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

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

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 novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis. KEY RESULTS: BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels. CONCLUSIONS AND IMPLICATIONS: BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development

Assessment of wind and solar power in global low-carbon energy scenarios: An introduction

This preface introduces the special section on the assessment of wind and solar in global low-carbon energy scenarios. The special section documents the results of a coordinated research effort to improve the representation of variable renewable energies (VRE), including wind and solar power, in Integrated Assessment Models (IAM) and presents an overview of the results obtained in the underlying coordinated model inter-comparison exercise

Marginalization of end-use technologies in energy innovation for climate protection

Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies