A Comparison of ACE Measurements of Galactic Cosmic-Ray Abundances and Energy Spectra for Two Successive Solar Minima

Using current solar minimum measurements from the Cosmic Ray Isotope Spectrometer (CRIS) onboard the Advanced Composition Explorer (ACE), we report the observed elemental abundances and energy spectra for C, O, Si, and Fe in the energy range of ~50-500MeV/nucleon. These measurements are compared to prior CRIS observations for the 1997-98 solar minimum period, when the solar magnetic field was of the opposite polarity. By April 2009, the current solar minimum intensities for each of the four elements has surpassed the peak intensities observed during the previous solar minimum. We also examine the correlation of the galactic cosmic ray intensities with the tilt angle of the heliospheric current sheet. These studies will be important for understanding solar modulation processes, such as changes in drift effects during a solar cycle

Lower edge of locked Main Himalayan Thrust unzipped by the 2015 Gorkha earthquake

Large earthquakes are thought to release strain on previously locked faults. However, the details of how earthquakes are initiated, grow and terminate in relation to pre-seismically locked and creeping patches is unclear ^1-4. The 2015 Mw 7.8 Gorkha, Nepal earthquake occurred close to Kathmandu in a region where the prior pattern of fault locking is well documented ^5. Here we analyze this event using seismological records measured at teleseismic distances and Synthetic Aperture Radar imagery. We show that the earthquake originated northwest of Kathmandu within a cluster of background seismicity that fringes the bottom of the locked portion of the Main Himalayan Thrust fault (MHT). The rupture propagated eastwards for about 140 km, unzipping the lower edge of the locked portion of the fault. High-frequency seismic waves radiated continuously as the slip pulse propagated at about 2.8 km s-1 along this zone of presumably high and heterogeneous pre-¬seismic stress at the seismic-aseismic transition. Eastward unzipping of the fault resumed during the Mw 7.3 aftershock on May 12. The transfer of stress to neighbouring regions during the Gorkha earthquake should facilitate future rupture of the areas of the MHT adjacent and up-dip of the Gorkha earthquake rupture.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo251

The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs

Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme

A quantitative systems pharmacology consortium approach to managing immunogenicity of therapeutic proteins

Immunogenicity is a major challenge in drug development and patient care. Currently, most efforts are dedicated to the elimination of the unwanted immune responses through T‐cell epitope prediction and protein engineering. However, because it is unlikely that this approach will lead to complete eradication of immunogenicity, we propose that quantitative systems pharmacology models should be developed to predict and manage immunogenicity. The potential impact of such a mechanistic model‐based approach is precedented by applications of physiologically‐based pharmacokinetics

Surface ruptures of large Himalayan earthquakes in Western Nepal: Evidence along a reactivated strand of the Main Boundary Thrust

International audienceThe chronology of the seismic ruptures along the active faults of Western Nepal remains almost unconstrained despite their high seismogenic potential. We present here a slip history of one of these structures, a 120 km-long reactivated segment of the Main Boundary Thrust named the Surkhet–Gorahi fault. This slip history is based on geomorphologic and neotectonic mapping of active faults deduced from the analysis of a high resolution total station digital elevation model and 15 detrital charcoals radiocarbon ages constraining the age of deposition or abandonment of 4 alluvial terraces of the Bheri river in Botechaur. Our results show that the last two earthquakes occurred on this fault after 1860 and 640 BP, respectively, and accommodated slip greater than 8 m each, a value corresponding to the incremental vertical offset of the terraces. Such events released a significant part of the slip deficit accumulated on the Main Himalayan thrust fault. However, given the geometry of this fault system as well as the date of occurrence of the last events, the ruptures could be associated with major earthquakes also rupturing the Main Frontal Thrust, such as the great 1505 earthquake

Width control on event-scale deposition and evacuation of sediment in bedrock-confined channels

Abstract In mixed bedrock–alluvial rivers, the response of the system to a flood event can be affected by a number of factors, including coarse sediment availability in the channel, sediment supply from the hillslopes and upstream, flood sequencing and coarse sediment grain size distribution. However, the impact of along-stream changes in channel width on bedload transport dynamics remains largely unexplored. We combine field data, theory and numerical modelling to address this gap. First, we present observations from the Daan River gorge in western Taiwan, where the river flows through a 1 km long 20–50 m wide bedrock gorge bounded upstream and downstream by wide braidplains. We documented two flood events during which coarse sediment evacuation and redeposition appear to cause changes of up to several metres in channel bed elevation. Motivated by this case study, we examined the relationships between discharge, channel width and bedload transport capacity, and show that for a given slope narrow channels transport bedload more efficiently than wide ones at low discharges, whereas wider channels are more efficient at high discharges. We used the model sedFlow to explore this effect, running a random sequence of floods through a channel with a narrow gorge section bounded upstream and downstream by wider reaches. Channel response to imposed floods is complex, as high and low discharges drive different spatial patterns of erosion and deposition, and the channel may experience both of these regimes during the peak and recession periods of each flood. Our modelling suggests that width differences alone can drive substantial variations in sediment flux and bed response, without the need for variations in sediment supply or mobility. The fluctuations in sediment transport rates that result from width variations can lead to intermittent bed exposure, driving incision in different segments of the channel during different portions of the hydrograph. © 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Lt

Molecular Tracing of Riverine Soil Organic Matter From the Central Himalaya

International audienc