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At least 649 records · Page 36

A mouse pancreatic organoid model to compare PD-L1 blocking antibodies

Immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape for cancer patients, but diabetes, a rare, severe immune-related endocrinopathy, is linked to ICI therapy. It is unclear whether glycosylation of ICIs may play a role in the development of this adverse event and how the physiological effects of different ICIs on pancreatic cells should be evaluated. We used a mouse pancreatic organoid model to compare three PD-L1 blocking antibodies in the presence or absence of IFNγ using a metabolic bioanalyzer. Modulation of ICI glycosylation altered its metabolic effects on mouse pancreatic organoids, suggesting that this model could be used to monitor and compare ICIs and to study the mechanisms underlying the development of IC-mediated diabetes.

60 APPLIED LIFE SCIENCES↗

COMPARING THE ACCRETION DISK EVOLUTION OF BLACK HOLE AND NEUTRON STAR X-RAY BINARIES FROM LOW TO SUPER-EDDINGTON LUMINOSITY

Low-mass X-ray binaries (LMXBs) are systems in which a low-mass companion transfers mass via Roche-lobe overflow onto a black hole (BH) or a weakly magnetized neutron star (NS). It is believed that both the solid surface and the magnetic field of an NS can affect the accretion flow and show some observable effects. Using the disk emission dominant data, we compare the disk evolution of the two types of systems from low luminosity to super-Eddington luminosity. As the luminosity decreases the disk in the NS LMXB 4U1608-522 begins to leave the innermost stable circular orbit (ISCO) at much higher luminosity ({approx}0.1 L{sub Edd}), compared with BH LMXBs at much lower luminosity ({approx}0.03 L{sub Edd}), due to the interaction between the NS magnetosphere and accretion flow. However, as the luminosity increases above a critical luminosity, the disks in BH and NS LMXBs trace the same evolutionary pattern, because the magnetosphere is restricted inside ISCO, and then both the NS surface emission and (dipole) magnetic field do not significantly affect the secular evolution of the accretion disk, which is driven by the increased radiation pressure in the inner region. We further suggest that the NS surface emission provides additional information about the accretion disk not available in BH systems. Through the observed NS surface emission, we argue that the disk thickness H/R is less than 0.3-0.4, and that the significant outflow from the inner disk edge exists at a luminosity close to Eddington luminosity.

79 ASTRONOMY AND ASTROPHYSICS↗

Comparing the fluorination of Pb+ and Po+: insights into p-block relativistic effects for superheavy elements

It is expected that the chemical properties of the heaviest of the superheavy elements (SHEs, = 113 – 118) do not align with what is suggested by their current positions on the periodic table. Specifically, the onset of significant relativistic effects, including increased spin–orbit splitting of the p-orbitals may lead to enhanced stability of low-oxidation states. Notably, it is predicted that flerovium ( = 114) may exhibit pseudo-noble gas behavior from a electron configuration that acts as an ‘inert pair’. Even though it is expected that the – splitting becomes pronounced toward the end of the p-block’s sixth row, there is currently limited experimental evidence to confirm its extent or impact. Here, the production of gas-phase lead ( = 82) and polonium ( = 84) fluoride cations (PbF and PoF ) were compared to elucidate differences in accessible oxidation states. The PoF and PbF species were produced and identified with the FIONA spectrometer at the Lawrence Berkeley National Laboratory 88-Inch Cylctron Facility. Polonium showed notably different fluorination chemistry than lead, producing PoF and PoF as primary products compared to lead’s PbF and PbF . The distribution of PoF products observed offer insights as to the role of spin–orbit splitting for polonium. Similar studies of superheavy elements would elucidate the accessibility of their low-oxidation states as well as to inform chemical predictions for eighth-row elements not yet discovered.

