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Discovery of 2,586 Orphan Genes in Rosa Chinensis Provides Insights Into Stress Adaptation and Flower Development

A research team has identified 2,586 orphan genes (OGs) in Rosa chinensis, offering new insights into the role of these unique genes in flower development, stress response, and environmental adaptation.




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N. Korea Jams GPS Signals for Fifth Straight Day

[Politics] :
The South Korean military announced Tuesday that North Korea has attempted to disrupt GPS signals in the western inter-Korean border region for the fifth straight day. During a regular press briefing, Joint Chiefs of Staff(JCS) spokesperson Lee Sung-jun said the latest GPS-jamming attempts occurred ...

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NYT: US Official Confirms ‘Significant Number’ of N. Korean Troops Killed in Combat against Ukraine

[International] :
A high-level U.S. government official reportedly confirmed that many North Korean troops deployed to Russia have been killed in combat against Ukraine. On Tuesday, the New York Times quoted the official as saying “a significant number” were killed in action, with the exact time of the armed conflict ...

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Putin Signs into Law Mutual Defense Treaty with N. Korea

[International] :
Russian President Vladimir Putin has reportedly signed into law a treaty on the country's strategic partnership with North Korea, which includes a mutual defense provision. According to Russia's state-run TASS news agency, Putin signed the comprehensive strategic partnership treaty on ...

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Archangel Roles and Significance in Christianity and Catholicism

In Christian tradition, an archangel is among of the most revered and powerful spiritual beings in the celestial hierarchy. Mentioned directly in both the Old and New Testaments, these angels serve as messengers, protectors and agents of God's divine will.




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Gov't Designates '2024 Hangeul Week' to Celebrate Creation of Korean Alphabet

[Culture] :
The government has designated the seven days from Friday to next Thursday as the "2024 Hangeul Week," on the occasion of the 578th Hangeul Day on October 9 to mark the creation of the Korean alphabet. According to the culture ministry on Monday, a number of cultural events that can help participants better ...

[more...]




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How to End an E-Mail: 21 Professional and Personal Sign-Offs

The perfect email deserves the perfect ending. But what is the right way to close an email? Well, that depends on who will be reading it.




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Google Easter Eggs: Sweet Treats Hidden in Plain Sight

Google is home to a ton of super fun hidden Easter eggs you can check out right from your browser. Go ahead, try a couple. You won't be disappointed.




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What Makes Virgo Men So Unique? Zodiac Insights

Explore Virgo men's traits, compatibility, and relationship dynamics. Learn what makes a Virgo man unique in love and if he's the right zodiac match for you.




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Zodiac Signs Elements: Discover the Power Behind Each Element

Discover the unique traits of each zodiac element—fire, earth, air, and water. Uncover how these elements shape personalities and compatibility in astrology.





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Structural insights into 1,4-bis­(neopent­yloxy)pillar[5]arene and the pyridine host–guest system

The crystal structure of a neo­pentyl­oxypillar[5]arene with two pyridine mol­ecules encapsulated in the macrocyclic cavity is reported.




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X-ray crystal structure of a designed rigidified imaging scaffold in the ligand-free conformation

Imaging scaffolds composed of designed protein cages fused to designed ankyrin repeat proteins (DARPins) have enabled the structure determination of small proteins by cryogenic electron microscopy (cryo-EM). One particularly well characterized scaffold type is a symmetric tetrahedral assembly composed of 24 subunits, 12 A and 12 B, which has three cargo-binding DARPins positioned on each vertex. Here, the X-ray crystal structure of a representative tetrahedral scaffold in the apo state is reported at 3.8 Å resolution. The X-ray crystal structure complements recent cryo-EM findings on a closely related scaffold, while also suggesting potential utility for crystallographic investigations. As observed in this crystal structure, one of the three DARPins, which serve as modular adaptors for binding diverse `cargo' proteins, present on each of the vertices is oriented towards a large solvent channel. The crystal lattice is unusually porous, suggesting that it may be possible to soak crystals of the scaffold with small (≤30 kDa) protein cargo ligands and subsequently determine cage–cargo structures via X-ray crystallography. The results suggest the possibility that cryo-EM scaffolds may be repurposed for structure determination by X-ray crystallography, thus extending the utility of electron-microscopy scaffold designs for alternative structural biology applications.




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Crystal structure and Hirshfeld-surface analysis of an etoxazole metabolite designated R13

The crystal structure of a metabolite of the insecticide/acaricide etoxazole, designated R13 is presented along with a Hirshfeld surface analysis of inter­molecular inter­actions present in the crystal structure.




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Crystal structure and Hirshfeld-surface analysis of an etoxazole metabolite designated R13

The etoxazole metabolite R13, systematic name 4-(4-tert-butyl-2-ethoxyphenyl)-2-(2,6-difluorophenyl)oxazole (C21H21F2NO2), results from the oxidation of etoxazole, a chitin synthesis inhibitor belonging to the oxazoline class, widely used as an insecticide/acaricide since 1998. The structure of R13 features a central oxazole ring with attached 2,6-difluorophenyl and 4-t-butyl-2-ethoxyphenyl moieties. The overall conformation gives dihedral angles between these rings and the oxazole of 24.91 (5)° (with difluorophenyl) and 15.30 (6)° (with t-butyl-ethoxyphenyl), indicating an overall deviation from planarity. Additionally, torsion angles of the ethoxy and t-butyl groups define the orientation of these substituents relative to their benzene ring. In the crystal packing, no significant hydrogen bonds are present, but a Hirshfeld surface analysis highlights weak intermolecular contacts leading to π–π-stacked dimers linked by weak C—H...N contacts. The packing analysis confirms that most intermolecular interactions involve hydrogen atoms.




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Extracting the electronic structure signal from X-ray and electron scattering in the gas phase

X-ray and electron scattering from free gas-phase molecules is examined using the independent atom model (IAM) and ab initio electronic structure calculations. The IAM describes the effect of the molecular geometry on the scattering, but does not account for the redistribution of valence electrons due to, for instance, chemical bonding. By examining the total, i.e. energy-integrated, scattering from three molecules, fluoroform (CHF3), 1,3-cyclohexadiene (C6H8) and naphthalene (C10H8), the effect of electron redistribution is found to predominantly reside at small-to-medium values of the momentum transfer (q ≤ 8 Å−1) in the scattering signal, with a maximum percent difference contribution at 2 ≤ q ≤ 3 Å−1. A procedure to determine the molecular geometry from the large-q scattering is demonstrated, making it possible to more clearly identify the deviation of the scattering from the IAM approximation at small and intermediate q and to provide a measure of the effect of valence electronic structure on the scattering signal.




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Wavefront analysis and phase correctors design using SHADOW

Knife-edge imaging is a successful method for determining the wavefront distortion of focusing optics such as Kirkpatrick–Baez mirrors or compound refractive lenses. In this study, the wavefront error of an imperfect elliptical mirror is predicted by developing a knife-edge program using the SHADOW/OASYS platform. It is shown that the focusing optics can be aligned perfectly by minimizing the parabolic and cubic coefficients of the wavefront error. The residual wavefront error provides precise information about the figure/height errors of the focusing optics suggesting it as an accurate method for in situ optical metrology. A Python program is developed to design a customized wavefront refractive corrector to minimize the residual wavefront error. Uniform beam at and out of focus and higher peak intensity are achieved by the wavefront correction in comparison with ideal focusing. The developed code provides a quick way for wavefront error analysis and corrector design for non-ideal optics especially for the new-generation diffraction-limited sources, and saves considerable experimental time and effort.




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Signal-to-noise and spatial resolution in in-line imaging. 1. Basic theory, numerical simulations and planar experimental images

Signal-to-noise ratio and spatial resolution are quantitatively analysed in the context of in-line (propagation based) X-ray phase-contrast imaging. It is known that free-space propagation of a coherent X-ray beam from the imaged object to the detector plane, followed by phase retrieval in accordance with Paganin's method, can increase the signal-to-noise in the resultant images without deteriorating the spatial resolution. This results in violation of the noise-resolution uncertainty principle and demonstrates `unreasonable' effectiveness of the method. On the other hand, when the process of free-space propagation is performed in software, using the detected intensity distribution in the object plane, it cannot reproduce the same effectiveness, due to the amplification of photon shot noise. Here, it is shown that the performance of Paganin's method is determined by just two dimensionless parameters: the Fresnel number and the ratio of the real decrement to the imaginary part of the refractive index of the imaged object. The relevant theoretical analysis is performed first, followed by computer simulations and then by a brief test using experimental images collected at a synchrotron beamline. More extensive experimental tests will be presented in the second part of this paper.




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Structural insights into 1,4-bis­(neopent­yloxy)pillar[5]arene and the pyridine host–guest system

The crystal structure of 1,4-bis­(neopent­yloxy)pillar[5]arene, C95H140N2O10 (TbuP), featuring two encapsulated pyridine mol­ecules, reveals significant host–guest inter­actions. Inter­estingly, the pyridine guests are positioned near the neopent­yloxy substituents instead of the electron-rich aromatic core of the pillar[5]arene. This spatial arrangement suggests a preference for the pyridine mol­ecules to engage with the aliphatic regions of the host. Detailed analysis of the structural characteristics of this host–guest system (TbuP·2Py), as well as its packing pattern within the crystal network, is presented and discussed.




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2,4-Di­aryl­pyrroles: synthesis, characterization and crystallographic insights

Three 2,4-di­aryl­pyrroles were synthesized starting from 4-nitro­butano­nes and the crystal structures of two derivatives were analysed. These are 4-(4-meth­oxy­phen­yl)-2-(thio­phen-2-yl)-1H-pyrrole, C15H13NOS, and 3-(4-bromo­phen­yl)-2-nitroso-5-phenyl-1H-pyrrole, C16H11BrN2O. Although pyrroles without sub­stituents at the α-position with respect to the N atom are very air sensitive and tend to polymerize, we succeeded in growing an adequate crystal for X-ray diffraction analysis. Further derivatization using sodium nitrite afforded a nitrosyl pyrrole derivative, which crystallized in the triclinic space group Poverline{1} with Z = 6. Thus, herein we report the first crystal structure of a nitrosyl pyrrole. Inter­estingly, the co-operative hydrogen bonds in this NO-substituted pyrrole lead to a trimeric structure with bifurcated halogen bonds at the ends, forming a two-dimensional (2D) layer with inter­stitial voids having a radius of 5 Å, similar to some reported macrocyclic porphyrins.




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The crystal structure of mycothiol disulfide reductase (Mtr) provides mechanistic insight into the specific low-molecular-weight thiol reductase activity of Actinobacteria

Low-molecular-weight (LMW) thiols are involved in many processes in all organisms, playing a protective role against reactive species, heavy metals, toxins and antibiotics. Actinobacteria, such as Mycobacterium tuberculosis, use the LMW thiol mycothiol (MSH) to buffer the intracellular redox environment. The NADPH-dependent FAD-containing oxidoreductase mycothiol disulfide reductase (Mtr) is known to reduce oxidized mycothiol disulfide (MSSM) to MSH, which is crucial to maintain the cellular redox balance. In this work, the first crystal structures of Mtr are presented, expanding the structural knowledge and understanding of LMW thiol reductases. The structural analyses and docking calculations provide insight into the nature of Mtrs, with regard to the binding and reduction of the MSSM substrate, in the context of related oxidoreductases. The putative binding site for MSSM suggests a similar binding to that described for the homologous glutathione reductase and its respective substrate glutathione disulfide, but with distinct structural differences shaped to fit the bulkier MSSM substrate, assigning Mtrs as uniquely functioning reductases. As MSH has been acknowledged as an attractive antitubercular target, the structural findings presented in this work may contribute towards future antituberculosis drug development.




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EMinsight: a tool to capture cryoEM microscope configuration and experimental outcomes for analysis and deposition

The widespread adoption of cryoEM technologies for structural biology has pushed the discipline to new frontiers. A significant worldwide effort has refined the single-particle analysis (SPA) workflow into a reasonably standardized procedure. Significant investments of development time have been made, particularly in sample preparation, microscope data-collection efficiency, pipeline analyses and data archiving. The widespread adoption of specific commercial microscopes, software for controlling them and best practices developed at facilities worldwide has also begun to establish a degree of standardization to data structures coming from the SPA workflow. There is opportunity to capitalize on this moment in the maturation of the field, to capture metadata from SPA experiments and correlate the metadata with experimental outcomes, which is presented here in a set of programs called EMinsight. This tool aims to prototype the framework and types of analyses that could lead to new insights into optimal microscope configurations as well as to define methods for metadata capture to assist with the archiving of cryoEM SPA data. It is also envisaged that this tool will be useful to microscope operators and facilities looking to rapidly generate reports on SPA data-collection and screening sessions.




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New insights into the domain of unknown function (DUF) of EccC5, the pivotal ATPase providing the secretion driving force to the ESX-5 secretion system

Type VII secretion (T7S) systems, also referred to as ESAT-6 secretion (ESX) systems, are molecular machines that have gained great attention due to their implications in cell homeostasis and in host–pathogen interactions in mycobacteria. The latter include important human pathogens such as Mycobacterium tuberculosis (Mtb), the etiological cause of human tuberculosis, which constitutes a pandemic accounting for more than one million deaths every year. The ESX-5 system is exclusively found in slow-growing pathogenic mycobacteria, where it mediates the secretion of a large family of virulence factors: the PE and PPE proteins. The secretion driving force is provided by EccC5, a multidomain ATPase that operates using four globular cytosolic domains: an N-terminal domain of unknown function (EccC5DUF) and three FtsK/SpoIIIE ATPase domains. Recent structural and functional studies of ESX-3 and ESX-5 systems have revealed EccCDUF to be an ATPase-like fold domain with potential ATPase activity, the functionality of which is essential for secretion. Here, the crystal structure of the MtbEccC5DUF domain is reported at 2.05 Å resolution, which reveals a nucleotide-free structure with degenerated cis-acting and trans-acting elements involved in ATP binding and hydrolysis. This crystallographic study, together with a biophysical assessment of the interaction of MtbEccC5DUF with ATP/Mg2+, supports the absence of ATPase activity proposed for this domain. It is shown that this degeneration is also present in DUF domains from other ESX and ESX-like systems, which are likely to exhibit poor or null ATPase activity. Moreover, based on an in silico model of the N-terminal region of MtbEccC5DUF, it is hypothesized that MtbEccC5DUF is a degenerated ATPase domain that may have retained the ability to hexamerize. These observations draw attention to DUF domains as structural elements with potential implications in the opening and closure of the membrane pore during the secretion process via their involvement in inter-protomer interactions.




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High-confidence placement of low-occupancy fragments into electron density using the anomalous signal of sulfur and halogen atoms

Fragment-based drug design using X-ray crystallography is a powerful technique to enable the development of new lead compounds, or probe molecules, against biological targets. This study addresses the need to determine fragment binding orientations for low-occupancy fragments with incomplete electron density, an essential step before further development of the molecule. Halogen atoms play multiple roles in drug discovery due to their unique combination of electronegativity, steric effects and hydrophobic properties. Fragments incorporating halogen atoms serve as promising starting points in hit-to-lead development as they often establish halogen bonds with target proteins, potentially enhancing binding affinity and selectivity, as well as counteracting drug resistance. Here, the aim was to unambiguously identify the binding orientations of fragment hits for SARS-CoV-2 nonstructural protein 1 (nsp1) which contain a combination of sulfur and/or chlorine, bromine and iodine substituents. The binding orientations of carefully selected nsp1 analogue hits were focused on by employing their anomalous scattering combined with Pan-Dataset Density Analysis (PanDDA). Anomalous difference Fourier maps derived from the diffraction data collected at both standard and long-wavelength X-rays were compared. The discrepancies observed in the maps of iodine-containing fragments collected at different energies were attributed to site-specific radiation-damage stemming from the strong X-ray absorption of I atoms, which is likely to cause cleavage of the C—I bond. A reliable and effective data-collection strategy to unambiguously determine the binding orientations of low-occupancy fragments containing sulfur and/or halogen atoms while mitigating radiation damage is presented.




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Utilizing anomalous signals for element identification in macromolecular crystallography

AlphaFold2 has revolutionized structural biology by offering unparalleled accuracy in predicting protein structures. Traditional methods for determining protein structures, such as X-ray crystallography and cryo-electron microscopy, are often time-consuming and resource-intensive. AlphaFold2 provides models that are valuable for molecular replacement, aiding in model building and docking into electron density or potential maps. However, despite its capabilities, models from AlphaFold2 do not consistently match the accuracy of experimentally determined structures, need to be validated experimentally and currently miss some crucial information, such as post-translational modifications, ligands and bound ions. In this paper, the advantages are explored of collecting X-ray anomalous data to identify chemical elements, such as metal ions, which are key to understanding certain structures and functions of proteins. This is achieved through methods such as calculating anomalous difference Fourier maps or refining the imaginary component of the anomalous scattering factor f''. Anomalous data can serve as a valuable complement to the information provided by AlphaFold2 models and this is particularly significant in elucidating the roles of metal ions.




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Crystal structure of human peptidylarginine deiminase type VI (PAD6) provides insights into its inactivity

Human peptidylarginine deiminase isoform VI (PAD6), which is predominantly limited to cytoplasmic lattices in the mammalian oocytes in ovarian tissue, is essential for female fertility. It belongs to the peptidylarginine deiminase (PAD) enzyme family that catalyzes the conversion of arginine residues to citrulline in proteins. In contrast to other members of the family, recombinant PAD6 was previously found to be catalytically inactive. We sought to provide structural insight into the human homologue to shed light on this observation. We report here the first crystal structure of PAD6, determined at 1.7 Å resolution. PAD6 follows the same domain organization as other structurally known PAD isoenzymes. Further structural analysis and size-exclusion chromatography show that PAD6 behaves as a homodimer similar to PAD4. Differential scanning fluorimetry suggests that PAD6 does not coordinate Ca2+ which agrees with acidic residues found to coordinate Ca2+ in other PAD homologs not being conserved in PAD6. The crystal structure of PAD6 shows similarities with the inactive state of apo PAD2, in which the active site conformation is unsuitable for catalytic citrullination. The putative active site of PAD6 adopts a non-productive conformation that would not allow protein–substrate binding due to steric hindrance with rigid secondary structure elements. This observation is further supported by the lack of activity on the histone H3 and cytokeratin 5 substrates. These findings suggest a different mechanism for enzymatic activation compared with other PADs; alternatively, PAD6 may exert a non-enzymatic function in the cytoplasmic lattice of oocytes and early embryos.




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Structural insights into the molecular mechanism of phytoplasma immunodominant membrane protein

Immunodominant membrane protein (IMP) is a prevalent membrane protein in phytoplasma and has been confirmed to be an F-actin-binding protein. However, the intricate molecular mechanisms that govern the function of IMP require further elucidation. In this study, the X-ray crystallographic structure of IMP was determined and insights into its interaction with plant actin are provided. A comparative analysis with other proteins demonstrates that IMP shares structural homology with talin rod domain-containing protein 1 (TLNRD1), which also functions as an F-actin-binding protein. Subsequent molecular-docking studies of IMP and F-actin reveal that they possess complementary surfaces, suggesting a stable interaction. The low potential energy and high confidence score of the IMP–F-actin binding model indicate stable binding. Additionally, by employing immunoprecipitation and mass spectrometry, it was discovered that IMP serves as an interaction partner for the phytoplasmal effector causing phyllody 1 (PHYL1). It was then shown that both IMP and PHYL1 are highly expressed in the S2 stage of peanut witches' broom phytoplasma-infected Catharanthus roseus. The association between IMP and PHYL1 is substantiated through in vivo immunoprecipitation, an in vitro cross-linking assay and molecular-docking analysis. Collectively, these findings expand the current understanding of IMP interactions and enhance the comprehension of the interaction of IMP with plant F-actin. They also unveil a novel interaction pathway that may influence phytoplasma pathogenicity and host plant responses related to PHYL1. This discovery could pave the way for the development of new strategies to overcome phytoplasma-related plant diseases.




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Structural insight into piezo-solvatochromism of Reichardt's dye

To date, accurate modelling of the solvation process is challenging, often over-simplifying the solvent–solute interactions. The interplay between the molecular arrangement associated with the solvation process and crystal nucleation has been investigated by analysis of the piezo-solvatochromic behaviour of Reichardt's dye, ET(1), in methanol, ethanol and acetone under high pressure. High-pressure single-crystal X-ray diffraction and UV–Vis spectroscopy reveal the impact of solute–solvent interactions on the optical properties of ET(1). The study underscores the intricate relationship between solvent properties, molecular conformation and crystal packing. The connection between liquid and solid phases emphasizes the capabilities of high-pressure methods for expanding the field of crystal engineering. The high-pressure environment allowed the determination of the crystal structures reported here that are built from organic molecules fourfold solvated with ethanol or methanol: ET(1)·4CH3OH and ET(1)·4C2H5OH·H2O. The observed piezo-solvatochromic effects highlight the potential of ET(1) in nonlinear optoelectronics and expand the application of solvatochromic chemical indicators to pressure sensors.




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Structural characterization of TIR-domain signalosomes through a combination of structural biology approaches

The TIR (Toll/interleukin-1 receptor) domain represents a vital structural element shared by proteins with roles in immunity signalling pathways across phyla (from humans and plants to bacteria). Decades of research have finally led to identifying the key features of the molecular basis of signalling by these domains, including the formation of open-ended (filamentous) assemblies (responsible for the signalling by cooperative assembly formation mechanism, SCAF) and enzymatic activities involving the cleavage of nucleotides. We present a historical perspective of the research that led to this understanding, highlighting the roles that different structural methods played in this process: X-ray crystallography (including serial crystallography), microED (micro-crystal electron diffraction), NMR (nuclear magnetic resonance) spectroscopy and cryo-EM (cryogenic electron microscopy) involving helical reconstruction and single-particle analysis. This perspective emphasizes the complementarity of different structural approaches.




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Supramolecular synthons in hydrates and solvates of lamotrigine: a tool for cocrystal design

The molecule of anti-epileptic drug lamotrigine [LAM; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is capable of the formation of multicomponent solids. Such an enhanced tendency is related to the diverse functionalities of the LAM chemical groups able to form hydrogen bonds. Two robust synthons are recognized in the supramolecular structure of LAM itself formed via N—H⋯N hydrogen bond: homosynthon, so-called aminopyridine dimer or synthon 1 [R22(8)] and larger homosynthon 2 [R32(8)]. The synthetic procedures for a new hydrate and 11 solvates of LAM (in the series: with acetone, ethanol: two polymorphs: form I and form II, 2-propanol, n-butanol, tert-butanol, n-pentanol, benzonitrile, acetonitrile, DMSO and dioxane) were performed. The comparative solid state structural analysis of a new hydrate and 11 solvates of LAM has been undertaken in order to establish robustness of the supramolecular synthons 1 and 2 found in the crystal structure of LAM itself as well as LAM susceptibility to build methodical solid state supramolecular architecture in the given competitive surrounding of potential hydrogen bonds. The aminopyridine dimer homosynthon 1 [R22(8)] has been switched from para-para (P-P) topology to ortho-ortho (O-O) topology in all crystal structures, except in LAM:n-pentanol:water solvate where it remains P-P. Homosynthon 2 [R32(8)] of the LAM crystal structure imitates in the LAM solvates as a heterosynthon by replacing the triazine nitrogen proton acceptor atoms of LAM with the proton acceptors of solvates molecules.




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New insights into the magnetism and magnetic structure of LuCrO3 perovskite

A polycrystalline sample LuCrO3 has been characterized by neutron powder diffraction (NPD) and magnetization measurements. Its crystal structure has been Rietveld refined from NPD data in space group Pnma; this perovskite contains strongly tilted CrO6 octahedra with extremely bent Cr—O—Cr superexchange angles of ∼142°. The NPD data show that below Néel temperature (TN ≃ 131 K), the magnetic structure can be defined as an A-type antiferromagnetic arrangement of Cr3+ magnetic moments, aligned along the b axis, with a canting along the c axis. A noticeable magneto­strictive effect is observed in the unit-cell parameters and volume upon cooling down across TN. The AC magnetic susceptibility indicates the onset of magnetic ordering below 112.6 K; the magnetization isotherms below TN show a nonlinear behaviour that is associated with the described canting of the Cr3+ magnetic moments. From the Curie–Weiss law, the effective moment of the Cr3+ sublattice is found to be μeff = 3.55 μB (calculated 3.7 μB) while the ΘCW parameter yields a value of −155 K, indicating antiferromagnetic interactions. There is a conspicuous increase of TN upon the application of external pressure, which must be due to shortening of the Cr—O bond length under compression that increases the orbital overlap integral.




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Multi-segment cooling design of a reflection mirror based on the finite-element method

Through numerical optimization of cooling lengths and cooling groove positions for the first reflection mirror of a free-electron laser [OK?], the root mean square of the height error of the mirror's thermal deformation was minimized. The optimized mirror design effectively mitigated stray light and enhanced the peak intensity of the focus spot at the sample, thereby enhancing the optical performance of the high-heat-load mirror under high repetition rates at beamline FEL-II of the SHINE facility.




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Enhancing the Efficiency of a Wavelength-Dispersive Spectrometer based upon a Slit-less Design Using a Single-Bounce Monocapillary

A slit-less wavelength-dispersive spectrometer design using a single-bounce monocapillary that aligns the sample on the Rowland circle, enhancing photon throughput and maintaining resolution. The compact design supports flexibility and reconfiguration in facilities without complex beamline infrastructure, significantly improving detection efficiency.




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(U)SAXS characterization of porous microstructure of chert: insights into organic matter preservation

This study characterizes the microstructure and mineralogy of 132 (ODP sample), 1000 and 1880 million-year-old chert samples. By using ultra-small-angle X-ray scattering (USAXS), wide-angle X-ray scattering and other techniques, the preservation of organic matter (OM) in these samples is studied. The scarce microstructural data reported on chert contrast with many studies addressing porosity evolution in other sedimentary rocks. The aim of this work is to solve the distribution of OM and silica in chert by characterizing samples before and after combustion to pinpoint the OM distribution inside the porous silica matrix. The samples are predominantly composed of alpha quartz and show increasing crystallite sizes up to 33 ± 5 nm (1σ standard deviation or SD). In older samples, low water abundances (∼0.03%) suggest progressive dehydration. (U)SAXS data reveal a porous matrix that evolves over geological time, including, from younger to older samples, (1) a decreasing pore volume down to 1%, (2) greater pore sizes hosting OM, (3) decreasing specific surface area values from younger (9.3 ± 0.1 m2 g−1) to older samples (0.63 ± 0.07 m2 g−1, 1σ SD) and (4) a lower background intensity correlated to decreasing hydrogen abundances. The pore-volume distributions (PVDs) show that pores ranging from 4 to 100 nm accumulate the greater volume fraction of OM. Raman data show aromatic organic clusters up to 20 nm in older samples. Raman and PVD data suggest that OM is located mostly in mesopores. Observed structural changes, silica–OM interactions and the hydro­phobicity of the OM could explain the OM preservation in chert.




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INSIGHT: in situ heuristic tool for the efficient reduction of grazing-incidence X-ray scattering data

INSIGHT is a Python-based software tool for processing and reducing 2D grazing-incidence wide- and small-angle X-ray scattering (GIWAXS/GISAXS) data. It offers the geometric transformation of the 2D GIWAXS/GISAXS detector image to reciprocal space, including vectorized and parallelized pixel-wise intensity correction calculations. An explicit focus on efficient data management and batch processing enables full control of large time-resolved synchrotron and laboratory data sets for a detailed analysis of kinetic GIWAXS/GISAXS studies of thin films. It processes data acquired with arbitrarily rotated detectors and performs vertical, horizontal, azimuthal and radial cuts in reciprocal space. It further allows crystallographic indexing and GIWAXS pattern simulation, and provides various plotting and export functionalities. Customized scripting offers a one-step solution to reduce, process, analyze and export findings of large in situ and operando data sets.




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Design and fabrication of 3D-printed in situ crystallization plates for probing microcrystals in an external electric field

X-ray crystallography is an established tool to probe the structure of macromolecules with atomic resolution. Compared with alternative techniques such as single-particle cryo-electron microscopy and micro-electron diffraction, X-ray crystallography is uniquely suited to room-temperature studies and for obtaining a detailed picture of macromolecules subjected to an external electric field (EEF). The impact of an EEF on proteins has been extensively explored through single-crystal X-ray crystallography, which works well with larger high-quality protein crystals. This article introduces a novel design for a 3D-printed in situ crystallization plate that serves a dual purpose: fostering crystal growth and allowing the concurrent examination of the effects of an EEF on crystals of varying sizes. The plate's compatibility with established X-ray crystallography techniques is evaluated.




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Five-analyzer Johann spectrometer for hard X-ray photon-in/photon-out spectroscopy at the Inner Shell Spectroscopy beamline at NSLS-II: design, alignment and data acquisition

Here, a recently commissioned five-analyzer Johann spectrometer at the Inner Shell Spectroscopy beamline (8-ID) at the National Synchrotron Light Source II (NSLS-II) is presented. Designed for hard X-ray photon-in/photon-out spectroscopy, the spectrometer achieves a resolution in the 0.5–2 eV range, depending on the element and/or emission line, providing detailed insights into the local electronic and geometric structure of materials. It serves a diverse user community, including fields such as physical, chemical, biological, environmental and materials sciences. This article details the mechanical design, alignment procedures and data-acquisition scheme of the spectrometer, with a particular focus on the continuous asynchronous data-acquisition approach that significantly enhances experimental efficiency.




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Biden Signs A Law To Memorialize Victims Of The Pulse Nightclub Mass Shooting

Alana Wise | NPR

President Biden signed a memorial bill to recognize the victims of the 2016 Pulse nightclub shooting and offered his condolences to people who are awaiting news on their loved ones in the wake of the deadly Surfside, Fla., partial condo collapse.

Biden — who was vice president when a 29-year-old man killed 49 people and wounded 53 more in the nightclub mass shooting — signed the bill to enshrine a monument to the dozens killed in the Latin Night massacre.

The shooting occurred at a gay nightclub in Orlando, Fla., in June 2016. The month of June is celebrated annually as LGBTQ Pride Month in the United States.

"May a president never have to sign another monument like this," Biden said.

Biden also offered his thoughts to the victims and loved ones of those affected by the catastrophic collapse this week of a Miami-Dade County condo. Authorities say four people have been declared dead and an additional 159 are considered missing in the rubble.

"I just want to say, I've spoken to Gov. [Ron] DeSantis, and we've provided all the help that they have, they need," Biden said. "We sent the best people from FEMA down there. We're going to stay with them."

Copyright 2021 NPR. To see more, visit https://www.npr.org.

This content is from Southern California Public Radio. View the original story at SCPR.org.




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Questlove On His Directorial Debut “Summer Of Soul” And The Significance Of The 1969 Harlem Cultural Festival

Questlove attends Questlove's "Summer Of Soul" screening & live concert at Marcus Garvey Park in Harlem on June 19, 2021 in New York City.; Credit: Roy Rochlin/Getty Images

Manny Valladares | FilmWeek

The 1960s was a decade that held a lot of historical markers for American history. For the Black community, social inequality and systemic racism lead to political action in many different forms.

The end of the decade saw the death of many integral leaders to the civil rights movement, which led to more civil unrest and mourning. One way this community was able to get through this moment in history was through the power of music. The 1969 Harlem Cultural Festival was a special moment in musical and Black history that was all a product of the other 8 years prior to it.

It’s a historical marker for Harlem that Ahmir “Questlove” Thompson’s film “Summer of Soul” depicts in-depth, bringing this story to life using archival footage and interviews. The Harlem Cultural Festival took place for 6 weeks, having some of the greatest Black musical acts the world has ever seen. Through this communal experience, attendees found themselves at ease with artists like Stevie Wonder, Nina Simone and the 5th Dimension bringing this community of Harlem residents together. 

Today on FilmWeek, Larry Mantle speaks with Ahmir “Questlove” Thompson about his feature directorial debut, “Summer of Soul (...Or, When the Revolution Could Not Be Televised),” and its chronicling of a major point in African American history.

Guest:

Ahmir “Questlove” Thompson, director of the documentary “Summer of Soul (...Or, When the Revolution Could Not Be Televised),” drummer for The Roots and The Tonight Show with Jimmy Fallon; he tweets @questlove

This content is from Southern California Public Radio. View the original story at SCPR.org.




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New way for bridges to withstand earthquakes: Support column design

Full Text:

Bridges make travel faster and more convenient, but, in an earthquake, these structures are subject to forces that can cause extensive damage and make them unsafe. Now civil and environmental engineer Petros Sideris of Texas A&M University is leading a National Science Foundation (NSF)-funded research project to investigate the performance of hybrid sliding-rocking (HSR) columns. HSR columns provide the same support as conventional bridge infrastructure columns but are more earthquake-resistant. HSR columns are a series of individual concrete segments held together by steel cables that allow for controlled sliding and rocking. This allows the columns to shift without damage, while post-tensioning strands ensure that at the end of an earthquake the columns are pushed back to their original position. Conventional bridges are cast-in-place monolithic concrete elements that are strong but inflexible. Structural damage in these bridge columns, typically caused by a natural disaster, often forces a bridge to close until repairs are completed. But bridges with HSR columns can withstand large earthquakes with minimal damage and require minor repairs, likely without bridge closures. Such infrastructure helps with post-disaster response and recovery and can save thousands in taxpayer dollars. In an earthquake, HSR columns provide "multiple advantages to the public," Sideris said. "By preventing bridge damage, we can maintain access to affected areas immediately after an event for response teams to be easily deployed, and help affected communities recover faster. In mitigating losses related to post-event bridge repairs and bridge closures, more funds can be potentially directed to supporting the recovery of the affected communities." According to Joy Pauschke, NSF program director for natural hazards engineering, "NSF invests in fundamental engineering research so that, in the future, the nation's infrastructure can be more resilient to earthquakes, hurricanes, and other forces of nature."

Image credit: Texas A&M University




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Pharma Stock Has Significant Upside Potential, Analyst Says

Source: Dr. Joseph Pantginis 11/04/2024

"We believe significant upside potential exists," H.C. Wainwright & Co. analysts wrote about Lexicon Pharmaceuticals Inc. (LXRX:NASDAQ) in an updated research note.

H.C. Wainwright & Co. analysts Dr. Joseph Pantginis, Dr. Lander Egaña Gorroño, Dr. Joshua Korsen, Dr. Matthew Keller, and Dr. Sara Nik, in a research report published on November 4, 2024, maintained their Buy rating on Lexicon Pharmaceuticals Inc. (LXRX:NASDAQ) with a price target of US$6.00. The report follows Lexicon's presentation of preclinical data for LX9851, its ACSL5 inhibitor for obesity, at ObesityWeek 2024.

The analysts highlighted key findings from the presentations, stating, "LX9851 promotes reduction of fat mass without affecting lean body mass" and "LX9851 improves and sustains GLP-1 RA-mediated weight loss, even after semaglutide discontinuation." They added that "Mechanistic studies suggest that LX9851-mediated ACSL5 inhibition activates the ileal brake."

Regarding the drug's potential, they noted, "LX9851 is a first-in-class, oral small molecule ACSL5 inhibitor designed to enhance and maintain weight loss promoted by incretin mimetics (GLP-1 receptor agonists), and offer improved treatment alternatives for obesity and related metabolic disorders."

The report also addressed recent developments with sotagliflozin, detailing the AdCom voting results and potential scenarios for FDA action. The analysts stated, "Although we anticipate favorable feedback from the agency regarding eGFR ≥60 to <90 range, our bet is that a confirmatory trial may be required to validate sota's efficacy in this subpopulation and obtain approval."

H.C. Wainwright & Co.'s valuation methodology is based on a clinical net present value (NPV) model. The analysts explained, "Our valuation is based on our clinical net present value (NPV) model, which allows us to flex multiple assumptions affecting a drug's profile. We currently value Lexicon solely on sotagliflozin sales in the U.S. for HF (INPEFA), HCM, and LX9211 for DPNP."

They added, "We believe significant upside potential exists, based on: (1) attaining higher market penetration for HF, and HCM; and (2) adding the earlier stage assets."

In conclusion, H.C. Wainwright & Co.'s maintenance of their Buy rating and US$6 price target reflects confidence in Lexicon's pipeline potential, particularly with LX9851 and sotagliflozin. The share price at the time of the report of US$1.22 represents a potential return of approximately 392% to the analysts' target price, highlighting the significant upside potential if the company's development programs prove successful.

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Disclosures for H.C. Wainwright & Co., Lexicon Pharmaceuticals Inc., November 4, 2024

This material is confidential and intended for use by Institutional Accounts as defined in FINRA Rule 4512(c). It may also be privileged or otherwise protected by work product immunity or other legal rules. If you have received it by mistake, please let us know by e-mail reply to unsubscribe@hcwresearch.com and delete it from your system; you may not copy this message or disclose its contents to anyone. The integrity and security of this message cannot be guaranteed on the Internet. H.C. WAINWRIGHT & CO, LLC RATING SYSTEM: H.C. Wainwright employs a three tier rating system for evaluating both the potential return and risk associated with owning common equity shares of rated firms. The expected return of any given equity is measured on a RELATIVE basis of other companies in the same sector. The price objective is calculated to estimate the potential movements in price that a given equity could reach provided certain targets are met over a defined time horizon. Price objectives are subject to external factors including industry events and market volatility.

H.C. Wainwright & Co, LLC (the “Firm”) is a member of FINRA and SIPC and a registered U.S. Broker-Dealer. I, Joseph Pantginis, Ph.D., Lander Egaña Gorroño, Ph.D., Joshua Korsen, Ph.D., Matthew Keller, Ph.D. and Sara Nik, Ph.D. , certify that 1) all of the views expressed in this report accurately reflect my personal views about any and all subject securities or issuers discussed; and 2) no part of my compensation was, is, or will be directly or indirectly related to the specific recommendation or views expressed in this research report; and 3) neither myself nor any members of my household is an officer, director or advisory board member of these companies. None of the research analysts or the research analyst’s household has a financial interest in the securities of Lexicon Pharmaceuticals, Inc. (including, without limitation, any option, right, warrant, future, long or short position). As of September 30, 2024 neither the Firm nor its affiliates beneficially own 1% or more of any class of common equity securities of Lexicon Pharmaceuticals, Inc..

Neither the research analyst nor the Firm knows or has reason to know of any other material conflict of interest at the time of publication of this research report. The research analyst principally responsible for preparation of the report does not receive compensation that is based upon any specific investment banking services or transaction but is compensated based on factors including total revenue and profitability of the Firm, a substantial portion of which is derived from investment banking services. The firm or its affiliates received compensation from Lexicon Pharmaceuticals, Inc. for non-investment banking services in the previous 12 months. The Firm or its affiliates did not receive compensation from Lexicon Pharmaceuticals, Inc. for investment banking services within twelve months before, but will seek compensation from the companies mentioned in this report for investment banking services within three months following publication of the research report. The Firm does not make a market in Lexicon Pharmaceuticals, Inc. as of the date of this research report.

The securities of the company discussed in this report may be unsuitable for investors depending on their specific investment objectives and financial position. Past performance is no guarantee of future results. This report is offered for informational purposes only, and does not constitute an offer or solicitation to buy or sell any securities discussed herein in any jurisdiction where such would be prohibited. This research report is not intended to provide tax advice or to be used to provide tax advice to any person. Electronic versions of H.C. Wainwright & Co., LLC research reports are made available to all clients simultaneously. No part of this report may be reproduced in any form without the expressed permission of H.C. Wainwright & Co., LLC. Additional information available upon request. H.C. Wainwright & Co., LLC does not provide individually tailored investment advice in research reports. This research report is not intended to provide personal investment advice and it does not take into account the specific investment objectives, financial situation and the particular needs of any specific person. Investors should seek financial advice regarding the appropriateness of investing in financial instruments and implementing investment strategies discussed or recommended in this research report. H.C. Wainwright & Co., LLC’s and its affiliates’ salespeople, traders, and other professionals may provide oral or written market commentary or trading strategies that reflect opinions that are contrary to the opinions expressed in this research report. H.C. Wainwright & Co., LLC and its affiliates, officers, directors, and employees, excluding its analysts, will from time to time have long or short positions in, act as principal in, and buy or sell, the securities or derivatives (including options and warrants) thereof of covered companies referred to in this research report. The information contained herein is based on sources which we believe to be reliable but is not guaranteed by us as being accurate and does not purport to be a complete statement or summary of the available data on the company, industry or security discussed in the report. All opinions and estimates included in this report constitute the analyst’s judgment as of the date of this report and are subject to change without notice. Securities and other financial instruments discussed in this research report: may lose value; are not insured by the Federal Deposit Insurance Corporation; and are subject to investment risks, including possible loss of the principal amount invested.

( Companies Mentioned: LXRX:NASDAQ, )




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Seesaws Built On U.S. Border Wall Win Prestigious Design Prize

American and Mexican families play with a seesaw installation at the border near Ciudad Juarez, Mexico, in July 2019. London's Design Museum recognized the project with an award for best design of 2020.; Credit: Luis Torres/AFP via Getty Images

Bill Chappell | NPR

An art project that turned the border wall at the U.S.-Mexico border into the temporary base for pink seesaws – inviting children on each side to come play together – has won the London's Design Museum award for best design of 2020.

"We are totally surprised by this unexpected honor," said Ronald Rael, who designed the project with fellow architect Virginia San Fratello. They share the award, he said, with the Ciudad Juárez, Mexico-based art collective Colectivo Chopeke.

"That's amazing," San Fratello said in a video feed announcing the prize. The seesaw installation won both the overall prize and in the transportation category.

"Most importantly, it comes at a time when we are hopeful for change and that we start building more bridges instead of walls," Rael added.

"The Beazley Designs of the Year are the Oscars of the design world," said Razia Iqbal, a journalist who chaired the Design Museum's panel of judges. The award, she noted, highlights work that pushes boundaries of creativity and innovation.

The metal wall was meant to be a stark barrier dividing the U.S. and Mexico, the centerpiece of President Trump's aggressive immigration policies. But in one spot, it became a junction point instead – a fulcrum for a series of seesaws that let children in the two countries share a playground toy.

The project, officially named Teeter-Totter Wall, was first installed in July 2019 when workers slid steel beams through the slats of the border near El Paso, Texas, and Ciudad Juárez.

"For the first time, children from both El Paso, Texas, and the Anapra community in Mexico were invited to connect with their [neighbors], in an attempt to create unity at the politically divisive border," the museum said.

"Everyone was very happy and excited to engage the seesaws," Rael told NPR at the time. The installation went smoothly, turning an idea that had been growing for 10 years into a reality.

"It was peaceful and fun — a day at a park for the children and mothers of Anapra," Rael said.

"The project resonated with people around the world in a way that we didn't anticipate," San Fratello said when the award was announced. "It speaks to the fact that most people are excited about being together, and about optimism and about possibility and the future. And the divisiveness actually comes from the minority."

Rael is a professor at the University of California, Berkeley; San Fratello teaches at San José State University.

