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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Emerging Role of Exosomal Long Non-coding RNAs in Spaceflight-Associated Risks in Astronauts

During spaceflight, astronauts are exposed to multiple unique environmental factors, particularly microgravity and ionizing radiation, that can cause a range of harmful health consequences. Over the past decades, increasing evidence demonstrates that the space environment can induce changes in gene expression and RNA processing. Long non-coding RNA (lncRNA) represent an emerging area of focus in molecular biology as they modulate chromatin structure and function, the transcription of neighboring genes, and affect RNA splicing, stability, and translation. They have been implicated in cancer development and associated with diverse cardiovascular conditions and associated risk factors. However, their role on astronauts’ health after spaceflight remains poorly understood. In this perspective article, we provide new insights into the potential role of exosomal lncRNA after spaceflight. We analyzed the transcriptional profile of exosomes isolated from peripheral blood plasma of three astronauts who flew on various Shuttle missions between 1998–2001 by RNA-sequencing. Computational analysis of the transcriptome of these exosomes identified 27 differentially expressed lncRNAs with a Log 2 fold change, with molecular, cellular, and clinical implications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Multiplexed characterization of rationally designed promoter architectures deconstructs combinatorial logic for IPTG-inducible systems

Abstract A crucial step towards engineering biological systems is the ability to precisely tune the genetic response to environmental stimuli. In the case of Escherichia coli inducible promoters, our incomplete understanding of the relationship between sequence composition and gene expression hinders our ability to predictably control transcriptional responses. Here, we profile the expression dynamics of 8269 rationally designed, IPTG-inducible promoters that collectively explore the individual and combinatorial effects of RNA polymerase and LacI repressor binding site strengths. We then fit a statistical mechanics model to measured expression that accurately models gene expression and reveals properties of theoretically optimal inducible promoters. Furthermore, we characterize three alternative promoter architectures and show that repositioning binding sites within promoters influences the types of combinatorial effects observed between promoter elements. In total, this approach enables us to deconstruct relationships between inducible promoter elements and discover practical insights for engineering inducible promoters with desirable characteristics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein

IGHV3-33 -encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparum circumsporozoite protein (PfCSP). Among VH3-33 antibodies, cross-reactivity between PfCSP major repeat (NANP), minor (NVDP), and junctional (NPDP) motifs is associated with high affinity and potent parasite inhibition. However, the molecular basis of antibody cross-reactivity and the relationship with efficacy remain unresolved. Here, we perform an extensive structure-function characterization of 12 VH3-33 anti-PfCSP monoclonal antibodies (mAbs) with varying degrees of cross-reactivity induced by immunization of mice expressing a human immunoglobulin gene repertoire. We identify residues in the antibody paratope that mediate cross-reactive binding and delineate four distinct epitope conformations induced by antibody binding, with one consistently associated with high protective efficacy and another that confers comparably potent inhibition of parasite liver invasion. Our data show a link between molecular features of cross-reactive VH3-33 mAb binding to PfCSP and mAb potency, relevant for the development of antibody-based interventions against malaria.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

SIRT1 targeted by miR ‐211‐5p regulated proliferation and apoptosis of Dex‐treated growth plate chondrocytes via mediating SOX2

Abstract Dexamethasone (Dex) is reported to cause bone growth retardation in children, which is associated with the increased apoptosis and decreased proliferation of growth plate chondrocytes. Sirtuin 1 (SIRT1) plays an important role in chondrocyte function and homeostasis. Thus, we further explored the regulatory mechanism of SIRT1 in Dex‐induced growth plate chondrocyte dysfunction. SIRT1 expression was detected in Dex‐treated growth plate chondrocytes using RT‐qPCR and western blot assay. The modulation of SIRT1 on SOX2 expression was evaluated. Besides, we identified that SIRT1 was targeted by miR‐211‐5p using TargetScan and RNA pull‐down assay. A loss‐of‐function assay was performed to evaluate the effects of miR‐211‐5p on Dex‐induced growth plate chondrocyte dysfunction in vitro and in vivo. We found that SIRT1 was downregulated in Dex‐treated growth plate chondrocytes. The expression of SOX2 was upregulated by overexpression SIRT1. Meanwhile, downregulation of SOX2 weakened the positive function of SIRT1 overexpression on Dex‐induced growth plate chondrocytes dysfunction. Subsequently, we confirmed that SIRT1 was targeted by miR‐211‐5p. MiR‐211‐5p inhibitor increased the expression levels of SIRT1 and SOX2, and restored the Dex‐treated growth plate chondrocyte function. Animal assays further demonstrated that the effects of miR‐211‐5p on the growth plate chondrogenesis. In conclusion, our data suggest that SIRT1 exerts a protective effect on growth plate chondrocyte under Dex stimulation. MiR‐211‐5p/SIRT1/SOX2 axis regulates the process of Dex‐inhibited growth plate chondrogenesis.

Cheng, Deliang↗
DOE OSTI2020

Improved two–stage protein expression and purification via autoinduction of both autolysis and auto DNA/RNA hydrolysis conferred by phage lysozyme and DNA/RNA endonuclease

We report improved release of recombinant proteins in Escherichia coli, which relies on combined cellular autolysis and DNA/RNA autohydrolysis, conferred by the tightly controlled autoinduction of both phage lysozyme and the nonspecific DNA/RNA endonuclease from Serratia marcescens. Autoinduction occurs in a two–stage process wherein heterologous protein expression and autolysis enzymes are induced upon entry into stationary phase by phosphate depletion. Cytoplasmic lysozyme and periplasmic endonuclease are kept from inducing lysis until membrane integrity is disrupted. After cell harvest, the addition of detergent (0.1% Triton X–100) and a single 30 min freeze–thaw cycle results in >90% release of protein, green fluorescent protein. Here, this cellular lysis is accompanied by complete oligonucleotide hydrolysis. The approach has been validated for shake flask cultures, high–throughput cultivation in microtiter plates, and larger scale stirred–tank bioreactors. This tightly controlled system enables robust growth and resistance to lysis in routine media when cells are propagated and autolysis/hydrolysis genes are only induced upon phosphate depletion

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Engineering sensitivity and specificity of AraC-based biosensors responsive to triacetic acid lactone and orsellinic acid

Abstract We previously described the design of triacetic acid lactone (TAL) biosensor ‘AraC-TAL1’, based on the AraC regulatory protein. Although useful as a tool to screen for enhanced TAL biosynthesis, this variant shows elevated background (leaky) expression, poor sensitivity and relaxed inducer specificity, including responsiveness to orsellinic acid (OA). More sensitive biosensors specific to either TAL or OA can aid in the study and engineering of polyketide synthases that produce these and similar compounds. In this work, we employed a TetA-based dual-selection to isolate new TAL-responsive AraC variants showing reduced background expression and improved TAL sensitivity. To improve TAL specificity, OA was included as a ‘decoy’ ligand during negative selection, resulting in the isolation of a TAL biosensor that is inhibited by OA. Finally, to engineer OA-specific AraC variants, the iterative protein redesign and optimization computational framework was employed, followed by 2 rounds of directed evolution, resulting in a biosensor with 24-fold improved OA/TAL specificity, relative to AraC-TAL1.

Wang, Zhiqing↗
DOE OSTI2026

An mRNA vaccine encoding the Ebola virus glycoprotein induces high neutralizing antibody titers and provides strong protection against lethal infections in mouse models

Ebola virus (EBOV) is the causative agent of Ebola disease (EBOD), a viral hemorrhagic fever with a notably high case fatality rate. Current treatments for EBOD are limited to monoclonal antibodies or two licensed viral vector vaccines, a recombinant vesicular stomatitis virus (rVSV)-vectored vaccine or an adenovirus and modified vaccinia Ankara regimen. However, comparisons of protection, efficacy, and durability with alternative nucleotide platforms remain understudied. Here, we evaluated the immunogenicity of an mRNA vaccine expressing the EBOV glycoprotein (GP) in parallel with rVSV- and DNA-based vaccine platforms. The mRNA EBOV-GP vaccine, formulated in lipid nanoparticles, elicited significantly higher levels of total IgG and neutralizing antibody titers compared to the rVSV-EBOV-GP vaccine. Linear antibody epitope analysis indicated a preference for targeting the mucin-like domain in EBOV-GP1 following rVSV-based vaccination, while the mRNA platform distinctly targeted the internal fusion loop of EBOV-GP2. After characterizing the immunogenicity of the mRNA vaccine, two models of EBOD were used to demonstrate its protective efficacy: a surrogate rVSV-based challenge model of EBOD using type-I interferon deficient C57BL/6 mice and infection of BALB/c mice with authentic mouse-adapted EBOV. In both studies, the EBOV mRNA vaccine fully protected the mouse cohorts against morbidity and mortality. Additionally, the EBOV mRNA vaccine produced greater neutralizing antibody titers compared to the DNA EBOV-GP vaccine. These results suggest that an mRNA vaccine expressing EBOV-GP can induce robust, functional humoral responses that are protective against EBOD, warranting further development as an alternative to, or as part of a vaccine strategy including, viral vectored vaccines.

DNA vaccines↗
DOE OSTI2022

Nonlinear quantum interferometric spectroscopy with entangled photon pairs

Here, we develop closed expressions for a time-resolved photon counting signal induced by an entangled photon pair in an interferometric spectroscopy setup. Superoperator expressions in Liouville-space are derived that can account for relaxation and dephasing induced by coupling to a bath. Interferometric setups mix matter and light variables non-trivially, which complicates their interpretation. We provide an intuitive modular framework for this setup that simplifies its description. Based on the separation between the detection stage and the light–matter interaction processes, we show that the pair entanglement time and the interferometric time-variables control the observed physics time scale. Only a few processes contribute in the limiting case of small entanglement time with respect to the sample response, and specific contributions can be singled out.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis

Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single-molecule long-read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation, or incomplete cDNA synthesis. We present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 169,000 transcripts—twice that of the best current Arabidopsis transcriptome and including over 1500 novel genes. Seventy-eight percent of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We develop novel methods to determine splice junctions and transcription start and end sites accurately. Mismatch profiles around splice junctions provide a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identify high-confidence transcription start and end sites and remove fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provides higher resolution of transcript expression profiling and identifies cold-induced differential transcription start and polyadenylation site usage. AtRTD3 is the most comprehensive Arabidopsis transcriptome currently. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage analysis from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single-molecule sequencing analysis from any species.

transcription start and end sites↗
DOE OSTI2023

Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression

Synthetic biology tools for regulating gene expression have many useful biotechnology and therapeutic applications. Most tools developed for this purpose control gene expression at the level of transcription, and relatively few methods are available for regulating gene expression at the translational level. Here, we design and engineer split orthogonal aminoacyl-tRNA synthetases (o-aaRS) as unique tools to control gene translation in bacteria and mammalian cells. Using chemically induced dimerization domains, we developed split o-aaRSs that mediate gene expression by conditionally suppressing stop codons in the presence of the small molecules rapamycin and abscisic acid. Furthermore, by activating o-aaRSs, these molecular switches induce stop codon suppression, and in their absence stop codon suppression is turned off. We demonstrate, in Escherichia coli and in human cells, that split o-aaRSs function as genetically encoded AND gates where stop codon suppression is controlled by two distinct molecular inputs. In addition, we show that split o-aaRSs can be used as versatile biosensors to detect therapeutically relevant protein–protein interactions, including those involved in cancer, and those that mediate severe acute respiratory syndrome-coronavirus-2 infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Low dose rate γ-irradiation protects fruit fly chromosomes from double strand breaks and telomere fusions by reducing the esi-RNA biogenesis factor Loquacious

Abstract It is still continuously debated whether the low-dose/dose-rate (LDR) of ionizing radiation represents a hazard for humans. Model organisms, such as fruit flies, are considered valuable systems to reveal insights into this issue. We found that, in wild-type Drosophila melanogaster larval neuroblasts, the frequency of Chromosome Breaks (CBs), induced by acute γ-irradiation, is considerably reduced when flies are previously exposed to a protracted dose of 0.4 Gy delivered at a dose rate of 2.5 mGy/h. This indicates that this exposure, which is associated with an increased expression of DNA damage response proteins, induces a radioadaptive response (RAR) that protects Drosophila from extensive DNA damage. Interestingly, the same exposure reduces the frequency of telomere fusions (TFs) from Drosophila telomere capping mutants suggesting that the LDR can generally promote a protective response on chromatin sites that are recognized as DNA breaks. Deep RNA sequencing revealed that RAR is associated with a reduced expression of Loquacious D (Loqs-RD) gene that encodes a well-conserved dsRNA binding protein required for esiRNAs biogenesis. Remarkably, loss of Loqs mimics the LDR-mediated chromosome protection as it decreases the IR-induced CBs and TFs frequency. Thus, our molecular characterization of RAR identifies Loqs as a key factor in the cellular response to LDR and in the epigenetic routes involved in radioresistance.

Porrazzo, A.↗
DOE OSTI2021

Laboratory Evaluation of the Thermal Breakout Method for Maximum Horizontal Stress Measurement

Measuring in situ stress is essential for many problems in geomechanics, and the maximum horizontal stress is the most difficult to constrain. We are developing an extension of the breakout method to measure maximum horizontal stress in regions where natural breakouts do not occur. In the novel thermal breakout method, additional compression which leads to breakout development is induced by heating the borehole wall. In the present study, we validated the method experimentally in a true-triaxial apparatus on samples with predrilled boreholes. Two rocks were selected for laboratory testing: high-porosity Berea sandstone and low-porosity Niagaran dolomite. Prior to main true-triaxial tests, we carried out standard testing to characterize the strength, elasticity and thermal properties. The true-triaxial experiments consisted of: (1) room-temperature tests where samples were first loaded mechanically until the breakout formed, and (2) elevated-temperature tests where samples were loaded mechanically within the elastic range with additional compression induced thermally. Breakout initiation was monitored by acoustic emission sensors mounted on the pistons that applied horizontal stresses. Furthermore, the magnitude of induced thermal stress was calculated from temperature measurements around the borehole wall. In both rock types, we created thermally induced breakouts and examined analytical expressions to constrain maximum horizontal stress based on strength, elastic and thermal properties of the rocks.

58 GEOSCIENCES↗
DOE OSTI2020

Escherichia coli Cas1/2 Endonuclease Complex Modifies Self-Targeting CRISPR/Cascade Spacers Reducing Silencing Guide Stability

CRISPR-based interference has become common in various applications from genetic circuits to dynamic metabolic control. In E. coli, the native CRISPR Cascade system can be utilized for silencing by deletion of the cas3 nuclease along with expression of guide RNA arrays, where multiple genes can be silenced from a single transcript. We notice the loss of spacer sequences from guide arrays utilized for dynamic silencing. Here, we report that unstable guide arrays are due to expression of the Cas1/2 endonuclease complex. We propose a model wherein basal Cas1/2 endonuclease activity results in the loss of spacers from guide arrays. Subsequently, mutant guide arrays can be amplified through selection. Replacing a constitutive promoter driving Cascade complex expression with a tightly controlled inducible promoter improves guide array stability, while minimizing leaky gene silencing. Additionally, these results demonstrate the potential of Cas1/2 mediated guide deletion as a mechanism to avoid CRISPR based autoimmunity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Interdependent iron and phosphorus availability controls photosynthesis through retrograde signaling

