In the east Pacific (EP) intertropical convergence zone (ITCZ), Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) latent heating retrievals suggest a top-heavy structure; however, ...light precipitation and its associated low-level heating are underestimated by the PR. This study uses stratiform and deep convective precipitation from the TRMM PR and shallow precipitation from the more sensitive CloudSat radar to assess the seasonal latent heating structure in the EP ITCZ (1308–908W) for 1998–2014. This study also uses reanalyses (MERRA-2, ERA-Interim, and NCEP–NCAR) to analyze the meridional circulation linked to variations in ITCZ heating. The TRMM/CloudSat heating profiles suggest a distinct seasonality. During DJF, latent heating peaks at 800 hPa because of the predominance of shallow convection and rises to 700 hPa during MAM as the contribution from deep convective rain increases. During JJA and SON, stratiform precipitation increases and the latent heating has a double peak at 700 and 400 hPa. Additionally, the EP ITCZ heating has a meridional slope throughout most of the year as a result of the prevalence of shallow (deep) convection in the southern (northern) part of the ITCZ. While the reanalyses agree that the most bottom-heavy heating occurs in DJF and the most top-heavy heating occurs in JJA, they underestimate heating aloft compared to the satellite retrievals throughout the year and show varying ability in representing the shallow meridional circulation and deeper Hadley cell overturning.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Leg morphology is an important outcome of evolution. A remarkable morphological leg feature is the existence of biarticular muscles that span adjacent joints. Diverse studies from different fields of ...research suggest a less coherent understanding of the muscles' functionality in cyclic, sagittal plane locomotion. We structured this review of biarticular muscle function by reflecting biomechanical template models, human experiments and robotic system designs. Within these approaches, we surveyed the contribution of biarticular muscles to the locomotor subfunctions (
,
and
). While mono- and biarticular muscles do not show physiological differences, the reviewed studies provide evidence for complementary and locomotor subfunction-specific contributions of mono- and biarticular muscles. In
, biarticular muscles coordinate joint movements, improve economy (e.g. by transferring energy) and secure the zig-zag configuration of the leg against joint overextension. These commonly known functions are extended by an explicit role of biarticular muscles in controlling the angular momentum for
and
. Human-like leg arrangement and intrinsic (compliant) properties of biarticular structures improve the controllability and energy efficiency of legged robots and assistive devices. Future interdisciplinary research on biarticular muscles should address their role for sensing and control as well as non-cyclic and/or non-sagittal motions, and non-static moment arms.
Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT ...HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy.
Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T + P ± weekly paclitaxel (pac) at 80 mg/m2. Early response was defined as proliferation decrease ≥30% of Ki-67 (versus baseline) or low cellularity (<500 invasive tumor cells) in the 3-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T + P arm versus all chemotherapy-treated patients.
From February 2014 to December 2015, 160 patients were screened, 92 were randomized to T + P and 42 to T + P+pac. Baseline characteristics were well balanced (median age 54 versus 51.5 years, cT2 51.1 versus 52.4%, cN0 54.3 versus 61.9%); 91.3% of patients completed T + P per protocol and 92.9% T + P+pac. The pCR rate in the T + P+pac arm was 90.5%, compared with 36.3% in the T + P arm as a whole. In the T + P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared with 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92). No new safety signals were observed in the study population.
Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared with dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Observations and Modeling of the Green Ocean Amazon (GoAmazon2014/5) Experiment was carried out in the environs of Manaus, Brazil, in the central region of the Amazon basin for 2 years from ...1 January 2014 through 31 December 2015. The experiment focused on the complex interactions among vegetation, atmospheric chemistry, and aerosol production on the one hand and their connections to aerosols, clouds, and precipitation on the other. The objective was to understand and quantify these linked processes, first under natural conditions to obtain a baseline and second when altered by the effects of human activities. To this end, the pollution plume from the Manaus metropolis, superimposed on the background conditions of the central Amazon basin, served as a natural laboratory. The present paper, as the introduction to the special issue of GoAmazon2014/5, presents the context and motivation of the GoAmazon2014/5 Experiment. The nine research sites, including the characteristics and instrumentation of each site, are presented. The sites range from time point zero (T0) upwind of the pollution, to T1 in the midst of the pollution, to T2 just downwind of the pollution, to T3 furthest downwind of the pollution (70 km). In addition to the ground sites, a low-altitude G-159 Gulfstream I (G-1) observed the atmospheric boundary layer and low clouds, and a high-altitude Gulfstream G550 (HALO) operated in the free troposphere. During the 2-year experiment, two Intensive Operating Periods (IOP1 and IOP2) also took place that included additional specialized research instrumentation at the ground sites as well as flights of the two aircraft. GoAmazon2014/5 IOP1 was carried out from 1 February to 31 March 2014 in the wet season. GoAmazon2014/5 IOP2 was conducted from 15 August to 15 October 2014 in the dry season. The G-1 aircraft flew during both IOP1 and IOP2, and the HALO aircraft flew during IOP2. In the context of the Amazon basin, the two IOPs also correspond to the clean and biomass burning seasons, respectively. The Manaus plume is present year-round, and it is transported by prevailing northeasterly and easterly winds in the wet and dry seasons, respectively. This introduction also organizes information relevant to many papers in the special issue. Information is provided on the vehicle fleet, power plants, and industrial activities of Manaus. The mesoscale and synoptic meteorologies relevant to the two IOPs are presented. Regional and long-range transport of emissions during the two IOPs is discussed based on satellite observations across South America and Africa. Fire locations throughout the airshed are detailed. In conjunction with the context and motivation of GoAmazon2014/5 as presented in this introduction, research articles including thematic overview articles are anticipated in this special issue to describe the detailed results and findings of the GoAmazon2014/5 Experiment.
Buildings can be effectively cooled by a bioinspired sweating‐like action based on thermoresponsive hydrogels (PNIPAM), which press out their stored water when exceeding the lower critical solution ...temperature. The surface temperature is reduced by 15 °C compared to that of a conventional hydrogel (pHEMA) and by 25 °C compared to the bare ground.
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Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and ...greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.
Isotopic fractionation of cationic species during diffusive transport provides a novel means of constraining the style and timing of metamorphic transformations. Here we document a major (1ppt) ...decrease in the Mg isotopic composition of the reaction front of an exhumed contact between rocks of subducted crust and serpentinite in the Syros melange zone. This isotopic perturbation extends over a notable length scale (1 m), implicating diffusion of Mg through an intergranular fluid network over a period of 100 kyr. These novel observations confirm models of diffusion-controlled growth of reaction zones formed between rocks of contrasting compositions, such as found at the slab-mantle interface in subduction zones. The results also demonstrate that diffusive processes can result in exotic stable isotope compositions of major elements with implications for mantle xenoliths and complex intrusions.
Constraining conditions and mechanisms of the early stages of exhumation from within subduction zones is challenging. Although pressure, temperature, and age can be inferred from the exhumed rock ...record, it is generally difficult to derive each of these parameters from any single rock, thus demanding assumptions that diverse data from multiple samples can be safely combined into a single pressure‐temperature‐time (P‐T‐t) path that might then be used to infer tectonic context and mechanisms of exhumation. Here, we present new thermobarometric and geochronologic information preserved in a single sample from Syros, Greece, to deduce the conditions and rates of the earliest phase of exhumation as a part of the well‐preserved high‐pressure metamorphic rocks of the Cycladic Blueschist Unit (CBU). The sample studied here is a garnet‐bearing, quartz‐mica schist that records two distinct metamorphic events. Results from thermodynamic models and quartz‐in‐garnet elastic geobarometry show that metamorphic garnet cores formed as P‐T conditions evolved from ∼485°C and 2.2 GPa to 530°C and 2.0 GPa, and that garnet rims formed as conditions evolved from ∼560°C and 2.1 GPa to ∼550°C and 1.6 GPa. Sm‐Nd geochronology on garnet cores and rims yields ages of 45.3 ± 1.0 and 40.5 ± 1.9 Ma, respectively, thus indicating a 4.8 ± 2.1 Myr growth span. Given the decompression path calculated based on garnet core and rim P‐T estimates, we conclude that the distinct phases of garnet growth preserve evidence of the initial exhumation of portions of the CBU.
Plain Language Summary
Constraining the evolution of rocks formed at great depths (>60 km) and their subsequent returned to Earth's surface is a challenging endeavor, because information regarding the pressure, temperature, and timing of formation is typically elucidated through the study of multiple samples and thus through the comparison of different datasets. Here, we present pressure, temperature, and age data that were derived by analyzing garnet crystals within a single sample from a well‐known paleo‐subduction zone locate in Syros, Greece. Our results show that the sample records two metamorphic events that occurred as a result of initial ascent to the surface from depths of ∼66 to 48 km.
Key Points
Metamorphic garnets record two stages of growth during HP/LT metamorphism and exhumation of the Cycladic Blueschist Unit (CBU) on Syros, Greece
Garnet growth spanned 4.8 ± 2.1 Myr including decompression from 2.1 to 1.6 GPa
Garnets in this sample record a part of the CBU that was exhumed as a series of tectonic slices on Syros
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Hepatic stellate cells (HSC), which can participate in liver regeneration and fibrogenesis, have recently been identified as liver-resident mesenchymal stem cells. During their activation HSC adopt a ...myofibroblast-like phenotype accompanied by profound changes in the gene expression profile. DNA methylation changes at single genes have been reported during HSC activation and may participate in the regulation of this process, but comprehensive DNA methylation analyses are still missing. The aim of the present study was to elucidate the role of DNA methylation during in vitro activation of HSC.
The analysis of DNA methylation changes by antibody-based assays revealed a strong decrease in the global DNA methylation level during culture-induced activation of HSC. To identify genes which may be regulated by DNA methylation, we performed a genome-wide Methyl-MiniSeq EpiQuest sequencing comparing quiescent and early culture-activated HSC. Approximately 400 differentially methylated regions with a methylation change of at least 20% were identified, showing either hypo- or hypermethylation during activation. Further analysis of selected genes for DNA methylation and expression were performed revealing a good correlation between DNA methylation changes and gene expression. Furthermore, global DNA demethylation during HSC activation was investigated by 5-bromo-2-deoxyuridine assay and L-mimosine treatment showing that demethylation was independent of DNA synthesis and thereby excluding a passive DNA demethylation mechanism.
In summary, in vitro activation of HSC initiated strong DNA methylation changes, which were associated with gene regulation. These results indicate that epigenetic mechanisms are important for the control of early HSC activation. Furthermore, the data show that global DNA demethylation during activation is based on an active DNA demethylation mechanism.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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