Progress and challenges in glacial lake outburst flood research (2017–2021):a research community perspective

Glacial lake outburst floods (GLOFs) are among the most concerning consequences of retreating glaciers in mountain ranges worldwide. GLOFs have attracted significant attention amongst scientists and practitioners in the past 2 decades, with particular interest in the physical drivers and mechanisms of GLOF hazard and in socioeconomic and other human-related developments that affect vulnerabilities to GLOF events. This increased research focus on GLOFs is reflected in the gradually increasing number of papers published annually. This study offers an overview of recent GLOF research by analysing 594 peer-reviewed GLOF studies published between 2017 and 2021 (Web of Science and Scopus databases), reviewing the content and geographical focus as well as other characteristics of GLOF studies. This review is complemented with perspectives from the first GLOF conference (7-9 July 2021, online) where a global GLOF research community of major mountain regions gathered to discuss the current state of the art of integrated GLOF research. Therefore, representatives from 17 countries identified and elaborated trends and challenges and proposed possible ways forward to navigate future GLOF research, in four thematic areas: (i) understanding GLOFs - timing and processes; (ii) modelling GLOFs and GLOF process chains; (iii) GLOF risk management, prevention and warning; and (iv) human dimensions of GLOFs and GLOF attribution to climate change.Fil: Emmer, Adam. University of Graz; AustriaFil: Allen, Simon K.. Universitat Zurich; Suiza. Universidad de Ginebra; SuizaFil: Carey, Mark. University of Oregon; Estados UnidosFil: Frey, Holger. Universitat Zurich; SuizaFil: Huggel, Christian. Universitat Zurich; SuizaFil: Korup, Oliver. Universitat Potsdam; AlemaniaFil: Mergili, Martin. University of Graz; AustriaFil: Sattar, Ashim. Universitat Zurich; SuizaFil: Veh, Georg. Universitat Potsdam; AlemaniaFil: Chen, Thomas Y.. Columbia University; Estados UnidosFil: Cook, Simon J.. University Of Dundee; Reino Unido. Unesco. Centre For Water Law, Policy And Science; Reino UnidoFil: Correas Gonzalez, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Das, Soumik. Jawaharlal Nehru University; IndiaFil: Diaz Moreno, Alejandro. Reynolds International Ltd; Reino UnidoFil: Drenkhan, Fabian. Pontificia Universidad Católica de Perú; PerúFil: Fischer, Melanie. Universitat Potsdam; AlemaniaFil: Immerzeel, Walter W.. Utrecht University; Países BajosFil: Izagirre, Eñaut. Universidad del País Vasco; EspañaFil: Joshi, Ramesh Chandra. Kumaun University India; IndiaFil: Kougkoulos, Ioannis. American College Of Greece; GreciaFil: Kuyakanon Knapp, Riamsara. University of Oslo; Noruega. University of Cambridge; Estados UnidosFil: Li, Dongfeng. National University Of Singapore; SingapurFil: Majeed, Ulfat. University Of Kashmir; IndiaFil: Matti, Stephanie. Haskoli Islands; IslandiaFil: Moulton, Holly. University of Oregon; Estados UnidosFil: Nick, Faezeh. Utrecht University; Países BajosFil: Piroton, Valentine. Université de Liège; BélgicaFil: Rashid, Irfan. University Of Kashmir; IndiaFil: Reza, Masoom. Kumaun University India; IndiaFil: Ribeiro De Figueiredo, Anderson. Universidade Federal do Rio Grande do Sul; BrasilFil: Riveros, Christian. Instituto Nacional de Investigación En Glaciares y Ecosistemas de Montaña; PerúFil: Shrestha, Finu. International Centre For Integrated Mountain Development Nepal; NepalFil: Shrestha, Milan. Arizona State University; Estados UnidosFil: Steiner, Jakob. International Centre For Integrated Mountain Development Nepal; NepalFil: Walker-Crawford, Noah. Colegio Universitario de Londres; Reino UnidoFil: Wood, Joanne L.. University of Exeter; Reino UnidoFil: Yde, Jacob C.. Western Norway University Of Applied Sciences; Suiz

Inclusive search for supersymmetry using razor variables in pp collisions at root s=13 TeV

Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Denkmal der schuldigen Hochachtung und Liebe gestiftet dem weiland Hochwürdigen und Hochgelarten Herrn D. Gotthilf August Francken, Königl. Preußl. [!] Consistorialrath im Herzogtum Magdeburg, der Friedrichsuniversität, der Theologischen Facultät und des Stadt-Ministerii Senior und ersten Inspector im Saalkreis, wie auch des Pädagogii Regii und des Waisenhauses Director / Nunmehr gesamlet und herausgegeben von D. Johann Georg Knapp, der Gottesgelartheit ordentlichem Lehrer, wie auch des Pädagogii Regii und Waisenhauses Director

DENKMAL DER SCHULDIGEN HOCHACHTUNG UND LIEBE GESTIFTET DEM WEILAND HOCHWÜRDIGEN UND HOCHGELARTEN HERRN D. GOTTHILF AUGUST FRANCKEN, KÖNIGL. PREUSSL. [!] CONSISTORIALRATH IM HERZOGTUM MAGDEBURG, DER FRIEDRICHSUNIVERSITÄT, DER THEOLOGISCHEN FACULTÄT UND DES STADT-MINISTERII SENIOR UND ERSTEN INSPECTOR IM SAALKREIS, WIE AUCH DES PÄDAGOGII REGII UND DES WAISENHAUSES DIRECTOR / NUNMEHR GESAMLET UND HERAUSGEGEBEN VON D. JOHANN GEORG KNAPP, DER GOTTESGELARTHEIT ORDENTLICHEM LEHRER, WIE AUCH DES PÄDAGOGII REGII UND WAISENHAUSES DIRECTOR Denkmal der schuldigen Hochachtung und Liebe gestiftet dem weiland Hochwürdigen und Hochgelarten Herrn D. Gotthilf August Francken, Königl. Preußl. [!] Consistorialrath im Herzogtum Magdeburg, der Friedrichsuniversität, der Theologischen Facultät und des Stadt-Ministerii Senior und ersten Inspector im Saalkreis, wie auch des Pädagogii Regii und des Waisenhauses Director / Nunmehr gesamlet und herausgegeben von D. Johann Georg Knapp, der Gottesgelartheit ordentlichem Lehrer, wie auch des Pädagogii Regii und Waisenhauses Director (1) Einband (1) Frontispiz (Portrait, Kupferstich) (8) Titelblatt (9) Vorrede. (11) Svpremvm Honorem Fvneri Theologi De Academia Et Civitate Christi Vniversa Meritissimi ... (21) Gedächtnisrede den 17ten Nov. 1769 auf dem Waisenhause gehalten (57) Des sel. Herrn Consistorialraths, D. Gotthilf August Franckens, Lebenslauf. (97) Epicedia oder Trauer- und Trost-Schriften. (157) Fotodokumentation (302

An die werthesten Eltern, die ihre Töchter in die Schule des Waisenhauses schicken : [Halle den 18 May 1792.]

[J. L. Schulze, G. C. Knapp, A. H. Niemeyer, Director und Mitdirectoren des Waisenhauses]KopftitelErscheinungsjahr nach Datierung am Textend

A Chemical Toolbox for Labeling and Degrading Engineered Cas Proteins

[Image: see text] The discovery of clustered regularly interspaced short palindromic repeats and their associated proteins (Cas) has revolutionized the field of genome and epigenome editing. A number of new methods have been developed to precisely control the function and activity of Cas proteins, including fusion proteins and small-molecule modulators. Proteolysis-targeting chimeras (PROTACs) represent a new concept using the ubiquitin-proteasome system to degrade a protein of interest, highlighting the significance of chemically induced protein-E3 ligase interaction in drug discovery. Here, we engineered Cas proteins (Cas9, dCas9, Cas12, and Cas13) by inserting a Phe-Cys-Pro-Phe (FCPF) amino acid sequence (known as the π-clamp system) and demonstrate that the modified Cas(FCPF) proteins can be (1) labeled in live cells by perfluoroaromatics carrying the fluorescein or (2) degraded by a perfluoroaromatics-functionalized PROTAC (PROTAC-FCPF). A proteome-wide analysis of PROTAC-FCPF-mediated Cas9(FCPF) protein degradation revealed a high target specificity, suggesting a wide range of applications of perfluoroaromatics-induced proximity in the regulation of stability, activity, and functionality of any FCPF-tagging protein