The Chisholm firestorm: observed microstructure, precipitation and lightning activity of a pyro-cumulonimbus

International audienceA fire storm that occurred on 28 May 2001 and devastated the town of Chisholm, ~150 km north of Edmonton, Alberta, induced a violent fire-invigorated cumulonimbus cloud. This pyro-cumulonimbus (pyro-Cb) had overshooting tops of 2.5?3 km above the tropopause, and injected massive amounts of smoke into the lower stratosphere. Fortunately, this event occurred under good coverage of radar, rain gauge, lightning and satellite measurements, which allowed in-depth documentation of the event, and gave us an opportunity to study the cloud top morphology and microstructure, precipitation and cloud electrification of the pyro-Cb. The combination of heat and smoke created a cloud with extremely small drops, which ascended rapidly in violent updrafts. There appeared to be little freezing up to the homogeneous freezing isotherm level of ?38°C. A cloud with such small and short-lived highly supercooled drops is incapable of producing precipitation except for few large graupel and hail, which produced the observed radar echoes and charged the cloud with positive lightning. The small cloud drops froze homogeneously to equally small ice particles, for which there is no mechanism to aggregate into precipitation particles, and which hence remain in the anvil. The lack of significant precipitation implies that only a small fraction of the smoke is scavenged, so that most of it is exhausted through the anvil to the upper troposphere and lower stratosphere. Comparisons with other cases suggest that a pyro-Cb does not have to be as violent as the Chisholm case for precipitation to be strongly suppressed. However, this level of convective vigor is necessary to create the overshooting updraft that injects the smoke into the lower stratosphere

Towards a Better Understanding of Disparities in Scenarios of Decarbonization: Sectorally Explicit Results from the RECIPE Project

This paper presents results from a model intercomparison exercise among regionalized global energy-economy models conducted in the context of the RECIPE project. The economic adjustment effects of long-term climate policy aiming at stabilization of atmospheric CO2 concentrations at 450 ppm are investigated based on the cross-comparison of the intertemporal optimization models REMIND-R and WITCH as well as the recursive dynamic computable general equilibrium model IMACLIM-R. The models applied in the project differ in several respects and the comparison exercise tracks differences in the business as usual forecasts as well as in the mitigation scenarios to conceptual differences in the model structures and assumptions. In particular, the models have different representation of the sectoral structure of the energy system. A detailed sectoral analysis conducted as part of this study reveals that the sectoral representation is a crucial determinant of the mitigation strategy and costs. While all models project that the electricity sector can be decarbonized readily, emissions abatement in the non-electric sectors, particularly transport, is much more challenging. Mitigation costs and carbon prices were found to depend strongly on the availability of low-carbon options in the non-electric sectors.Decarbonization, Energy and Climate Policy

Structural optimization and biological evaluation of 2-substituted 5-hydroxyindole-3-carboxylates as potent inhibitors of human 5-lipoxygenase.

Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5- hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 μM, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 μM) and significantly prevented leukotriene B4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics

Time to act now? Assessing the costs of delaying climate measures and benefits of early action

This paper compares the results of the three state of the art climate-energy-economy models IMACLIM-R, ReMIND-R, and WITCH to assess the costs of climate change mitigation in scenarios in which the implementation of a global climate agreement is delayed or major emitters decide to participate in the agreement at a later stage only. We find that for stabilizing atmospheric GHG concentrations at 450 ppm CO2-only, postponing a global agreement to 2020 raises global mitigation costs by at least about half and a delay to 2030 renders ambitious climate targets infeasible to achieve. In the standard policy scenario—in which allocation of emission permits is aimed at equal per-capita levels in the year 2050—regions with above average emissions (such as the EU and the US alongside the rest of Annex-I countries) incur lower mitigation costs by taking early action, even if mitigation efforts in the rest of the world experience a delay. However, regions with low per-capita emissions which are net exporters of emission permits (such as India) can possibly benefit from higher future carbon prices resulting from a delay. We illustrate the economic mechanism behind these observations and analyze how (1) lock-in of carbon intensive infrastructure, (2) differences in global carbon prices, and (3) changes in reduction commitments resulting from delayed action influence mitigation costs.ou

Weltklimagipfel in Kopenhagen: Welche Erfolgsaussichten hat ein globales Klimaabkommen?

Auf dem Weltklimagipfel in Kopenhagen im Dezember 2009 wird ein globales Klimaabkommen verhandelt. Können dort Strukturen geschaffen werden, die einen effizienten und kostengünstigen Klimaschutz ermöglichen? Entscheidend sei es, nach Meinung von Hubertus Bardt, Institut der deutschen Wirtschaft Köln, die Klimaschutzziele mit möglichst geringem Kostenaufwand zu erreichen. Möchte man international einen möglichst effizienten Klimaschutz betreiben, müssten die Maßnahmen zur Vermeidung von Treibhausgasemissionen an den Orten vorgenommen werden, wo dies je vermiedener Einheit am billigsten sei. Oftmals dürften diese Möglichkeiten in den Entwicklungs- und Schwellenländern liegen, während in den klimapolitisch aktiven Industrieländern preiswerte Vermeidungspotentiale bereits zu einem guten Teil ausgeschöpft seien. Ein neues internationales Klimaabkommen müsse also dazu beitragen, dass die global günstigsten Vermeidungspotentiale realisiert werden. Ottmar Edenhofer, Brigitte Knopf und Gunnar Luderer, Potsdam-Institut für Klimafolgengforschung, sehen eine sinnvolle Architektur der Klimapolitik hauptsächlich in drei Maßnahmen: 1) in einer Einigung über die Kohlenstoffmenge, die noch bis zum Ende des Jahrhunderts in der Atmosphäre abgelagert werden darf, 2) in der Verteilung der Emissionsrechte nach einem gerechten Schlüssel auf alle Nationen und 3) in der Schaffung der institutionellen Voraussetzungen für einen globalen Emissionshandel. Für Sabine Schlacke, Universität Bremen, scheint das "Ob" und "Wie" eines Post-Kyoto-Abkommens "derzeit mehr als ungewiss". Ein Scheitern der internationalen Verhandlungen könne aber durchaus auch die Möglichkeit eröffnen, über einen Systemwandel bei der internationalen Architektur des Klimaschutzes nachzudenken

Molecularly targeted therapies in multiple myeloma

Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients will eventually relapse or become refractory to the treatments. Although the treatments have improved, the major problem in MM is the resistance to therapy. Novel agents are currently in development for the treatment of relapsed/refractory MM, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, cell signaling targeted therapies, and strategies targeting the tumor microenvironment. We have previously reviewed in detail the contemporary immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies therapies for MM. Therefore, in this review, we focused on the role of molecular targeted therapies in the treatment of relapsed/refractory multiple myeloma, including cell signaling targeted therapies (HDAC, PI3K/AKT/mTOR, p38 MAPK, Hsp90, Wnt, Notch, Hedgehog, and cell cycle) and strategies targeting the tumor microenvironment (hypoxia, angiogenesis, integrins, CD44, CXCR4, and selectins). Although these novel agents have improved the therapeutic outcomes for MM patients, further development of new therapeutic agents is warranted

Weltklimagipfel in Kopenhagen: Welche Erfolgsaussichten hat ein globales Klimaabkommen?

Auf dem Weltklimagipfel in Kopenhagen im Dezember 2009 wird ein globales Klimaabkommen verhandelt. Können dort Strukturen geschaffen werden, die einen effizienten und kostengünstigen Klimaschutz ermöglichen? Entscheidend sei es, nach Meinung von Hubertus Bardt, Institut der deutschen Wirtschaft Köln, die Klimaschutzziele mit möglichst geringem Kostenaufwand zu erreichen. Möchte man international einen möglichst effizienten Klimaschutz betreiben, müssten die Maßnahmen zur Vermeidung von Treibhausgasemissionen an den Orten vorgenommen werden, wo dies je vermiedener Einheit am billigsten sei. Oftmals dürften diese Möglichkeiten in den Entwicklungs- und Schwellenländern liegen, während in den klimapolitisch aktiven Industrieländern preiswerte Vermeidungspotentiale bereits zu einem guten Teil ausgeschöpft seien. Ein neues internationales Klimaabkommen müsse also dazu beitragen, dass die global günstigsten Vermeidungspotentiale realisiert werden. Ottmar Edenhofer, Brigitte Knopf und Gunnar Luderer, Potsdam-Institut für Klimafolgengforschung, sehen eine sinnvolle Architektur der Klimapolitik hauptsächlich in drei Maßnahmen: 1) in einer Einigung über die Kohlenstoffmenge, die noch bis zum Ende des Jahrhunderts in der Atmosphäre abgelagert werden darf, 2) in der Verteilung der Emissionsrechte nach einem gerechten Schlüssel auf alle Nationen und 3) in der Schaffung der institutionellen Voraussetzungen für einen globalen Emissionshandel. Für Sabine Schlacke, Universität Bremen, scheint das "Ob" und "Wie" eines Post-Kyoto-Abkommens "derzeit mehr als ungewiss". Ein Scheitern der internationalen Verhandlungen könne aber durchaus auch die Möglichkeit eröffnen, über einen Systemwandel bei der internationalen Architektur des Klimaschutzes nachzudenken.Umweltabkommen, Internationale Umweltpolitik, Klimaschutz, Finanzierung, Welt

Reactions of (-)-sparteine with alkali metal HMDS complexes : conventional meets the unconventional

Conventional (-)-sparteine adducts of lithium and sodium 1,1,1,3,3,3-hexamethyldisilazide (HMDS) were prepared and characterised, along with an unexpected and unconventional hydroxyl-incorporated sodium sodiate, [(-)-sparteine·Na(-HMDS)Na·(-)-sparteine]+[Na4(-HMDS)4(OH)]--the complex anion of which is the first inverse crown ether anion

Spotlight on ixazomib: Potential in the treatment of multiple myeloma

Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib

The Chisholm firestorm: observed microstructure, precipitation and lightning activity of a pyro-Cb

International audienceA fire storm that occured on 28 May 2001 devastated the town of Chisholm, ~150 km north of Edmonton, Alberta, induced a violent fire-invigorated cumulonimbus cloud. This pyro-cumulonimbus (pyro-Cb) had overshooting tops of 2.5?3 km above the tropopause, and injected massive amounts of smoke into the lower stratosphere. Fortunately, this event occurred under good coverage of radar, rain gauge, lightning and satellite measurements, which allowed in-depth documentation of the event. The combination of heat and smoke created a cloud with extremely small drops, which ascended rapidly in violent updrafts. There appeared to be little freezing up to the homogeneous freezing isotherm level of ?38°C. A cloud with such small and short-lived highly supercooled drops is incapable of producing precipitation except for few large graupel and hail, which produced the observed radar echoes and charged the cloud with positive lightning. The small cloud drops froze homogeneously to equally small ice particles, for which there is no mechanism to aggregate into precipitation particles that hence remain in the anvil. The small precipitation efficiency implies that only a small fraction of the smoke is scavenged, so that most of it is exhausted through the anvil to the upper troposphere and lower stratosphere. Comparisons with other cases suggest that a pyro-Cb does not have to be as violent as the Chisholm case to have strongly suppressed precipitation. However, this level of convective vigor is necessary to create the overshooting updraft that injects the smoke into the lower stratosphere