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At least 613 records · Page 34

The differing effects of a dual acting regulator on SIRT1

SIRT1 is an NAD + -dependent protein deacetylase that has been shown to play a significant role in many biological pathways, such as insulin secretion, tumor formation, lipid metabolism, and neurodegeneration. There is great interest in understanding the regulation of SIRT1 to better understand SIRT1-related diseases and to better design therapeutic approaches that target SIRT1. There are many known protein and small molecule activators and inhibitors of SIRT1. One well-studied SIRT1 regulator, resveratrol, has historically been regarded as a SIRT1 activator, however, recent studies have shown that it can also act as an inhibitor depending on the identity of the peptide substrate. The inhibitory nature of resveratrol has yet to be studied in detail. Understanding the mechanism behind this dual behavior is crucial for assessing the potential side effects of STAC-based therapeutics. Here, we investigate the detailed mechanism of substrate-dependent SIRT1 regulation by resveratrol. We demonstrate that resveratrol alters the substrate recognition of SIRT1 by affecting the K M values without significantly impacting the catalytic rate k cat ). Furthermore, resveratrol destabilizes SIRT1 and extends its conformation, but the conformational changes differ between the activation and inhibition scenarios. We propose that resveratrol renders SIRT1 more flexible in the activation scenario, leading to increased activity, while in the inhibition scenario, it unravels the SIRT1 structure, compromising substrate recognition. Our findings highlight the importance of substrate identity in resveratrol-mediated SIRT1 regulation and provide insights into the allosteric control of SIRT1. This knowledge can guide the development of targeted therapeutics for diseases associated with dysregulated SIRT1 activity.

59 BASIC BIOLOGICAL SCIENCES↗

Developing nanometer scale, atomically precise metallo-catalysts with Molecular Lego

We propose to create atomically precise, highly robust, nanometer scale macromolecules that organize biomimetic metal binding groups in designed three-dimensional pockets to accelerate specific polymerization reactions. These atomically precise catalysts will create atomically precise polymers with improved mechanical and environmental properties from renewable building blocks. We seek to create and study nanometer scale catalysts that mimic metallo-enzymes in their activity and selectivity because these larger catalysts will be able to make more extensive non-covalent contacts with the transition state of the growing polymer. These catalysts will have extended lifetimes because they will better protect the metals and higher activity because additional reactive groups can be brought in close contact with the active site to enhance reactivity. They will be far more tolerant to extremes of temperature and will not denature in non-aqueous solvents because they are held together by multiple, strong, covalent bonds. Our approach to catalysts could be used to develop catalysts to replace noble metal-based catalysts when targeting other reactions, because the geometry of the active site enforced by the Molecular Lego scaffolding will access new reactivity, mimicking how nature uses earth abundant metals for much of its catalysis. We will initially target Lewis acid-based catalysts that assemble aliphatic polyesters with improved stereoselectivity, tacticity and complex alternation of monomers. Aliphatic polyesters have received growing attention as attractive, environmentally benign, and sustainable alternatives to polymers developed from petroleum feedstocks. Aliphatic polyesters are environmentally friendly because they undergo facile hydrolytic degradation to benign products, and they have excellent properties and high biocompatibility. We will assemble these catalysts using unique “Spiroligomers” (aka Molecular Lego) chemistry developed in the Schafmeister group combined with the organometallic chemistry expertise of the Dobereiner group. Polymers are an attractive synthetic target of nanoscale atomically precise catalysts because their resulting structure, stereochemistry and tacticity has profound impact on their properties (crystalline vs amorphous) and provides a readout of the catalytic mechanism. Polymer synthesis also serves as an example of “atomically precise manufacturing” where atomically precise nanoscale catalysts construct polymers with atomic precision at increasing length scales.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

A Pseudo Planar Heterojunction Structure for Eco‐Friendly Printable Organic Solar Cells Achieving 19.05% Efficiency

Abstract Obtaining a well‐accurate vertical distribution active layer morphology through the air‐printing process is an essential task for achieving efficient scalable large‐area organic solar cells (OSCs). In this target, the desired and controllable pseudo planar heterojunction (PPHJ) active layer structure with suitable phase separation is developed by pre‐deposited D18‐Cl layer under the PM6:BTP‐eC9 film via an eco‐friendly manufacturing method. The addition of the D18‐Cl regulates molecular crystallization and leads to an ideal vertical stratification while simultaneously suppressing voltage loss, optimizing energetic disorder, and carrier management. Impressively, the optimal PPHJ devices perform superior power conversion efficiencies (PCEs) of 19.05% (100 nm), 17.33% (300 nm), and 14.14% (4 cm 2 ) compared to the BHJ devices. Importantly, the PPHJ OSCs also exhibit an impressive extrapolated T 80 (the time required to reach 80% of initial PCE) of long‐time storage and operational stability, as well as thermal stability.

Chemistry↗

NASA, Remote Sensing and Archaeology: An Example from Southeast Louisiana

NASA Stennis Space Center, located in Mississippi, USA, undertook an archaeological survey of the southeastern Louisiana marshes beginning in 2003. Progress on this activity was severely hampered by the 2005 hurricane season when both Katrina and Rita devastated the study area. In 2008, the NASA team reinitiated the analysis of the project data and that work continues today. The project was conducted initially in partnership with the U.S. Army, Corps of Engineers New Orleans District and Tulane University. NASA and its partners utilized a wide variety of satellite and airborne remote sensing instruments combined with field verification surveys to identify prehistoric archeological sites in the Southeastern Louisiana delta, both known and still undiscovered. The main approach was to carefully map known sites and use the spectral characteristics of these sites to locate high probability targets elsewhere in the region. The archaeological activities were conducted in support of Coast 2050 whose stated goals is to sustain and restore a coastal ecosystem that supports and protects the environment, economy and culture of southern Louisiana. As the Coast 2050 report states: [T]he rate of coastal land loss in Louisiana has reached catastrophic proportions. Within the last 50 years, land loss rates have exceeded 40 square miles per year, and in the 1990's the rate has been estimated to be between 25 and 35 square miles each year. This loss represents 80% of the coastal wetland loss in the entire continental United States.

Giardino, Marco J.↗

The Southern African Regional Science Initiative (SAFARI 2000). Dry-Season Campaign: An Overview

The Southern African Regional Science Initiative (SAFARI 2000) is an international science project investigating the southern African earth-atmosphere-human system. The experiment was conducted over a two-year period March 1999 - March 2001. The dry season field campaign (August-Steptember 2000) was the most intensive activity and involving over 200 scientists from 18 different nations. The main objectives of this campaign were to characterize and quantify the biogenic, pyrogenic and anthropogenic aerosol and trace gas emissions and their transport and transformations in the atmosphere and to validate the NASA Earth Observing System (EOS) satellite Terra within a scientific context. Five aircraft, namely two South African Weather Service aircraft, University of Washington CV-580, the UK Meteorological Office C-130 and the NASA ER-2, with different altitude capabilities, participated in the campaign. Additional airborne sampling of southern African air masses that had moved downwind of the subcontinent was conducted by the CSIRO over Australia. Multiple observations were taken in various sectors for a variety of synoptic conditions. Flight missions were designed to maximize synchronous over-flights of the NASA TERRA satellite platform, above regional ground validation and science targets. Numerous smaller-scale ground validation activities took place throughout the region during the campaign period.

Swap, R. J.↗

Activity coefficient acquisition with thermodynamics–informed active learning for phase diagram construction

This work explores the use of thermodynamics-informed Gaussian processes (GPs) and active learning (AL) to model activity coefficients and construct phase diagrams. Relying on synthetic data generated from an excess Gibbs energy model, GPs were found to accurately describe the activity coefficients of several binary mixtures across large composition and temperature ranges. Moreover, GPs could estimate their own uncertainty and identify composition/temperature regions where activity coefficient data provide the most information to the models. This was leveraged to build AL algorithms targeted at modeling phase equilibria. In many cases, a single active-learning-acquired data point was sufficient to describe the phase diagrams studied. Lastly, the ability of AL to greatly reduce the amount of data needed to obtain accurate models was further verified on experimental case studies, namely individual ion activity coefficients, the solid–liquid and vapor–liquid equilibrium of deep eutectic solvents, and phase equilibria in ternary mixtures.

25 ENERGY STORAGE↗

A transcriptional relationship with a natural product disrupts mitochondrial biogenesis

Discovery of new compound leads and oncology targets to treat cancer will require overcoming resistance to traditional therapies such as BRAF and mitogen-activated protein kinase inhibitors (MAPKi). In addition, potent new therapies will benefit from selective localization at the cancer site rather than general cell toxicity which can lead to undesired side effects. This selectivity can be gained by identifying new compound leads that are “prodrugs”, that is they are activated by mechanisms selective to cancer cells leading to strong pharmacological activity (Zhang, 2017). Continuing discovery of anticancer agents that overcome resistance and take advantage of cancer cell mechanisms will be greatly augmented by returning to the potent well of natural products; in fact, an analysis of a 70-year period ending in 2014 showed that nearly 50% of approved anticancer drugs are or are derived from natural products (Newman, 2016). Discovery of new agents with high potency and selectivity will require natural product research focused on discovering biologically active compounds with unique structures and mechanisms of action that utilize target cell functions.

Wright, Aaron T.↗

Discrete-Layer Piezoelectric Plate and Shell Models for Active Tip-Clearance Control

The objectives of this work were to develop computational tools for the analysis of active-sensory composite structures with added or embedded piezoelectric layers. The targeted application for this class of smart composite laminates and the analytical development is the accomplishment of active tip-clearance control in turbomachinery components. Two distinct theories and analytical models were developed and explored under this contract: (1) a discrete-layer plate theory and corresponding computational models, and (2) a three dimensional general discrete-layer element generated in curvilinear coordinates for modeling laminated composite piezoelectric shells. Both models were developed from the complete electromechanical constitutive relations of piezoelectric materials, and incorporate both displacements and potentials as state variables. This report describes the development and results of these models. The discrete-layer theories imply that the displacement field and electrostatic potential through-the-thickness of the laminate are described over an individual layer rather than as a smeared function over the thickness of the entire plate or shell thickness. This is especially crucial for composites with embedded piezoelectric layers, as the actuating and sensing elements within these layers are poorly represented by effective or smeared properties. Linear Lagrange interpolation polynomials were used to describe the through-thickness laminate behavior. Both analytic and finite element approximations were used in the plane or surface of the structure. In this context, theoretical developments are presented for the discrete-layer plate theory, the discrete-layer shell theory, and the formulation of an exact solution for simply-supported piezoelectric plates. Finally, evaluations and results from a number of separate examples are presented for the static and dynamic analysis of the plate geometry. Comparisons between the different approaches are provided when possible, and initial conclusions regarding the accuracy and limitations of these models are given.

Heyliger, P. R.↗

Increased enhancer–promoter interactions during developmental enhancer activation in mammals

Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here, in this study, we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. Sixty-one percent of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer-promoter and enhancer-enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer-promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general importance of enhancer-promoter physical proximity for developmental gene activation in mammals.

59 BASIC BIOLOGICAL SCIENCES↗

Advanced Materials for Exploration Task Research Results

The Advanced Materials for Exploration (AME) Activity in Marshall Space Flight Center s (MSFC s) Exploration Science and Technology Directorate coordinated activities from 2001 to 2006 to support in-space propulsion technologies for future missions. Working together, materials scientists and mission planners identified materials shortfalls that are limiting the performance of long-term missions. The goal of the AME project was to deliver improved materials in targeted areas to meet technology development milestones of NASA s exploration-dedicated activities. Materials research tasks were targeted in five areas: (1) Thermal management materials, (2) propulsion materials, (3) materials characterization, (4) vehicle health monitoring materials, and (5) structural materials. Selected tasks were scheduled for completion such that these new materials could be incorporated into customer development plans.

Cook, M. B.↗

Radio and X-ray emission from main-sequence K stars

A small VLA radio continuum survey of 12 selected active, main-sequence K stars is presented. The targets are uniformly distributed between spectral types K0 and K8; five are single stars, five are spectroscopic binaries, and two are visual binaries. All targets are within 25 pc and were selected based on strong X-rays, rapid rotation, or strong Ca II emission lines. Seven targets were detected at the observing frequency of 8.5 GHz (3.6 cm), while sensitive upper limits are reported for the nondetections. The radio luminosities are comparable to active M dwarfs. Radio and X-ray luminosities LR and LX fulfil a relation that was previously found for M dwarfs, with LR varies as LX over 3 orders of magnitude. We further find that the more rapidly rotating K dwarfs are stronger radio emitters, irrespective of spectral type.

Gudel, M.↗

GLAST Large Area Telescope Multiwavelength Opportunities

The Gamma-ray Large Area Space Telescope (GLAST) is scheduled for launch this year. Because the GLAST Large Area Telescope (LAT) has a huge field of view and the GLAST Observatory will be operated in scanning mode, it will survey the entire sky daily. The GLAST Mission and the LAT Collaboration invite cooperative efforts from theorists and observers at all wavelengths to help optimize the science. Possible topics include: (1) Blazars: These Active Galactic Nuclei are expected to be a major source class for LAT. Identifying new blazars, monitoring their variability, and joining programs to carry out planned or Target of Opportunity multiwavelength campaigns will all be important activities. The study of AGN gamma-ray jets can help link the accretion processes close to the black hole with the large-scale interaction of the AGN with its environment. (2) Unidentified Gamma-ray Sources: Modeling of possible gamma-ray sources is important to establish testable hypotheses. New gamma-ray sources need first to be identified with known objects by position, spectrum, or time variability, and then multiwavelength studies can be used to explore the astrophysical implications of high-energy radiation from these sources. The LAT team is committed to releasing a preliminary source list about six months after the start of science operations.

Thompson, David↗

Simulation of cosmic irradiation conditions in thick target arrangements

One approach to simulate 2-pi irradiation conditions of planetary surfaces which has been widely applied in the past are bombardments of so called thick targets. A very large thick target was exposed recently to 2.1 GeV protons at the Bevatron-Bevalac in Berkeley. In a 100x100x180 cm steel-surrounded granodiorite target radioactive medium and high energy spallation products of the incident primary and of secondary particles were analyzed along the beam axis down to depths of 140 g/cm(2) in targets such as Cu, Ni, Co, Fe, T, Si, SiO2 and Al. Activities of these nuclides were exclusively determined via instrumental gamma-ray spectroscopy. Relative yields of neutron capture and spallation products induced in Co and Cu targets during the thick target bombardment are shown as a function of depth. The majority of the medium energy products such as Co-58 from Co targets exhibit a maximum at shallow depths of 40-60 g/cm(2) and then decrease exponentially. In a comparable 600 MeV proton bombarded thick target such a slight maximum for medium energy products was not observed. Rather, Co-58 activities in Co decreased steadily with the highest activity at the surface. The activities of the n-capture product Co-60 increase steadily starting at the surface. This indicates the rapidly growing flux of low energy neutrons within the target.

Theis, S.↗

Second Report of the Nuclear Data Subcommittee of the Nuclear Science Advisory Committee

The central importance of the nuclear data curated by the US Nuclear Data Program (USNDP) for clean energy generation, national security, nonproliferation, medical applications, and space exploration as well as basic science was described in a prior report issued by the DOE/NSF Nuclear Science Advisory Committee subcommittee on Nuclear Data (NSAC-ND) in September 2022. In this report, we present a set of fourteen (14) recommendations that will enhance and advance DOE-NP's stewardship of nuclear data. The first three recommendations focus on the existing core USNDP capabilities, namely: 1) Support the nuclear structure evaluation workforce to improve the currency, consistency, and accessibility of the Evaluated Nuclear Structure Data File (ENSDF); 2) Enhance nuclear reaction evaluation within the USNDP in support of the Evaluated Nuclear Data File (ENDF) through expansion of the workforce and integration of high-performance computing, automation, and machine learning and; 3) Continue atomic mass evaluation in support AME and NUBASE databases. This is followed by eight (8) recommendations representing new cross-cutting initiatives involving both measurement and evaluation to address outstanding nuclear data needs. These new initiatives require a highly trained, diverse workforce that includes personnel with expertise from both inside and outside the nuclear physics community from which evaluators have traditionally been recruited. As such, many of these initiatives are accomplished via a Topical Nuclear Data Collaborations (TNDC). A TNDC is made up of domestic and international stakeholders, subject matter and nuclear data experts, and nuclear data evaluators and features a workforce development plan to ensure that nuclear data evaluators maintain currency in the relevant applications and are seen as equity partners in the endeavor. These include: 1) Establish a coordinated effort to improve evaluation and modeling in nuclear astrophysics for stellar dynamics, multi-messenger astronomy and nucleosynthesis; 2) Initiate a TNDC to develop and maintain nuclear structure evaluation beyond discrete states, including nuclear level densities, photon strength functions and photonuclear data for improved reaction modeling, and exploring nuclear structure at finite temperature; 3) Create a TNDC to perform correlated fission data evaluation, including cross sections, fragment yields, v(A), v(E n ) for nuclear energy, national security, nonproliferation and basic science; 4) From a panel of subject matter experts to establish and annually update a roster of key decay data to nurture its accelerated dissemination including both measurement and evaluation for targeted high-value nuclides for national security, nonproliferation and medical applications; 5) Comprehensive, consistent neutron-induced structure and reaction data for nuclear energy, national security, nonproliferation and planetary nuclear spectroscopy; 6) Charged-particle stopping powers for detector design, space effects and ion beam therapy; 7) High-energy reactions for space exploration and medical nuclide production, and; 8) The creation of an infrastructure for open data and data preservation for use by the entire nuclear physics community. All told, these initiatives require approximately $6.5M increase in NP support of the USNDP in fiscal year 2023 dollars and would require at least 3-5 years to carry out due to the length of time needed to recruit and train new nuclear data researchers. This relatively modest investment would help ensure that the fruits of the nuclear data research carried out by DOE-NP and its collaborators would be brought to bear to address some of the most important needs of our nation and the world. To ensure effective execution of this plan, we present an overview of recruitment, training, and retention goals for the USNDP, the centerpiece of which is a mutually agreed upon code of conduct. Finally, we identify the facility and instrumentation needed to perform the recommended experimental activities. This includes a short review of target fabrication capabilities, reactors, neutron beam, light- and heavy-stable ion, gamma-ray, high-energy and radioactive ion beam facilities. Lastly, a more complete appendix of experimental facilities previously compiled is included with new input provided for 6 facilities.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β–mediated AML progression

Identifying and targeting microenvironment-driven pathways that are active across acute myeloid leukemia (AML) genetic subtypes should allow the development of more broadly effective therapies. The proinflammatory cytokine interleukin-1β (IL-1β) is abundant in the AML microenvironment and promotes leukemic growth. Through RNA-sequencing analysis, we identify that IL-1β–upregulated ASF1B (antisilencing function-1B), a histone chaperone, in AML progenitors compared with healthy progenitors. ASF1B, along with its paralogous protein ASF1A, recruits H3-H4 histones onto the replication fork during S-phase, a process regulated by Tousled-like kinase 1 and 2 (TLKs). Although ASF1s and TLKs are known to be overexpressed in multiple solid tumors and associated with poor prognosis, their functional roles in hematopoiesis and inflammation-driven leukemia remain unexplored. In this study, we identify that ASF1s and TLKs are overexpressed in multiple genetic subtypes of AML. We demonstrate that depletion of ASF1s significantly reduces leukemic cell growth in both in vitro and in vivo models using human cells. Using a murine model, we show that overexpression of ASF1B accelerates leukemia progression. Moreover, Asf1b or Tlk2 deletion delayed leukemia progression, whereas these proteins are dispensable for normal hematopoiesis. Through proteomics and phosphoproteomics analyses, we uncover that the TLK-ASF1 pathway promotes leukemogenesis by affecting the cell cycle and DNA damage pathways. Collectively, our findings identify the TLK1-ASF1 pathway as a novel mediator of inflammatory signaling and a promising therapeutic target for AML treatment across diverse genetic subtypes. Finally, selective inhibition of this pathway offers potential opportunities to intervene effectively, address intratumoral heterogeneity, and ultimately improve clinical outcomes in AML.

60 APPLIED LIFE SCIENCES↗

Radiobiology, Omics and Microdosimetry of Systemic and Targeted Radiotherapeutics Workshop

The Radiobiology, Omics and Microdosimetry of Systemic and Targeted Radiotherapeutics Workshop fostered engagement across disciplines on critical topics that impact the development of targeted radionuclide therapies, bringing together scientific and medical professionals actively involved in radiotherapeutic design, optimization testing, patient treatment, and clinical trials along with basic science researchers, whose novel techniques have the potential to further our understanding of targeted radionuclide therapy. Discussion of the applications of radiotherapeutics to pediatric and adult, brain, prostate and blood cancers, and metastatic disease allowed scientific research to be presented in the context of real-world medical applications and provided an important backdrop to the basic research performed in computers, laboratories, and animal facilities. The workshop format, presentations, and panel discussions were designed to consider a holistic approach to the development of systemic and targeted radiotherapies, integrating radiobiology and microdosimetry, biological assessments on the microscale, and physiologically relevant models of tumor and tissue microenvironments. Important needs highlighted in the workshop include better models to assess the biological effects of radionuclide therapy, novel strategies to target radiotherapeutics to disease sites with high specificity, and new dosimetry techniques that address the importance of tumor microenvironments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A Deep Imaging Survey of NGC 6475 and a Deep Survey of the Young Open Cluster Alpha Persei

We have published three papers directly related to the x-ray data (see below), and one other paper directly related to the optical photometry obtained in connection to the ROSAT data analysis (also listed below). In addition, we have used the x-ray data in combination with the optical photometry and with high resolution optical spectra that we have obtained (to derive spectroscopic rotational velocities) to address questions related to the dependence of coronal activity on the rotation rate, mass, and other characteristics of the target stars. The overall goal of our ROSAT projects has been to determine the time evolution of coronal activity in low mass stars, and from that behavior place constraints on the physical processes involved in generating coronal activity. NGC 6475 and Alpha Persei are important parts of that process. We are now beginning to address how these data constrain theoretical models of angular momentum evolution and dynamo magnetic field generation (see paper by Stauffer et al. and Krishnamurthi et al. listed below in the "related papers" section). We are still working on two papers pertaining to this grant (rotational velocities and chromospheric activity of Alpha Persei x-ray sources and rotational velocities and lithium abundances of NGC 6475 sources), but we will publish those papers using funds from other grants.

Stauffer, John R.↗

The activity of antimicrobial peptoids against multidrug-resistant ocular pathogens

Background: Ocular infections caused by antibiotic-resistant pathogens can result in partial or complete vision loss. The development of pan-resistant microbial strains poses a significant challenge for clinicians as there are limited antimicrobial options available. Synthetic peptoids, which are sequence-specific oligo-N-substituted glycines, offer potential as alternative antimicrobial agents to target multidrug-resistant bacteria. Methods: The antimicrobial activity of synthesised peptoids against multidrug-resistant (MDR) ocular pathogens was evaluated using the microbroth dilution method. Hemolytic propensity was assessed using mammalian erythrocytes. Peptoids were also incubated with proteolytic enzymes, after which their minimum inhibitory activity against bacteria was re-evaluated. Results: Several alkylated and brominated peptoids showed good inhibitory activity against multidrug-resistant Pseudomonas aeruginosa strains at concentrations of ≤15 μg mL -1 (≤12 µM). Similarly, most brominated compounds inhibited the growth of methicillin-resistant Staphylococcus aureus at 1.9 to 15 μg mL -1 (12 µM). The N-terminally alkylated peptoids caused less toxicity to erythrocytes. The peptoid denoted as TM5 had a high therapeutic index, being non-toxic to either erythrocytes or corneal epithelial cells, even at 15 to 22 times its MIC. Additionally, the peptoids were resistant to protease activity. Conclusions: Peptoids studied here demonstrated potent activity against various multidrug-resistant ocular pathogens. Their properties make them promising candidates for controlling vision-related morbidity associated with eye infections by antibiotic-resistant strains.

60 APPLIED LIFE SCIENCES↗