NASICON materials - a long neglected class of solid electrolytes

The so-called NASICON materials AT2P3O12 (A = alkaline metal, T = tetravalent transition metal) are known since the 1970s [1] and are derived from the first “Na+ super-ionic conductor”, Na3Zr2Si2PO12, of this group of materials. The aims of current investigations are on the one hand the better understanding of the ionic conduction and on the other hand the search for new materials with very high ionic conductivity. For this purpose, new and simple synthesis methods have been developed, which deliver very homogeneous powders with reduced temperatures for the preparation of ceramics. In this way a lithium ion conductor with the composition Li1.5Al0.5Ti1.5P3O12 was manufactured. After sintering to highly dense ceramics a total conductivity of 0.7 mS/cm was achieved at room temperature [2] and therefore this material belongs to the best known solid oxidic Li+ ion conductors. NMR and impedance spectroscopy investigations [3-5] have shown that the bulk conductivity amounts to 3-5 mS/cm and that the grain boundaries determine the quality of the material. In the case of Na+ ion conductors, the prototype Na3Zr2Si2PO12 was newly synthesized and gave a previously not achieved conductivity of 1 mS/cm [6]. The modification of the composition by substitution with scandium delivered conductivities of 0.8 mS/cm (Na3.4Sc2Si0.4P2.6O12) [7] and 4 mS/cm (Na3.4Zr1.6Sc0.4Si2PO12) [8]. The latter composition possesses one of the highest known Na+ ion conductivities of oxide ceramics and reaches the conductivity of liquid electrolytes. The mentioned compositions confirm the empirical criteria which are necessary for achieving high ionic conductivities in NASICON materials [9]. References: [1] H. Y. P. Hong, Mater. Res. Bull. 11 (1976) 173-182; H. Y. P. Hong, J. B. Goodenough, J. A. Kafalas, Mater. Res. Bull. 11 (1976) 203-220 [2] Q. Ma, Q. Xu, C.-L. Tsai, F. Tietz, O. Guillon, J. Am. Ceram. Soc., (2016), in press [3] V. Epp, Q. Ma, F. Tietz, M. Wilkening, Phys. Chem. Chem. Phys., 17 (2015) 32115-32121 [4] S. Breuer, D. Prutsch, V. Epp, Q. Ma, F. Preishuber-Pflügl, F. Tietz, M. Wilkening, J. Mater. Chem. A, 3 (2015) 21343-21350 [5] D. Rettenwander, A. Welzl, S. Pristat, F. Tietz, S. Taibl, G. J. Redhammer, J. Fleig, J. Chem. Mater. A, 4 (2016) 1506-1513 [6] S. Naqash, Q. Ma, Tietz, O. Guillon, in preparation [7] M. Guin, F. Tietz, O. Guillon, in preparation [8] Q. Ma, M. Guin, S. Naqash, C.-L. Tsai, F. Tietz, O. Guillon, in preparation [9] M. Guin, F. Tietz, J. Power Sources, 273 (2015) 1056-106

Discovery and characterization of small molecules that target the Ral GTPase

The Ras-like GTPases RalA and B are important drivers of tumor growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here, we used protein structure analysis and virtual screening to identify drug-like molecules that bind a site on the GDP-form of Ral. Compounds RBC6, RBC8 and RBC10 inhibited Ral binding to its effector RalBP1, Ral-mediated cell spreading in murine fibroblasts and anchorage-independent growth of human cancer cell lines. Binding of RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasma resonance and 15N-HSQC NMR. RBC8 and BQU57 show selectivity for Ral relative to Ras or Rho and inhibit xenograft tumor growth similar to depletion of Ral by siRNA. Our results show the utility of structure-based discovery for development of therapeutics for Ral-dependent cancers

Regional Emission Analysis Using Travel Demand Models and MOVES-Matrix

DTRT13-G-UTC29Citation: Xiaodan Xu, Haobing Liu, Yanzhi \u201cAnn\u201d Xu, Michael O. Rodgers, and Randall L. Guensler (2018) Regional Emission Analysis using Travel Demand Models and MOVES-Matrix, 97th Annual Meeting of the Transportation Research Board, Washington, D.C., January 7-11, 2018.Travel demand models (TDM) are developed by Metropolitan Planning Organizations (MPOs) for analyzing regional travel patterns but are often used to prepare activity inputs for use with the U.S. Environmental Protection Agency\u2019s (EPA) MOtor Vehicle Emission Simulator (MOVES) emissions model for air quality conformity analysis. This latter application requires modelers to either prepare multiple MOVES runs for various scenarios, or to develop their own pre- and post-processors for emission modeling. Both approaches involve a cumbersome and time consuming process

Inventory of the chemicals and the exposure of the workers’ skin to these at two leather factories in Indonesia

PURPOSE: Tannery workers are exposed to hazardous chemicals. Tannery work is outsourced to newly industrialized countries (NICs) where attention into occupational health hazards is limited. In this study, we investigated the skin exposure to hazardous chemicals in tannery workers and determined the prevalence of occupational skin diseases (OSDs) at tanneries in a NIC. METHODS: A cross-sectional study on the observation of the working process and an inventory and risk assessment of the chemicals used. Classification of chemicals as potential sensitizers/irritants and a qualitative assessment of exposure to these chemicals. Workers were examined and interviewed using Nordic Occupational Skin Questionnaire-2002/LONG. RESULTS: The risk of OSDs at the investigated tanneries was mainly related to the exposure of the workers' skin to chemicals in hot and humid environmental conditions. In 472 workers, 12% reported a current OSD and 9% reported a history of OSD. In 10% of all cases, an OSD was confirmed by a dermatologist and 7.4% had an occupational contact dermatitis (OCD). We observed that personal protective equipment (PPE) used was mainly because of skin problems in the past and not as a primary protection against OSD. CONCLUSION: We observed a high frequency and prolonged exposure to many skin hazardous factors in tannery work although PPE was relatively easily available and which was generally used as a secondary preventative measure. The observed point-prevalence in this study was at the same level as that reported for other high-risk OSDs in Western countries and other tanneries in NICs. However, the observed point-prevalence in this study was lower than that reported in India and Korea. The results of our study and those of other studies at tanneries from other NICs were probably influenced by Healthy Worker Survivor Effect (HWSE)

Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for vascular protection in chronic systemic inflammation

Aims Premature cardiovascular events complicate chronic inflammatory conditions. Low-dose weekly methotrexate (MTX), the most widely used disease-modifying drug for rheumatoid arthritis (RA), reduces disease-associated cardiovascular mortality. MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK). We hypothesised that MTX specifically protects the vascular endothelium against inflammatory injury via induction of AMPK-regulated protective genes. Methods/results In the (NZW×BXSB)F1 murine model of inflammatory vasculopathy, MTX 1 mg/kg/week significantly reduced intramyocardial vasculopathy and attenuated end-organ damage. Studies of human umbilical vein endothelial cells (HUVEC) and arterial endothelial cells (HAEC) showed that therapeutically relevant concentrations of MTX phosphorylate AMPKαThr172, and induce cytoprotective genes including manganese superoxide dismutase (MnSOD) and haem oxygenase-1 (HO-1). These responses were preserved when HUVECs were pretreated with tumour necrosis factor-α to mimic dysfunctional endothelium. Furthermore, MTX protected against glucose deprivation-induced endothelial apoptosis. Mechanistically, MTX treatment led to cyclic AMP response element-binding protein (CREB)Ser133 phosphorylation, while AMPK depletion attenuated this response and the induction of MnSOD and HO-1. CREB siRNA inhibited upregulation of both cytoprotective genes by MTX, while chromatin immunoprecipitation demonstrated CREB binding to the MnSOD promoter in MTX-treated EC. Likewise, treatment of (NZW×BXSB)F1 mice with MTX enhanced AMPKαThr172 phosphorylation and MnSOD, and reduced aortic intercellular adhesion molecule-1 expression. Conclusions These data suggest that MTX therapeutically conditions vascular endothelium via activation of AMPK-CREB. We propose that this mechanism contributes to the protection against cardiovascular events seen in patients with RA treated with MTX

The pursuit of happiness: the social and scientific origins of Hans Selye’s natural philosophy of life

© The Author(s) 2012. Open access article.In 1956, Hans Selye tentatively suggested that the scientific study of stress could ‘help us to formulate a precise program of conduct’ and ‘teach us the wisdom to live a rich and meaningful life’. Nearly two decades later, Selye expanded this limited vision of social order into a full-blown philosophy of life. In Stress without Distress, first published in 1974, he proposed an ethical code of conduct designed to mitigate personal and social problems. Basing his arguments on contemporary understandings of the biological processes involved in stress reactions, Selye referred to this code as ‘altruistic egotism’. This article explores the origins and evolution of Selye’s ‘natural philosophy of life’, analysing the links between his theories and adjacent intellectual developments in biology, psychosomatic and psychosocial medicine, cybernetics and socio-biology, and situating his work in the broader cultural framework of modern western societies.Wellcome Trus

Understanding the Emission Impacts of High-Occupancy Vehicle (HOV) to High-Occupancy Toll (Hot) Lane Conversions: Experience From Atlanta, Georgia

DTRT13-G-UTC29Open Access Select Journal: Yanzhi (Ann) Xu, Haobing Liu, Michael O. Rodgers, Angshuman Guin,Michael Hunter, Adnan Sheikh & Randall Guensler (2017) Understanding the emission impactsof high-occupancy vehicle (HOV) to high-occupancy toll (HOT) lane conversions: Experiencefrom Atlanta, Georgia, Journal of the Air & Waste Management Association, 67:8, 910-922, DOI: https://doi.org/10.1080/10962247.2017.1302518Converting a congested high-occupancy vehicle (HOV) lane into a high-occupancy toll (HOT) lane is a viable option for improving travel time reliability for carpools and buses that use the managed lane. However, the emission impacts of HOV-to-HOT conversions are not well understood. The lack of emission impact quantification for HOT conversions creates a policy challenge for agencies making transportation funding choices. The goal of this paper is to evaluate the case study of before-and-after changes in vehicle emissions for the Atlanta, Georgia, I-85 HOV/HOT lane conversion project, implemented in October 2011

Multicenter external validation of the liverpool uveal melanoma prognosticator online: An OOG collaborative study

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3’s performance using discrimination and calibration methods. LUMPO3’s ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers

Recent advances in organic synthesis using light-mediated n-heterocyclic carbene catalysis

The combination of photocatalysis with other ground state catalytic systems have attracted much attention recently due to the enormous synthetic potential offered by a dual activation mode. The use of N-heterocyclic carbene (NHC) as organocatalysts emerged as an important synthetic tool. Its ability to harness umpolung reactivity by the formation of the Breslow intermediate has been employed in the synthesis of thousands of biologically important compounds. However, the available coupling partners are relatively restricted, and its combination with other catalytic systems might improve its synthetic versatility. Thus, merging photoredox and N-heterocyclic carbene (NHC) catalysis has emerged recently as a powerful strategy to develop new transformations and give access to a whole new branch of synthetic possibilities. This review compiles the NHC catalyzed methods mediated by light, either in the presence or absence of an external photocatalyst, that have been described so far, and aims to give an accurate overview of the potential of this activation modeL.M. acknowledges the Autonomous Community of Madrid (CAM) for the financial support (PEJD-2019-PRE/AMB-16640 and SI1/PJI/ 2019-00237) and for an “Atracción de Talento Investigador” contract (2017-T2/AMB-5037