New Deterministic Algorithms for Solving Parity Games

We study parity games in which one of the two players controls only a small number $k$ of nodes and the other player controls the $n-k$ other nodes of the game. Our main result is a fixed-parameter algorithm that solves bipartite parity games in time $k^{O(\sqrt{k})}\cdot O(n^3)$, and general parity games in time $(p+k)^{O(\sqrt{k})} \cdot O(pnm)$, where $p$ is the number of distinct priorities and $m$ is the number of edges. For all games with $k = o(n)$ this improves the previously fastest algorithm by Jurdzi{\'n}ski, Paterson, and Zwick (SICOMP 2008). We also obtain novel kernelization results and an improved deterministic algorithm for graphs with small average degree

Multi-Player and Multi-Choice Quantum Game

We investigate a multi-player and multi-choice quantum game. We start from two-player and two-choice game and the result is better than its classical version. Then we extend it to N-player and N-choice cases. In the quantum domain, we provide a strategy with which players can always avoid the worst outcome. Also, by changing the value of the parameter of the initial state, the probabilities for players to obtain the best payoff will be much higher that in its classical version.Comment: 4 pages, 1 figur

Transcriptional regulation of the urokinase receptor (u-PAR) - A central molecule of invasion and metastasis

The phenomenon of tumor-associated proteolysis has been acknowledged as a decisive step in the progression of cancer. This short review focuses on the urokinase receptor (u-PAR), a central molecule involved in tumor-associated invasion and metastasis, and summarizes the transcriptional regulation of u-PAR. The urokinase receptor (u-PAR) is a heavily glycosylated cell surface protein and binds the serine protease urokinase specifically and with high affinity. It consists of three similar cysteine-rich repeats and is anchored to the cell membrane via a GPI-anchor. The u-PAR gene comprises 7 exons and is located on chromosome 19q13. Transcriptional activation of the u-PAR promoter region can be induced by binding of transcription factors (Sp1, AP-1, AP-2, NF-kappaB). One current study gives an example for transcriptional downregulation of u-PAR through a PEA3/ets transcriptional silencing element. Knowledge of the molecular regulation of this molecule in tumor cells could be very important for diagnosis and therapy in the near future

Climate and southern Africa's water-energy-food nexus

In southern Africa, the connections between climate and the water-energy-food nexus are strong. Physical and socioeconomic exposure to climate is high in many areas and in crucial economic sectors. Spatial interdependence is also high, driven for example, by the regional extent of many climate anomalies and river basins and aquifers that span national boundaries. There is now strong evidence of the effects of individual climate anomalies, but associations between national rainfall and Gross Domestic Product and crop production remain relatively weak. The majority of climate models project decreases in annual precipitation for southern Africa, typically by as much as 20% by the 2080s. Impact models suggest these changes would propagate into reduced water availability and crop yields. Recognition of spatial and sectoral interdependencies should inform policies, institutions and investments for enhancing water, energy and food security. Three key political and economic instruments could be strengthened for this purpose; the Southern African Development Community, the Southern African Power Pool, and trade of agricultural products amounting to significant transfers of embedded water

Climate impact research: Beyond patchwork

Despite significant progress in climate impact research, the narratives that science can presently piece together of a 2, 3, 4, or 5 °C warmer world remain fragmentary. Here we briefly review past undertakings to characterise comprehensively and quantify climate impacts based on multi-model approaches. We then report on the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), a community-driven effort to compare impact models across sectors and scales systematically, and to quantify the uncertainties along the chain from greenhouse gas emissions and climate input data to the modelling of climate impacts themselves. We show how ISI-MIP and similar efforts can substantially advance the science relevant to impacts, adaptation and vulnerability, and we outline the steps that need to be taken in order to make the most of the available modelling tools. We discuss pertinent limitations of these methods and how they could be tackled. We argue that it is time to consolidate the current patchwork of impact knowledge through integrated cross-sectoral assessments, and that the climate impact community is now in a favourable position to do so

Repurposing anthelmintic agents to eradicate resistant leukemia

Despite rapid progress in genomic profiling in acute lymphoblastic leukemia (ALL), identification of actionable targets and prediction of response to drugs remains challenging. To identify specific vulnerabilities in ALL, we performed a drug screen using primary human ALL samples cultured in a model of the bone marrow microenvironment combined with high content image analysis. Among the 2487 FDA-approved compounds tested, anthelmintic agents of the class of macrocyclic lactones exhibited potent anti-leukemia activity, similar to the already known anti-leukemia agents currently used in induction chemotherapy. Ex vivo validation in 55 primary ALL samples of both precursor B cell and T-ALL including refractory relapse cases confirmed strong anti-leukemia activity with IC50 values in the low micromolar range. Anthelmintic agents increased intracellular chloride levels in primary leukemia cells, inducing mitochondrial outer membrane depolarization and cell death. Supporting the notion that simultaneously targeting cell death machineries at different angles may enhance the cell death response, combination of anthelmintic agents with the BCL-2 antagonist navitoclax or with the chemotherapeutic agent dexamethasone showed synergistic activity in primary ALL. These data reveal anti-leukemia activity of anthelmintic agents and support exploiting drug repurposing strategies to identify so far unrecognized anti-cancer agents with potential to eradicate even refractory leukemia

Spectroscopic evidence for a gold-coloured metallic water solution

Insulating materials can in principle be made metallic by applying pressure. In the case of pure water, this is estimated1 to require a pressure of 48 megabar, which is beyond current experimental capabilities and may only exist in the interior of large planets or stars2–4. Indeed, recent estimates and experiments indicate that water at pressures accessible in the laboratory will at best be superionic with high protonic conductivity5, but not metallic with conductive electrons1. Here we show that a metallic water solution can be prepared by massive doping with electrons upon reacting water with alkali metals. Although analogous metallic solutions of liquid ammonia with high concentrations of solvated electrons have long been known and characterized6–9, the explosive interaction between alkali metals and water10,11 has so far only permitted the preparation of aqueous solutions with low, submetallic electron concentrations12–14. We found that the explosive behaviour of the water–alkali metal reaction can be suppressed by adsorbing water vapour at a low pressure of about 10−4 millibar onto liquid sodium–potassium alloy drops ejected into a vacuum chamber. This set-up leads to the formation of a transient gold-coloured layer of a metallic water solution covering the metal alloy drops. The metallic character of this layer, doped with around 5 × 1021 electrons per cubic centimetre, is confirmed using optical reflection and synchrotron X-ray photoelectron spectroscopies

Climate impact research: Beyond patchwork

Despite significant progress in climate impact research, the narratives that science can presently piece together of a 2, 3, 4, or 5 degrees C warmer world remain fragmentary. Here we briefly review past undertakings to characterise comprehensively and quantify climate impacts based on multi-model approaches. We then report on the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), a community-driven effort to compare impact models across sectors and scales systematically, and to quantify the uncertainties along the chain from greenhouse gas emissions and climate input data to the modelling of climate impacts themselves. We show how ISI-MIP and similar efforts can substantially advance the science relevant to impacts, adaptation and vulnerability, and we outline the steps that need to be taken in order to make the most of the available modelling tools. We discuss pertinent limitations of these methods and how they could be tackled. We argue that it is time to consolidate the current patchwork of impact knowledge through integrated cross-sectoral assessments, and that the climate impact community is now in a favourable position to do so

Outcome for pediatric adreno-cortical tumors is best predicted by the COG stage and five-item microscopic score — report from the German MET studies

Background: Adrenocortical tumors (ACTs) encompassing the adrenocortical adenoma (ACA), carcinoma (ACC), and tumors of undetermined malignant potential (ACx) are rare endocrine neoplasms with a poor prognosis. We report on pediatric ACT patients registered with the Malignant Endocrine Tumor studies and explore the EXPeRT recommendations for management. Patients: Data from the ACT patients (<18 years) were analyzed. For the risk prediction, the patients were retrospectively assigned to the COG stages and the five-item score. Results: By December 2021, 161 patients with ACT (ACA n = 51, ACx n = 19, and ACC n = 91) had been reported (the median age at the diagnosis was 4.3 years with a range of 0.1–17.8), with lymph node and distant metastases in 10.7% and 18.9% of the patients with ACC/ACx. The mean follow-up was 4.5 years (with a range of 0–16.7). The three-year overall (OS) and event-free survival (EFS) rates were 65.5% and 50.6%. In the univariate analyses, the OS was impaired for patients aged ≥ 4 years (p = 0.001) with the initial biopsy (p = 0.016), tumor spillage (p = 0.028), incomplete tumor resection (p < 0.001), unfavorable histology (p = 0.047), and COG stages III/IV (p = 0.002). Multivariate analysis revealed COG stages III/IV and an unfavorable five-item score as independent negative prognostic factors for the EFS and OS. Conclusions: Age defines the clinical presentation and prognosis in pediatric ACTs. The outcome is best predicted by the COG stage and five-item score

Refractory and relapsed paediatric ACC in the MET studies – a challenging situation necessitating novel diagnostic and therapeutic concepts

Background Paediatric adrenocortical carcinomas (ACC) are highly aggressive malignancies with a dismal prognosis in advanced and metastatic disease. Little is known about outcome of patients with refractory and relapsed (r/r) disease. Procedure National retrospective multicentre study including r/r ACC diagnosed in patients aged <18 years registered in the MET studies between January 1997 and December 2021 Results A total of 16 patients (5 male; median age 12.9 years) with refractory disease were included. Median time to progression was 0.6 years [0.0-1.3]. Site of progression was locoregional (n=1), distant (n=3), and combined (n=12). 3-year overall (OS) and progression-free (PFS) survival were both 0%. Thirty patients with relapse (11 male; median age 7.3 years) were identified. Median time to relapse was 0.7 years [0.1-3.2]. Site of relapse was locoregional (n=8), distant (n=15), and combined (n=7). At last follow-up, 20 patients had died of disease or complications or were alive with disease, 10 patients were in second complete remission (median follow-up: 6.8 years [0-10.5]). 3-year OS and PFS following relapse were 39.1% and 31.9%. Survival was superior in patients with distant relapse (59.6%) compared to locoregional (28.6%) and combined (14.3%) (p=0.028) and in patients with complete surgical resection of all sites of recurrence (70.0%) compared to incomplete (21.4%) and no surgery (0%) (p=0.003). Conclusions For patients nonresponsive to first-line therapy or who experience relapse, prognosis is dismal and options are scarce. Site of relapse and resectability define prognosis. Novel therapeutic concepts are needed to improve the outcome of paediatric patients with r/r ACC