In‐situ Bragg coherent X‐ray diffraction during tensile testing of an individual Au nanowire

Nanomechanical testing methods have drawn significant attention in both scientific and industrial research fields owing to unique deformation mechanisms in constrained volumes that underpin new property regimes. In-situ imaging equipment is now routinely employed to monitor the live evolution of material response during mechanical loading, with many of the testing developments tailored for electron microscopes (EMs). More recently, progress towards quantitative in-situ testing at synchrotron beamlines1–3 enabled by innovations in source brightness, focusing optics, and large size detectors has been made. Novel techniques such as Bragg coherent X-ray diffraction promise 3D information with phase information related to displacement fields (elastic strain, defects) within the material. However, despite the rich information that can be collected, many challenges arise in the realization of in-situ imaging of single nanostructures using such methods, including meticulous sample preparation and complex data analysis in retrieving phase information. In this work, we present the first successful systematic single nanowire tensile test while simultaneously recording 3D Bragg peaks using coherent X-rays. Defect free single crystalline \u3c110\u3e oriented Au nanowires were grown by physical vapor deposition4 and a 100 nm nanowire was harvested from the substrate and transferred to a nanotensile stage within a microelectromechanical system chip, which can be mounted to a coherent X-ray beamline. 3D Bragg peaks were recorded with nanofocused beam combined with 2D detector at each displacement step to discuss the evolution of strain and rotation of the nanowire during the tensile test. The movement of the peak sensitively depicted evolution of the deformation of the nanowire. In addition, the 3D Bragg coherent X-ray diffraction followed by phase retrieval has shown to reveal the internal strain state of nanostructure5 and this advanced technique is expected to reveal unique surface effects that mediate the overall mechanical performance of nano-scaled materials. 1. Cornelius, T. W. et al. In situ three-dimensional reciprocal-space mapping during mechanical deformation. J. Synchrotron Radiat. 19, 688–694 (2012). 2. Ren, Z. et al. Scanning force microscope for in situ nanofocused X-ray diffraction studies. J. Synchrotron Radiat. 21, 1128–1133 (2014). 3. Leclere, C. et al. In situ bending of an Au nanowire monitored by micro Laue diffraction. J. Appl. Crystallogr. 48, 291–296 (2015). 4. Richter, G. et al. Ultrahigh strength single crystalline nanowhiskers grown by physical vapor deposition. Nano Lett. 9, 3048–3052 (2009). 5. Haag, S. et al. Anomalous coherent diffraction of core-shell nano-objects: A methodology for determination of composition and strain fields. Phys. Rev. B 87, 35408 (2013)

TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes.

A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea

The impact of teach-back on comprehension of discharge instructions and satisfaction among emergency patients with limited health literacy: A randomized, controlled study

OBJECTIVE: Recommended as a ‘universal precaution’ for improving provider–patient communication, teach-back has a limited evidence base. Discharge from the emergency department (ED) to home is an important high-risk transition of care with potential for miscommunication of critical information. We examined whether teach-back improves: comprehension and perceived comprehension of discharge instructions and satisfaction among patients with limited health literacy (LHL) in the ED. METHODS: We performed a randomized, controlled study among adult patients with LHL, to teach-back or standard discharge instructions. Patients completed an audio-recorded structured interview evaluating comprehension and perceived comprehension of (1) diagnosis, (2) ED course, (3) post-ED care, and (4) reasons to return and satisfaction using four Consumer Assessment of Healthcare Providers and Systems questions. Concordance with the medical record was rated using a five-level scale. We analyzed differences between groups using multivariable ordinal logistic regression. RESULTS: Patients randomized to receive teach-back had higher comprehension of post-ED care areas: post-ED medication (P < 0.02), self-care (P < 0.03), and follow-up instructions (P < 0.0001), but no change in patient satisfaction or perceived comprehension. CONCLUSION: Teach-back appears to improve comprehension of post-ED care instructions but not satisfaction or perceived comprehension. Our data from a randomized, controlled study support the effectiveness of teach-back in a busy clinical setting. Further research is needed to test the utility and feasibility of teach-back for routine use including its impacts on distal outcomes

How the AIS can Improve its Contributions to the UN’s Sustainability Development Goals: Towards A Framework for Scaling Collaborations and Evaluating Impact

In June, 2019, the Association for Information Systems (AIS) adopted a new approach to addressing global sustainability issues by establishing the AIS Sustainability Task Force (AIS STF). This initiative focuses on building on the outcomes from the United Nations (UN) Millennium Development Goals (MDG, 2000-2015) and applying them to address the challenges associated with the UN Sustainable Development Goals (SDG, 2016-2030). In this paper, we review the challenges and outcomes from the UN sustainability programs with their potential relevance to IS in general and the AIS in particular to inform and assist increased efforts to achieve the global sustainability goals. The initial event, the AIS Sustainability Summit held at ICIS 2019, provided a forum for AIS groups and communities to share their current interests, plans, activities, and experiences relevant to the MDG and SDG. The event primarily focused on facilitating opportunities to scale the AIS’s sustainability activities through multi-disciplinary collaboration across the AIS and its communities. Members from four AIS special interest groups and the STF’s Education Workgroup presented exemplary projects at the summit that demonstrated how one can apply applied IS and research capabilities to address sustainability challenges. The sustainability summit’s also explored opportunities to achieve positive impact in addressing the SDG’s global challenges through applying AIS members’ knowledge, skills, and capabilities in relevant ways in collaboration with suitable organizations outside the AIS. Potential organizations include business, government, societal groups, and UN bodies. We presented and discussed the AIS STF’s aims, plans, outcomes, and impact. By analyzing details and options for cross-organizational collaboration, the representatives of organizations at the sustainability summit developed a proposed framework for scaling contributions and evaluating impact. Finally, they drew conclusions about the proposed activities, approaches, and framework for the AIS to improve the scope and scale of its contributions in addressing the SDG. Critically, the AIS needs to ensure that its proposed activities, contributions, and impact are examined by an internationally recognized independent process. We propose a model for the AIS to realize this requirement for evaluation in 2021

Indirect adjustment for multiple missing variables applicable to environmental epidemiology

AbstractObjectivesDevelop statistical methods for survival models to indirectly adjust hazard ratios of environmental exposures for missing risk factors.MethodsA partitioned regression approach for linear models is applied to time to event survival analyses of cohort study data. Information on the correlation between observed and missing risk factors is obtained from ancillary data sources such as national health surveys. The relationship between the missing risk factors and survival is obtained from previously published studies. We first evaluated the methodology using simulations, by considering the Weibull survival distribution for a proportional hazards regression model with varied baseline functions, correlations between an adjusted variable and an adjustment variable as well as selected censoring rates. Then we illustrate the method in a large, representative Canadian cohort of the association between concentrations of ambient fine particulate matter and mortality from ischemic heart disease.ResultsIndirect adjustment for cigarette smoking habits and obesity increased the fine particulate matter-ischemic heart disease association by 3%–123%, depending on the number of variables considered in the adjustment model due to the negative correlation between these two risk factors and ambient air pollution concentrations in Canada. The simulations suggested that the method yielded small relative bias (<40%) for most cohort designs encountered in environmental epidemiology.ConclusionsThis method can accommodate adjustment for multiple missing risk factors simultaneously while accounting for the associations between observed and missing risk factors and between missing risk factors and health endpoints

KMT-2018-BLG-1292: A Super-Jovian Microlens Planet in the Galactic Plane

We report the discovery of KMT-2018-BLG-1292Lb, a super-Jovian $M_{\rm planet} = 4.5\pm 1.3\,M_J$ planet orbiting an F or G dwarf $M_{\rm host} = 1.5\pm 0.4\,M_\odot$, which lies physically within {\cal O}(10\,\pc) of the Galactic plane. The source star is a heavily extincted $A_I\sim 5.2$ luminous giant that has the lowest Galactic latitude, $b=-0.28^\circ$, of any planetary microlensing event. The relatively blue blended light is almost certainly either the host or its binary companion, with the first explanation being substantially more likely. This blend dominates the light at $I$ band and completely dominates at $R$ and $V$ bands. Hence, the lens system can be probed by follow-up observations immediately, i.e., long before the lens system and the source separate due to their relative proper motion. The system is well characterized despite the low cadence $\Gamma=0.15$--$0.20\,{\rm hr^{-1}}$ of observations and short viewing windows near the end of the bulge season. This suggests that optical microlensing planet searches can be extended to the Galactic plane at relatively modest cost.Comment: 35 pages, 3 Tables, 8 figure

Caspase-11 Activation in Response to Bacterial Secretion Systems That Access the Host Cytosol

Inflammasome activation is important for antimicrobial defense because it induces cell death and regulates the secretion of IL-1 family cytokines, which play a critical role in inflammatory responses. The inflammasome activates caspase-1 to process and secrete IL-1β. However, the mechanisms governing IL-1α release are less clear. Recently, a non-canonical inflammasome was described that activates caspase-11 and mediates pyroptosis and release of IL-1α and IL-1β. Caspase-11 activation in response to Gram-negative bacteria requires Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor-inducing interferon-β (TRIF)-dependent interferon production. Whether additional bacterial signals trigger caspase-11 activation is unknown. Many bacterial pathogens use specialized secretion systems to translocate effector proteins into the cytosol of host cells. These secretion systems can also deliver flagellin into the cytosol, which triggers caspase-1 activation and pyroptosis. However, even in the absence of flagellin, these secretion systems induce inflammasome activation and the release of IL-1α and IL-1β, but the inflammasome pathways that mediate this response are unclear. We observe rapid IL-1α and IL-1β release and cell death in response to the type IV or type III secretion systems of Legionella pneumophila and Yersinia pseudotuberculosis. Unlike IL-1β, IL-1α secretion does not require caspase-1. Instead, caspase-11 activation is required for both IL-1α secretion and cell death in response to the activity of these secretion systems. Interestingly, whereas caspase-11 promotes IL-1β release in response to the type IV secretion system through the NLRP3/ASC inflammasome, caspase-11-dependent release of IL-1α is independent of both the NAIP5/NLRC4 and NLRP3/ASC inflammasomes as well as TRIF and type I interferon signaling. Furthermore, we find both overlapping and non-redundant roles for IL-1α and IL-1β in mediating neutrophil recruitment and bacterial clearance in response to pulmonary infection by L. pneumophila. Our findings demonstrate that virulent, but not avirulent, bacteria trigger a rapid caspase-11-dependent innate immune response important for host defense

Interaction between Liprin-α and GIT1 Is Required for AMPA Receptor Targeting

Liprin-alpha is a multidomain protein that interacts with the LAR family of receptor protein tyrosine phosphatases and the GRIP/ABP family of AMPA receptor-interacting proteins. Previous studies have indicated that liprin-alpha regulates the development of presynaptic active zones and that the association of liprin-alpha with GRIP is required for postsynaptic targeting of AMPA receptors. However, the underlying molecular mechanisms are not well understood. Here we report that liprin-alpha directly interacts with GIT1, a multidomain protein with GTPase-activating protein activity for the ADP-ribosylation factor family of small GTPases known to regulate protein trafficking and the actin cytoskeleton. Electron microscopic analysis indicates that GIT1 distributes to the region of postsynaptic density (PSD) as well as presynaptic active zones. GIT1 is enriched in PSD fractions and forms a complex with liprin-alpha, GRIP, and AMPA receptors in brain. Expression of dominant-negative constructs interfering with the GIT1-liprin-alpha interaction leads to a selective and marked reduction in the dendritic and surface clustering of AMPA receptors in cultured neurons. These results suggest that the GIT1-liprin-alpha interaction is required for AMPA receptor targeting and that GIT1 may play an important role in the organization of presynaptic and postsynaptic multiprotein complexes