set contains all probability distributions within a certain Wasserstein distance to a reference distribution. The first approximation replaces the chance constraint with a bound on the conditional value-at-risk, the second approximation decouples different safety conditions via Bonferroni's inequality, and the third approximation restricts the expected violation of the safety condition(s) so that the chance constraint is satisfied. We show that the conditional value-at-risk approximation can be characterized as a tight convex approximation, which complements earlier findings on classical (non-robust) chance constraints, and we offer a novel interpretation in terms of transportation savings. We also show that the three approximations can perform arbitrarily poorly in data-driven settings, and that they are generally incomparable with each other., Comment: arXiv admin note: substantial text overlap with arXiv:1809.00210

The aim of this study was to compare the ability of endogenous Lactobacillus paracasei ATR6 to grow in unsupplemented bovine cheese whey (CW) and ricotta whey (RW), and to evaluate the efficiency of these media as encapsulating agents for the spray-drying (SD) of this bacterium. Growth assays indicated that both CW and RW are adequate culture media since L. paracasei ATR6 grew satisfactorily (~ 4 log cycles) in both compared to the control medium (skimmed milk). Concerning their potential as encapsulating agents, results showed that survival rates after SD were similar for CW and RW (> 78%), as were the yields (> 47%) of this process. CW allowed the formation of smaller capsules (5.31 ± 1.27 μm) than RW (15.21 ± 7.24 μm), with lower moisture: 8.60% and 13.52%, respectively. Powders were stored at 25 °C for 60 days, during which CW and RW maintained satisfactory bacterial viability. Water activity increased, yet remained below 0.3. Moisture content of CW and RW powders was relatively stable throughout the 60 days; however, values obtained in this study are considered to lie outside the adequate range (4–7%) for product stability. We did not observe color changes in CW and RW microcapsules during storage. Due to its lower protein content, RW offered less protection, which led to higher loss in acidification ability of the strain. CW and RW are suitable culture media and encapsulating agents for the growth of L. paracasei ATR6; however, the former offered better protection, which enabled the maintenance of biological activity.

A "Fábrica de Software" foi realizada como um projeto de ensino, com o objetivo de aproximar os objetivos formadores esperados do curso de Bacharelado em Engenharia de Software com o desenvolvimento de softwares reais, em um processo que simula uma indústria de software. O projeto teve duração de cinco meses, contou com o apoio de docentes do curso e a participação ativa de cinco discentes de diferentes períodos. O presente artigo relata o desenvolvimento desse projeto, resultados e desafios observados. Destacaram-se o contato e aprendizado com problemas reais, e a sobrecarga com atividades decorrentes do ensino remoto.

Daniel Kuhn: Als der Krieg vor der Haustür stand. Der Erste Weltkrieg in Baden und Württemberg. Tübingen (Silberburg) 2014. 220 S., 105 Fotografien und Abb.

Computational approaches in drug discovery and development hold great promise, with artificial intelligence methods undergoing widespread contemporary use, but the experimental validation of these new approaches is frequently inadequate. We are initiating Critical Assessment of Computational Hit-finding Experiments (CACHE) as a public benchmarking project that aims to accelerate the development of small molecule hit-finding algorithms by competitive assessment. Compounds will be identified by participants using a wide range of computational methods for dozens of protein targets selected for different types of prediction scenarios, as well as for their potential biological or pharmaceutical relevance. Community-generated predictions will be tested centrally and rigorously in an experimental hub(s), and all data, including the chemical structures of experimentally tested compounds, will be made publicly available without restrictions. The ability of a range of computational approaches to find novel compounds will be evaluated, compared, and published. The overarching goal of CACHE is to accelerate the development of computational chemistry methods by providing rapid and unbiased feedback to those developing methods, with an ancillary and valuable benefit of identifying new compound-protein binding pairs for biologically interesting targets. The initiative builds on the power of crowd sourcing and expands the open science paradigm for drug discovery.

Computational approaches in drug discovery and development hold great promise, with artificial intelligence methods undergoing widespread contemporary use, but the experimental validation of these new approaches is frequently inadequate. We are initiating Critical Assessment of Computational Hit-finding Experiments (CACHE) as a public benchmarking project that aims to accelerate the development of small molecule hit-finding algorithms by competitive assessment. Compounds will be identified by participants using a wide range of computational methods for dozens of protein targets selected for different types of prediction scenarios, as well as for their potential biological or pharmaceutical relevance. Community-generated predictions will be tested centrally and rigorously in an experimental hub(s), and all data, including the chemical structures of experimentally tested compounds, will be made publicly available without restrictions. The ability of a range of computational approaches to find novel compounds will be evaluated, compared, and published. The overarching goal of CACHE is to accelerate the development of computational chemistry methods by providing rapid and unbiased feedback to those developing methods, with an ancillary and valuable benefit of identifying new compound-protein binding pairs for biologically interesting targets. The initiative builds on the power of crowd sourcing and expands the open science paradigm for drug discovery., ACKNOWLEDGEMENTS The Structural Genomics Consortium is a registered charity (no: 1097737) that receives funds from Bayer AG, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Genome Canada through Ontario Genomics Institute [OGI-196], Janssen, Merck KGaA (aka EMD in Canada and US), Pfizer, Takeda and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875510. The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and Ontario Institute for Cancer Research, Royal Institution for the Advancement of Learning McGill University, Kungliga Tekniska Hoegskolan, Diamond Light Source Limited. This communication reflects the views of the authors and the JU is not liable for any use that may be made of the information contained herein. M. K. Gilson acknowledges funding from National Institute of General Medical Sciences (GM061300). J. J. Irwin acknowledges funding from National Institute of General Medical Sciences (GM133836). These findings are solely of the authors and do not necessarily represent the views of the NIH. The Lee laboratory at the University of Cambridge receives funding from multiple sources, including Pfizer, AstraZeneca, the Engineering and Physical Sciences Research Council and the Winton Programme for the Physics of Sustainability. T.I. Oprea and C. G. Bologa acknowledge funding from the National Institutes of Health Common Fund program, Illuminating the Druggable Genome (CA224370 and TR002278). COMPETING INTERESTS M. K. Gilson has an equity interest in and is a cofounder and scientific advisor of VeraChem LLC. J. J. Irwin is a co-founder of Blue Dolphin LLC, which undertakes fee-for-service ligand discovery. A.A. Lee is the chief scientific officer and a shareholder of PostEra Inc. T. I. Oprea has received honoraria from or consulted for Abbott, AstraZeneca, Chiron, Genentech, Infinity Pharmaceuticals, Merz Pharmaceuticals, Merck Darmstadt, Mitsubishi Tanabe, Novartis, Ono Pharmaceuticals, Pfizer, Roche, Sanofi and Wyeth, and is on the Scientific Advisory Board of ChemDiv and InSilico Medicine.

Mikrohistorische Studien aus einem halben Jahrtausend. Untersuchungen aus Krieg und Frieden vom 16. bis zum 20. Jahrhundert, hg. von Gerhard Fritz (Historegio 11). Remshalden: Manfred Hennecke 2020. 422 S., zahlr. Abb. ISBN 978-3-948138-03-5. Brosch. € 22,80

Ines Mayer / Reinhold Weber (Hg.), Menschen, die uns bewegten, 20 deutsche Biografien im 20. Jahrhundert, Köln: Emons Verlag 2014. 184 S. ISBN 978-3-95451-412-0. € 24,95

Gerhard Fritz (Hg.), Schwäbisch Gmünd und der Erste Weltkrieg, Schwäbisch Gmünd: einhorn-Verlag 2014. 351 S. ISBN 978-3-95747-012-6. € 16,80

Rezzo Schlauch / Reinhold Weber, Keine Angst vor der Macht, Die Grünen in Baden-Württemberg, Köln: Emons-Verlag 2015. 240 S. ISBN 978-3-95451-732-9. € 22,95

Michael Berg, Betriebswirtschaftlicher BALLAST oder verkehrsgeschichtliches KULTURGUT? Eine Beurteilung der geschichtlichen Relevanz der Bodensee-Motorpassagierschiffe „Baden“ und „Schwaben“ als Grundlage für Überlegungen zu einem möglichen weiteren Erhalt, Ubstadt-Weiher: verlag regionalkultur 2015, zugl. Univ. Diss. Karlsruhe 2015. 442 S., inkl. DVD. ISBN 978-3-89735-894-2. € 39,80

Daniel Kuhn, Franz Quarthal, Reinhold Weber: Die Geschichte des Weines in Baden und Württemberg Kohlhammer-Verlag Stuttgart 2015, 224 Seiten, 249 Abbildungen, kartoniert, € 39,99, ISBN 978-3-17-028560-6

Karl Wilhelm Castendyck, Kriegschronik der evangelischen Pfarrei Eichen-Erbstadt 1914 – 1918, hg. von Jürgen Müller unter Mitwirkung von Katja Alt und Friederike Erichsen-Wendt (Quellen und Forschungen zur hessischen Geschichte 176), Darmstadt und Marburg: Hessische Historische Kommission 2017. 244 S. ISBN 978-3-88443-331-7. € 28,80

Lactic acid bacteria (LAB) are applied in the food industry as fermentation agents for a variety of products. Cheese whey (CW) and second cheese whey (SCW) are the two main by-products of cheese production, and can be reused for biotechnological purposes. In this context, this review aims to summarise literature on the use of CW and SCW as culture media for the growth of LAB, as cryoprotectants for freeze-drying and as encapsulating agents for the spray-drying of these microorganisms. CW contains several nutrients that are reported to enhance the growth of LAB. As for SCW, research shows that it has potential to be applied as culture medium, although bacterial growth remains at least one or two log orders lower than CW. Regarding freeze-drying and spray-drying, reports indicate that whey-based cryoprotectants and CW as encapsulating agent offer significant protection from the stressful conditions employed in these processes.

Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological targets that recently gained interest for anticancer therapy in Wnt pathway dependent tumors. 2-Aryl-quinazolinones were identified and optimized into potent tankyrase inhibitors through SAR exploration around the quinazolinone core and the 4'-position of the phenyl residue. These efforts were supported by analysis of TNKS X-ray and WaterMap structures and resulted in compound 5k, a potent, selective tankyrase inhibitor with favorable pharmacokinetic properties. The X-ray structure of 5k in complex with TNKS1 was solved and confirmed the design hypothesis. Modulation of Wnt pathway activity was demonstrated with this compound in a colorectal xenograft model in vivo.