Mabel Engineering Flights, 2010-2013: Flight Report

In December 2010, NASA deployed for the first time the Multiple Altimeter Beam Experimental Lidar (MABEL), an airborne simulator for Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) algorithm development. Between 2010 and 2013, engineering flights were conducted in the continental United States, to ready the instrument for deployments to Alaska and Iceland, where flight lines could be designed and flown over sea ice and grounded ice. Ultimately, MABEL engineering missions included: 1) flights based out of NASA Armstrong Flight Research Center (California, formerly Dryden Flight Research Center) in 2010, 2011, and 2012; flights based out of NASA Wallops Flight Facility (Virginia) in 2012; flights based out of NASA Langley Research Center (Virginia) in 2013; and flights based out of the Mojave Air and Space Port (California) in 2013

NASA's SnowEx Campaign: Observing Seasonal Snow in a Forested Environment

SnowEx is a multi-year airborne snow campaign with the primary goal of addressing the question: How much water is stored in Earth's terrestrial snow-covered regions? Year 1(2016-17) focused on the distribution of snow-water equivalent (SWE) and the snow energy balance in a forested environment. The year 1 primary site was Grand Mesa and the secondary site was the Senator Beck Basin, both in western Colorado, USA. Nine sensors on five aircraft made observations using a broad range of sensing techniques - active and passive microwave, and active and passive optical/infrared - to determine the sensitivity and accuracy of these potential satellite remote sensing techniques, along with models, to measure snow under a range of forest conditions. SnowEx also included an extensive range of ground truth measurements - in-situ manual samples, snow pits, ground based remote sensing measurements, and sophisticated new techniques. A detailed description of the data collected will be given and some preliminary results will be presented

Comparing the microstructure and photovoltaic performance of 3 perylene imide acceptors with similar energy levels but different packing tendencies

[Abstract] While it is widely recognized that microstructure plays an important role in the performance of organic photovoltaics (OPV), systematic studies are often challenging, as varying the molecular packing through typical chemical means (such as sidechain tuning) often affects the molecular energy levels, thus preventing a clear correlation. In this work we present the synthesis of three perylene imide (PI) based electron acceptors with almost identical energy levels, but distinct packing tendencies. We confirm our initial hypothesis by measuring solution and solid-state absorption, and cyclic voltammetry as well as characterizing the films by grazing incidence wide angle X-ray scattering (GIWAXS). In a second step, we repeat the characterization of the three materials in blends with two polymer donors, namely PCDTBT or PBDBT, whose energy levels are well aligned with those of the PI acceptors, and which, additionally, exhibit different degrees of structural order. We show how the initial strong difference between acceptors is partially blurred in blends, but still critical. Finally, we correlate our structural data with OPV devices made with the corresponding six blends. Our data suggest that a good donor acceptor marriage should ensure good energy alignment but also exhibit complementary crystallization tendencies of the two components.Ministerio de Ciencia e Innovación; CEX2019-000917-SMinisterio de Ciencia e Innovación; PGC2018-095411-B-I00Ministerio de Ciencia e Innovación; PID2019-106268GB-C33MInisterio de Ciencia e Innovación; PID2019-110305GB-I00Universidad Complutense de Madrid; INV.GR.00.1819.10759Universidad Complutense de Madrid; CT20/19-CT21/19/PEJD-2018-POST/IND-8661PAIJunta de Andalucía; UMA18-FEDERJA-08

Analysis of Soil Freeze/Thaw Signatures During Slapex F/T Campaign

Permanently frozen and seasonally frozen soils occur over a large portion of the Earth's land surface. Changes in the freeze/thaw state of the land surface reflects major changes in thermal and hydraulic properties as well as acting as a "switch" for many ecological processes. In short, soil freeze/thaw state is a fundamental land surface variable in the water and energy cycles, and it connects to the carbon cycle. Surface freeze/thaw state is observable by passive and active microwave sensors. For example, NASA's Soil Moisture Active Passive (SMAP) mission includes a freeze/thaw data product. Such satellite sensing offers routine all-season and all-weather global observations of soil freeze/thaw state with the application of suitable algorithms. We describe early finding from the SLAPex Freeze/Thaw campaign, believed to be the first airborne campaign of its type, focusing on soil freeze/thaw

Comparing the microstructure and photovoltaic performance of 3 perylene imide acceptors with similar energy levels but different packing tendencies

While it is widely recognized that microstructure plays an important role in the performance of organic photovoltaics (OPV), systematic studies are often challenging, as varying the molecular packing through typical chemical means (such as sidechain tuning) often affects the molecular energy levels, thus preventing a clear correlation. In this work we present the synthesis of three perylene imide (PI) based electron acceptors with almost identical energy levels, but distinct packing tendencies. We confirm our initial hypothesis by measuring solution and solid-state absorption, cyclic voltammetry as well as characterizing the films by grazing incident wide angle X-ray scattering (GIWAXS). In a second step, we repeat the characterization of the three materials in blends with two polymer donors, namely PCDTBT or PBDBT, whose energy levels are well aligned with those of the PI acceptors, and which, additionally, exhibit different degrees of structural order. We show how the initial strong difference between acceptors is partially blurred in blends, but still critical. Finally, we correlate our structural data with OPV devices made with the corresponding six blends. Our data suggest that a good donor acceptor marriage should ensure good energy alignment but also exhibit complementary crystallization tendencies of the two components.The authors acknowledge financial support from the Spanish Ministry of Science and Innovation through the Severo Ochoa” Program for Centers of Excellence in R&D (No. CEX2019-000917-S), and projects PGC2018-095411-B-I00, PID2019-106268GB-C33 and PID2019-110305GB-I00, as well as the European Commission through the Horizon 2020 Marie Sklodowska-Curie ITN Programme, SEPOMO, Grant Number: 722651, and the UCM (INV.GR.00.1819.10759). E.G. specially acknowledges Comunidad de Madrid and Universidad Complutense de Madrid for a post-doctoral contract (CT20/19- CT21/19/PEJD-2018-POST/IND-8661PAI). M.J.A.N. acknowledges URJC for a post-doctoral contract. R.P.O and A.H. also acknowledge support from Junta de Andalucía (projects UMA18-FEDERJA-080). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Anti-NMDAR Encephalitis in the Netherlands, Focusing on Late-Onset Patients and Antibody Test Accuracy

BACKGROUND AND OBJECTIVES: To describe the clinical features of anti-NMDAR encephalitis, emphasizing on late-onset patients and antibody test characteristics in serum and CSF. METHODS: Nationwide observational Dutch cohort study, in patients diagnosed with anti-NMDAR encephalitis between 2007 and 2019. RESULTS: One hundred twenty-six patients with anti-NMDAR encephalitis were included with a median age of 24 years (range 1-86 years). The mean annual incidence was 1.00/million (95% CI 0.62-1.59). Patients ≥45 years of age at onset (19%) had fewer seizures (46% vs 71%, p = 0.021), fewer symptoms during disease course (3 vs 6 symptoms, p = 0.020), and more often undetectable serum antibodies compared with younger patients (p = 0.031). In the late-onset group, outcome was worse, and all tumors were carcinomas (both p < 0.0001). CSF was more accurate than serum to detect anti-NMDAR encephalitis (sensitivity 99% vs 68%, p < 0.0001). Using cell-based assay (CBA), CSF provided an unconfirmed positive test result in 11/2,600 patients (0.4%); 6/11 had a neuroinflammatory disease (other than anti-NMDAR encephalitis). Patients with anti-NMDAR encephalitis, who tested positive in CSF only, had lower CSF antibody titers (p = 0.003), but appeared to have an equally severe disease course. DISCUSSION: Anti-NMDAR encephalitis occurs at all ages and is less rare in the elderly patients than initially anticipated. In older patients, the clinical phenotype is less outspoken, has different tumor association, and a less favorable recovery. Detection of antibodies in CSF is the gold standard, and although the CBA has very good validity, it is not perfect. The clinical phenotype should be leading, and confirmation in a research laboratory is recommended, when in doubt

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Human Papillomavirus-16 E7 Interacts with Glutathione S-Transferase P1 and Enhances Its Role in Cell Survival

Background:Human Papillomavirus (HPV)-16 is a paradigm for "high-risk" HPVs, the causative agents of virtually all cervical carcinomas. HPV E6 and E7 viral genes are usually expressed in these tumors, suggesting key roles for their gene products, the E6 and E7 oncoproteins, in inducing malignant transformation.Methodology/Principal Findings:By protein-protein interaction analysis, using mass spectrometry, we identified glutathione S-transferase P1-1 (GSTP1) as a novel cellular partner of the HPV-16 E7 oncoprotein. Following mapping of the region in the HPV-16 E7 sequence that is involved in the interaction, we generated a three-dimensional molecular model of the complex between HPV-16 E7 and GSTP1, and used this to engineer a mutant molecule of HPV-16 E7 with strongly reduced affinity for GSTP1.When expressed in HaCaT human keratinocytes, HPV-16 E7 modified the equilibrium between the oxidized and reduced forms of GSTP1, thereby inhibiting JNK phosphorylation and its ability to induce apoptosis. Using GSTP1-deficient MCF-7 cancer cells and siRNA interference targeting GSTP1 in HaCaT keratinocytes expressing either wild-type or mutant HPV-16 E7, we uncovered a pivotal role for GSTP1 in the pro-survival program elicited by its binding with HPV-16 E7.Conclusions/Significance:This study provides further evidence of the transforming abilities of this oncoprotein, setting the groundwork for devising unique molecular tools that can both interfere with the interaction between HPV-16 E7 and GSTP1 and minimize the survival of HPV-16 E7-expressing cancer cells. © 2009 Mileo et al

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons