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The Seoul Metropolitan Government will run a campaign to promote standardized naming of Korean dishes in foreign languages. According to city officials on Thursday, the campaign, in cooperation with the Seoul Tourism Organization and the Korea Food Service Industry Association, is set to continue through ...

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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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Foreign investors were net sellers in the South Korean stock market for the third month in October. According to data from the Bank of Korea(BOK) on Friday, foreigners sold a net four-point-17 billion U.S. dollars worth of stocks last month. But the latest figure is lower than September’s total of ...

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BGS signs memorandum of understanding with Serviço Geológico do Brasil  British Geological Survey

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.

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.

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.

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.

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.

During beam time at a research facility, alignment and optimization of instrumentation, such as spectrometers, is a time-intensive task and often needs to be performed multiple times throughout the operation of an experiment. Despite the motorization of individual components, automated alignment solutions are not always available. In this study, a novel approach that combines optimisers with neural network surrogate models to significantly reduce the alignment overhead for a mobile soft X-ray spectrometer is proposed. Neural networks were trained exclusively using simulated ray-tracing data, and the disparity between experiment and simulation was obtained through parameter optimization. Real-time validation of this process was performed using experimental data collected at the beamline. The results demonstrate the ability to reduce alignment time from one hour to approximately five minutes. This method can also be generalized beyond spectrometers, for example, towards the alignment of optical elements at beamlines, making it applicable to a broad spectrum of research facilities.

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.

The management and processing of synchrotron and neutron computed tomography data can be a complex, labor-intensive and unstructured process. Users devote substantial time to both manually processing their data (i.e. organizing data/metadata, applying image filters etc.) and waiting for the computation of iterative alignment and reconstruction algorithms to finish. In this work, we present a solution to these problems: TomoPyUI, a user interface for the well known tomography data processing package TomoPy. This highly visual Python software package guides the user through the tomography processing pipeline from data import, preprocessing, alignment and finally to 3D volume reconstruction. The TomoPyUI systematic intermediate data and metadata storage system improves organization, and the inspection and manipulation tools (built within the application) help to avoid interrupted workflows. Notably, TomoPyUI operates entirely within a Jupyter environment. Herein, we provide a summary of these key features of TomoPyUI, along with an overview of the tomography processing pipeline, a discussion of the landscape of existing tomography processing software and the purpose of TomoPyUI, and a demonstration of its capabilities for real tomography data collected at SSRL beamline 6-2c.

Cryo-electron tomography (cryo-ET) enables molecular-resolution 3D imaging of complex biological specimens such as viral particles, cellular sections and, in some cases, whole cells. This enables the structural characterization of molecules in their near-native environments, without the need for purification or separation, thereby preserving biological information such as conformational states and spatial relationships between different molecular species. Subtomogram averaging is an image-processing workflow that allows users to leverage cryo-ET data to identify and localize target molecules, determine high-resolution structures of repeating molecular species and classify different conformational states. Here, STOPGAP, an open-source package for subtomogram averaging that is designed to provide users with fine control over each of these steps, is described. In providing detailed descriptions of the image-processing algorithms that STOPGAP uses, this manuscript is also intended to serve as a technical resource to users as well as for further community-driven software development.

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.

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.

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.

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.

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.

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.

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.

Small-angle X-ray and neutron scattering (SAXS and SANS) patterns from certain semicrystalline polymers and liquid crystals contain discrete reflections from ordered assemblies and central diffuse scattering (CDS) from uncorrelated structures. Systems with imperfectly ordered lamellar structures aligned by stretching or by a magnetic field produce four distinct SAXS patterns: two-point `banana', four-point pattern, four-point `eyebrow' and four-point `butterfly'. The peak intensities of the reflections lie not on a layer line, or the arc of a circle, but on an elliptical trajectory. Modeling shows that randomly placed lamellar stacks modified by chain slip and stack rotation or interlamellar shear can create these forms. On deformation, the isotropic CDS becomes an equatorial streak with an oval, diamond or two-bladed propeller shape, which can be analyzed by separation into isotropic and oriented components. The streak has elliptical intensity contours, a natural consequence of the imperfect alignment of the elongated scattering objects. Both equatorial streaks and two- and four-point reflections can be fitted in elliptical coordinates with relatively few parameters. Equatorial streaks can be analyzed to obtain the size and orientation of voids, fibrils or surfaces. Analyses of the lamellar reflection yield lamellar spacing, stack orientation (interlamellar shear) angle α and chain slip angle ϕ, as well as the size distribution of the lamellar stacks. Currently available computational tools allow these microstructural parameters to be rapidly refined.

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.

Autonomous methods to align beamlines can decrease the amount of time spent on diagnostics, and also uncover better global optima leading to better beam quality. The alignment of these beamlines is a high-dimensional expensive-to-sample optimization problem involving the simultaneous treatment of many optical elements with correlated and nonlinear dynamics. Bayesian optimization is a strategy of efficient global optimization that has proved successful in similar regimes in a wide variety of beamline alignment applications, though it has typically been implemented for particular beamlines and optimization tasks. In this paper, we present a basic formulation of Bayesian inference and Gaussian process models as they relate to multi-objective Bayesian optimization, as well as the practical challenges presented by beamline alignment. We show that the same general implementation of Bayesian optimization with special consideration for beamline alignment can quickly learn the dynamics of particular beamlines in an online fashion through hyperparameter fitting with no prior information. We present the implementation of a concise software framework for beamline alignment and test it on four different optimization problems for experiments on X-ray beamlines at the National Synchrotron Light Source II and the Advanced Light Source, and an electron beam at the Accelerator Test Facility, along with benchmarking on a simulated digital twin. We discuss new applications of the framework, and the potential for a unified approach to beamline alignment at synchrotron facilities.

A passenger wearing a protective face covering to combat the spread of the coronavirus, checks her phone while travelling on a bus along Oxford Street in central London on July 5, 2021.; Credit: DANIEL LEAL-OLIVAS/AFP via Getty Images

In our continuing series looking at the latest medical research and news on COVID-19, Larry Mantle speaks with Professor Kristen Choi of UCLA. 

Topics today include:

• Biden to announce new efforts on vaccination campaign as Delta variant spreads

• Hospitalization rates getting worse for black residents of L.A. County 

• Which parts of the U.S. could be breeding grounds for variants?

• New Israeli data about effectiveness of Pfizer against Delta variant

• England to lift mask restrictions

• Cases on rise in immigration detention centers in the U.S. 

• Bay area zoo is vaccinating big cats and some other animals 

Guest:

Kristen R. Choi, professor of nursing and public health at UCLA; registered nurse practicing at Gateways Hospital, based in Echo Park

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

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."

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

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

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.

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

Source: Dr. Joseph Pantginis 11/04/2024

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, )

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

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.

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

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.

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

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

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.

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.

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.

A bold national initiative is needed to reduce the enormous health burden of sexually transmitted diseases (STDs) in the United States, according to a new report from a committee of the Institute of Medicine.

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.

The National Academy of Engineering (NAE) has elected 67 new members and 11 foreign associates, announced NAE President C.D. (Dan) Mote Jr. today. This brings the total U.S. membership to 2,250 and the number of foreign associates to 214.

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.

Veterans who participated in a series of tests during the 1960s known as Project SHAD (Shipboard Hazard and Defense) show no significant increase in adverse health outcomes, specific causes of death, or death rates compared with a similar group of veterans who were not involved in the tests, says a new report from a committee of the National Academies of Sciences, Engineering, and Medicine.

Conducting clinical investigations of mitochondrial replacement techniques (MRT) in humans is ethically permissible as long as significant conditions and principles are met, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Although individual anglers – people who fish recreationally – generally take small numbers of fish, collectively, a large number of them can have a substantial impact on the overall stock.

A new book from the National Academies of Sciences, Engineering, and Medicine outlines how educators can develop and adapt student assessments for the classroom that reflect the approach to learning and teaching science described in the Next Generation Science Standards (NGSS) and similar standards.

The U.S. DRIVE Partnership – a government-industry partnership that fosters the development of precompetitive and innovative technologies for clean and efficient light-duty vehicles – has made significant progress in many technical areas including advanced combustion technologies, durability and cost of hydrogen fuel cells, and electric drive systems such as motors, power electronics, and batteries, says a new report by the National Academies of Sciences, Engineering, and Medicine.

Cognitive training, blood pressure management for people with hypertension, and increased physical activity all show modest but inconclusive evidence that they can help prevent cognitive decline and dementia, but there is insufficient evidence to support a public health campaign encouraging their adoption, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The U.S. lacks icebreaking capability in the Arctic and Antarctic and should build four polar icebreakers with heavy icebreaking capability to help minimize the life-cycle costs of icebreaker acquisition and operations, says a new congressionally mandated letter report from the National Academies of Sciences, Engineering, and Medicine.

Although the process used to develop the Dietary Guidelines for Americans (DGA) has become more evidence-based since its inception more than 30 years ago, it is not currently positioned to effectively adapt to changes such as food diversity and chronic disease prevalence, while also ensuring the integrity of the process, says a new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

A new report from the National Academies of Sciences, Engineering, and Medicine calls for an international, multi-institutional comprehensive campaign of research, observation, and analysis activities that would help improve understanding and prediction of the Gulf of Mexico’s Loop Current System (LCS).

The National Academy of Engineering has elected 83 new members and 16 foreign members, announced NAE President C. D. (Dan) Mote, Jr., today.

The National Academy of Sciences elected 84 new members and 21 foreign associates in recognition of their distinguished and continuing achievements in original research.