1,639 research outputs found
Ultraviolet Spectrometer and Polarimeter (UVSP) software development and hardware tests for the solar maximum mission
An analysis of UVSP wavelength drive hardware, problems, and recovery procedures; radiative power loss from solar plasmas; and correlations between observed UV brightness and inferred photospheric currents are given
High-throughput analysis of the RNA-induced silencing complex in myotonic dystrophy type 1 patients identifies the dysregulation of miR-29c and its target ASB2
Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by abnormally expanded stretches of CTG DNA triplets in the DMPK gene, leading to mutated-transcript RNA-toxicity. MicroRNAs (miRNAs) are short non-coding RNAs that, after maturation, are loaded onto the RISC effector complex that destabilizes target mRNAs and represses their translation. In DM1 muscle biopsies not only the expression, but also the intracellular localization of specific miRNAs is disrupted, leading to the dysregulation of the relevant mRNA targets. To investigate the functional alterations of the miRNA/target interactions in DM1, we analyzed by RNA-sequencing the RISC-associated RNAs in skeletal muscle biopsies derived from DM1 patients and matched controls. The mRNAs found deregulated in DM1 biopsies were involved in pathways and functions relevant for the disease, such as energetic metabolism, calcium signaling, muscle contraction and p53-dependent apoptosis. Bioinformatic analysis of the miRNA/mRNA interactions based on the RISC enrichment profiles, identified 24 miRNA/mRNA correlations. Following validation in 21 independent samples, we focused on the couple miR-29c/ASB2 because of the role of miR-29c in fibrosis (a feature of late-stage DM1 patients) and of ASB2 in the regulation of muscle mass. Luciferase reporter assay confirmed the direct interaction between miR-29c and ASB2. Moreover, decreased miR-29c and increased ASB2 levels were verified also in immortalized myogenic cells and primary fibroblasts, derived from biopsies of DM1 patients and controls. CRISPR/Cas9-mediated deletion of CTG expansions rescued normal miR-29c and ASB2 levels, indicating a direct link between the mutant repeats and the miRNA/target expression. In conclusion, functionally relevant miRNA/mRNA interactions were identified in skeletal muscles of DM1 patients, highlighting the dysfunction of miR-29c and ASB2
Lanthanide(III) Ions and 5-Methylisophthalate Ligand Based Coordination Polymers: An Insight into Their Photoluminescence Emission and Chemosensing for Nitroaromatic Molecules
The work presented herein reports on the synthesis, structural and physico-chemical characterization, luminescence properties and luminescent sensing activity of a family of isostructural coordination polymers (CPs) with the general formula [Ln2(ÎŒ4-5Meip)3(DMF)]n (where Ln(III) = Sm (1Sm), Eu (2Eu), Gd (3Gd), Tb (4Tb) and Yb (5Yb) and 5Meip = 5-methylisophthalate, DMF = N,N-dimethylmethanamide). Crystal structures consist of 3D frameworks tailored by the linkage between infinite lanthanide(III)-carboxylate rods by means of the tetradentate 5Meip ligands. Photoluminescence measurements in solid state at variable temperatures reveal the best-in-class properties based on the capacity of the 5Meip ligand to provide efficient energy transfers to the lanthanide(III) ions, which brings intense emissions in both the visible and near-infrared (NIR) regions. On the one hand, compound 5Yb displays characteristic lanthanide-centered bands in the NIR with sizeable intensity even at room temperature. Among the compounds emitting in the visible region, 4Tb presents a high QY of 63%, which may be explained according to computational calculations. At last, taking advantage of the good performance as well as high chemical and optical stability of 4Tb in water and methanol, its sensing capacity to detect 2,4,6-trinitrophenol (TNP) among other nitroaromatic-like explosives has been explored, obtaining high detection capacity (with Ksv around 105 Mâ1), low limit of detection (in the 10â6â10â7 M) and selectivity among other molecules (especially in methanol).This work has been funded by University of the Basque Country (GIU20/028), Gobierno Vasco/Eusko Jaurlaritza (IT1755-22 and IT1500-22), Junta de AndalucĂa (FQM-394 and B-FQM-734-UGR20, B-FQM-478-UGR20 and ProyExcel_00386) and the Spanish Ministry of Economy and Competitiveness (MCIU/AEI/FEDER, UE) (PGC2018-102052-A-C22, PGC2018-102052-B-C21 and PID2020-117344RB-I00)
Lanthanide(III) Ions and 5-Methylisophthalate Ligand Based Coordination Polymers: An Insight into Their Photoluminescence Emission and Chemosensing for Nitroaromatic Molecules
Acknowledgments: O.P.C. is grateful to the UPV/EHU for his predoctoral grant. S.R. acknowledges
the Juan de la Cierva IncorporaciĂłn Fellowship (grant agreement no. IJC2019-038894-I). The authors
thank the technical and human support provided by SGIker (UPV/EHU/ERDF, EU).Funding: This work has been funded by University of the Basque Country (GIU20/028), Gobierno
Vasco/Eusko Jaurlaritza (IT1755-22 and IT1500-22), Junta de AndalucĂa (FQM-394 and B-FQM-
734-UGR20, B-FQM-478-UGR20 and ProyExcel_00386) and the Spanish Ministry of Economy and
Competitiveness (MCIU/AEI/FEDER, UE) (PGC2018-102052-A-C22, PGC2018-102052-B-C21 and
PID2020-117344RB-I00).The work presented herein reports on the synthesis, structural and physico-chemical characterization, luminescence properties and luminescent sensing activity of a family of isostructural coordination polymers (CPs) with the general formula [Ln2(ÎŒ4-5Meip)3(DMF)]n (where Ln(III) = Sm (1Sm), Eu (2Eu), Gd (3Gd), Tb (4Tb) and Yb (5Yb) and 5Meip = 5-methylisophthalate, DMF = N,N-dimethylmethanamide). Crystal structures consist of 3D frameworks tailored by the linkage between infinite lanthanide(III)-carboxylate rods by means of the tetradentate 5Meip ligands. Photoluminescence measurements in solid state at variable temperatures reveal the best-in-class properties based on the capacity of the 5Meip ligand to provide efficient energy transfers to the lanthanide(III) ions, which brings intense emissions in both the visible and near-infrared (NIR) regions. On the one hand, compound 5Yb displays characteristic lanthanide-centered bands in the NIR with sizeable intensity even at room temperature. Among the compounds emitting in the visible region, 4Tb presents a high QY of 63%, which may be explained according to computational calculations. At last, taking advantage of the good performance as well as high chemical and optical stability of 4Tb in water and methanol, its sensing capacity to detect 2,4,6-trinitrophenol (TNP) among other nitroaromatic-like explosives has been explored, obtaining high detection capacity (with Ksv around 105 Mâ1), low limit of detection (in the 10â6â10â7 M) and selectivity among other molecules (especially in methanol).University of the Basque Country (GIU20/028)Gobierno Vasco/Eusko Jaurlaritza (IT1755-22 and IT1500-22)Junta de AndalucĂa (FQM-394 and B-FQM- 734-UGR20, B-FQM-478-UGR20 and ProyExcel_00386)Spanish Ministry of Economy and Competitiveness (MCIU/AEI/FEDER, UE) (PGC2018-102052-A-C22, PGC2018-102052-B-C21 and PID2020-117344RB-I00
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A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.
Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains Ύ-tubulin and Δ-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening
New Challenges in Neutrosophic Theory and Applications
Neutrosophic theory has representatives on all continents and, therefore, it can be said to be a universal theory. On the other hand, according to the three volumes of âThe Encyclopedia of Neutrosophic Researchersâ (2016, 2018, 2019), plus numerous others not yet included in Encyclopedia book series, about 1200 researchers from 73 countries have applied both the neutrosophic theory and method. Neutrosophic theory was founded by Professor Florentin Smarandache in 1998; it constitutes further generalization of fuzzy and intuitionistic fuzzy theories. The key distinction between the neutrosophic set/logic and other types of sets/logics lies in the introduction of the degree of indeterminacy/neutrality (I) as an independent component in the neutrosophic set. Thus, neutrosophic theory involves the degree of membership-truth (T), the degree of indeterminacy (I), and the degree of non-membership-falsehood (F). In recent years, the field of neutrosophic set, logic, measure, probability and statistics, precalculus and calculus, etc., and their applications in multiple fields have been extended and applied in various fields, such as communication, management, and information technology. We believe that this book serves as useful guidance for learning about the current progress in neutrosophic theories. In total, 22 studies have been presented and reflect the call of the thematic vision. The contents of each study included in the volume are briefly described as follows. The first contribution, authored by Wadei Al-Omeri and Saeid Jafari, addresses the concept of generalized neutrosophic pre-closed sets and generalized neutrosophic pre-open sets in neutrosophic topological spaces. In the article âDesign of Fuzzy Sampling Plan Using the Birnbaum-Saunders Distributionâ, the authors Muhammad Zahir Khan, Muhammad Farid Khan, Muhammad Aslam, and Abdur Razzaque Mughal discuss the use of probability distribution function of BirnbaumâSaunders distribution as a proportion of defective items and the acceptance probability in a fuzzy environment. Further, the authors Derya Bakbak, Vakkas Ulucžay, and Memet Sžahin present the âNeutrosophic Soft Expert Multiset and Their Application to Multiple Criteria Decision Makingâ together with several operations defined for them and their important algebraic properties. In âNeutrosophic Multigroups and Applicationsâ, Vakkas Ulucžay and Memet Sžahin propose an algebraic structure on neutrosophic multisets called neutrosophic multigroups, deriving their basic properties and giving some applications to group theory. Changxing Fan, Jun Ye, Sheng Feng, En Fan, and Keli Hu introduce the âMulti-Criteria Decision-Making Method Using Heronian Mean Operators under a Bipolar Neutrosophic Environmentâ and test the effectiveness of their new methods. Another decision-making study upon an everyday life issue which empowered us to organize the key objective of the industry developing is given in âNeutrosophic Cubic Einstein Hybrid Geometric Aggregation Operators with Application in Prioritization Using Multiple Attribute Decision-Making Methodâ written by Khaleed Alhazaymeh, Muhammad Gulistan, Majid Khan, and Seifedine Kadry
"TOF2H": A precision toolbox for rapid, high density/high coverage hydrogen-deuterium exchange mass spectrometry via an LC-MALDI approach, covering the data pipeline from spectral acquisition to HDX rate analysis
<p>Abstract</p> <p>Background</p> <p>Protein-amide proton hydrogen-deuterium exchange (HDX) is used to investigate protein conformation, conformational changes and surface binding sites for other molecules. To our knowledge, software tools to automate data processing and analysis from sample fractionating (LC-MALDI) mass-spectrometry-based HDX workflows are not publicly available.</p> <p>Results</p> <p>An integrated data pipeline (Solvent Explorer/TOF2H) has been developed for the processing of LC-MALDI-derived HDX data. Based on an experiment-wide template, and taking an <it>ab initio </it>approach to chromatographic and spectral peak finding, initial data processing is based on accurate mass-matching to fully deisotoped peaklists accommodating, in MS/MS-confirmed peptide library searches, ambiguous mass-hits to non-target proteins. Isotope-shift re-interrogation of library search results allows quick assessment of the extent of deuteration from peaklist data alone. During raw spectrum editing, each spectral segment is validated in real time, consistent with the manageable spectral numbers resulting from LC-MALDI experiments. A semi-automated spectral-segment editor includes a semi-automated or automated assessment of the quality of all spectral segments as they are pooled across an XIC peak for summing, centroid mass determination, building of rates plots on-the-fly, and automated back exchange correction. The resulting deuterium uptake rates plots from various experiments can be averaged, subtracted, re-scaled, error-barred, and/or scatter-plotted from individual spectral segment centroids, compared to solvent exposure and hydrogen bonding predictions and receive a color suggestion for 3D visualization. This software lends itself to a "divorced" HDX approach in which MS/MS-confirmed peptide libraries are built via nano or standard ESI without source modification, and HDX is performed via LC-MALDI using a standard MALDI-TOF. The complete TOF2H package includes additional (eg LC analysis) modules.</p> <p>Conclusion</p> <p>"TOF2H" provides a comprehensive HDX data analysis package that has accelerated the processing of LC-MALDI-based HDX data in the authors' lab from weeks to hours. It runs in a standard MS Windows (XP or Vista) environment, and can be downloaded <url>http://tof2h.bio.uci.edu</url> or obtained from the authors at no cost.</p
Photophysics and stereomutation of aromatic sulfoxides
Aromatic sulfoxides are photochemically active molecules. At 77 K in ether/isopentane/ethanol (EPA) glass, aromatic sulfoxides are shown to have weak phosphorescence. The triplet energies are a few kilocalories per mole higher than the corresponding ketones. The diaryl sulfoxides are about 3 kcal/mol lower than the corresponding ketones, and the diaryl sulfoxides are about 3 kcal/mol lower than the corresponding aryl methyl sulfoxides. The lifetimes of emission are generally under 100 ms. From the diffuse vibrational structure of the spectra, the lifetimes, and the effect of solvent on the triplet energy, it is concluded that the triplets are delocalized aromatic states that involve substantial charge transfer off the oxygen atom;The effect of a methanesulfinyl group on the photophysics of several aromatic chromophores has been investigated. Compared to the parent arenes, the spectroscopic singlet energies and the triplet energies are relatively unchanged by the substitution (+/-2 kcal/mol). The fluorescence quantum yields are reduced by at least one order of magnitude, whereas the phosphorescence quantum yields at 77 K are enhanced. Fluorescence lifetimes are greatly shortened, consistent with the reduced phiF. The triplet yields at room temperature are slightly enhanced by the substitution. Unusual fluorescence quantum yield enhancements are observed on cooling the samples to 77 K. For instance, a 15-fold increase of fluorescence of 1-methanesulfinylpyrene is observed upon freezing the sample whereas only a factor of 2 is seen in the unsubstituted pyrene. An attempt to relate the observed photophysics to photoinduced racemization is made, since the photoracemization is negligible at 173 K. Racemization yields as a function of temperature have also been obtained. For methanesulfinyl pyrene, the activation barrier of photoracemization is estimated to be 2--7 kcal/mol;Aromatic sulfoxides quench singlet excited states of sensitizers whose singlet energies render energy transfer unlikely as a mechanism. Well over 50 rate constants for singlet quenching of various sensitizers by a series sulfoxides have been obtained, as have estimates of the redox potentials for the series of sulfoxides. These data strongly suggest that the mechanism for quenching involves electron transfer and/or exciplex formation. Charge (electron) transfer is from the sensitizer to the sulfoxide
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