Robust Flows over Time: Models and Complexity Results

We study dynamic network flows with uncertain input data under a robust optimization perspective. In the dynamic maximum flow problem, the goal is to maximize the flow reaching the sink within a given time horizon $T$, while flow requires a certain travel time to traverse an edge. In our setting, we account for uncertain travel times of flow. We investigate maximum flows over time under the assumption that at most $\Gamma$ travel times may be prolonged simultaneously due to delay. We develop and study a mathematical model for this problem. As the dynamic robust flow problem generalizes the static version, it is NP-hard to compute an optimal flow. However, our dynamic version is considerably more complex than the static version. We show that it is NP-hard to verify feasibility of a given candidate solution. Furthermore, we investigate temporally repeated flows and show that in contrast to the non-robust case (that is, without uncertainties) they no longer provide optimal solutions for the robust problem, but rather yield a worst case optimality gap of at least $T$. We finally show that the optimality gap is at most $O(\eta k \log T)$, where $\eta$ and $k$ are newly introduced instance characteristics and provide a matching lower bound instance with optimality gap $\Omega(\log T)$ and $\eta = k = 1$. The results obtained in this paper yield a first step towards understanding robust dynamic flow problems with uncertain travel times

Spatially-resolved Assessment of Land and Water Use Scenarios for Shale Gas Development: Poland and Germany

The analysis presented in this report focuses specifically on two issues of potential concern with respect to shale gas development in EU member states using hydraulic fracturing technologies: pressure on freshwater resources, and land use competition. Potential alternative technologies, such as “dry fracking”, are not considered, because they are still at the research and development stage. We reviewed available literature in order to identify important variables that may influence the land and water requirements associated with shale gas development. We further derived a range of representative values spanning worst-, average- and best-case scenarios for each variable. We then coupled specific technology scenarios (incorporating these variables) regarding water and land use requirements for shale gas development from 2013-2028 with spatially-resolved water and land availability/demand modeling tools (i.e. using the European Land Use Modelling Platform (LUMP)). Scenario analyses (intended to represent worst-, average- and best-case assumptions) were subsequently implemented that incorporate a subset of the identified variables for shale gas development in the Lower Paleozoic Baltic-Podlasie-Lublin basin in Poland and for Germany as a whole from 2013-2028. In addition, we undertook a screening-level risk assessment of potential human and ecosystem health impacts attributable to accidental or operational release of chemicals used in hydraulic fracturing of shale formations, as well as the average gaseous emissions (per active well) associated with shale gas development activities that might be anticipated within a shale play. Finally, we developed a qualitative discussion of necessary considerations to support future air quality impact assessments for shale gas development activities.JRC.H.8-Sustainability Assessmen

Genetic and epigenetic characterization of posterior pituitary tumors

Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets

Storytelling in den Vereinten Nationen: Mahbub ul Haq und menschliche Entwicklung

Ausgehend von der Beobachtung, dass Mitarbeiter der Vereinten Nationen eine wichtige Rolle in Prozessen des ideellen Wandels auf internationaler Ebene spielen können, beschäftigt sich dieser Beitrag mit einer bestimmten Form individuellem Einflusses – dem storytelling. Mein Verständnis von storytelling als Einflusstaktik kombiniert dabei kollektive Elemente der soziologischen Praxistheorie mit den reflexiven, akteursbezogenen Überlegungen von Michel de Certeau. Ich analysiere storytelling anhand von drei analytischen Elementen: einem (chronologischen) Plot, einer Reihe von Charakteren und einem interpretativen Thema – die jeweils ihre Wirkung im Zusammenspiel mit der Subjektivität ihres storytellers entfalten. Ich illustriere diese theoretischen Überlegungen mit dem Fall von Mahbub ul Haq, dem es als Sonderberater des United Nations Development Programme (UNDP)-Administrators zu Beginn der 1990er Jahre gelungen ist, die Idee der menschlichen Entwicklung im System der Vereinten Nationen und der internationalen Entwicklungspolitik zu etablieren

Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition

SummarySmoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant

Circular economy inspired imaginaries for sustainable innovations

In this chapter, Narayan and Tidström draw on the concept of imaginaries to show how Circular Economy (CE) can facilitate values that enable sustainable innovation. Innovation is key for sustainability, however, understanding and implementing sustainable innovation is challenging, and identifying the kind of actions that could direct sustainable innovations is important. The findings of this study indicate that CE-inspired imaginaries enable collaboration and by relating such imaginaries to common and shared social and cultural values, intermediaries could motivate actors into taking actions that contribute to sustainable innovation.fi=vertaisarvioitu|en=peerReviewed

Archiving primary data: solutions for long-term studies

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Concern with COVID-19 pandemic threat and attitudes towards immigrants: The mediating effect of the desire for tightness

Tightening social norms is thought to be adaptive for dealing with collective threat yet it may have negative consequences for increasing prejudice. The present research investigated the role of desire for cultural tightness, triggered by the COVID-19 pandemic, in increasing negative attitudes towards immigrants. We used participant-level data from 41 countries (N = 55,015) collected as part of the PsyCorona project, a crossnational longitudinal study on responses to COVID-19. Our predictions were tested through multilevel and SEM models, treating participants as nested within countries. Results showed that people’s concern with COVID19 threat was related to greater desire for tightness which, in turn, was linked to more negative attitudes towards immigrants. These findings were followed up with a longitudinal model (N = 2,349) which also showed that people’s heightened concern with COVID-19 in an earlier stage of the pandemic was associated with an increase in their desire for tightness and negative attitudes towards immigrants later in time. Our findings offer insight into the trade-offs that tightening social norms under collective threat has for human groups

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics