Near-Optimal Min-Sum Motion Planning for Two Square Robots in a Polygonal Environment

Let $\mathcal{W} \subset \mathbb{R}^2$ be a planar polygonal environment (i.e., a polygon potentially with holes) with a total of $n$ vertices, and let $A,B$ be two robots, each modeled as an axis-aligned unit square, that can translate inside $\mathcal{W}$. Given source and target placements $s_A,t_A,s_B,t_B \in \mathcal{W}$ of $A$ and $B$, respectively, the goal is to compute a \emph{collision-free motion plan} $\mathbf{\pi}^*$, i.e., a motion plan that continuously moves $A$ from $s_A$ to $t_A$ and $B$ from $s_B$ to $t_B$ so that $A$ and $B$ remain inside $\mathcal{W}$ and do not collide with each other during the motion. Furthermore, if such a plan exists, then we wish to return a plan that minimizes the sum of the lengths of the paths traversed by the robots, $\left|\mathbf{\pi}^*\right|$. Given $\mathcal{W}, s_A,t_A,s_B,t_B$ and a parameter $\varepsilon > 0$, we present an $n^2\varepsilon^{-O(1)} \log n$-time $(1+\varepsilon)$-approximation algorithm for this problem. We are not aware of any polynomial time algorithm for this problem, nor do we know whether the problem is NP-Hard. Our result is the first polynomial-time $(1+\varepsilon)$-approximation algorithm for an optimal motion planning problem involving two robots moving in a polygonal environment.Comment: The conference version of the paper is accepted to SODA 202

Optical and Near-IR Microwave Kinetic Inductance Detectors (MKIDs) in the 2020s

Optical and near-IR Microwave Kinetic Inductance Detectors, or MKIDs, are superconducting photon counting detectors capable of measuring the energy and arrival time of individual OIR photons without read noise or dark current. In this whitepaper we will discuss the current status of OIR MKIDs and MKID-based instruments.Comment: Astro2020 APC Whitepaper. 16 pages, 10 figure

Semiautomatic Assessment of the Terminal Ileum and Colon in Patients with Crohn Disease Using MRI (the VIGOR++ Project)

Rationale and Objectives: The objective of this study was to develop and validate a predictive magnetic resonance imaging (MRI) activity score for ileocolonic Crohn disease activity based on both subjective and semiautomatic MRI features. Materials and Methods: An MRI activity score (the “virtual gastrointestinal tract [VIGOR]” score) was developed from 27 validated magnetic resonance enterography datasets, including subjective radiologist observation of mural T2 signal and semiautomatic measurements of bowel wall thickness, excess volume, and dynamic contrast enhancement (initial slope of increase). A second subjective score was developed based on only radiologist observations. For validation, two observers applied both scores and three existing scores to a prospective dataset of 106 patients (59 women, median age 33) with known Crohn disease, using the endoscopic Crohn's Disease Endoscopic Index of Severity (CDEIS) as a reference standard. Results: The VIGOR score (17.1 × initial slope of increase + 0.2 × excess volume + 2.3 × mural T2) and other activity scores all had comparable correlation to the CDEIS scores (observer 1: r = 0.58 and 0.59, and observer 2: r = 0.34–0.40 and 0.43–0.51, respectively). The VIGOR score, however, improved interobserver agreement compared to the other activity scores (intraclass correlation coefficient = 0.81 vs 0.44–0.59). A diagnostic accuracy of 80%–81% was seen for the VIGOR score, similar to the other scores. Conclusions: The VIGOR score achieves comparable accuracy to conventional MRI activity scores, but with significantly improved reproducibility, favoring its use for disease monitoring and therapy evaluation

Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylation(low) tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylation(low)/IFNsign(high) and Methylation(high)/IFNsign(low) PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived Kras(G12D)/Trp53(−/−) mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylation(low)/IFNsign(high) subtype potentially targetable by agents blocking intrinsic IFN-signaling

Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.

The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest KrasMUTlevels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1 or Nfkb2), which collaborate with heterozygous KrasMUTin driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgfβ-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer.The work was supported by the German Cancer Consortium Joint Funding Program, the Helmholtz Gemeinschaft (PCCC Consortium), the German Research Foundation (SFB1243; A13/A14) and the European Research Council (ERC CoG number 648521)

Eine stringente Suchtpolitik aus der Hermeneutik der Sozialen Arbeit: Betrachtung der Suchtpolitik mithilfe des Trippelmandates

Die Suchtpolitik der Schweiz hat zum Ziel, die Gesellschaft sowie das Individuum vor negativen Auswirkungen durch den Konsum psychoaktiver Substanzen zu schützen. Die Gesetzgebung baut auf der Vergangenheit auf und entspricht nicht den heutigen Konsumrealitäten. Die Repression verfehlt ihr Ziel und wirkt sich negativ darauf aus. Die Soziale Arbeit ist in den Arbeitsfeldern der Suchtpolitik präsent und das bio-psycho-soziale Erklärungsmodell von Abhängigkeit betont die Wichtigkeit der sozialen Komponente. In dieser Arbeit wird untersucht, wie die Suchtpolitik aus der Hermeneutik der Sozialen Arbeit besser an die Bedürfnisse von Individuum und Gesellschaft angepasst werden kann. Die Literatur beantwortet diese Fragestellung durch die Analyse der drei Mandate der Sozialen Arbeit. Dadurch werden die aktuellen Handlungsmöglichkeiten der Sozialen Arbeit ersichtlich, was es zur Gestaltung einer kohärenten Suchtpolitik bedarf und wie die Handlungsmöglichkeiten der Sozialen Arbeit in einer überarbeiteten Suchtpolitik aussähen. Um die Bedürfnisse von Gesellschaft und Individuum zu vereinen, muss die Politik beachten, dass vulnerable Personengruppen geschützt werden, Kriminalität vermindert wird und Konsumierende sicheren Zugang zu Wissen und qualitativen Substanzen erhalten. Dies kann durch einen legalen und regulierten Markt von psychoaktiven Substanzen erreicht werden. Die Regulierung bedarf einer besonders geschickten Ausarbeitung, um die Freiheitsrechte zu gewähren, das gesundheitliche Potenzial auszuschöpfen und die Risiken zu minimieren. Für diese Entwicklung ist das gesellschaftliche Verständnis der Thematik zu beachten. Die Aufklärung der Öffentlichkeit kommt dabei eine wichtige Funktion zu.+ Code Diss LU: hslusa basa + Fussnote: Bachelor-Arbeit, Hochschule Luzern – Soziale Arbeit, Studienrichtung Sozialarbeit, 2023 + NL-Code: NLLUHSA20230