Abstract Iron deficiency hampers photosynthesis and is associated with chlorosis. We recently showed that iron deficiency-induced chlorosis depends on phosphorus availability. How plants integrate these cues to control chlorophyll accumulation is unknown. Here, we show that iron limitation downregulates photosynthesis genes in a phosphorus-dependent manner. Using transcriptomics and genome-wide association analysis, we identify two genes, PHT4;4 encoding a chloroplastic ascorbate transporter and bZIP58 , encoding a nuclear transcription factor, which prevent the downregulation of photosynthesis genes leading to the stay-green phenotype under iron-phosphorus deficiency. Joint limitation of these nutrients induces ascorbate accumulation by activating expression of an ascorbate biosynthesis gene, VTC4 , which requires bZIP58. Furthermore, we demonstrate that chloroplastic ascorbate transport prevents the downregulation of photosynthesis genes under iron-phosphorus combined deficiency through modulation of ROS homeostasis. Our study uncovers a ROS-mediated chloroplastic retrograde signaling pathway to adapt photosynthesis to nutrient availability.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

High-throughput feedback-enabled optogenetic stimulation and spectroscopy in microwell plates

Abstract The ability to perform sophisticated, high-throughput optogenetic experiments has been greatly enhanced by recent open-source illumination devices that allow independent programming of light patterns in single wells of microwell plates. However, there is currently a lack of instrumentation to monitor such experiments in real time, necessitating repeated transfers of the samples to stand-alone analytical instruments, thus limiting the types of experiments that could be performed. Here we address this gap with the development of the optoPlateReader (oPR), an open-source, solid-state, compact device that allows automated optogenetic stimulation and spectroscopy in each well of a 96-well plate. The oPR integrates an optoPlate illumination module with a module called the optoReader, an array of 96 photodiodes and LEDs that allows 96 parallel light measurements. The oPR was optimized for stimulation with blue light and for measurements of optical density and fluorescence. After calibration of all device components, we used the oPR to measure growth and to induce and measure fluorescent protein expression in E. coli . We further demonstrated how the optical read/write capabilities of the oPR permit computer-in-the-loop feedback control, where the current state of the sample can be used to adjust the optical stimulation parameters of the sample according to pre-defined feedback algorithms. The oPR will thus help realize an untapped potential for optogenetic experiments by enabling automated reading, writing, and feedback in microwell plates through open-source hardware that is accessible, customizable, and inexpensive.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Biosensors for the detection of chorismate and cis,cis -muconic acid in Corynebacterium glutamicum

Abstract Corynebacterium glutamicum ATCC 13032 is a promising microbial chassis for industrial production of valuable compounds, including aromatic amino acids derived from the shikimate pathway. In this work, we developed two whole-cell, transcription factor based fluorescent biosensors to track cis,cis-muconic acid (ccMA) and chorismate in C. glutamicum. Chorismate is a key intermediate in the shikimate pathway from which value-added chemicals can be produced, and a shunt from the shikimate pathway can divert carbon to ccMA, a high value chemical. We transferred a ccMA-inducible transcription factor, CatM, from Acinetobacter baylyi ADP1 into C. glutamicum and screened a promoter library to isolate variants with high sensitivity and dynamic range to ccMA by providing benzoate, which is converted to ccMA intracellularly. The biosensor also detected exogenously supplied ccMA, suggesting the presence of a putative ccMA transporter in C. glutamicum, though the external ccMA concentration threshold to elicit a response was 100-fold higher than the concentration of benzoate required to do so through intracellular ccMA production. We then developed a chorismate biosensor, in which a chorismate inducible promoter regulated by natively expressed QsuR was optimized to exhibit a dose-dependent response to exogenously supplemented quinate (a chorismate precursor). A chorismate–pyruvate lyase encoding gene, ubiC, was introduced into C. glutamicum to lower the intracellular chorismate pool, which resulted in loss of dose dependence to quinate. Further, a knockout strain that blocked the conversion of quinate to chorismate also resulted in absence of dose dependence to quinate, validating that the chorismate biosensor is specific to intracellular chorismate pool. The ccMA and chorismate biosensors were dually inserted into C. glutamicum to simultaneously detect intracellularly produced chorismate and ccMA. Biosensors, such as those developed in this study, can be applied in C. glutamicum for multiplex sensing to expedite pathway design and optimization through metabolic engineering in this promising chassis organism. One-Sentence Summary High-throughput screening of promoter libraries in Corynebacterium glutamicum to establish transcription factor based biosensors for key metabolic intermediates in shikimate and β-ketoadipate pathways.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

De novo transcriptome in roots of switchgrass ( Panicum virgatum L. ) reveals gene expression dynamic and act network under alkaline salt stress

Background: Soil salinization is a major limiting factor for crop cultivation. Switchgrass is a perennial rhizomatous bunchgrass that is considered an ideal plant for marginal lands, including sites with saline soil. Here we investigated the physiological responses and transcriptome changes in the roots of Alamo (alkaline-tolerant genotype) and AM314/MS-155 (alkaline-sensitive genotype) under alkaline salt stress. Results: Alkaline salt stress significantly affected the membrane, osmotic adjustment and antioxidant systems in switchgrass roots, and the ASTTI values between Alamo and AM-314/MS-155 were divergent at different time points. A total of 108,319 unigenes were obtained after reassembly, including 73,636 unigenes in AM-314/MS-155 and 65,492 unigenes in Alamo. A total of 10,219 DEGs were identified, and the number of upregulated genes in Alamo was much greater than that in AM-314/MS-155 in both the early and late stages of alkaline salt stress. The DEGs in AM-314/MS-155 were mainly concentrated in the early stage, while Alamo showed greater advantages in the late stage. These DEGs were mainly enriched in plant-pathogen interactions, ubiquitin-mediated proteolysis and glycolysis/gluconeogenesis pathways. We characterized 1480 TF genes into 64 TF families, and the most abundant TF family was the C2H2 family, followed by the bZIP and bHLH families. A total of 1718 PKs were predicted, including CaMK, CDPK, MAPK and RLK. WGCNA revealed that the DEGs in the blue, brown, dark magenta and light steel blue 1 modules were associated with the physiological changes in roots of switchgrass under alkaline salt stress. The consistency between the qRT-PCR and RNA-Seq results confirmed the reliability of the RNA-seq sequencing data. A molecular regulatory network of the switchgrass response to alkaline salt stress was preliminarily constructed on the basis of transcriptional regulation and functional genes. Conclusions: Alkaline salt tolerance of switchgrass may be achieved by the regulation of ion homeostasis, transport proteins, detoxification, heat shock proteins, dehydration and sugar metabolism. These findings provide a comprehensive analysis of gene expression dynamic and act network induced by alkaline salt stress in two switchgrass genotypes and contribute to the understanding of the alkaline salt tolerance mechanism of switchgrass and the improvement of switchgrass germplasm.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Full solution of the medium-induced radiation spectrum

New measurements of jet quenching observables at RHIC and at the LHC, such as jet substructure observables, demand an increased precision in the theory calculations describing medium-induced radiation of gluons. Closed expressions for the gluon spectrum including a full resummation of multiple scatterings have been known for the past 20 years. Still they have only been evaluated in specific limits either taking a few terms in an opacity expansion or by employing a Gaussian approximation for the interaction potential -- which misses essential physical effects. We present here a new flexible method to compute the full spectrum for a realistic interaction potential, thus allowing us for the first time to properly quantify the effect of the all-order resummation of multiple scatterings. This new approach paves the way for precision phenomenological studies including multiple scattering effects such as coherence phenomena.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