Showing papers by "Moscow Institute of Physics and Technology published in 2021"

Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources

Abstract: The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons—cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3–6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators. Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.

Giant optical anisotropy in transition metal dichalcogenides for next-generation photonics.

Abstract: Large optical anisotropy observed in a broad spectral range is of paramount importance for efficient light manipulation in countless devices. Although a giant anisotropy has been recently observed in the mid-infrared wavelength range, for visible and near-infrared spectral intervals, the problem remains acute with the highest reported birefringence values of 0.8 in BaTiS3 and h-BN crystals. This issue inspired an intensive search for giant optical anisotropy among natural and artificial materials. Here, we demonstrate that layered transition metal dichalcogenides (TMDCs) provide an answer to this quest owing to their fundamental differences between intralayer strong covalent bonding and weak interlayer van der Waals interaction. To do this, we made correlative far- and near-field characterizations validated by first-principle calculations that reveal a huge birefringence of 1.5 in the infrared and 3 in the visible light for MoS2. Our findings demonstrate that this remarkable anisotropy allows for tackling the diffraction limit enabling an avenue for on-chip next-generation photonics. Optical anisotropy in a broad spectral range is pivotal to efficient light manipulation. Here, the authors measure a birefringence of 1.5 in the infrared range and 3 in the visible light for MoS2.

Jet energy scale and resolution measured in proton-proton collisions at s =13 TeV with the ATLAS detector

Abstract: Jet energy scale and resolution measurements with their associated uncertainties are reported for jets using 36-81 fb$^{-1}$ of proton-proton collision data with a centre-of-mass energy of $\sqrt{s}=13$ TeV collected by the ATLAS detector at the LHC. Jets are reconstructed using two different input types: topo-clusters formed from energy deposits in calorimeter cells, as well as an algorithmic combination of charged-particle tracks with those topo-clusters, referred to as the ATLAS particle-flow reconstruction method. The anti-$k_t$ jet algorithm with radius parameter $R=0.4$ is the primary jet definition used for both jet types. Jets are initially calibrated using a sequence of simulation-based corrections. Next, several $\textit{in situ}$ techniques are employed to correct for differences between data and simulation and to measure the resolution of jets. The systematic uncertainties in the jet energy scale for central jets ($|\eta| 2.5$ TeV). The relative jet energy resolution is measured and ranges from ($24 \pm 1.5$)% at 20 GeV to ($6 \pm 0.5$)% at 300 GeV.

Electron and photon reconstruction and identification with the CMS experiment at the CERN LHC

Abstract: The performance is presented of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC. The reported results are based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb$^{-1}$. Results obtained from lead-lead collision data collected at $\sqrt{s_\mathrm{NN}}=$ 5.02 TeV are also presented. Innovative techniques are used to reconstruct the electron and photon signals in the detector and to optimize the energy resolution. Events with electrons and photons in the final state are used to measure the energy resolution and energy scale uncertainty in the recorded events. The measured energy resolution for electrons produced in Z boson decays in proton-proton collision data ranges from 2 to 5%, depending on electron pseudorapidity and energy loss through bremsstrahlung in the detector material. The energy scale in the same range of energies is measured with an uncertainty smaller than 0.1 (0.3)% in the barrel (endcap) region in proton-proton collisions and better than 1 (3)% in the barrel (endcap) region in heavy ion collisions. The timing resolution for electrons from Z boson decays with the full 2016-2018 proton-proton collision data set is measured to be 200 ps.

Nonlinear second-order photonic topological insulators

Abstract: Higher-order topological insulators are a novel topological phase beyond the framework of conventional bulk–boundary correspondence1,2. In these peculiar systems, the topologically non-trivial boundary modes are characterized by a co-dimension of at least two3,4. Despite several promising preliminary considerations regarding the impact of nonlinearity in such systems5,6, the flourishing field of experimental higher-order topological insulator research has thus far been confined to the linear evolution of topological states. As such, the observation of the interplay between nonlinearity and the dynamics of higher-order topological phases in conservative systems remains elusive. Here we experimentally demonstrate nonlinear higher-order topological corner states. Our photonic platform enables us to observe nonlinear topological corner states as well as the formation of solitons in such topological structures. Our work paves the way towards the exploration of topological properties of matter in the nonlinear regime, and may herald a new class of compact devices that harnesses the intriguing features of topology in an on-demand fashion. The nonlinear properties of photonic topological insulators remain largely unexplored, as band topology is linked to linear systems. But nonlinear topological corner states and solitons can form in a second-order topological insulator, as shown by experiments.

Insight into the Critical Role of Exchange Current Density on Electrodeposition Behavior of Lithium Metal

Abstract: Due to an ultrahigh theoretical specific capacity of 3860 mAh g-1, lithium (Li) is regarded as the ultimate anode for high-energy-density batteries. However, the practical application of Li metal anode is hindered by safety concerns and low Coulombic efficiency both of which are resulted fromunavoidable dendrite growth during electrodeposition. This study focuses on a critical parameter for electrodeposition, the exchange current density, which has attracted only little attention in research on Li metal batteries. A phase-field model is presented to show the effect of exchange current density on electrodeposition behavior of Li. The results show that a uniform distribution of cathodic current density, hence uniform electrodeposition, on electrode is obtained with lower exchange current density. Furthermore, it is demonstrated that lower exchange current density contributes to form a larger critical radius of nucleation in the initial electrocrystallization that results in a dense deposition of Li, which is a foundation for improved Coulombic efficiency and dendrite-free morphology. The findings not only pave the way to practical rechargeable Li metal batteries but can also be translated to the design of stable metal anodes, e.g., for sodium (Na), magnesium (Mg), and zinc (Zn) batteries.

A dual approach for optimal algorithms in distributed optimization over networks

Abstract: We study dual-based algorithms for distributed convex optimization problems over networks, where the objective is to minimize a sum ∑ i = 1 m f i ( z ) of functions over in a network. We provide co...

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon.

Abstract: We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.

Ni substitution effect on the structure, magnetization, resistivity and permeability of zinc ferrites

Abstract: Zn1−xNixFe2O4 ferrites up to x = 1.0 with Δx = 0.2 have been synthesized via solid state reactions and the sol–gel autocombustion technique with step-by-step co-firing. Data on the chemical composition and the surface morphology of the samples have been obtained using a scanning electron microscope. An X-ray powder diffractometer has been used to establish the phase purity and to determine the unit cell parameters. It has been found that the obtained samples had a spinel structure with the Fdm (No. 227) space group. The unit cell parameters decrease with increasing nickel concentration. The a unit cell parameter decreases almost linearly from ∼8.443 A for x = 0.0 down to ∼8.337 A for x = 1.0. The V unit cell volume decreases almost linearly from ∼601.72 A3 for x = 0.0 down to ∼579.52 A3 for x = 1.0. The magnetic characteristics of the obtained samples are determined and discussed. The Curie point of obtained samples varies in the range of 803.5–572.7 K. The maximum spontaneous magnetization of ∼74.6 emu g−1 at room temperature was fixed for the solid solution with x = 0.6. Ac-resistivity drops by more than 3 orders of magnitude in the frequency range 1–106 Hz. The composition with x = 0.6 has the minimum ac-resistivity of 5.3 kOm cm at a frequency of 106 Hz. The maximum value of the (μ′) real part of ∼11.2 and (μ′′) imaginary part of ∼5.2 of the permeability in the frequency range of 50 MHz–10 GHz is observed for the composition with x = 0.4. The composite samples for the microwave study were prepared by mixing of the ferrite powders with molten paraffin wax. The volume fraction of the ferrite filler in the composites was 25%. The largest value of the (μ′) real part of ∼3 and (μ′′) imaginary part of ∼0.63 of permeability is found for the x = 0.4 composite. The formation of the composite significantly reduces permeability.

Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at √ s = 13 TeV

Abstract: This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 $$\hbox {fb}^{-1}$$ fb - 1 of pp collision data at $$\sqrt{s}=13$$ s = 13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of $$Z\rightarrow \mu \mu $$ Z → μ μ and $$J/\psi \rightarrow \mu \mu $$ J / ψ → μ μ decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of $$|\eta |<2.7$$ | η | < 2.7 .

Evidence for Higgs boson decay to a pair of muons

Abstract: Evidence for Higgs boson decay to a pair of muons is presented. This result combines searches in four exclusive categories targeting the production of the Higgs boson via gluon fusion, via vector boson fusion, in association with a vector boson, and in association with a top quark-antiquark pair. The analysis is performed using proton-proton collision data at $ \sqrt{s} $ = 13 TeV, corresponding to an integrated luminosity of 137 fb$^{−1}$, recorded by the CMS experiment at the CERN LHC. An excess of events over the back- ground expectation is observed in data with a significance of 3.0 standard deviations, where the expectation for the standard model (SM) Higgs boson with mass of 125.38 GeV is 2.5. The combination of this result with that from data recorded at $ \sqrt{s} $ = 7 and 8 TeV, corresponding to integrated luminosities of 5.1 and 19.7 fb$^{−1}$, respectively, increases both the expected and observed significances by 1%. The measured signal strength, relative to the SM prediction, is $ {1.19}_{-0.39}^{+0.40}{\left(\mathrm{stat}\right)}_{-0.14}^{+0.15}\left(\mathrm{syst}\right) $. This result constitutes the first evidence for the decay of the Higgs boson to second generation fermions and is the most precise measurement of the Higgs boson coupling to muons reported to date.[graphic not available: see fulltext]

Mutational drivers of cancer cell migration and invasion.

Abstract: Genomic instability and mutations underlie the hallmarks of cancer-genetic alterations determine cancer cell fate by affecting cell proliferation, apoptosis and immune response, and increasing data show that mutations are involved in metastasis, a crucial event in cancer progression and a life-threatening problem in cancer patients. Invasion is the first step in the metastatic cascade, when tumour cells acquire the ability to move, penetrate into the surrounding tissue and enter lymphatic and blood vessels in order to disseminate. A role for genetic alterations in invasion is not universally accepted, with sceptics arguing that cellular motility is related only to external factors such as hypoxia, chemoattractants and the rigidity of the extracellular matrix. However, increasing evidence shows that mutations might trigger and accelerate the migration and invasion of different types of cancer cells. In this review, we summarise data from published literature on the effect of chromosomal instability and genetic mutations on cancer cell migration and invasion.

Stochastic quasi-gradient methods: variance reduction via Jacobian sketching

Abstract: We develop a new family of variance reduced stochastic gradient descent methods for minimizing the average of a very large number of smooth functions. Our method—JacSketch—is motivated by novel developments in randomized numerical linear algebra, and operates by maintaining a stochastic estimate of a Jacobian matrix composed of the gradients of individual functions. In each iteration, JacSketch efficiently updates the Jacobian matrix by first obtaining a random linear measurement of the true Jacobian through (cheap) sketching, and then projecting the previous estimate onto the solution space of a linear matrix equation whose solutions are consistent with the measurement. The Jacobian estimate is then used to compute a variance-reduced unbiased estimator of the gradient. Our strategy is analogous to the way quasi-Newton methods maintain an estimate of the Hessian, and hence our method can be seen as a stochastic quasi-gradient method. Our method can also be seen as stochastic gradient descent applied to a controlled stochastic optimization reformulation of the original problem, where the control comes from the Jacobian estimates. We prove that for smooth and strongly convex functions, JacSketch converges linearly with a meaningful rate dictated by a single convergence theorem which applies to general sketches. We also provide a refined convergence theorem which applies to a smaller class of sketches, featuring a novel proof technique based on a stochastic Lyapunov function. This enables us to obtain sharper complexity results for variants of JacSketch with importance sampling. By specializing our general approach to specific sketching strategies, JacSketch reduces to the celebrated stochastic average gradient (SAGA) method, and its several existing and many new minibatch, reduced memory, and importance sampling variants. Our rate for SAGA with importance sampling is the current best-known rate for this method, resolving a conjecture by Schmidt et al. (Proceedings of the eighteenth international conference on artificial intelligence and statistics, AISTATS 2015, San Diego, California, 2015). The rates we obtain for minibatch SAGA are also superior to existing rates and are sufficiently tight as to show a decrease in total complexity as the minibatch size increases. Moreover, we obtain the first minibatch SAGA method with importance sampling.

Search for resonant and nonresonant new phenomena in high-mass dilepton final states at √s = 13 TeV

Abstract: A search is presented for physics beyond the standard model (SM) using electron or muon pairs with high invariant mass. A data set of proton-proton collisions collected by the CMS experiment at the LHC at s = 13 TeV from 2016 to 2018 corresponding to a total integrated luminosity of up to 140 fb−1 is analyzed. No significant deviation is observed with respect to the SM background expectations. Upper limits are presented on the ratio of the product of the production cross section and the branching fraction to dileptons of a new narrow resonance to that of the Z boson. These provide the most stringent lower limits to date on the masses for various spin-1 particles, spin-2 gravitons in the Randall-Sundrum model, as well as spin-1 mediators between the SM and dark matter particles. Lower limits on the ultraviolet cutoff parameter are set both for four-fermion contact interactions and for the Arkani-Hamed, Dimopoulos, and Dvali model with large extra dimensions. Lepton flavor universality is tested at the TeV scale for the first time by comparing the dimuon and dielectron mass spectra. No significant deviation from the SM expectation of unity is observed.

Amyloid-type Protein Aggregation and Prion-like Properties of Amyloids.

