Newtonian Planetary Ephemerides 1800-2000 - Development Ephemeris Number 28

Computer-calculated Newtonian ephemerides, 1800-2000, for nine principal planets - Development ephemeris number 2

Studies on CrO_x/La₂O₃/ZrO₂ catalysts modified by Mg

Lanthana–zirconia supported chromium oxide and magnesium chromium mixed oxide catalysts were studied in the dehydrocyclization of n-octane and characterized by temperature-programmed desorption of NH3, temperature-programmed reduction, XPS and DRIFTS. The Mg-free catalyst shows the highest activity, but suffers from rapid deactivation due to coke formation. The addition of Mg decreases the initial activity of the supported chromium oxide and retards its deactivation. The characterization results reveal that the deactivation retarding effect of Mg species not only consists in the deletion of strong acid sites but also in the decoration and/or dilution of Cr3+ oxide cluster, supposedly due to the formation of Mg–Cr surface compounds and, thus, in preventing the formation of coke

Understanding, justifying, and optimizing radiation exposure for CT imaging in nephrourology

An estimated 4-5 million CT scans are performed in the USA every year to investigate nephrourological diseases such as urinary stones and renal masses. Despite the clinical benefits of CT imaging, concerns remain regarding the potential risks associated with exposure to ionizing radiation. To assess the potential risk of harmful biological effects from exposure to ionizing radiation, understanding the mechanisms by which radiation damage and repair occur is essential. Although radiation level and cancer risk follow a linear association at high doses, no strong relationship is apparent below 100 mSv, the doses used in diagnostic imaging. Furthermore, the small theoretical increase in risk of cancer incidence must be considered in the context of the clinical benefit derived from a medically indicated CT and the likelihood of cancer occurrence in the general population. Elimination of unnecessary imaging is the most important method to reduce imaging-related radiation; however, technical aspects of medically justified imaging should also be optimized, such that the required diagnostic information is retained while minimizing the dose of radiation. Despite intensive study, evidence to prove an increased cancer risk associated with radiation doses below ~100 mSv is lacking; however, concerns about ionizing radiation in medical imaging remain and can affect patient care. Overall, the principles of justification and optimization must remain the basis of clinical decision-making regarding the use of ionizing radiation in medicine

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2

Chronic kidney disease; Pediatric nephrology; UrologyMalaltia renal crònica; Nefrologia pediàtrica; UrologiaEnfermedad renal crónica; Nefrología pediátrica; UrologíaNedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90–180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs −1664 [1190], respectively; difference, 5172; 95% CI 2929–7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH

The theory of canonical perturbations applied to attitude dynamics and to the Earth rotation. Osculating and nonosculating Andoyer variables

The Hamiltonian theory of Earth rotation, known as the Kinoshita-Souchay theory, operates with nonosculating Andoyer elements. This situation parallels a similar phenomenon that often happens (but seldom gets noticed) in orbital dynamics, when the standard Lagrange-type or Delaunay-type planetary equations unexpectedly render nonosculating orbital elements. In orbital mechanics, osculation loss happens when a velocity-dependent perturbation is plugged into the standard planetary equations. In attitude mechanics, osculation is lost when an angular-velocity-dependent disturbance is plugged in the standard dynamical equations for the Andoyer elements. We encounter exactly this situation in the theory of Earth rotation, because this theory contains an angular-velocity-dependent perturbation (the switch from an inertial frame to that associated with the precessing ecliptic of date). While the osculation loss does not influence the predictions for the figure axis of the planet, it considerably alters the predictions for the instantaneous spin-axis' orientation. We explore this issue in great detail

Reconsidering the galactic coordinate system

Initially defined by the IAU in 1958, the galactic coordinate system was thereafter in 1984 transformed from the B1950.0 FK4-based system to the J2000.0 FK5-based system. In 1994, the IAU recommended that the dynamical reference system FK5 be replaced by the ICRS, which is a kinematical non-rotating system defined by a set of remote radio sources. However the definition of the galactic coordinate system was not updated. We consider that the present galactic coordinates may be problematic due to the unrigorous transformation method from the FK4 to the FK5, and due to the non-inertiality of the FK5 system with respect to the ICRS. This has led to some confusions in applications of the galactic coordinates. We tried to find the transformation matrix in the framework of the ICRS after carefully investigating the definition of the galactic coordinate system and transformation procedures, however we could not find a satisfactory galactic coordinate system that is connected steadily to the ICRS. To avoid unnecessary misunderstandings, we suggest to re-consider the definition of the galactic coordinate system which should be directly connected with the ICRS for high precise observation at micro-arcsecond level.Comment: 10 pages, 3 figures, accepted for publication in A&

Polycystic kidney disease in patients on the renal transplant waiting list: trends in hematocrit and survival

BACKGROUND: The patient characteristics and mortality associated with autosomal dominant polycystic kidney disease (PKD) have not been characterized for a national sample of end stage renal disease (ESRD) patients on the renal transplant waiting list. METHODS: 40,493 patients in the United States Renal Data System who were initiated on ESRD therapy between 1 April 1995 and 29 June 1999 and later enrolled on the renal transplant waiting list were analyzed in an historical cohort study of the relationship between hematocrit at the time of presentation to ESRD and survival (using Cox Regression) in patients with PKD as a cause of ESRD. RESULTS: Hematocrit levels at presentation to ESRD increased significantly over more recent years of the study. Hematocrit rose in parallel in patients with and without PKD, but patients with PKD had consistently higher hemoglobin. PKD was independently associated with higher hematocrit in multiple linear regression analysis (p < 0.0001). In logistic regression, higher hematocrit was independently associated with PKD. In Cox Regression analysis, PKD was associated with statistically significant improved survival both in comparison with diabetic (hazard ratio, 0.64, 95% CI 0.53–0.77, p < 0.001) and non-diabetic (HR 0.68, 95% CI 0.56–0.82, p = 0.001) ESRD patients, adjusted for all other factors. CONCLUSIONS: Hematocrit at presentation to ESRD was significantly higher in patients with PKD compared with patients with other causes of ESRD. The survival advantage of PKD in ESRD persisted even adjusted for differences in hematocrit and in comparison with patients on the renal transplant waiting list

A First Assessment of the Corrections for the Consistency of the IAU2000 and IAU2006 Precession-Nutation Models

The Earth precession-nutation model endorsed by resolutions of each the International Astronomical Union and the International Union of Geodesy and Geophysics is composed of two theories developed independently, namely IAU2006 precession and IAU2000A nutation. The IAU2006 precession was adopted to supersede the precession part of the IAU 2000A precession-nutation model and tried to get the new precession theory dynamically consistent with the IAU2000A nutation. However, full consistency was not reached, and slight adjustments of the IAU2000A nutation amplitudes at the micro arcsecond level were required to ensure consistency. The first set of formulae for these corrections derived by Capitaine et al. (Astrophys 432(1):355–367, 2005), which was not included in IAU2006 but provided in some standards and software for computing nutations. Later, Escapa et al. showed that a few additional terms of the same order of magnitude have to be added to the 2005 expressions to get complete dynamical consistency between the official precession and nutation models. In 2018 Escapa and Capitaine made a joint review of the problem and proposed three alternative ways of nutation model and its parameters to achieve consistency to certain different extents, although no estimation of their respective effects could be worked out to illustrate the proposals. Here we present some preliminary results on the assessment of the effects of each of the three sets of corrections suggested by Escapa and Capitaine (Proceedings of the Journées, des Systémes de Référence et de la Rotation Terrestre: Furthering our Knowledge of Earth Rotation, Alicante, 2018) by testing them in conjunction with the conventional celestial pole offsets given in the IERS EOP14C04 time series.The four first authors were partially supported by Spanish Project AYA2016-79775-P (AEI/FEDER, UE)

Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site