On 14 November 2016, northeastern South Island of New Zealand was struck by a major moment magnitude (
) 7.8 earthquake. Field observations, in conjunction with interferometric synthetic aperture ...radar, Global Positioning System, and seismology data, reveal this to be one of the most complex earthquakes ever recorded. The rupture propagated northward for more than 170 kilometers along both mapped and unmapped faults before continuing offshore at the island's northeastern extent. Geodetic and field observations reveal surface ruptures along at least 12 major faults, including possible slip along the southern Hikurangi subduction interface; extensive uplift along much of the coastline; and widespread anelastic deformation, including the ~8-meter uplift of a fault-bounded block. This complex earthquake defies many conventional assumptions about the degree to which earthquake ruptures are controlled by fault segmentation and should motivate reevaluation of these issues in seismic hazard models.
The 2016 moment magnitude (Mw) 7.8 Kaikoura earthquake was one of the largest ever to hit New Zealand. Hamling et al. show with a new slip model that it was an incredibly complex event. Unlike most ...earthquakes, multiple faults ruptured to generate the ground shaking. A remarkable 12 faults ruptured overall, with the rupture jumping between faults located up to 15 km away from each other. The earthquake should motivate rethinking of certain seismic hazard models, which do not presently allow for this unusual complex rupture pattern. Science, this issue p. eaam7194 On 14 November 2016 (local time), northeastern South Island of New Zealand was struck by a major moment magnitude (Mw) 7.8 earthquake. The Kaikoura earthquake was the most powerful experienced in the region in more than 150 years. The whole of New Zealand reported shaking, with widespread damage across much of northern South Island and in the capital city, Wellington. The earthquake straddled two distinct seismotectonic domains, breaking multiple faults in the contractional North Canterbury fault zone and the dominantly strike-slip Marlborough fault system. Earthquakes are conceptually thought to occur along a single fault. Although this is often the case, the need to account for multiple segment ruptures challenges seismic hazard assessments and potential maximum earthquake magnitudes. Field observations from many past earthquakes and numerical models suggest that a rupture will halt if it has to step over a distance as small as 5 km to continue on a different fault. The Kaikoura earthquake's complexity defies many conventional assumptions about the degree to which earthquake ruptures are controlled by fault segmentation and provides additional motivation to rethink these issues in seismic hazard models. Field observations, in conjunction with interferometric synthetic aperture radar (InSAR), Global Positioning System (GPS), and seismology data, reveal the Kaikoura earthquake to be one of the most complex earthquakes ever recorded with modern instrumental techniques. The rupture propagated northward for more than 170 km along both mapped and unmapped faults before continuing offshore at the island's northeastern extent. A tsunami of up to 3 m in height was detected at Kaikoura and at three other tide gauges along the east coast of both the North and South Islands. Geodetic and geological field observations reveal surface ruptures along at least 12 major crustal faults and extensive uplift along much of the coastline. Surface displacements measured by GPS and satellite radar data show horizontal offsets of ~6 m. In addition, a fault-bounded block (the Papatea block) was uplifted by up to 8 m and translated south by 4 to 5 m. Modeling suggests that some of the faults slipped by more than 20 m, at depths of 10 to 15 km, with surface slip of ~10 m consistent with field observations of offset roads and fences. Although we can explain most of the deformation by crustal faulting alone, global moment tensors show a larger thrust component, indicating that the earthquake also involved some slip along the southern end of the Hikurangi subduction interface, which lies ~20 km beneath Kaikoura. Including this as a fault source in the inversion suggests that up to 4 m of predominantly reverse slip may have occurred on the subduction zone beneath the crustal faults, contributing ~10 to 30% of the total moment. Although the unusual multifault rupture observed in the Kaikoura earthquake may be partly related to the geometrically complex nature of the faults in this region, this event emphasizes the importance of reevaluating how rupture scenarios are defined for seismic hazard models in plate boundary zones worldwide. (A and B ) Photos showing the coastal uplift of 2 to 3 m associated with the Papatea block labeled in (C). The inset in (A) shows an aerial view of New Zealand. Red lines denote the location of known active faults. The black box indicates the Marlborough fault system. (C ) Three-dimensional displacement field derived from satellite radar data. The vectors represent the horizontal displacements, and the colored background shows the vertical displacements. On 14 November 2016, northeastern South Island of New Zealand was struck by a major moment magnitude (Mw) 7.8 earthquake. Field observations, in conjunction with interferometric synthetic aperture radar, Global Positioning System, and seismology data, reveal this to be one of the most complex earthquakes ever recorded. The rupture propagated northward for more than 170 kilometers along both mapped and unmapped faults before continuing offshore at the island's northeastern extent. Geodetic and field observations reveal surface ruptures along at least 12 major faults, including possible slip along the southern Hikurangi subduction interface; extensive uplift along much of the coastline; and widespread anelastic deformation, including the ~8-meter uplift of a fault-bounded block. This complex earthquake defies many conventional assumptions about the degree to which earthquake ruptures are controlled by fault segmentation and should motivate reevaluation of these issues in seismic hazard models.
The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall ...(making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
Patients who are critically ill frequently accrue substantial nutrition deficits due to multiple episodes of prolonged fasting prior to procedures. Existing literature suggests that, for most ...patients receiving tube feeding, the aspiration risk is low. Yet, national and international guidelines do not address fasting times for tube feeding, promoting uncertainty regarding optimal preprocedural fasting practice. We aimed to characterize current institutional fasting practices in the United States for patients with and without a secure airway, with variable types of enteral access, for representative surgical procedures.
The survey was distributed to a purposive sample of academic institutions in the United States. Reponses were reported as restrictive (6-8 h preprocedurally) or permissive (<6 h or continued intraprocedurally) feeding policies. Differences between level 1 trauma centers and others, and between burn centers and others, were evaluated.
The response rate was 40.3% (56 of 139 institutions). Responses revealed a wide variability with respect to current practices, with more permissive policies reported in patients with secure airways. In patients with a secure airway, Level 1 trauma centers were significantly more likely to have permissive fasting policies for patients undergoing an extremity incision and drainage for each type of feeding tube surveyed.
Current hospital policies for preprocedural fasting in patients receiving tube feeds are conflicting and are frequently more permissive than guidelines for healthy patients receiving oral nutrition. Prospective research is needed to establish the safety and clinical effects of various fasting practices in tube-fed patients.
The ability to modulate and enhance the anti-tumor immune responses is critical in developing novel therapies in cancer. The Tumor Necrosis Factor (TNF) Receptor Super Family (TNFRSF) are potentially ...excellent targets for modulation which result in specific anti-tumor immune responses. CD40 is a member of the TNFRSF and several clinical therapies are under development. CD40 signaling plays a pivotal role in regulating the immune system from B cell responses to myeloid cell driven activation of T cells. The CD40 signaling axis is well characterized and here we compare next generation HERA-Ligands to conventional monoclonal antibody based immune modulation for the treatment of cancer.
HERA-CD40L is a novel molecule that targets CD40 mediated signal transduction and demonstrates a clear mode of action in generating an activated receptor complex via recruitment of TRAFs, cIAP1, and HOIP, leading to TRAF2 phosphorylation and ultimately resulting in the enhanced activation of key inflammatory/survival pathway and transcription factors such asNFkB, AKT, p38, ERK1/2, JNK, and STAT1 in dendritic cells. Furthermore, HERA-CD40L demonstrated a strong modulation of the tumor microenvironment (TME) via the increase in intratumoral CD8+ T cells and the functional switch from pro-tumor macrophages (TAMs) to anti-tumor macrophages that together results in a significant reduction of tumor growth in a CT26 mouse model. Furthermore, radiotherapy which may have an immunosuppressive modulation of the TME, was shown to have an immunostimulatory effect in combination with HERA-CD40L. Radiotherapy in combination with HERA-CD40L treatment resulted in an increase in detected intratumoral CD4+/8+ T cells compared to RT alone and, additionally, the repolarization of TAMs was also observed, resulting in an inhibition of tumor growth in a TRAMP-C1 mouse model.
Taken together, HERA-CD40L resulted in activating signal transduction mechanisms in dendritic cells, resulting in an increase in intratumoral T cells and manipulation of the TME to be pro-inflammatory, repolarizing M2 macrophages to M1, enhancing tumor control.
Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing data from 2,511 individuals in the Pan-Cancer Analysis of ...Whole Genomes (PCAWG) study as well as 489 individuals from four prospective cohorts and found distinct regional mutation type-specific frequencies in tissue and cell-free DNA from patients with cancer that were associated with replication timing and other chromatin features. A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected >90% of patients with lung cancer, including those with stage I and II disease. The fixed model was validated in an independent cohort, detected patients with cancer earlier than standard approaches and could be used to monitor response to therapy. This approach lays the groundwork for non-invasive cancer detection using genome-wide mutation features that may facilitate cancer screening and monitoring.
Lower physical activity levels in old age are thought to contribute to the age‐related decline in peak aerobic and anaerobic power. Master athletes maintain high levels of physical activity with ...advancing age and endurance or power training may influence the extent to which these physical functions decline with advancing age. To investigate, 37‐90‐year‐old power (n = 20, 45% female) and endurance (n = 19, 58% female) master athletes were recruited. Maximal aerobic power was assessed when cycling two‐legged (VO2Peak2‐leg) and cycling one‐legged (VO2Peak1‐leg), while peak jumping (anaerobic) power was assessed by a countermovement jump. Men and women had a similar VO2Peak2‐leg (mL/kg/min, P = 0.138) and similar ratio of VO2Peak1‐leg to VO2Peak2‐leg (P = 0.959) and similar ratio of peak aerobic to anaerobic power (P = 0.261). The VO2Peak2‐leg (mL/kg/min) was 17% (P = 0.022) and the peak rate of fat oxidation (FATmax) during steady‐state cycling was 45% higher in endurance than power athletes (P = 0.001). The anaerobic power was 33% higher in power than endurance athletes (P = 0.022). The VO2Peak1‐leg:VO2Peak2‐leg ratio did not differ significantly between disciplines, but the aerobic to anaerobic power ratio was 40% higher in endurance than power athletes (P = 0.002). Anaerobic power, VO2Peak2‐leg, VO2Peak1‐leg, and power at FATmax decreased by around 7%‐14% per decade in male and female power and endurance athletes. The cross‐sectional data from 37‐90‐year‐old master athletes in the present study indicate that peak anaerobic and aerobic power decline by around 7%‐14% per decade and this does not differ between athletic disciplines or sexes.
The recent surge in obesity has provided an impetus to better understand the mechanisms of adipogenesis, particularly in brown adipose tissue (BAT) because of its potential utilization for ...antiobesity therapy. Postnatal brown adipocytes arise from early muscle progenitors, but how brown fat lineage is determined is not completely understood. Here, we show that a multifunctional protein, Ewing Sarcoma (EWS), is essential for determining brown fat lineage during development. BATs from Ews null embryos and newborns are developmentally arrested. Ews mutant brown preadipocytes fail to differentiate due to loss of Bmp7 expression, a critical early brown adipogenic factor. We demonstrate that EWS, along with its binding partner Y-box binding protein 1 (YBX1), activates Bmp7 transcription. Depletion of either Ews or Ybx1 leads to loss of Bmp7 expression and brown adipogenesis. Remarkably, Ews null BATs and brown preadipocytes ectopically express myogenic genes. These results demonstrate that EWS is essential for early brown fat lineage determination.
Display omitted
•Embryonic BAT development is arrested in Ews KO animals•Ews KO cells fail to undergo BAT differentiation due to loss of Bmp7 expression•EWS and YBX1 activate Bmp7 transcription and promote brown fat differentiation•Ews haploinsufficiency attenuates the formation of thermogenic brown fat cells
BMP7 drives brown fat specification and thus impacts thermogenesis and metabolic regulation. Park et al. identify a transcriptional regulatory complex of EWS and YBX1 that controls these events. Without EWS, mice fail to activate adipose BMP7 expression; both embryonic and adaptive thermogenic differentiation are disrupted.
Optogenetic switches are emerging molecular tools for studying cellular processes as they offer higher spatiotemporal and quantitative precision than classical, chemical-based switches. ...Light-controllable gene expression systems designed to upregulate protein expression levels meanwhile show performances superior to their chemical-based counterparts. However, systems to reduce protein levels with similar efficiency are lagging behind. Here, we present a novel two-component, blue light-responsive optogenetic OFF switch ('Blue-OFF'), which enables a rapid and quantitative down-regulation of a protein upon illumination. Blue-OFF combines the first light responsive repressor KRAB-EL222 with the protein degradation module B-LID (blue light-inducible degradation domain) to simultaneously control gene expression and protein stability with a single wavelength. Blue-OFF thus outperforms current optogenetic systems for controlling protein levels. The system is described by a mathematical model which aids in the choice of experimental conditions such as light intensity and illumination regime to obtain the desired outcome. This approach represents an advancement of dual-controlled optogenetic systems in which multiple photosensory modules operate synergistically. As exemplified here for the control of apoptosis in mammalian cell culture, the approach opens up novel perspectives in fundamental research and applications such as tissue engineering.
PDF