Pore, Jennifer L [Nuclear Science Division, Lawren↗

Theoretical and experimental study of temperature effect on electronic and optical properties of TiO 2 : Comparing rutile and anatase

To gain fundamental understanding of the high-temperature optical gas-sensing and light-energy conversion materials, we comparatively investigate the temperature effects on the band gap and optical properties of rutile and anatase TiO 2 experimentally and theoretically. Given that the electronic structures of rutile and anatase are fundamentally different, i.e. direct band gap in rutile and indirect gap in anatase, it is not clear whether these materials exhibit different electronic structure renormalizations with temperature. Using ab initio methods, we show that the electron-phonon interaction is the dominant factor for temperature band gap renormalization compared to the thermal expansion. As a result of different contributions from the acoustic and optical phonons, the band gap is found to widen with temperature up to 300 K, and to narrow at higher temperatures.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Probing neutrino mass hierarchy by comparing the charged-current and neutral-current interaction rates of supernova neutrinos

The neutrino mass hierarchy is one of the neutrino fundamental properties yet to be determined. We introduce a method to determine neutrino mass hierarchy by comparing the interaction rate of neutral current (NC) interactions, ν(ν-bar)+p→ν(ν-bar)+p, and inverse beta decays (IBD), ν-bar{sub e}+p→n+e{sup +}, of supernova neutrinos in scintillation detectors. Neutrino flavor conversions inside the supernova are sensitive to neutrino mass hierarchy. Due to Mikheyev-Smirnov-Wolfenstein effects, the full swapping of ν-bar{sub e} flux with the ν-bar{sub x} (x=μ, τ) one occurs in the inverted hierarchy, while such a swapping does not occur in the normal hierarchy. As a result, more high energy IBD events occur in the detector for the inverted hierarchy than the high energy IBD events in the normal hierarchy. By comparing IBD interaction rate with the mass hierarchy independent NC interaction rate, one can determine the neutrino mass hierarchy.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

A Digitization Scheme of Sub-Microampere Current Using a Commercial Comparator with Hysteresis and FPGA-Based Wave Union TDC

A digitization scheme of sub-microampere current using a commercial comparator with adjustable hysteresis and FPGA-based Wave Union TDC has been tested. The comparator plus a few passive components forms a current controlled oscillator and the input current is sent into the hysteresis control pin. The input current is converted into the transition times of the oscillations, which are digitized with a Wave Union TDC in FPGA and the variation of the transition times reflects the variation of the input current. Preliminary tests show that input charges < 25 fC can be measured at > 50 M samples/s without a preamplifier.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Comparative Study of Effects of CO 2 Concentration and pH on Microbial Communities from a Saline Aquifer, a Depleted Oil Reservoir, and a Freshwater Aquifer

Injected CO 2 from geologic carbon storage is expected to impact the microbial communities of proposed storage sites, such as depleted oil reservoirs and deep saline aquifers, as well as overlying freshwater aquifers at risk of receiving leaking CO 2 . Microbial community change in these subsurface sites may affect injectivity of CO 2 , permanence of stored CO 2 , and shallow subsurface water quality. The effect of CO 2 concentration on the microbial communities in fluid collected from a depleted oil reservoir and a freshwater aquifer was examined at subsurface pressures and temperatures. The community was exposed to 0%, 1%, 10%, and 100% pCO 2 for 56 days. Bacterial community structure was analyzed through 16S rRNA gene clone libraries, and total bacterial abundance was estimated through quantitative polymerase chain reaction. Changes in the microbial community observed in the depleted oil reservoir samples and freshwater samples were compared to previous results from CO 2 -exposed deep saline aquifer fluids. Overall, results suggest that CO 2 exposure to microbial communities will result in pH-dependent population change, and the CO 2 -selected microbial communities will vary among sites. In conclusion, this is the first study to compare the response of multiple subsurface microbial communities at conditions expected during geologic carbon storage, increasing the understanding of environmental drivers for microbial community changes in CO 2 -exposed environments.

54 ENVIRONMENTAL SCIENCES↗

GenomeDepot: data management system for microbial comparative genomics

Summary GenomeDepot is an open-source web-based platform for annotation, management, and comparative analysis of microbial genomic sequences and associated data including ortholog families, protein domains, operons, regulatory interactions, strain taxonomy, and sample metadata. GenomeDepot supports rapid creation of websites for user-defined genome collections that include bioinformatic tools for interactive genome browsing, Basic Local Alignment Search Tool (BLAST) search, annotation search, comparative genomic neighborhood visualization, and sequence download. Gene function annotations are generated by a customizable annotation pipeline. The pipeline runs annotation tools in Conda environments and can be easily extended with additional user-specified tools. Availability and implementation GenomeDepot is open source and distributed under the GNU General Public License via GitHub (https://github.com/aekazakov/genome-depot). GenomeDepot is implemented in Python and was tested in Ubuntu Linux. Full installation instructions and documentation are available at https://aekazakov.github.io/genome-depot/. GenomeDepot demo server is freely accessible at https://iseq.lbl.gov/demogd/.

Kazakov, Alexey [Lawrence Berkeley National Labora↗

Reference-independent comparative metagenomics using cross-assembly: crAss

Motivation: Metagenomes are often characterized by high levels of unknown sequences. Reads derived from known microorganisms can easily be identified and analyzed using fast homology search algorithms and a suitable reference database, but the unknown sequences are often ignored in further analyses, biasing conclusions. Nevertheless, it is possible to use more data in a comparative metagenomic analysis by creating a cross-assembly of all reads, i.e. a single assembly of reads from different samples. Comparative metagenomics studies the interrelationships between metagenomes from different samples. Using an assembly algorithm is a fast and intuitive way to link (partially) homologous reads without requiring a database of reference sequences. Results: Here, we introduce crAss, a novel bioinformatic tool that enables fast simple analysis of cross-assembly files, yielding distances between all metagenomic sample pairs and an insightful image displaying the similarities.

59 BASIC BIOLOGICAL SCIENCES↗

Mycoparasites, Gut Dwellers, and Saprotrophs: Phylogenomic Reconstructions and Comparative Analyses of Kickxellomycotina Fungi

Improved sequencing technologies have profoundly altered global views of fungal diversity and evolution. High-throughput sequencing methods are critical for studying fungi due to the cryptic, symbiotic nature of many species, particularly those that are difficult to culture. However, the low coverage genome sequencing (LCGS) approach to phylogenomic inference has not been widely applied to fungi. Here we analyzed 171 Kickxellomycotina fungi using LCGS methods to obtain hundreds of marker genes for robust phylogenomic reconstruction. Additionally, we mined our LCGS data for a set of nine rDNA and protein coding genes to enable analyses across species for which no LCGS data were obtained. The main goals of this study were to: 1) evaluate the quality and utility of LCGS data for both phylogenetic reconstruction and functional annotation, 2) test relationships among clades of Kickxellomycotina, and 3) perform comparative functional analyses between clades to gain insight into putative trophic modes. In opposition to previous studies, our nine-gene analyses support two clades of arthropod gut dwelling species and suggest a possible single evolutionary event leading to this symbiotic lifestyle. Furthermore, we resolve the mycoparasitic Dimargaritales as the earliest diverging clade in the subphylum and find four major clades of Coemansia species. Finally, functional analyses illustrate clear variation in predicted carbohydrate active enzymes and secondary metabolites (SM) based on ecology, that is biotroph versus saprotroph. Saprotrophic Kickxellales broadly lack many known pectinase families compared with saprotrophic Mucoromycota and are depauperate for SM but have similar numbers of predicted chitinases as mycoparasitic.

59 BASIC BIOLOGICAL SCIENCES↗

Comparative cell-specific transcriptomics reveals differentiation of C 4 photosynthesis pathways in switchgrass and other C 4 lineages

Almost all C4 plants require the co-ordination of the adjacent and fully differentiated cell types, mesophyll (M) and bundle sheath (BS). The C4 photosynthetic pathway operates through two distinct subtypes based on how malate is decarboxylated in BS cells; through NAD-malic enzyme (NAD-ME) or NADP-malic enzyme (NADP-ME). The diverse or unique cell-specific molecular features of M and BS cells from separate C4 subtypes of independent lineages remain to be determined. We here provide an M/BS cell type-specific transcriptome data set from the monocot NAD-ME subtype switchgrass (Panicum virgatum). A comparative transcriptomics approach was then applied to compare the M/BS mRNA profiles of switchgrass, monocot NADP-ME subtype C4 plants maize and Setaria viridis, and dicot NAD-ME subtype Cleome gynandra. We evaluated the convergence in the transcript abundance of core components in C4 photosynthesis and transcription factors to establish Kranz anatomy, as well as gene distribution of biological functions, in these four independent C4 lineages. We also estimated the divergence between NAD-ME and NADP-ME subtypes of C4 photosynthesis in the two cell types within C4 species, including differences in genes encoding decarboxylating enzymes, aminotransferases, and metabolite transporters, and differences in the cell-specific functional enrichment of RNA regulation and protein biogenesis/homeostasis. We suggest that C4 plants of independent lineages in both monocots and dicots underwent convergent evolution to establish C4 photosynthesis, while distinct C4 subtypes also underwent divergent processes for the optimization of M and BS cell co-ordination. The comprehensive data sets in our study provide a basis for further research on evolution of C4 species.

09 BIOMASS FUELS↗

Comparative Performance of Three Eye-Tracking Devices in Detection of Mild Traumatic Brain Injury in Acute Versus Chronic Subject Populations

ABSTRACT Introduction Presently, traumatic brain injury (TBI) triage in field settings relies on symptom-based screening tools such as the updated Military Acute Concussion Evaluation. Objective eye-tracking may provide an alternative means of neurotrauma screening due to sensitivity to neurotrauma brain-health changes. Previously, the US Army Medical Research and Development Command Non-Invasive NeuroAssessment Devices (NINAD) Integrated Product Team identified 3 commercially available eye-tracking devices (SyncThink EYE-SYNC, Oculogica EyeBOX, NeuroKinetics IPAS) as meeting criteria toward being operationally effective in the detection of TBI in service members. We compared these devices to assess their relative performance in the classification of mild traumatic brain injury (mTBI) subjects versus normal healthy controls. Materials and Methods Participants 18 to 45 years of age were assigned to Acute mTBI, Chronic mTBI, or Control group per study criteria. Each completed a TBI assessment protocol with all 3 devices counterbalanced across participants. Acute mTBI participants were tested within 72 hours following injury whereas time since last injury for the Chronic mTBI group ranged from months to years. Discriminant analysis was undertaken to determine device classification performance in separating TBI subjects from controls. Area Under the Curves (AUCs) were calculated and used to compare the accuracy of device performance. Device-related factors including data quality, the need to repeat tests, and technical issues experienced were aggregated for reporting. Results A total of 63 participants were recruited as Acute mTBI subjects, 34 as Chronic mTBI subjects, and 119 participants without history of TBI as controls. To maximize outcomes, poorer quality data were excluded from analysis using specific criteria where possible. Final analysis utilized 49 (43 male/6 female, mean [x̅] age = 24.3 years, SD [s] = 5.1) Acute mTBI subjects, and 34 (33 male/1 female, x̅ age = 38.8 years, s = 3.9) Chronic mTBI subjects were age- and gender-matched as closely as possible with Control subjects. AUCs obtained with 80% of total dataset ranged from 0.690 to 0.950 for the Acute Group and from 0.753 to 0.811 for the Chronic mTBI group. Validation with the remaining 20% of dataset produced AUCs ranging from 0.600 to 0.750 for Acute mTBI group and 0.490 to 0.571 for the Chronic mTBI group. Conclusions Potential eye-tracking detection of mTBI, per training model outcomes, ranged from acceptable to excellent for the Acute mTBI group; however, it was less consistent for the Chronic mTBI group. The self-imposed targeted performance (AUC of 0.850) appears achievable, but further device improvements and research are necessary. Discriminant analysis models differed for the Acute versus Chronic mTBI groups, suggesting performance differences in eye-tracking. Although eye-tracking demonstrated sensitivity in the Chronic group, a more rigorous and/or longitudinal study design is required to evaluate this observation. mTBI injuries were not controlled for this study, potentially reducing eye-tracking assessment sensitivity. Overall, these findings indicate that while eye-tracking remains a viable means of mTBI screening, device-specific variability in data quality, length of testing, and ease of use must be addressed to achieve NINAD objectives and DoD implementation.

General & Internal Medicine↗

Mapping the magnetic field in the Taurus/B211 filamentary cloud with SOFIA HAWC + and comparing with simulation

ABSTRACT Optical and infrared polarization mapping and recent Planck observations of the filametary cloud L1495 in Taurus show that the large-scale magnetic field is approximately perpendicular to the long axis of the cloud. We use the HAWC + polarimeter on SOFIA to probe the complex magnetic field in the B211 part of the cloud. Our results reveal a dispersion of polarization angles of 36°, about five times that measured on a larger scale by Planck. Applying the Davis–Chandrasekhar–Fermi (DCF) method with velocity information obtained from Institut de Radioastronomie Millimétrique 30 m C18O(1-0) observations, we find two distinct sub-regions with magnetic field strengths differing by more than a factor 3. The quieter sub-region is magnetically critical and sub-Alfv$\acute{\rm e}$nic; the field is comparable to the average field measured in molecular clumps based on Zeeman observations. The more chaotic, super-Alfv$\acute{\rm e}$nic sub-region shows at least three velocity components, indicating interaction among multiple substructures. Its field is much less than the average Zeeman field in molecular clumps, suggesting that the DCF value of the field there may be an underestimate. Numerical simulation of filamentary cloud formation shows that filamentary substructures can strongly perturb the magnetic field. DCF and true field values in the simulation are compared. Pre-stellar cores are observed in B211 and are seen in our simulation. The appendices give a derivation of the standard DCF method that allows for a dispersion in polarization angles that is not small, present an alternate derivation of the structure function version of the DCF method, and treat fragmentation of filaments.

79 ASTRONOMY AND ASTROPHYSICS↗

A comparative study of the physical properties for a representative sample of Narrow and Broad-line Seyfert galaxies

ABSTRACT We present a comparative study of the physical properties of a homogeneous sample of 144 Narrow line Seyfert 1 (NLSy1) and 117 Broad-line Seyfert 1 (BLSy1) galaxies. These two samples are in a similar luminosity and redshift range and have optical spectra available in the 16th data release of Sloan Digital Sky Survey (SDSS-DR16) and X-ray spectra in either XMM-NEWTON or ROSAT. Direct correlation analysis and a principal component analysis (PCA) have been performed using ten observational and physical parameters obtained by fitting the optical spectra and the soft X-ray photon indices as another parameter. We confirm that the established correlations for the general quasar population hold for both types of galaxies in this sample despite significant differences in the physical properties. We characterize the sample also using the line shape parameters, namely the asymmetry and kurtosis indices. We find that the fraction of NLSy1 galaxies showing outflow signatures, characterized by blue asymmetries, is higher by a factor of about 3 compared to the corresponding fraction in BLSy1 galaxies. The presence of high iron content in the broad-line region of NLSy1 galaxies in conjunction with higher Eddington ratios can be the possible reason behind this phenomenon. We also explore the possibility of using asymmetry in the emission lines as a tracer of outflows in the inner regions of Active Galactic Nuclei. The PCA results point to the NLSy1 and BLSy1 galaxies occupying different parameter spaces, which challenges the notion that NLSy1 galaxies are a subclass of BLSy1 galaxies.

79 ASTRONOMY AND ASTROPHYSICS↗

The outer stellar mass of massive galaxies: a simple tracer of halo mass with scatter comparable to richness and reduced projection effects

ABSTRACT Using the weak gravitational lensing data from the Hyper Suprime-Cam Subaru Strategic Program (HSC survey), we study the potential of different stellar mass estimates in tracing halo mass. We consider galaxies with log10(M⋆/M⊙) > 11.5 at 0.2 < z < 0.5 with carefully measured light profiles, and clusters from the redMaPPer and CAMIRA richness-based algorithms. We devise a method (the ‘Top-N test’) to evaluate the scatter in the halo mass–observable relation for different tracers, and to inter-compare halo mass proxies in four number density bins using stacked galaxy–galaxy lensing profiles. This test reveals three key findings. Stellar masses based on CModel photometry and aperture luminosity within R <30 kpc are poor proxies of halo mass. In contrast, the stellar mass of the outer envelope is an excellent halo mass proxy. The stellar mass within R = [50, 100] kpc, M⋆, [50, 100], has performance comparable to the state-of-the-art richness-based cluster finders at log10Mvir ≳ 14.0 and could be a better halo mass tracer at lower halo masses. Finally, using N-body simulations, we find that the lensing profiles of massive haloes selected by M⋆, [50, 100] are consistent with the expectation for a sample without projection or mis-centring effects. Richness-selected clusters, on the other hand, display an excess at R ∼ 1 Mpc in their lensing profiles, which may suggest a more significant impact from selection biases. These results suggest that M⋆-based tracers have distinct advantages in identifying massive haloes, which could open up new avenues for cluster cosmology. The codes and data used in this work can be found here:

