Station coordinates from LLR analysis as contribution to the next ITRF

Lunar Laser Ranging (LLR) wird seit mehr als 43 Jahren durchgeführt. Der vorhandene Datensatz wird in einer kleinsten-Quadrate-Ausgleichung analysiert, um verschiedene Parameter des Erde-Mond-Systems zu bestimmen, z.B. den Mondorbit, die Erdorientierungsparameter, die Koordinaten der Retro-Reflektoren auf der Mondoberfläche und die Stationskoordinaten auf der Erde. Nun wurde die Analyse der LLR-Daten so modifiziert, dass die ermittelten Stationskoordinaten in einer Kombination für das nächste ITRF verwendet werden können. Hier werden erste Ergebnisse vorgestellt, wie gut die aus LLR bestimmten Koordinaten zur Lösung des DTRF2008 passen

DTRF2020

When using this data please cite Seitz M., Bloßfeld M., Angermann D., Glomsda M., Rudenko S., Zeitlhöfler J., Seitz F. DTRF2020: ITRS 2020 realization of DGFI-TUM, Data Set, DOI 10.5281/zenodo.8220524. A reference paper describing the DTRF2020 in detail is in progress. More information on the DTRF2020 and to individual stations are given at the webpage https://dtrf.dgfi.tum.de/en/dtrf2020/ Summary The DTRF2020 is an independent realization of the International Terrestrial Reference System, ITRS (Petit and Luzum, 2010), by DGFI-TUM. It was computed in 2021/2022 and is based on input data provided by the IAG Scientific Services of the four geodetic space techniques VLBI, SLR, GNSS and DORIS (IVS, ILRS, IGS, IDS). The observation time spans cover 27 to 41 years until the end of 2020. DTRF2020 is characterized by the following innovations. Innovations since the previous ITRS realization, DTRF2014 (Seitz et al., 2022): Six more years of observation data. New stations, satellites and technically improved stations. The technique-specific input data series are calculated according to the latest general and technique-specific models. GNSS provides for the first time an independent scale realization, made possible by the disclosure of the Galileo satellite calibrations. For DTRF2020 the scale is realized for the first time from VLBI and GNSS observations. DTRF2020 considers for the first time all three components of non-tidal loading: the atmospheric, the hydrological and the oceanic part, consistently derived by the Global Geophysical Fluid Center, GGFC. The data cover the full observation time span of the space-geodetic techniques (1979 - 2021.0). For the first time, post-seismic deformation (PSD) of stations affected by earthquakes are modelled and considered in the DTRF computation. An interactive map providing information on the individual stations is available at https://dtrf.dgfi.tum.de/en/dtrf2020/interactive-map/. Updates Version v2: 2023-09-22 (see also IERS Message No. 489) non-tidal loading (NTL) time series referring to CM and CF and the files listing the offsets and trends by which the time series are reduced. post-seismic deformation (PSD) time series for GILCREEK/VLBI DTRF2020 solution description Data Format Description SINEX files of DTRF2020 per technique with full variance-covariance matrix (note: there is a list of GNSS stations without DOMES numbers) DTRF2020_{technique}.snx.gz EOP file of DTRF2020 in IERS 20 C04 format DTRF2020_EOP.20C04_format.txt NTL corrections in [x,y,z] and [North,East,up] applied in DTRF2020 as time series per station. The time series refer to the center of mass of the Earth (CM). In addition, we provide NTL series referring to the center of figure (CF) of the Earth in the same format. Both types of series are provided from the respective start of the observation period of a technique until 2021.0. The NTL series are reduced by offset and drift obtained for the valid observation time span of the individual station. The offsets and drifts are also provided (see below). NTL_{CM|CF}_{technique}_{xyz|neu}.tar Mean offsets and drifts removed from individual NTL correction time series before applying them in DTRF2020 (for atmospheric, hydrological and oceanic effect and the sum) in [x,y,z] and [North,East,up]. The values are provided for the applied CM-referred series and for the CF-referred series (see above). NTL_{CM|CF}_{technique}_reduced_offsets_and_drifts.tar PSD corrections as time series in [x,y,z] applied in DTRF2020 for stations affected by a significant post-seismic deformation. For solution numbers whose observation period extents beyond the end of the DTRF2020 period, long time series are provided up to epoch 2031-01-01. PSD_{technique}.tar Station position residual time series in [North, East, up] resulting from 7-parameter similarity transformations of technique-specific solution series with respect to DTRF2020. Important note: The solution series for the individual techniques are based on the NEQs that are used for the DTRF2020 calculation, i.e., on NEQs reduced by the NTL displacements. Station_Residual_Time_Series_{technique}.tar SLR translation time series with respect to DTRF2020 SLR_translation_wrt_DTRF2020.tx

Combination of GNSS and SLR observations using satellite co-locations

Satellite Laser Ranging (SLR) observations to Global Navigation Satellite System (GNSS) satellites may be used for several purposes. On one hand, the range measurement may be used as an independent validation for satellite orbits derived solely from GNSS microwave observations. On the other hand, both observation types may be analyzed together to generate a combined orbit. The latter procedure implies that one common set of orbit parameters is estimated from GNSS and SLR data. We performed such a combined processing of GNSS and SLR using the data of the year 2008. During this period, two GPS and four GLONASS satellites could be used as satellite co-locations. We focus on the general procedure for this type of combined processing and the impact on the terrestrial reference frame (including scale and geocenter), the GNSS satellite antenna offsets (SAO) and the SLR range biases. We show that the combination using only satellite co-locations as connection between GNSS and SLR is possible and allows the estimation of SLR station coordinates at the level of 1-2cm. The SLR observations to GNSS satellites provide the scale allowing the estimation of GNSS SAO without relying on the scale of any a priori terrestrial reference frame. We show that the necessity to estimate SLR range biases does not prohibit the estimation of GNSS SAO. A good distribution of SLR observations allows a common estimation of the two parameter types. The estimated corrections for the GNSS SAO are 119mm and −13mm on average for the GPS and GLONASS satellites, respectively. The resulting SLR range biases suggest that it might be sufficient to estimate one parameter per station representing a range bias common to all GNSS satellites. The estimated biases are in the range of a few centimeters up to 5cm. Scale differences of 0.9ppb are seen between GNSS and SL

The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung

BACKGROUND: Translocation of ultrafine particles (UFP) into the blood that returns from the lungs to the heart has been forwarded as a mechanism for particle-induced cardiovascular effects. The objective of this study was to evaluate the role of the endothelial barrier in the translocation of inhaled UFP from the lung into circulation. METHODS: The isolated perfused rat lung (IPRL) was used under negative pressure ventilation, and radioactive iridium particles (18 nm, CMD, (192)Ir-UFP) were inhaled during 60 minutes to achieve a lung burden of 100 – 200 μg. Particle inhalation was done under following treatments: i) control perfusion, ii) histamine (1 μM in perfusate, iii) luminal histamine instillation (1 mM), and iv) luminal instillation of H(2)O(2). Particle translocation to the perfusate was assessed by the radioactivity of (192)Ir isotope. Lung permeability by the use of Tc(99m)-labeled diethylene triamine pentaacetic acid (DTPA). In addition to light microscopic morphological evaluation of fixed lungs, alkaline phosphatase (AKP) and angiotensin converting enzyme (ACE) in perfusate were measured to assess epithelial and endothelial integrity. RESULTS: Particle distribution in the lung was homogenous and similar to in vivo conditions. No translocation of Ir particles at negative pressure inhalation was detected in control IPL, but lungs pretreated with histamine (1 μM) in the perfusate or with luminal H(2)O(2 )(0.5 mM) showed small amounts of radioactivity (2–3 % dose) in the single pass perfusate starting at 60 min of perfusion. Although the kinetics of particle translocation were different from permeability for (99m)Tc-DTPA, the pretreatments (H(2)O(2), vascular histamine) caused similar changes in the translocation of particles and soluble mediator. Increased translocation through epithelium and endothelium with a lag time of one hour occurred in the absence of epithelial and endothelial damage. CONCLUSION: Permeability of the lung barrier to UFP or nanoparticles is controlled both at the epithelial and endothelial level. Conditions that affect this barrier function such as inflammation may affect translocation of NP

Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium

BACKGROUND: There is ongoing discussion that inhaled nanoparticles (NPs, < 100 nm) may translocate from epithelial deposition sites of the lungs to systemic circulation. OBJECTIVES AND METHODS: We studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and bronchoalveolar lavage (BAL) measurements in healthy adult Wistar Kyoto (WKY) rats at various times over 6 months after administration of a single 60- to 100-min intratracheal inhalation of iridium-192 ((192)Ir)–radiolabeled NPs. A complete (192)Ir balance of all organs, tissues, excretion, remaining carcass, and BAL was performed at each time point. RESULTS: Directly after inhalation we found free NPs in the BAL; later, NPs were predominantly associated with alveolar macropages (AMs). After 3 weeks, lavageable NP fractions decreased to 0.06 of the actual NP lung burden. This is in stark contrast to the AM-associated fraction of micron-sized particles reported in the literature. These particles remained constant at about 0.8 throughout a 6-month period. Three weeks after inhalation, 80% of the retained Ir NPs was translocated into epithelium and interstitium. CONCLUSION: There is a strong size-selective difference in particle immobilization. Furthermore, AM-mediated NP transport to the larynx originates not only from the NP fraction retained on the epithelium but also from NPs being reentrained from the interstitium to the luminal side of epithelium. We conclude that NPs are much less phagocytized by AMs than large particles but are effectively removed from the lung surface into the interstitium. Even from these interstitial sites, they undergo AM-mediated long-term NP clearance to the larynx

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non alcohol -induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular.and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed. Dysregulation of metabolism, as a result of ethanol exposure, in the intestine leads to colon carcinogenesis. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota have been suggested. The clinical aspects of NASH, as part of the metabolic syndrome in the aging population, have been presented. The symposium addressed mechanisms and biomarkers of alcohol induced damage to different organs, as well as the role of the microbiome in this dialog. The microbiota regulates and acts as a key element in harmonizing immune responses at intestinal mucosal surfaces. It is known that microbiota is an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. The signals at the sites of inflammation mediate recruitment and differentiation in order to remove inflammatory inducers and promote tissue homeostasis restoration. The change in the intestinal microbiota also influences the change in obesity and regresses the liver steatosis. Evidence on the positive role of moderate alcohol consumption on heart and metabolic diseases as well on reducing steatosis have been looked up. Moreover nutrition as a therapeutic intervention in alcoholic liver disease has been discussed. In addition to the original data, we searched the literature (2008-2016) for the latest publication on the described subjects. In order to obtain the updated data we used the usual engines (Pub Med and Google Scholar). The intention of the eighth symposia was to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents

A Rapid, Highly Sensitive and Open-Access SARS-CoV-2 Detection Assay for Laboratory and Home Testing

RT-qPCR-based diagnostic tests play important roles in combating virus-caused pandemics such as Covid-19. However, their dependence on sophisticated equipment and the associated costs often limits their widespread use. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative nucleic acid detection method that overcomes these limitations. Here, we present a rapid, robust, and sensitive RT-LAMP-based SARS-CoV-2 detection assay. Our 40-min procedure bypasses the RNA isolation step, is insensitive to carryover contamination, and uses a colorimetric readout that enables robust SARS-CoV-2 detection from various sample types. Based on this assay, we have increased sensitivity and scalability by adding a nucleic acid enrichment step (Bead-LAMP), developed a version for home testing (HomeDip-LAMP), and identified open-source RT-LAMP enzymes that can be produced in any molecular biology laboratory. On a dedicated website, rtlamp.org (DOI: 10.5281/zenodo.6033689), we provide detailed protocols and videos. Our optimized, general-purpose RT-LAMP assay is an important step toward population-scale SARS-CoV-2 testing.MK was supported by the Vienna Science and Technology Fund (WWTF) through project COV20-031 (to JZ) and a Cambridge Trust LMB Cambridge Scholarship. Research in the AP lab is supported by the Austrian Science Fund (START Projekt Y 1031-B28, SFB “RNA-Deco” F 80) and EMBO-YIP; research in the JB lab is supported by the European Research Council (ERC- 2015-CoG - 682181). The IMP receives generous institutional funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter grant FFG-852936); IMBA is generously supported by the Austrian Academy of Sciences. Work in the LM-A laboratory is supported by grant PID2019- 104176RB-I00/AEI/10.13039/501100011033 of the Spanish Ministry of Science and Innovation, and an institutional grant of the Fundación Ramón Areces.Peer reviewe

Alcoholic and non-alcoholic steatohepatitis

This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism