Real-time observation of dynamic structure of liquid-vapor interface at nanometer resolution in electron irradiated sodium chloride crystals.

The dynamics and structure of the liquid and vapor interface has remained elusive for decades due to the lack of an effective tool for directly visualization beyond micrometer resolution. Here, we designed a simple liquid-cell for encapsulating the liquid state of sodium for transmission electron microscopic (TEM) observation. The real-time dynamic structure of the liquid-vapor interface was imaged and videoed by TEM on the sample of electron irradiated sodium chloride (NaCl) crystals, a well-studied sample with low melting temperature and quantum super-shells of clusters. The nanometer resolution images exhibit the fine structures of the capillary waves, composed of first-time observed three zones of structures and features, i.e. flexible nanoscale fibers, nanoparticles/clusters, and a low-pressure area that sucks the nanoparticles from the liquid to the interface. Although the phenomenons were observed based on irradiated NaCl crystals, the similarities of the phenomenons to predictions suggest our real-time ovserved  dynamic structure might be useful in validating long-debated theoretical models of the liquid-vapor interface, and enhancing our knowledge in understanding the non-equilibrium thermodynamics of the liquid-vapor interface to benefit future engineering designs in microfluidics

"Taking Care of a Fruit Tree": Nurturing as a Layer of Concern in Online Community Moderation

Care in communities has a powerful influence on potentially disruptive social encounters. Practising care in moderation means exposing a group's core values, which, in turn, has the potential to strengthen identity and relationships in communities. Dissent is as inevitable in online communities as it is in their offline counterparts. However, dissent can be productive by sparking discussions that drive the evolution of community norms and boundaries, and there is value in understanding the role of moderation in this process. Our work draws on an exploratory analysis of moderation practices in the MetaFilter community, focusing on cases of intervention and response. We identify and analyse MetaFilter moderation with the metaphor: ``taking care of a fruit tree'', which is quoted from an interview with moderators on MetaFilter. We address the relevance of care as it is evidenced in these MetaFilter exchanges, and discuss what it might mean to approach an analysis of online moderation practices with a focus on nurturing care. We consider how HCI researchers might make use of care-as-nurture as a frame to identify multi-faceted and nuanced concepts characterising dissent and to develop tools for the sustainable support of online communities and their moderators

Integrating Herbivore Population Dynamics Into a Global Land Biosphere Model: Plugging Animals Into the Earth System

Mammalian herbivores are an essential component of grassland and savanna ecosystems, and with feedbacks to the climate system. To date, the response and feedbacks of mammalian herbivores to changes in both abiotic and biotic factors are poorly quantified and not adequately represented in the current global land surface modeling framework. In this study, we coupled herbivore population dynamics in a global land model (the Dynamic Land Ecosystem Model, DLEM 3.0) to simulate populations of horses, cattle, sheep, and goats, and their responses to changes in multiple environmental factors at the site level across different continents during 1980–2010. Simulated results show that the model is capable of reproducing observed herbivore population dynamics across all sites for these animal groups. Our simulation results also indicate that during this period, climate extremes led to a maximum mortality of 27% of the total herbivores in Mongolia. Across all sites, herbivores reduced aboveground net primary productivity (ANPP) and heterotrophic respiration (Rh) by 14% and 15%, respectively (p \u3c 0.05). With adequate parameterization, the model can be used for historical assessment and future prediction of mammalian herbivore populations and their relevant impacts on biogeochemical cycles. Our simulation results demonstrate a strong coupling between primary producers and consumers, indicating that inclusion of herbivores into the global land modeling framework is essential to better understand the potentially large effect of herbivores on carbon cycles in grassland and savanna ecosystems

Chemometrics-assisted identification of anti-inflammatory compounds from the green alga klebsormidium flaccidum var. Zivo

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). The green alga Klebsormidium flaccidum var. zivo is a rich source of proteins, polyphenols, and bioactive small-molecule compounds. An approach involving chromatographic fractionation, anti-inflammatory activity testing, ultrahigh performance liquid chromatography-mass spectrometry profiling, chemometric analysis, and subsequent MS-oriented isolation was employed to rapidly identify its small-molecule anti-inflammatory compounds including hydroxylated fatty acids, chlorophyll-derived pheophorbides, carotenoids, and glycoglycerolipids. Pheophorbide a, which decreased intracellular nitric oxide production by inhibiting inducible nitric oxide synthase, was the most potent compound identified with an IC50 value of 0.24 µM in lipopolysaccharides-induced macrophages. It also inhibited nuclear factor kappaB activation with an IC50 value of 32.1 µM in phorbol 12-myristate 13-acetate-induced chondrocytes. Compared to conventional bioassay-guided fractionation, this approach is more efficient for rapid identification of multiple chemical classes of bioactive compounds from a complex natural product mixture

WHONDRS-GUI: a web application for global survey of surface water metabolites

Background The Worldwide Hydrobiogeochemistry Observation Network for Dynamic River Systems (WHONDRS) is a consortium that aims to understand complex hydrologic, biogeochemical, and microbial connections within river corridors experiencing perturbations such as dam operations, floods, and droughts. For one ongoing WHONDRS sampling campaign, surface water metabolite and microbiome samples are collected through a global survey to generate knowledge across diverse river corridors. Metabolomics analysis and a suite of geochemical analyses have been performed for collected samples through the Environmental Molecular Sciences Laboratory (EMSL). The obtained knowledge and data package inform mechanistic and data-driven models to enhance predictions of outcomes of hydrologic perturbations and watershed function, one of the most critical components in model-data integration. To support efforts of the multi-domain integration and make the ever-growing data package more accessible for researchers across the world, a Shiny/R Graphical User Interface (GUI) called WHONDRS-GUI was created. Results The web application can be run on any modern web browser without any programming or operational system requirements, thus providing an open, well-structured, discoverable dataset for WHONDRS. Together with a context-aware dynamic user interface, the WHONDRS-GUI has functionality for searching, compiling, integrating, visualizing and exporting different data types that can easily be used by the community. The web application and data package are available at https://data.ess-dive.lbl.gov/view/doi:10.15485/1484811, which enables users to simultaneously obtain access to the data and code and to subsequently run the web app locally. The WHONDRS-GUI is also available for online use at Shiny Server (https://xmlin.shinyapps.io/whondrs/)

Phase I clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibtion

<p>Abstract</p> <p>Background</p> <p>Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal antibody responses against HER2 that demonstrate enhanced anti-tumor activity when combined with lapatinib in murine models. We wished to test the clinical safety, immunogenicity, and activity of a HER2-based cancer vaccine, when combined with lapatinib.</p> <p>Methods</p> <p>We immunized women (n = 12) with metastatic, trastuzumab-refractory, HER2-overexpressing breast cancer with dHER2, a recombinant protein consisting of extracellular domain (ECD) and a portion of the intracellular domain (ICD) of HER2 combined with the adjuvant AS15, containing MPL, QS21, CpG and liposome. Lapatinib (1250 mg/day) was administered concurrently. Peripheral blood antibody and T cell responses were measured.</p> <p>Results</p> <p>This regimen was well tolerated, with no cardiotoxicity. Anti-HER2-specific antibody was induced in all patients whereas HER2-specific T cells were detected in one patient. Preliminary analyses of patient serum demonstrated downstream signaling inhibition in HER2 expressing tumor cells. The median time to progression was 55 days, with the majority of patients progressing prior to induction of peak anti-HER2 immune responses; however, 300-day overall survival was 92% (95% CI: 77-100%).</p> <p>Conclusions</p> <p>dHER2 combined with lapatinib was safe and immunogenic with promising long term survival in those with HER2-overexpressing breast cancers refractory to trastuzumab. Further studies to define the anticancer activity of the antibodies induced by HER2 vaccines along with lapatinib are underway.</p> <p>Trial registry</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00952692">NCT00952692</a></p

Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency-induced bone loss

While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-function mutant CaV1.2 to stem bone loss in ovariectomized female mice. We show that endogenous CaV1.2 is expressed in developing bone within proliferating chondrocytes and osteoblasts. Using primary BM stromal cell (BMSC) cultures, we found that Ca2+ influx through CaV1.2 activates osteogenic transcriptional programs and promotes mineralization. We used Prx1-, Col2a1-, or Col1a1-Cre drivers to express an inactivation-deficient CaV1.2 mutant in chondrogenic and/or osteogenic precursors in vivo and found that the resulting increased Ca2+ influx markedly thickened bone not only by promoting osteogenesis, but also by inhibiting osteoclast activity through increased osteoprotegerin secretion from osteoblasts. Activating the CaV1.2 mutant in osteoblasts at the time of ovariectomy stemmed bone loss. Together, these data highlight roles for CaV1.2 in bone and demonstrate the potential dual anabolic and anticatabolic therapeutic actions of tissue-specific CaV1.2 activation in osteoblasts

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint