Towards designing improved cancer immunotherapy targets with a peptide-MHC-I presentation model, HLApollo.

Based on the success of cancer immunotherapy, personalized cancer vaccines have emerged as a leading oncology treatment. Antigen presentation on MHC class I (MHC-I) is crucial for the adaptive immune response to cancer cells, necessitating highly predictive computational methods to model this phenomenon. Here, we introduce HLApollo, a transformer-based model for peptide-MHC-I (pMHC-I) presentation prediction, leveraging the language of peptides, MHC, and source proteins.

Nucleotide modifications enable rational design of TLR7-selective ligands by blocking RNase cleavage.

Toll-like receptors 7 (TLR7) and 8 (TLR8) each sense single-stranded RNA (ssRNA), but their activation results in different immune activation profiles. Attempts to selectively target either TLR7 or TLR8 have been hindered by their high degree of homology. However, recent studies revealed that TLR7 and TLR8 bind different ligands resulting from the processing of ssRNA by endolysosomal RNases.

Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines.

IL-1 and IL-1ra are key regulators of the inflammatory response to RNA vaccines.

The use of lipid-formulated RNA vaccines for cancer or COVID-19 is associated with dose-limiting systemic inflammatory responses in humans that were not predicted from preclinical studies. Here, we show that the 'interleukin 1 (IL-1)-interleukin 1 receptor antagonist (IL-1ra)' axis regulates vaccine-mediated systemic inflammation in a host-specific manner. In human immune cells, RNA vaccines induce production of IL-1 cytokines, predominantly IL-1β, which is dependent on both the RNA and lipid formulation.

The PET tracer [C]MK-6884 quantifies M4 muscarinic receptor in rhesus monkeys and patients with Alzheimer's disease.

Positron emission tomography (PET) ligands play an important role in the development of therapeutics by serving as target engagement or pharmacodynamic biomarkers. Here, we describe the discovery and translation of the PET tracer [C]MK-6884 from rhesus monkeys to patients with Alzheimer’s disease (AD). [H]MK-6884/[C]MK-6884 binds with high binding affinity and good selectivity to an allosteric site on M4 muscarinic cholinergic receptors (M4Rs) in vitro and shows a regional distribution in the brain consistent with M4R localization in vivo.

Measurement of the Lund Jet Plane Using Charged Particles in 13 TeV Proton-Proton Collisions with the ATLAS Detector.

The prevalence of hadronic jets at the LHC requires that a deep understanding of jet formation and structure is achieved in order to reach the highest levels of experimental and theoretical precision. There have been many measurements of jet substructure at the LHC and previous colliders, but the targeted observables mix physical effects from various origins. Based on a recent proposal to factorize physical effects, this Letter presents a double-differential cross-section measurement of the Lund jet plane using 139  fb^{-1} of sqrt[s]=13  TeV proton-proton collision data collected with the ATLAS detector using jets with transverse momentum above 675 GeV.

Associations between population density and clinical and sociodemographic factors in women living with HIV in the Southern United States.

To explore the associations of urbanicity with clinical/behavioral outcomes and sociodemographic factors among women living with HIV in the Southern United States, 523 participants of the Women's Interagency HIV Study were classified into population density quartiles. Rural-Urban Commuting Area codes revealed that 7% resided in areas where >30% commute to urban areas, 2% resided in small towns or rural areas, and 91% resided in varying densities of urban areas. Although women in lower density, mostly suburban areas reported higher socioeconomic indicators such as advanced education and greater annual household income, larger proportions of women in the lowest density quartile perceived discrimination in health care settings and agreed with several internalized HIV stigma scale items.

Measurement of Azimuthal Anisotropy of Muons from Charm and Bottom Hadrons in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

The elliptic flow of muons from the decay of charm and bottom hadrons is measured in pp collisions at sqrt[s]=13  TeV using a data sample with an integrated luminosity of 150  pb^{-1} recorded by the ATLAS detector at the LHC. The muons from heavy-flavor decay are separated from light-hadron decay muons using momentum imbalance between the tracking and muon spectrometers. The heavy-flavor decay muons are further separated into those from charm decay and those from bottom decay using the distance-of-closest-approach to the collision vertex.

Discovery of [C]MK-6884: A Positron Emission Tomography (PET) Imaging Agent for the Study of M4Muscarinic Receptor Positive Allosteric Modulators (PAMs) in Neurodegenerative Diseases.

The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed therapeutics. We and others have investigated muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of symptoms associated with neuropsychiatric disorders. In this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related M4 PAMs that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor.

Search for Magnetic Monopoles and Stable High-Electric-Charge Objects in 13 Tev Proton-Proton Collisions with the ATLAS Detector.

A search for magnetic monopoles and high-electric-charge objects is presented using 34.4  fb^{-1} of 13 TeV pp collision data collected by the ATLAS detector at the LHC during 2015 and 2016. The considered signature is based upon high ionization in the transition radiation tracker of the inner detector associated with a pencil-shape energy deposit in the electromagnetic calorimeter.

Observation of Electroweak Production of a Same-Sign W Boson Pair in Association with Two Jets in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter presents the observation and measurement of electroweak production of a same-sign W boson pair in association with two jets using 36.1  fb^{-1} of proton-proton collision data recorded at a center-of-mass energy of sqrt[s]=13  TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed in the detector fiducial phase-space region, defined by the presence of two same-sign leptons, electron or muon, and at least two jets with a large invariant mass and rapidity difference.

Observation of Light-by-Light Scattering in Ultraperipheral Pb+Pb Collisions with the ATLAS Detector.

This Letter describes the observation of the light-by-light scattering process, γγ→γγ, in Pb+Pb collisions at sqrt[s_{NN}]=5.02  TeV. The analysis is conducted using a data sample corresponding to an integrated luminosity of 1.

Comparison of Fragmentation Functions for Jets Dominated by Light Quarks and Gluons from pp and Pb+Pb Collisions in ATLAS.

Charged-particle fragmentation functions for jets azimuthally balanced by a high-transverse-momentum, prompt, isolated photon are measured in 25  pb^{-1} of pp and 0.49  nb^{-1} of Pb+Pb collision data at 5.02 TeV per nucleon pair recorded with the ATLAS detector at the Large Hadron Collider.

Combination of Searches for Invisible Higgs Boson Decays with the ATLAS Experiment.

Dark matter particles, if sufficiently light, may be produced in decays of the Higgs boson. This Letter presents a statistical combination of searches for H→invisible decays where H is produced according to the standard model via vector boson fusion, Z(ℓℓ)H, and W/Z(had)H, all performed with the ATLAS detector using 36.1  fb^{-1} of pp collisions at a center-of-mass energy of sqrt[s]=13  TeV at the LHC.

Erratum to: Measurement of the boson polarisation in events from collisions at in the lepton + jets channel with ATLAS.

[This corrects the article DOI: 10.1140/epjc/s10052-017-4819-4.].

Search for the Production of a Long-Lived Neutral Particle Decaying within the ATLAS Hadronic Calorimeter in Association with a Z Boson from pp Collisions at sqrt[s]=13 TeV.

This Letter presents a search for the production of a long-lived neutral particle (Z_{d}) decaying within the ATLAS hadronic calorimeter, in association with a standard model (SM) Z boson produced via an intermediate scalar boson, where Z→ℓ^{+}ℓ^{-} (ℓ=e, μ). The data used were collected by the ATLAS detector during 2015 and 2016 pp collisions with a center-of-mass energy of sqrt[s]=13  TeV at the Large Hadron Collider and correspond to an integrated luminosity of 36.1±0.

Search for doubly charged scalar bosons decaying into same-sign boson pairs with the ATLAS detector.

A search for doubly charged scalar bosons decaying into boson pairs is presented. It uses a data sample from proton-proton collisions corresponding to an integrated luminosity of 36.1 fb collected by the ATLAS detector at the LHC at a centre-of-mass energy of 13 TeV in 2015 and 2016.

Prolyl isomerization of FAAP20 catalyzed by PIN1 regulates the Fanconi anemia pathway.

The Fanconi Anemia (FA) pathway is a multi-step DNA repair process at stalled replication forks in response to DNA interstrand cross-links (ICLs). Pathological mutation of key FA genes leads to the inherited disorder FA, characterized by progressive bone marrow failure and cancer predisposition. The study of FA is of great importance not only to children suffering from FA but also as a model to study cancer pathogenesis in light of genome instability among the general population.

Combination of the Searches for Pair-Produced Vectorlike Partners of the Third-Generation Quarks at sqrt[s]=13 TeV with the ATLAS Detector.

A combination of the searches for pair-produced vectorlike partners of the top and bottom quarks in various decay channels (T→Zt/Wb/Ht, B→Zb/Wt/Hb) is performed using 36.1  fb^{-1} of pp collision data at sqrt[s]=13  TeV with the ATLAS detector at the Large Hadron Collider. The observed data are found to be in good agreement with the standard model background prediction in all individual searches.

Observation of Centrality-Dependent Acoplanarity for Muon Pairs Produced via Two-Photon Scattering in Pb+Pb Collisions at sqrt[s_{NN}]=5.02 TeV with the ATLAS Detector.

This Letter presents a measurement of γγ→μ^{+}μ^{-} production in Pb+Pb collisions recorded by the ATLAS detector at the Large Hadron Collider at sqrt[s_{NN}]=5.02  TeV with an integrated luminosity of 0.49  nb^{-1}.

Search for Resonant and Nonresonant Higgs Boson Pair Production in the bb[over ¯]τ^{+}τ^{-} Decay Channel in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

A search for resonant and nonresonant pair production of Higgs bosons in the bb[over ¯]τ^{+}τ^{-} final state is presented. The search uses 36.1  fb^{-1} of pp collision data with sqrt[s]=13  TeV recorded by the ATLAS experiment at the LHC in 2015 and 2016.

Search for heavy particles decaying into top-quark pairs using lepton-plus-jets events in proton-proton collisions at with the ATLAS detector.

A search for new heavy particles that decay into top-quark pairs is performed using data collected from proton-proton collisions at a centre-of-mass energy of 13  by the ATLAS detector at the Large Hadron Collider. The integrated luminosity of the data sample is 36.1 fb .

Probing the Quantum Interference between Singly and Doubly Resonant Top-Quark Production in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter presents a normalized differential cross-section measurement in a fiducial phase-space region where interference effects between top-quark pair production and associated production of a single top quark with a W boson and a b-quark are significant. Events with exactly two leptons (ee, μμ, or eμ) and two b-tagged jets that satisfy a multiparticle invariant mass requirement are selected from 36.1  fb^{-1} of proton-proton collision data taken at sqrt[s]=13  TeV with the ATLAS detector at the LHC in 2015 and 2016.

Measurement of the Soft-Drop Jet Mass in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

Jet substructure observables have significantly extended the search program for physics beyond the standard model at the Large Hadron Collider. The state-of-the-art tools have been motivated by theoretical calculations, but there has never been a direct comparison between data and calculations of jet substructure observables that are accurate beyond leading-logarithm approximation. Such observables are significant not only for probing the collinear regime of QCD that is largely unexplored at a hadron collider, but also for improving the understanding of jet substructure properties that are used in many studies at the Large Hadron Collider.