Min-ordering and max-ordering scalarization methods for multi-objective robust optimization

Several robustness concepts for multi-objective uncertain optimization have been developed during the last years, but not many solution methods. In this paper we introduce two methods to find min–max robust efficient solutions based on scalarizations: the min-ordering and the max-ordering method. We show that all point-based min–max robust weakly efficient solutions can be found with the max-ordering method and that the min-ordering method finds set-based min–max robust weakly efficient solutions, some of which cannot be found with formerly developed scalarization based methods. We then show how the scalarized problems may be approached for multi-objective uncertain combinatorial optimization problems with special uncertainty sets. We develop compact mixed-integer linear programming formulations for multi-objective extensions of bounded uncertainty (also known as budgeted or Γ-uncertainty). For interval uncertainty, we show that the resulting problems reduce to well-known single-objective problems

Lessons Learned aus der Iterativen Weiterentwicklung von Kollaborativer Online Lehre

Bereits vor der Pandemie stellten räumliche Distanz, fehlende Ausbildung im Bereich der Kollaborationskompetenzen, der Umgang mit digitalen Medien sowie in der interkulturellen Interaktion Hemmschwellen für die virtuelle Zusammenarbeit dar (Händel et al., 2021; Scherer et al., 2021). Potenziale für hochschul- und landesübergreifende Lehrangebote und Projekte zur Vernetzung werden weiterhin unzureichend umgesetzt. Existierende Projekte werden zumeist auf Basis von aufwändigen Reisen sowie Videokonferenzen abgehandelt. Der tatsächliche Austausch der Studierenden und der damit einhergehende Wissenstransfer durch Vernetzung rückt in diesen Umsetzungsvarianten in den Hintergrund. Einen alternativen Ansatz stellt die kollaborative Onlinelehre, mit starkem Fokus auf die Entwicklung der nötigen Kompetenzen, Vernetzungsaktivitäten, sowie asynchrone und synchrone Kollaborationstools, dar. In diesem Kontext stellt das Virtual Collaborative Learning (VCL) Framework erprobte Ansätze bereit, welche zur Entwicklung von Lehrangeboten genutzt werden können. Als Laborumgebung zur Weiterentwicklung des Frameworks werden Lehrangebote beforscht, durch iterative Weiterentwicklung neue Erkenntnisse gewonnen sowie bestehende Annahmen überprüft (Schoop et al., 2020). [Aus: Einführenden Beitrag

Local immune cell contributions to fracture healing in aged individuals – A novel role for interleukin 22

Aging: immune protein's role in delayed bone fracture healing Neutralizing a key cytokine, a signaling protein affecting the immune system could rejuvenate the healing process following prolonged inflammatory responses to bone fractures in elderly patients. Healing patterns vary widely in the elderly following injuries such as bone fractures, and scientists now believe that a patient's individual innate and adaptive immune profile directly affects the healing process. A short-lived pro-inflammatory response is needed to kickstart healthy healing, but a longer-lasting response can be damaging. In experiments on aged mouse models, the team led by Katharina Schmidt-Bleek at the Julius Wolff Institute in Berlin, Germany, demonstrated that high levels of the cytokine interleukin-22 impaired bone regeneration. Elevated interleukin-22 levels resulted from chronically elevated inflammation and inflammaging, prevalent in elderly patients. The team treated the mice to neutralize interleukin-22, which accelerated the healing process. With increasing age, the risk of bone fractures increases while regenerative capacity decreases. This variation in healing potential appears to be linked to adaptive immunity, but the underlying mechanism is still unknown. This study sheds light on immunoaging/inflammaging, which impacts regenerative processes in aging individuals. In an aged preclinical model system, different levels of immunoaging were analyzed to identify key factors that connect immunoaged/inflammaged conditions with bone formation after long bone fracture. Immunological facets, progenitor cells, the microbiome, and confounders were monitored locally at the injury site and systemically in relation to healing outcomes in 12-month-old mice with distinct individual levels of immunoaging. Bone tissue formation during healing was delayed in the immunoaged group and could be associated with significant changes in cytokine levels. A prolonged and amplified pro-inflammatory reaction was caused by upregulated immune cell activation markers, increased chemokine receptor availability and a lack of inhibitory signaling. In immunoaged mice, interleukin-22 was identified as a core cell signaling protein that played a central role in delayed healing. Therapeutic neutralization of IL-22 reversed this specific immunoaging-related disturbed healing. Immunoaging was found to be an influencing factor of decreased regenerative capacity in aged individuals. Furthermore, a novel therapeutic strategy of neutralizing IL-22 may successfully rejuvenate healing in individuals with advanced immune experiences

Phosphatase of regenerating liver-3 regulates cancer cell metabolism in multiple myeloma

publishedVersio

Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication

<p>Abstract</p> <p>Background</p> <p>Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported.</p> <p>Results</p> <p>In this study we describe 14 individuals with microdeletions of 3q29, including one family with a mildly affected mother and two affected children, identified among 14,698 individuals with idiopathic mental retardation who were analyzed by array CGH. Eleven individuals had typical 1.6-Mb deletions. Three individuals had deletions that flank, span, or partially overlap the commonly deleted region. Although the clinical presentations of individuals with typical-sized deletions varied, several features were present in multiple individuals, including mental retardation and microcephaly. We also identified 19 individuals with duplications of 3q29, five of which appear to be the reciprocal duplication product of the 3q29 microdeletion and 14 of which flank, span, or partially overlap the common deletion region. The clinical features of individuals with microduplications of 3q29 also varied with few common features. <it>De novo </it>and inherited abnormalities were found in both the microdeletion and microduplication cohorts illustrating the need for parental samples to fully characterize these abnormalities.</p> <p>Conclusion</p> <p>Our report demonstrates that array CGH is especially suited to identify chromosome abnormalities with unclear or variable presentations.</p

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

BackgroundThe ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur.AimWe aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available.MethodsHere we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology.ResultsThe workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive - Global (EVAg), a European Union infrastructure project.ConclusionThe present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks

Genetic Analysis Workshop 15: gene expression analysis and approaches to detecting multiple functional loci

National Institutes of Health (AR44422, N01-AR-7-2232, 5R01-HL049609-14, IR01-AG021917-01A1); Genome Canada and Associations AFP; Polyarctique-Groupe Taitbout; Rhumatisme et Travail; Arthritis Research Campaign; Unversity of Minnesota; Minnesota Supercomputing Institute; National Institute of General Medical Sciences (R01 GM31575

Survival at the frontier of Holy War: political expansion, crusading, commerce and the medieval colonizing settlement at Biała Gora, North Poland

Between the eleventh and thirteenth centuries AD, the Lower Vistula valley represented a permeable and shifting frontier between Pomerelia (eastern Pomerania), which had been incorporated into the Polish Christian state by the end of the tenth century, and the territories of western Prussian tribes, who had resisted attempts at Christianization. Pomeranian colonization eventually began to falter in the latter decades of the twelfth and early thirteenth centuries, most likely as a result of Prussian incursions, which saw the abandonment of sites across the borderland. Subsequently, the Teutonic Order and its allies led a protracted holy war against the Prussian tribes, which resulted in the conquest of the region and its incorporation into a theocratic state by the end of the thirteenth century. This was accompanied by a second wave of colonization, which resulted in the settlement pattern that is still visible in the landscape of north-central Poland today. However, not all colonies were destroyed or abandoned in between the two phases of colonization. The recently excavated site of Biała Góra, situated on the western side of the Forest of Sztum overlooking the River Nogat, represents a unique example of a transitional settlement that included both Pomeranian and Teutonic Order phases. The aim of this paper is to situate the site within its broader landscape context which can be characterized as a militarized frontier, where, from the later twelfth century and throughout much of the thirteenth century, political and economic expansion was combined with the ideology of Christian holy war and missionary activity. This paper considers how the colonists provisioned and sustained themselves in comparison to other sites within the region, and how Biała Góra may be tentatively linked to a documented but otherwise lost outpost in this volatile borderland

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts