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The spectral content of macroscopic neural activity evolves throughout development, yet how this maturation relates to underlying brain network formation and dynamics remains unknown. Here, we assess the developmental maturation of electroencephalogram spectra via Bayesian model inversion of the spectral graph model, a parsimonious whole-brain model of spatiospectral neural activity derived from linearized neural field models coupled by the structural connectome. Simulation-based inference was used to estimate age-varying spectral graph model parameter posterior distributions from electroencephalogram spectra spanning the developmental period. This model-fitting approach accurately captures observed developmental electroencephalogram spectral maturation via a neurobiologically consistent progression of key neural parameters: long-range coupling, axonal conduction speed, and excitatory:inhibitory balance. These results suggest that the spectral maturation of macroscopic neural activity observed during typical development is supported by age-dependent functional adaptations in localized neural dynamics and their long-range coupling across the macroscopic structural network.

Considering the growing interest in magnetic materials for unconventional computing, data storage, and sensor applications, there is active research not only on material synthesis but also characterisation of their properties. In addition to structural and integral magnetic characterisations, imaging of magnetisation patterns, current distributions and magnetic fields at nano- and microscale is of major importance to understand the material responses and qualify them for specific applications. In this roadmap, we aim to cover a broad portfolio of techniques to perform nano- and microscale magnetic imaging using superconducting quantum interference devices, spin centre and Hall effect magnetometries, scanning probe microscopies, x-ray- and electron-based methods as well as magnetooptics and nanoscale magnetic resonance imaging. The roadmap is aimed as a single access point of information for experts in the field as well as the young generation of students outlining prospects of the development of magnetic imaging technologies for the upcoming decade with a focus on physics, materials science, and chemistry of planar, three-dimensional and geometrically curved objects of different material classes including two-dimensional materials, complex oxides, semi-metals, multiferroics, skyrmions, antiferromagnets, frustrated magnets, magnetic molecules/nanoparticles, ionic conductors, superconductors, spintronic and spinorbitronic materials.

Context. The determination of accurate photometric redshifts (photo-zs) in large imaging galaxy surveys is key for cosmological studies. One of the most common approaches is machine learning techniques. These methods require a spectroscopic or reference sample to train the algorithms. Attention has to be paid to the quality and properties of these samples since they are key factors in the estimation of reliable photo-zs. Aims. The goal of this work is to calculate the photo-zs for the Year 3 (Y3) Dark Energy Survey (DES) Deep Fields catalogue using the Directional Neighborhood Fitting (DNF) machine learning algorithm. Moreover, we want to develop techniques to assess the incompleteness of the training sample and metrics to study how incompleteness affects the quality of photometric redshifts. Finally, we are interested in comparing the performance obtained by DNF on the Y3 DES Deep Fields catalogue with that of the EAzY template fitting approach. Methods. We emulated – at a brighter magnitude – the training incompleteness with a spectroscopic sample whose redshifts are known to have a measurable view of the problem. We used a principal component analysis to graphically assess the incompleteness and relate it with the performance parameters provided by DNF. Finally, we applied the results on the incompleteness to the photo-z computation on the Y3 DES Deep Fields with DNF and estimated its performance. Results. The photo-zs of the galaxies in the DES deep fields were computed with the DNF algorithm and added to the Y3 DES Deep Fields catalogue. We have developed some techniques to evaluate the performance in the absence of “true” redshift and to assess the completeness. We have studied the tradeoff in the training sample between the highest spectroscopic redshift quality versus completeness. We found some advantages in relaxing the highest-quality spectroscopic redshift requirements at fainter magnitudes in favour of completeness. The results achieved by DNF on the Y3 Deep Fields are competitive with the ones provided by EAzY, showing notable stability at high redshifts. It should be noted that the good results obtained by DNF in the estimation of photo-zs in deep field catalogues make DNF suitable for the future Legacy Survey of Space and Time (LSST) and Euclid data, which will have similar depths to the Y3 DES Deep Fields.

Radiative cooling of electron beams interacting with counter-propagating electromagnetic waves is analyzed, taking into account the quantum modification of the radiation friction force. Central attention is paid to the evolution of the energy spectrum of electrons accelerated by the laser wake field acceleration mechanism. As an electron beam loses energy to radiation, the mean energy decreases and the form of the energy distribution also changes due to quantum-mechanical spectral broadening.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

A well-mixed diluted sample is essential for unbiased measurement of cookstove emissions. Most cookstove testing labs employ a dilution tunnel, also referred to as a “duct,” to mix clean dilution air with cookstove emissions before sampling. It is important that the emissions be well-mixed and unbiased at the sampling port so that instruments can take representative samples of the emission plume. Some groups have employed mixing baffles to ensure the gaseous and aerosol emissions from cookstoves are well-mixed before reaching the sampling location [2, 4]. The goal of these baffles is to to dilute and mix the emissions stream with the room air entering the fume hood by creating a local zone of high turbulence. However, potential drawbacks of mixing baffles include increased flow resistance (larger blowers needed for the same exhaust flow), nuisance cleaning of baffles as soot collects, and, importantly, the potential for loss of PM2.5 particles on the baffles themselves,thus biasing results.A cookstove emission monitoring system with baffles will collect particles faster than the duct’s walls alone. This is mostly driven by the available surface area for deposition by processes of Brownian diffusion (through the boundary layer) and turbophoresis (i.e. impaction). The greater the surface area available for diffusive and advection-driven depositionto occur, the greater the particle loss will be at the sampling port. As a layer of larger particle “fuzz” builds on the mixing baffles, even greater PM2.5 loss could occur. The micro structure of the deposited aerosol will lead to increased rates of particle loss by interception and a tendency for smaller particles to deposit due to impaction on small features of themicro structure. If the flow stream could be well-mixed without the need for baffles, these drawbacks could be avoided and the cookstove emissions sampling system would be more robust.

It is widely accepted that the next lepton collider beyond a Higgs factory would require center-of-mass energy of the order of up to 15 TeV. Since, given reasonable space and cost restrictions, conventional accelerator technology reaches its limits near this energy, high-gradient advanced acceleration concepts are attractive. Advanced and novel accelerators (ANAs) are leading candidates due to their ability to produce acceleration gradients on the order of 1-100 GV/m, leading to compact acceleration facilities. However, intermediate energy facilities (IEF) are required to test the critical technology elements on the way towards multi-TeV-class collliders. Here a science case for a 20-100 GeV center-of-mass energy ANA-based lepton collider that can be a candidate for an intermediate energy facility is presented. The IEF can provide numerous opportunities for high energy physics studies including precision Quantum Chromodynamics and Beyond the Standard Model physics measurements, investigation of charged particle interactions with extreme electromagnetic fields, and exploring muon and proton beam acceleration. Possible applications of this collider include the studies of γγ and electron beam-fixed target/beamdump collider designs. Thus, the goal of the proposed IEF is to both carry out particle physics measurements in the 20-100 GeV ranges as well as to serve as an ANA demonstrator facility.

The cross-shell excited states of Si34 have been investigated via β decays of the 4- ground state and the 1+ isomeric state of Al34. Since the valence protons and valence neutrons occupy different major shells in the ground state as well as the intruder 1+ isomeric state of Al34, intruder levels of Si34 are populated via allowed β decays. Spin assignments to such intruder levels of Si34 were established through γ-γ angular correlation analysis for the negative-parity states with dominant configurations (νd3/2)-1⊗ - (νf7/2)1 as well as the positive-parity states with dominant configurations (νsd)-2⊗ - (νf7/2p3/2)2. The configurations of such intruder states play crucial roles in our understanding of the N=20 shell gap evolution. A configuration interaction model derived from the FSU Hamiltonian was utilized in order to interpret the intruder states in Si34. Shell model interaction derived from a more fundamental theory with the valence space in medium similarity renormalization group method was also employed to interpret the structure of Si34.

Rationale: The importance of reward-associated cues in eliciting behavior is well established, with stimuliassociated with drugs of abuse known to play a crucial role in recidivism. Recently, Redish (2004) proposed that drugs,acting as unconditional stimuli (US), remain associable even after being fully predicted by a conditional stimulus (CS),meaning that they are not susceptible to the blocking effect [1]; if correct, this may represent a possible mechanism toexplain exaggerated cue-controlled drug-seeking and reinstatement in nicotine dependence and substance dependenceproblems in general.Objectives: We tested whether pairings between nicotine and an environmental CS would convey conditionedreinforcement properties onto the CS, even when nicotine’s rewarding effects were already fully predicted by another cue(whether there was an absence of the blocking effect).Methods: 134 male Long-Evans rats were implanted with jugular catheters and assigned to either food- or nicotine-reward(0.06 mg/kg/inf) conditions. Each group was exposed to paired or unpaired presentations of their respective reward withone CS in 10 daily sessions; subsequently, they were exposed to 4 more daily sessions of paired presentations of thereward paired with a compound CS composed of the original CS and a second CS. Tests of the conditioned reinforcingvalue of both CSs using the active-lever-presses to total-presses ratio as an outcome were conducted following training.Results: Pressing for a blocked second CS (µ = 0.59, SD = 0.21) was significantly lower than pressing for an unblockedsecond CS (µ = 0.69, SD = 0.14) in the food-reward condition, but not in nicotine-rewarded animals, verifying thehypothesis that nicotine, but not food, is resilient to the blocking effect.Conclusion: The absence of blocking when nicotine is the reward may explain the powerful role for cues in supportingtobacco dependenceby allowing for the extension of nicotine’s rewarding value across numerous associated cues.acting as unconditional stimuli (US), remain associable even after being fully predicted by a conditional stimulus (CS),meaning that they are not susceptible to the blocking effect [1]; if correct, this may represent a possible mechanism toexplain exaggerated cue-controlled drug-seeking and reinstatement in nicotine dependence and substance dependenceproblems in general.

The Neuroscience Monoclonal Antibody Sequencing Initiative (NeuroMabSeq) is a concerted effort to determine and make publicly available hybridoma-derived sequences of monoclonal antibodies (mAbs) valuable to neuroscience research. Over 30 years of research and development efforts including those at the UC Davis/NIH NeuroMab Facility have resulted in the generation of a large collection of mouse mAbs validated for neuroscience research. To enhance dissemination and increase the utility of this valuable resource, we applied a high-throughput DNA sequencing approach to determine immunoglobulin heavy and light chain variable domain sequences from source hybridoma cells. The resultant set of sequences was made publicly available as a searchable DNA sequence database (neuromabseq.ucdavis.edu) for sharing, analysis and use in downstream applications. We enhanced the utility, transparency, and reproducibility of the existing mAb collection by using these sequences to develop recombinant mAbs. This enabled their subsequent engineering into alternate forms with distinct utility, including alternate modes of detection in multiplexed labeling, and as miniaturized single chain variable fragments or scFvs. The NeuroMabSeq website and database and the corresponding recombinant antibody collection together serve as a public DNA sequence repository of mouse mAb heavy and light chain variable domain sequences and as an open resource for enhancing dissemination and utility of this valuable collection of validated mAbs.

Assessing the lateral and vertical extent of permafrost is critical to understanding the fate of Arctic ecosystems under climate change. Yet, direct measurements of permafrost distribution and temperature are often limited to a small number of borehole locations. Here, we assess the use of co-located shallow temperature and electrical resistivity tomography (ERT) measurements to estimate at high-resolution the distribution of permafrost in three watersheds underlain by discontinuous permafrost. Synthetic modeling shows that co-located temperature and ERT measurements allow for supervised classification schemes that provide 60% higher accuracy compared to unsupervised methods. Linking resistivity and size of the identified permafrost bodies to surface observations, we show that tall vegetation (>0.5 m) and gentle slopes (

Background: Detailed spectroscopy of neutron-rich, heavy, deformed nuclei is of broad interest for nuclear astrophysics and nuclear structure. Nuclei in the r-process path and following freeze-out region impact the resulting r-process abundance distribution, and the structure of nuclei midshell in both proton and neutron number helps to understand the evolution of subshell gaps and large deformation in these nuclei. Purpose: We aim to improve the understanding of the nuclear structure of Gd160, specifically the Kπ=4+ bands, as well as study the β decay of Eu160 into Gd160. Methods: High-statistics decay spectroscopy of Gd160 resulting from the β-decay of Eu160 was collected using the GRIFFIN spectrometer at the TRIUMF-ISAC facility. Results: Two new excited states and ten new transitions were observed in Gd160. The β-decaying half-lives of the low- and high-spin isomers in Eu160 were determined, and the low-spin state's half-life was measured to be t1/2=26.0(8) s, ≈16% shorter than previous measurements. Lifetimes of the two Kπ=4+ bandheads in Gd160 were measured for the first time, as well as γ-γ angular correlations and mixing ratios of intense transitions out of those bandheads. Conclusions: Lifetimes and mixing ratios suggest that the hexadecapole phonon model of the Kπ=4+ bandheads in Gd160 is preferred over a simple two-state strong mixing scenario, although further theoretical calculations are needed to fully understand these states. Additionally, the 1999.0-keV state in Gd160 heavily populated in β decay is shown to have positive parity, which raises questions regarding the structure of the high-spin β-decaying state in Eu160.

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac ejection fraction. Furthermore, genetic ablation of Cspg4-expressing cells resulted in excessive vascular permeability, a decline in cardiac function, and increased mortality in the second week after MI. These data reveal an essential role for cardiac pericytes in the control of vascular homeostasis and the fibrotic response after acute ischemic injury, information that will help guide the development of novel strategies to preserve vascular integrity and attenuate pathological cardiac remodeling.

BackgroundTalimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases.MethodsIn this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs.ResultsBetween 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable.ConclusionsThe safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu β decay. By exploiting γ-γ angular correlation analysis, the 2_{2}^{+}, 3_{1}^{+}, 0_{2}^{+}, and 2_{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+}, 3_{1}^{+}, and 2_{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2_{3}^{+}→0_{2}^{+} and 2_{3}^{+}→4_{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.

Abstract Including millimeter-wave data in multiwavelength studies of the variability of active galactic nuclei (AGN) can provide insights into AGN physics that are not easily accessible at other wavelengths. We demonstrate in this work the potential of cosmic microwave background (CMB) telescopes to provide long-term, high-cadence millimeter-wave AGN monitoring over large fractions of sky. We report on a pilot study using data from the SPTpol instrument on the South Pole Telescope (SPT), which was designed to observe the CMB at arcminute and larger angular scales. Between 2013 and 2016, SPTpol was used primarily to observe a single 500 deg2 field, covering the entire field several times per day with detectors sensitive to radiation in bands centered at 95 and 150 GHz. We use SPT 150 GHz observations to create AGN light curves, and we compare these millimeter-wave light curves to those at other wavelengths, in particular γ-ray and optical. In this Letter, we focus on a single source, PKS 2326-502, which has extensive, day-timescale monitoring data in gamma-ray, optical, and now millimeter-wave between 2013 and 2016. We find PKS 2326-502 to be in a flaring state in the first 2 yr of this monitoring, and we present a search for evidence of correlated variability between millimeter-wave, optical R-band, and γ-ray observations. This pilot study is paving the way for AGN monitoring with current and upcoming CMB experiments such as SPT-3G, Simons Observatory, and CMB-S4, including multiwavelength studies with facilities such as Vera C. Rubin Observatories Large Synoptic Survey Telescope.

The availability of ever stronger, laser-generated electromagnetic fields underpins continuing progress in the study and application of nonlinear phenomena in basic physical systems, ranging from molecules and atoms to relativistic plasmas and quantum electrodynamics. This raises the question: how far will we be able to go with future lasers? One exciting prospect is the attainment of field strengths approaching the Schwinger critical field in the laboratory frame, such that the field invariant Ecr2 is reached. The feasibility of doing so has been questioned, on the basis that cascade generation of dense electron-positron plasma would inevitably lead to absorption or screening of the incident light. Here we discuss the potential for future lasers to overcome such obstacles, by combining the concept of multiple colliding laser pulses with that of frequency upshifting via a tailored laser-plasma interaction. This compresses the electromagnetic field energy into a region of nanometre size and attosecond duration, which increases the field magnitude at fixed power but also suppresses pair cascades. Our results indicate that laser facilities with peak power of tens of PW could be capable of reaching. Such a scenario opens up prospects for the experimental investigation of phenomena previously considered to occur only in the most extreme environments in the universe.

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector.

Abstract: The petawatt (PW) laser facility of the Berkeley Lab Laser Accelerator (BELLA) Center has recently commissioned its second laser pulse transport line. This new beamline can be operated in parallel with the first beamline and enables strong-field quantum electrodynamics (SF-QED) experiments at BELLA. In this paper, we present an overview of the upgraded BELLA PW facility with a SF-QED experimental layout in which intense laser pulses collide with GeV-class laser-wakefield-accelerated electron beams. We present simulation results showing that experiments will allow the study of laser-particle interactions from the classical to the SF-QED regime with a nonlinear quantum parameter of up to χ∼ 2. In addition, we show that experiments will enable the study and production of GeV-class, mrad-divergence positron beams via the Breit–Wheeler process. Graphical abstract: [Figure not available: see fulltext.].

The dynamics of charged particles in electromagnetic fields is an essential component of understanding the most extreme environments in our Universe. In electromagnetic fields of sufficient magnitude, radiation emission dominates the particle motion and effects of quantum electrodynamics (QED) in strong fields are crucial, which triggers electron-positron pair cascades and counterintuitive particle-Trapping phenomena. As a result of recent progress in laser technology, high-power lasers provide a platform to create and probe such fields in the laboratory. With new large-scale laser facilities on the horizon and the prospect of investigating these hitherto unexplored regimes, this review explores the basic physical processes of radiation reaction and QED in strong fields, how they are treated theoretically and in simulation, the new collective dynamics they unlock, recent experimental progress and plans, and possible applications for high-flux particle and radiation sources.

ATHENA has been designed as a general purpose detector capable of delivering the full scientific scope of the Electron-Ion Collider. Careful technology choices provide fine tracking and momentum resolution, high performance electromagnetic and hadronic calorimetry, hadron identification over a wide kinematic range, and near-complete hermeticity. This article describes the detector design and its expected performance in the most relevant physics channels. It includes an evaluation of detector technology choices, the technical challenges to realizing the detector and the R&D required to meet those challenges.

This report describes the physics case, the resulting detector requirements, and the evolving detector concepts for the experimental program at the Electron-Ion Collider (EIC). The EIC will be a powerful new high-luminosity facility in the United States with the capability to collide high-energy electron beams with high-energy proton and ion beams, providing access to those regions in the nucleon and nuclei where their structure is dominated by gluons. Moreover, polarized beams in the EIC will give unprecedented access to the spatial and spin structure of the proton, neutron, and light ions. The studies leading to this document were commissioned and organized by the EIC User Group with the objective of advancing the state and detail of the physics program and developing detector concepts that meet the emerging requirements in preparation for the realization of the EIC. The effort aims to provide the basis for further development of concepts for experimental equipment best suited for the science needs, including the importance of two complementary detectors and interaction regions. This report consists of three volumes. Volume I is an executive summary of our findings and developed concepts. In Volume II we describe studies of a wide range of physics measurements and the emerging requirements on detector acceptance and performance. Volume III discusses general-purpose detector concepts and the underlying technologies to meet the physics requirements. These considerations will form the basis for a world-class experimental program that aims to increase our understanding of the fundamental structure of all visible matter.

Introduction: Although immunosuppression is a known characteristic of glioma, no previous large studies have reported peripheral blood immune cell profiles prior to patient surgery and chemoradiation. This report describes blood immune cell characteristics and associated variables prior to surgery among typical glioma patients seen at a large University practice. Methods: We analyzed pre-surgery blood samples from 139 glioma patients diagnosed with a new or recurrent grade II/III glioma (LrGG, n = 64) or new glioblastoma (GBM, n = 75) and 454 control participants without glioma. Relative cell fractions of CD4, CD8, B-cells, Natural Killer cells, monocytes, and neutrophils, were estimated via a validated deconvolution algorithm from blood DNA methylation measures from Illumina EPIC arrays. Results: Dexamethasone use at time of blood draw varied by glioma type being highest among patients with IDH wild-type (wt) GBM (75%) and lowest for those with oligodendroglioma (14%). Compared to controls, glioma patients showed statistically significant lower cell fractions for all immune cell subsets except for neutrophils which were higher (all p-values < 0.001), in part because of the higher prevalence of dexamethasone use at time of blood draw for IDHwt GBM. Patients who were taking dexamethasone were more likely to have a low CD4 count (< 200, < 500), increased neutrophils, low absolute lymphocyte counts, higher total cell count and higher NLR. Conclusion: We show that pre-surgery blood immune profiles vary by glioma subtype, age, and more critically, by use of dexamethasone. Our results highlight the importance of considering dexamethasone exposures in all studies of immune profiles and of obtaining immune measures prior to use of dexamethasone, if possible.

We search for the signature of cosmological shocks in stacked gas pressure profiles of galaxy clusters using data from the South Pole Telescope (SPT). Specifically, we stack the latest Compton-y maps from the 2500 deg2 SPT-SZ survey on the locations of clusters identified in that same data set. The sample contains 516 clusters with mean mass 〈 M 200m〉 = 1014.9\, M⊙ and redshift z= 0.55. We analyse in parallel a set of zoom-in hydrodynamical simulations from the three hundred project. The SPT-SZ data show two features: (i) a pressure deficit at R/R200m = 1.08 ± 0.09, measured at 3.1σ significance and not observed in the simulations, and; (ii) a sharp decrease in pressure at R/R200m = 4.58 ± 1.24 at 2.0σ significance. The pressure deficit is qualitatively consistent with a shock-induced thermal non-equilibrium between electrons and ions, and the second feature is consistent with accretion shocks seen in previous studies. We split the cluster sample by redshift and mass, and find both features exist in all cases. There are also no significant differences in features along and across the cluster major axis, whose orientation roughly points towards filamentary structure. As a consistency test, we also analyse clusters from the Planck and Atacama Cosmology Telescope Polarimeter surveys and find quantitatively similar features in the pressure profiles. Finally, we compare the accretion shock radius (R sh,\, acc) with existing measurements of the splashback radius (Rsp) for SPT-SZ and constrain the lower limit of the ratio, R sh,\, acc/R sp\> 2.16\± 0.59.

We show the improvement to cosmological constraints from galaxy cluster surveys with the addition of cosmic microwave background (CMB)-cluster lensing data. We explore the cosmological implications of adding mass information from the 3.1σ detection of gravitational lensing of the CMB by galaxy clusters to the Sunyaev-Zel'dovich (SZ) selected galaxy cluster sample from the 2500 deg2 SPT-SZ survey and targeted optical and X-ray follow-up data. In the ΛCDM model, the combination of the cluster sample with the Planck power spectrum measurements prefers σ8ωm/0.30.5=0.831±0.020 . Adding the cluster data reduces the uncertainty on this quantity by a factor of 1.4, which is unchanged whether the 3.1σ CMB-cluster lensing measurement is included or not. We then forecast the impact of CMB-cluster lensing measurements with future cluster catalogs. Adding CMB-cluster lensing measurements to the SZ cluster catalog of the ongoing SPT-3G survey is expected to improve the expected constraint on the dark energy equation of state w by a factor of 1.3 to σ(w) = 0.19. We find the largest improvements from CMB-cluster lensing measurements to be for σ 8, where adding CMB-cluster lensing data to the cluster number counts reduces the expected uncertainty on σ 8 by respective factors of 2.4 and 3.6 for SPT-3G and CMB-S4.

In this paper we discuss design considerations and beam dynamics challenges associated with laser-driven plasma-based accelerators as applied to multi-TeV-scale linear colliders. Plasma accelerators provide ultra-high gradients and ultra-short bunches, offering the potential for compact linacs and reduced power requirements. We show that stable, efficient acceleration with beam quality preservation is possible in the nonlinear bubble regime of laser-plasma accelerators using beam shaping. Ion motion, naturally occuring for dense beams (i.e., low emittance and high energy) severely damps transverse beam instabilities. Coulomb scattering by the background ions is considered and it is shown that the strong focusing in the plasma strongly suppresses scattering-induced emittance growth. Betatron radiation emission from the transverse motion of the beam in the plasma will result in beam power loss and energy spread growth; however for sub-100 nm emittances, the beam power loss and energy spread growth will be sub-percent for multi-TeV-class plasma linacs.

A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a Z boson. The search uses proton-proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 , at a center-of-mass energy s = 13 TeV . No significant deviation from the standard model expectation is observed. Upper limits at 95% confidence level are set on model-independent Higgs boson decay branching fractions. Additionally, limits on dark photon and axion-like particle production, based on two specific models, are reported.

Global change experiments often observe shifts in bacterial community composition based on 16S rRNA gene sequences. However, this genetic region can mask a large amount of genetic and phenotypic variation among bacterial strains sharing even identical 16S regions. As such, it remains largely unknown whether variation at the sub-16S level, sometimes termed microdiversity, responds to environmental perturbations and whether such changes are relevant to ecosystem processes. Here, we investigated microdiversity within Curtobacterium, the dominant bacterium found in the leaf litter layer of soil, to simulated drought and nitrogen addition in a field experiment. We first developed and validated Curtobacterium-specific primers of the groEL gene to assess microdiversity within this lineage. We then tracked the response of this microdiversity to simulated global change in two adjacent plant communities, grassland and coastal sage scrub (CSS). Curtobacterium microdiversity responded to drought but not nitrogen addition, indicating variation within the genus of drought tolerance but not nitrogen response. Further, the response of microdiversity to drought depended on the ecosystem, suggesting that litter substrate selects for a distinct composition of microdiversity that is constrained in its response, perhaps related to tradeoffs in resource acquisition traits. Supporting this interpretation, a metagenomic analysis revealed that the composition of Curtobacterium-encoded carbohydrate-active enzymes (CAZymes) varied distinctly across the two ecosystems. Identifying the degree to which relevant traits are phylogenetically conserved may help to predict when the aggregated response of a 16S-defined taxon masks differential responses of finer-scale bacterial diversity to global change. IMPORTANCE Microbial communities play an integral role in global biogeochemical cycling, but our understanding of how global change will affect microbial community structure and functioning remains limited. Microbiome analyses typically aggregate large amounts of genetic diversity which may obscure finer variation in traits. This study found that fine-scale diversity (or microdiversity) within the bacterial genus Curtobacterium was affected by simulated global changes. However, the degree to which this was true depended on the type of global change, as the composition of Curtobacterium microdiversity was affected by drought, but not by nitrogen addition. Further, these changes were associated with variation in carbon degradation traits. Future work might improve predictions of microbial community responses to global change by considering microdiversity.

Background and purposeSelumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib.Materials and methodsChildren with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment.ResultsEach stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG.ConclusionsADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses.

We present component-separated maps of the primary cosmic microwave background/kinematic Sunyaev-Zel'dovich (SZ) amplitude and the thermal SZ Compton-y parameter, created using data from the South Pole Telescope (SPT) and the Planck satellite. These maps, which cover the a1/42500 deg2 of the southern sky imaged by the SPT-SZ survey, represent a significant improvement over previous such products available in this region by virtue of their higher angular resolution ( 1.′25 for our highest-resolution Compton-y maps) and lower noise at small angular scales. In this work we detail the construction of these maps using linear combination techniques, including our method for limiting the correlation of our lowest-noise Compton-y map products with the cosmic infrared background. We perform a range of validation tests on these data products to test our sky modeling and combination algorithms, and we find good performance in all of these tests. Recognizing the potential utility of these data products for a wide range of astrophysical and cosmological analyses, including studies of the gas properties of galaxies, groups, and clusters, we make these products publicly available at http://pole.uchicago.edu/public/data/sptsz_ymap and on the NASA/LAMBDA website.

SPT-3G is the third survey receiver operating on the South Pole Telescope dedicated to high-resolution observations of the cosmic microwave background (CMB). Sensitive measurements of the temperature and polarization anisotropies of the CMB provide a powerful data set for constraining cosmology. Additionally, CMB surveys with arcminute-scale resolution are capable of detecting galaxy clusters, millimeter-wave bright galaxies, and a variety of transient phenomena. The SPT-3G instrument provides a significant improvement in mapping speed over its predecessors, SPT-SZ and SPTpol. The broadband optics design of the instrument achieves a 430 mm diameter image plane across observing bands of 95, 150, and 220 GHz, with 1.2′ FWHM beam response at 150 GHz. In the receiver, this image plane is populated with 2690 dual-polarization, trichroic pixels ( 1/416,000 detectors) read out using a 68× digital frequency-domain multiplexing readout system. In 2018, SPT-3G began a multiyear survey of 1500 deg2 of the southern sky. We summarize the unique optical, cryogenic, detector, and readout technologies employed in SPT-3G, and we report on the integrated performance of the instrument.

Monte Carlo simulations are widely used in nuclear physics to model experimental systems. In cases where there are significant unknown quantities, such as energies of states, an iterative process of simulating and fitting is often required to describe experimental data. We describe a Bayesian approach to fitting experimental data, designed for data from a 12Be(d,p) reaction measurement, using simulations made with GEANT4. Q-values from the 12C(d,p) reaction to well-known states in 13C are compared with simulations using BayesOpt. The energies of the states were not included in the simulation to reproduce the situation for 13Be where the states are poorly known. Both cases had low statistics and significant resolution broadening owing to large proton energy losses in the solid deuterium target. Excitation energies of the lowest three excited states in 13C were extracted to better than 90 keV, paving a way for extracting information on 13Be.

BackgroundMagnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate allows real-time and pathway specific clinical detection of otherwise unimageable in vivo metabolism. However, the comparability between sites and protocols is unknown. Here, we provide initial experiences on the agreement of hyperpolarized MRI between sites and protocols by repeated imaging of same healthy volunteers in Europe and the US.MethodsThree healthy volunteers traveled for repeated multicenter brain MRI exams with hyperpolarized [1-13C]pyruvate within one year. First, multisite agreement was assessed with the same echo-planar imaging protocol at both sites. Then, this was compared to a variable resolution echo-planar imaging protocol. In total, 12 examinations were performed. Common metrics of 13C-pyruvate to 13C-lactate conversion were calculated, including the kPL, a model-based kinetic rate constant, and its model-free equivalents. Repeatability was evaluated with intraclass correlation coefficients (ICC) for absolute agreement computed using two-way random effects models.ResultsThe mean kPL across all examinations in the multisite comparison was 0.024 ± 0.0016 s-1. The ICC of the kPL was 0.83 (p = 0.14) between sites and 0.7 (p = 0.09) between examinations of the same volunteer at any of the two sites. For the model-free metrics, the lactate Z-score had similar site-to-site ICC, while it was considerably lower for the lactate-to-pyruvate ratio.ConclusionsEstimation of metabolic conversion from hyperpolarized [1-13C]pyruvate to lactate using model-based metrics such as kPL suggests close agreement between sites and examinations in volunteers. Our initial results support harmonization of protocols, support multicenter studies, and inform their design.