The seesaw project was chosen out of more than 70 nominees from dozens of countries, including a customized "stab-proof vest" that the artist Banksy designed for musician Stormzy.

Also considered: the gray and red rendering of SARS-CoV-2, the virus that causes COVID-19. Commissioned by the U.S. Centers for Disease Control and Prevention and designed by Alissa Eckert and Dan Higgins, the famous sphere, with its menacing clusters of crowns, won the design award in the graphics category.

The Impossible Burger 2.0 won in the crowded product category, which also included Lego Braille bricks and a self-sanitizing door handle.

Copyright 2021 NPR. To see more, visit https://www.npr.org.

This content is from Southern California Public Radio. View the original story at SCPR.org.




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George R.R. Martin Signs New Five Year Deal With HBO And HBO Max

Jeannette Muhammad | NPR

George R.R. Martin has entered into a five year deal with HBO to develop content for both HBO and HBO Max, the network said in a statement on Monday.

The best-selling fantasy author and four-time Emmy award winner, best known for his book series A Song of Ice and Fire and its television adaptation Game of Thrones, is attached to multiple projects in the pipeline for the media company and streaming service.

The Game of Thrones television series followed powerful families aiming for the iron throne in the continent of Westeros. It ran for eight years on HBO, with the final season wrapping in 2019.

Martin has a new drama series in the works, House of the Dragon, which is based on his Fire & Blood book. The Game of Thrones prequel follows House Targaryen and is set 300 years before the events of Game of Thrones.

The show has been given a ten episode order. Paddy Considine, Olivia Cooke, Matt Smith, and Emma D'Arcy have joined the series, with additional cast members to be announced.

The show is co-created by Martin and Ryan Condal, whose prior work includes Colony, Rampage, and Hercules. Condal and Miguel Sapochnik (Game of Thrones, Altered Carbon) serve as showrunners and producers with Martin and Vince Gerardis (Game of Thrones).

Martin is also set to executive produce HBO's Who Fears Death, a fantasy post-apocalyptic series with Tessa Thompson attached to star and adapted from the novel by Nnedi Okorafor; and Roadmarks, an adaptation of the sci-fi novel from Roger Zelazny.

Copyright 2021 NPR. To see more, visit https://www.npr.org.

This content is from Southern California Public Radio. View the original story at SCPR.org.




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Tropical Storm Elsa Is Lashing Cuba And Has Florida Next In Its Sights

Dan Charles | NPR

Updated July 5, 2021 at 11:33 AM ET

A tropical storm with 65-mile-an-hour winds is drenching Cuba, and is expected to reach Key West and the west coast of Florida within the next 48 hours.

The National Hurricane Center expects Tropical Storm Elsa to drop between 5 and 10 inches of rain on central and western Cuba, leading to significant flooding and mudslides. The storm probably will weaken somewhat as it crosses the island, but could strengthen again as it approaches Florida.

According to the Associated Press, Cuban officials evacuated 180,000 people as a precaution against the possibility of heavy flooding.

Most of those evacuated stayed at relatives' homes, others went to government shelters, and hundreds living in mountainous areas took refuge in caves prepared for emergencies. The storm had killed at least three people on other Caribbean islands before it reached Cuba

The National Weather Service says that the western coast of Florida, including Tampa Bay, can expect a storm surge that would lift water levels between two and four feet. Much of Florida could see heavy rainfall that could reach six inches in some places. The storm will then bring heavy rains to Georgia and the Carolinas later in the week.

Florida officials were worried that the storm could destabilize what was left of the condominium building that partially collapsed over a week ago. In order to avoid an uncontrolled collapse, they approved the demolition of the remaining portion of the building, which took place on Sunday night.

"The hurricane was coming, the potential for that building to fall on the pile with the victims in it was a tragic thought," Surfside Mayor Charles Burkett told NPR on Monday.

It's early in the hurricane season. The National Oceanic and Atmospheric Administration has predicted a busier-than-average Atlantic hurricane season, but it would be hard to top last year's, which set an all-time record with 30 named storms.

Tropical storms are fueled by warm water in the upper layers of the ocean, and ocean temperatures have been rising as heat is trapped by greenhouse gases.

Copyright 2021 NPR. To see more, visit https://www.npr.org.

This content is from Southern California Public Radio. View the original story at SCPR.org.




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Airtel signs up IBM to block unwanted calls

Bharti Airtel has awarded a multi-million-dollar contract to IBM to deploy a blockchain -based pan India network which will allow the telco to protect its 284 million subscribers from pesky calls and messages




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Jio likely to sign 5G gear deal with Nokia for $1.7 billion

Reliance Jio Infocomm is set to sign a $1.7bn deal with Nokia this week to purchase 5G network equipment. This follows the $2.1bn worth of equipment ordered by the Indian telecom operator from Ericsson in its attempt to roll out 5G across India this year. The company has already purchased 5G spectrum and plans to invest $25bn in 5G infrastructure, making its standalone mode the sole holder of the 700 MHz band in the country.




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Catawba Co., UNC-Charlotte sign agreement to collaborate on environmental and energy research at EcoComplex

Three applied research centers at the Charlotte Research Institute will install instrumentation and conduct experiments at the Eco-Complex, an expansion of innovative waste reduction and waste processing technology already underway at the Complex.




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Catawba County EMS designated as Permanent Car Seat Checking Station

As of October 1, 2012, Catawba County EMS has been named a Permanent Car Seat Checking Station by Buckle Up NC. Car seat checks will be conducted Monday thru Friday, from 9:00 a.m. to 4:00 p.m., by appointment, at the Newton EMS base, located at 1101 South Brady Ave, Newton, NC 28658.




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Climate Change Will Have A Significant Impact On Transportation Infrastructure And Operations

While every mode of transportation in the U.S. will be affected as the climate changes, potentially the greatest impact on transportation systems will be flooding of roads, railways, transit systems, and airport runways in coastal areas because of rising sea levels and surges brought on by more intense storms, says a new report from the National Research Council.




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U.S. Should Significantly Reduce Rate of Incarceration - Unprecedented Rise in Prison Population ‘Not Serving the Country Well,’ Says New Report

Given the minimal impact of long prison sentences on crime prevention and the negative social consequences and burdensome financial costs of U.S. incarceration rates, which have more than quadrupled in the last four decades, the nation should revise current criminal justice policies to significantly reduce imprisonment rates, says a new report from the National Research Council.