| 231. |
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| 232. |
- Payer, Stefan E., et al.
(författare)
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Regioselective para-Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase
- 2017
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 56:44, s. 13893-13897
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Tidskriftsartikel (refereegranskat)abstract
- The utilization of CO2 as a carbon source for organic synthesis meets the urgent demand for more sustainability in the production of chemicals. Herein, we report on the enzyme-catalyzed para-carboxylation of catechols, employing 3,4-dihydroxybenzoic acid decarboxylases (AroY) that belong to the UbiD enzyme family. Crystal structures and accompanying solution data confirmed that AroY utilizes the recently discovered prenylated FMN (prFMN) cofactor, and requires oxidative maturation to form the catalytically competent prFMN(iminium) species. This study reports on the in vitro reconstitution and activation of a prFMN-dependent enzyme that is capable of directly carboxylating aromatic catechol substrates under ambient conditions. A reaction mechanism for the reversible decarboxylation involving an intermediate with a single covalent bond between a quinoid adduct and cofactor is proposed, which is distinct from the mechanism of prFMN-associated 1,3-dipolar cycloadditions in related enzymes.
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| 233. |
- Piazza, I, et al.
(författare)
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A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4200-
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Tidskriftsartikel (refereegranskat)abstract
- Chemoproteomics is a key technology to characterize the mode of action of drugs, as it directly identifies the protein targets of bioactive compounds and aids in the development of optimized small-molecule compounds. Current approaches cannot identify the protein targets of a compound and also detect the interaction surfaces between ligands and protein targets without prior labeling or modification. To address this limitation, we here develop LiP-Quant, a drug target deconvolution pipeline based on limited proteolysis coupled with mass spectrometry that works across species, including in human cells. We use machine learning to discern features indicative of drug binding and integrate them into a single score to identify protein targets of small molecules and approximate their binding sites. We demonstrate drug target identification across compound classes, including drugs targeting kinases, phosphatases and membrane proteins. LiP-Quant estimates the half maximal effective concentration of compound binding sites in whole cell lysates, correctly discriminating drug binding to homologous proteins and identifying the so far unknown targets of a fungicide research compound.
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| 234. |
- Ramírez-Tannus, María Claudia, et al.
(författare)
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XUE : Molecular Inventory in the Inner Region of an Extremely Irradiated Protoplanetary Disk
- 2023
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 958:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results of the eXtreme UV Environments (XUE) James Webb Space Telescope (JWST) program, which focuses on the characterization of planet-forming disks in massive star-forming regions. These regions are likely representative of the environment in which most planetary systems formed. Understanding the impact of environment on planet formation is critical in order to gain insights into the diversity of the observed exoplanet populations. XUE targets 15 disks in three areas of NGC 6357, which hosts numerous massive OB stars, including some of the most massive stars in our Galaxy. Thanks to JWST, we can, for the first time, study the effect of external irradiation on the inner (<10 au), terrestrial-planet-forming regions of protoplanetary disks. In this study, we report on the detection of abundant water, CO, 12CO2, HCN, and C2H2 in the inner few au of XUE 1, a highly irradiated disk in NGC 6357. In addition, small, partially crystalline silicate dust is present at the disk surface. The derived column densities, the oxygen-dominated gas-phase chemistry, and the presence of silicate dust are surprisingly similar to those found in inner disks located in nearby, relatively isolated low-mass star-forming regions. Our findings imply that the inner regions of highly irradiated disks can retain similar physical and chemical conditions to disks in low-mass star-forming regions, thus broadening the range of environments with similar conditions for inner disk rocky planet formation to the most extreme star-forming regions in our Galaxy.
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| 235. |
- Reiter, E. O., et al.
(författare)
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Effect of Growth Hormone (GH) Treatment on the Final Height of 1258 Patients with Idiopathic GH Deficiency: Analysis of a Large International Database
- 2006
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Ingår i: The Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:6, s. 2047-2054
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Tidskriftsartikel (refereegranskat)abstract
- Context: Treatment with growth hormone (GH) has been used to correct the growth deficit in children with GH deficiency (GHD). Although successful in increasing height velocity, such treatment often falls short of helping patients achieve full genetic height potential. Objective: This study set out to analyze near final height data from a cohort of GH-treated children with idiopathic GHD. Design, Setting, and Participants: Of 1258 evaluable patients in the Pfizer International Growth Database (KIGS) with GHD, 980 were of Caucasian origin and 278 of Japanese origin; 747 had isolated GHD (IGHD), while 511 had multiple pituitary hormone deficiencies (MPHD). Main Outcome Measures: Near final height, relation to midparental height, and factors predictive of growth outcomes. Results: Median height SD scores (SDS) at start of treatment were -2.4 (IGHD) and -2.9 (MPHD) for Caucasian males and -2.6 (IGHD) and -3.4 (MPHD) for females, respectively; comparable starting heights were -2.9 (IGHD) and -3.6 (MPHD) for Japanese males and -3.3 (IGHD) and -4.0 (MPHD) for females, respectively. Corresponding near adult height SDS after GH treatment were -0.8 (IGHD) and -0.7 (MPHD) for Caucasian males and -1.0 (IGHD) and -1.1 (MPHD) for females, respectively; and -1.6 (IGHD) and -1.9 (MPHD) for Japanese males and -2.1 (IGHD) and -1.8 (MPHD) for females, respectively. Differences between near adult height and midparental height ranged between -0.6 and +0.2 SDS for the different groups, with the closest approximation to MPH occurring in Japanese males with MPHD. First-year increase in height SDS and prepubertal height gain were highly correlated with total height gain confirming importance of treatment before pubertal onset. Conclusions: It is possible to achieve final height within the midparental height range in patients with idiopathic GHD treated from an early age with GH, but absolute height outcomes remain in the lower part of the normal range. Patients with MPHD generally had a slightly better long term height outcome.
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| 236. |
- Reiter, P, et al.
(författare)
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Future RISING experiments at relativistic energies
- 2005
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 36:4, s. 1259-1268
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Tidskriftsartikel (refereegranskat)abstract
- The proposed experiments for the first RISING (Rare ISotope INvestigations at GSI) campaign will exploit secondary unstable beams at relativistic energies in the range from 100 MeV/u to 400 MeV/u. The RISING spectrometer will be employed for relativistic Coulomb excitation and for high-resolution gamma-spectroscopy experiments after secondary nucleon removal reactions and secondary fragmentation. New experimental methods for spectroscopy at relativistic energics will be investigated in order to measure nuclear structure observables beside the directly accessible level energies and quadrupole deformations. The future experiments will focus on: Shell structure of unstable doubly magic nuclei and their vicinity, symmetries along the N = Z line and mixed symmetry states, shapes and shape coexistence, collective modes and E1 strength distribution.
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| 237. |
- Taylor, M. J., et al.
(författare)
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A New Simulation Package to Model Detector Systems with Fragmentation Reactions and Ion Separators: Application to the LYCCA-0 System
- 2009
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 606:3, s. 589-597
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Tidskriftsartikel (refereegranskat)abstract
- A Monte-Carlo simulation package has been developed to model the response of a detector system for ion identification used in conjunction with ion separators following nuclear reactions. The simulation is written predominantly using the GEANT4 framework but utilises the ion transport code MOCADI for accurate separator and reaction modelling. A novel MOCADI-GEANT4 interface has been developed to utilise the parameter file output option of MOCADI as an event generator for the GEANT4 detector simulation. Test simulation results have been compared with experimental data and excellent agreement was observed. The simulation has successfully been used to model a new particle detection system prototype (Lund-York-Cologne CAlorimeter (LYCCA)-0) and validate a method of ion identification using energy and time-of-flight with this system. (C) 2009 Elsevier B.V. All rights reserved.
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| 238. |
- Ustun, Celalettin, et al.
(författare)
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Hematopoietic stem-cell transplantation for advanced systemic mastocytosis
- 2014
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:29, s. 3264-3274
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.PATIENTS AND METHODS: In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).RESULTS: Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.CONCLUSION: AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.
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| 239. |
- Valent, Peter, et al.
(författare)
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Advances in the Classification and Treatment of Mastocytosis : Current Status and Outlook toward the Future.
- 2017
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 77:6, s. 1261-1270
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Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis.
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| 240. |
- Willmann, Herbert, 1975-, et al.
(författare)
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Thermal stability of Al-Cr-N hard coatings
- 2006
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Ingår i: Scripta Materialia. - : Elsevier BV. - 1359-6462 .- 1872-8456. ; 54:11, s. 1847-1851
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Tidskriftsartikel (refereegranskat)abstract
- Heat treatment of arc-evaporated cubic Al0.7Cr0.3N hard coatings in Ar up to 1450 °C causes precipitation of AlN. The Cr-enriched matrix transforms into Cr via Cr2N under N2 release. These reactions are investigated by simultaneous thermal analysis, mass spectrometry, X-ray diffraction, and analytical transmission electron microscopy.
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