79 ASTRONOMY AND ASTROPHYSICS↗

Interacting galaxies in the IllustrisTNG simulations – V. Comparing the influence of star-forming versus passive companions

ABSTRACT We study interacting galaxy pairs in the TNG100-1 and TNG300-1 cosmological simulations using previously generated closest companion samples. We study the specific star-formation rates (sSFRs) of massive ($10^{10} \, {\rm M}_{\odot } \lt M_* \lt 10^{12} \, {\rm M}_{\odot }$ ) galaxies at z ≤ 0.2 as a function of separation from the closest companion galaxy. We split our sample based on whether the companion galaxy is star-forming or passive. We find that galaxies with close star-forming companions have sSFRs that are enhanced (on average) by a factor of 2.9 ± 0.3 in TNG100-1 and 2.27 ± 0.06 in TNG300-1 compared to controls, with enhancements present out to separations of ∼300 kpc. Galaxies with passive companions in TNG300-1 exhibit mild sSFR suppression (∼12 per cent) at 100–300 kpc and small sSFR enhancements at separations below 50 kpc. sSFR suppression is strongest in pairs where the galaxy’s stellar mass is more than 2 times that of its passive companion. By generating a stellar mass-matched (‘twinned’) sample in TNG300-1, we show that differences in sSFR trends between companion types are not a result of intrinsic stellar mass differences in star-forming versus passive galaxies. We compare with an analogous sample of galaxy pairs from SDSS, finding consistent results between observations and simulations. Overall, we find that star-forming galaxies show enhanced sSFRs regardless of companion type, but that galaxies with close passive companions are more likely to be passive themselves.

Astronomy & Astrophysics↗

Using elliptical galaxy kinematics to compare the strength of gravity in cosmological regions of differing gravitational potential – a first look

ABSTRACT Various models of modified gravity invoke ‘screening’ mechanisms that are sensitive to the value of the local gravitational potential. This could have observable consequences for galaxies. These consequences might be seen by comparing two proxies for galaxy mass – their luminosity and their internal kinematics – as a function of local galaxy density. Motivated by this prospect, we have compared the observed properties of luminous red galaxies (LRGs) inside and outside of voids in the cosmic large scale structure. We used archival measurements of line widths, luminosities, redshifts, colours, and positions of galaxies in conjunction with recent void catalogues to construct comparison LRG samples inside and outside of voids. We fitted these two samples to the well-established fundamental plane of elliptical galaxies to constrain any differences between the inferred value of the Newtonian gravitational constant G for the two samples. We obtained a null result, with an upper limit on any fractional difference in G within and outside of cosmological voids to be α = δG/G ∼ 40 per cent. This upper bound is dominated by the small-number statistics of our N ∼ 100 within-void LRG sample. With the caveat that environmental effects could influence various parameters such as star formation, we estimate that a 1 per cent statistical limit on α could be attained with data from 105 elliptical galaxies within voids. This is within the reach of future photometric and spectroscopic surveys, both of which are required to pursue this method.

79 ASTRONOMY AND ASTROPHYSICS↗

Matter power spectra in modified gravity: a comparative study of approximations and N -body simulations

ABSTRACT Testing gravity and the concordance model of cosmology, $\Lambda$CDM, at large scales is a key goal of this decade’s largest galaxy surveys. Here we present a comparative study of dark matter power spectrum predictions from different numerical codes in the context of three popular theories of gravity that induce scale-independent modifications to the linear growth of structure: nDGP, Cubic Galileon, and K-mouflage. In particular, we compare the predictions from N-body simulations solving the full scalar field equation, two N-body codes with approximate time integration schemes, a parametrized modified N-body implementation, and the analytic halo model reaction approach. We find the modification to the $\Lambda$CDM spectrum is in 2 per cent agreement at $z\le 1$ and $k\le 1~h\,{\rm Mpc}^{-1}$ over all gravitational models and codes, in accordance with many previous studies, indicating these modelling approaches are robust enough to be used in forthcoming survey analyses under appropriate scale cuts. We further make public the new code implementations presented, specifically the halo model reaction K-mouflage implementation and the relativistic Cubic Galileon implementation.

Bose, B. (ORCID:0000000319658614)↗