Abstract: This review will focus on the process of amyloid-type protein aggregation. Amyloid fibrils are an important hallmark of protein misfolding diseases and therefore have been investigated for decades. Only recently, however, atomic or near-atomic resolution structures have been elucidated from various in vitro and ex vivo obtained fibrils. In parallel, the process of fibril formation has been studied in vitro under highly artificial but comparatively reproducible conditions. The review starts with a summary of what is known and speculated from artificial in vitro amyloid-type protein aggregation experiments. A partially hypothetic fibril selection model will be described that may be suitable to explain why amyloid fibrils look the way they do, in particular, why at least all so far reported high resolution cryo-electron microscopy obtained fibril structures are in register, parallel, cross-β-sheet fibrils that mostly consist of two protofilaments twisted around each other. An intrinsic feature of the model is the prion-like nature of all amyloid assemblies. Transferring the model from the in vitro point of view to the in vivo situation is not straightforward, highly hypothetic, and leaves many open questions that need to be addressed in the future.

Coupled-Channel Interpretation of the LHCb Double- J / ψ Spectrum and Hints of a New State Near the J / ψ J / ψ Threshold

Abstract: Recently, the LHCb Collaboration reported pronounced structures in the invariant mass spectrum of $J/\ensuremath{\psi}$ pairs produced in proton-proton collisions at the Large Hadron Collider. In this Letter, we argue that the data can be very well described within two variants of a coupled-channel approach employing $T$ matrices consistent with unitarity: (i) with just two channels, $J/\ensuremath{\psi}J/\ensuremath{\psi}$ and $\ensuremath{\psi}(2S)J/\ensuremath{\psi}$, as long as energy-dependent interactions in these channels are allowed, or (ii) with three channels $J/\ensuremath{\psi}J/\ensuremath{\psi}$, $\ensuremath{\psi}(2S)J/\ensuremath{\psi}$, and $\ensuremath{\psi}(3770)J/\ensuremath{\psi}$ with just constant contact interactions. Both formulations hint at the existence of a near-threshold state in the $J/\ensuremath{\psi}J/\ensuremath{\psi}$ system with the quantum numbers ${J}^{PC}={0}^{++}$ or ${2}^{++}$, which we refer to as $X(6200)$. We suggest experimental tests to check the existence of this state and discuss what additional channels need to be studied experimentally to allow for distinctive tests between the two mechanisms proposed. If the molecular nature of $X(6200)$, as hinted by the three-channel approach, is confirmed, many other double-quarkonium states should exist driven by the same binding mechanism. In particular, there should be an ${\ensuremath{\eta}}_{c}{\ensuremath{\eta}}_{c}$ molecule with a similar binding energy.

Noise-assisted persistence and recovery of memory state in a memristive spiking neuromorphic network

Abstract: We investigate the constructive role of an external noise signal, in the form of a low-rate Poisson sequence of pulses supplied to all inputs of a spiking neural network, consisting in maintaining for a long time or even recovering a memory trace (engram) of the image without its direct renewal (or rewriting). In particular, this unique dynamic property is demonstrated in a single-layer spiking neural network consisting of simple integrate-and-fire neurons and memristive synaptic weights. This is carried out by preserving and even fine-tuning the conductance values of memristors in terms of dynamic plasticity, specifically spike-timing-dependent plasticity-type, driven by overlapping pre- and postsynaptic voltage spikes. It has been shown that the weights can be to a certain extent unreliable, due to such characteristics as the limited retention time of resistive state or the variation of switching voltages. Such a noise-assisted persistence of memory, on one hand, could be a prototypical mechanism in a biological nervous system and, on the other hand, brings one step closer to the possibility of building reliable spiking neural networks composed of unreliable analog elements.

Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin.

Abstract: Characterization of the progression of cellular states during human embryogenesis can provide insights into the origin of pediatric diseases. We examined the transcriptional states of neural crest- and mesoderm-derived lineages differentiating into adrenal glands, kidneys, endothelium and hematopoietic tissue between post-conception weeks 6 and 14 of human development. Our results reveal transitions connecting the intermediate mesoderm and progenitors of organ primordia, the hematopoietic system and endothelial subtypes. Unexpectedly, by using a combination of single-cell transcriptomics and lineage tracing, we found that intra-adrenal sympathoblasts at that stage are directly derived from nerve-associated Schwann cell precursors, similarly to local chromaffin cells, whereas the majority of extra-adrenal sympathoblasts arise from the migratory neural crest. In humans, this process persists during several weeks of development within the large intra-adrenal ganglia-like structures, which may also serve as reservoirs of originating cells in neuroblastoma.

Functional supramolecular systems: design and applications

Abstract: The interest in functional supramolecular systems for the design of innovative materials and technologies, able to fundamentally change the world, is growing at a high pace. The huge array of publications that appeared in recent years in the global literature calls for systematization of the structural trends inherent in the formation of these systems revealed at different molecular platforms and practically useful properties they exhibit. The attention is concentrated on the topics related to functional supramolecular systems that are actively explored in institutes and universities of Russia in the last 10–15 years, such as the chemistry of host–guest complexes, crystal engineering, self-assembly and self-organization in solutions and at interfaces, biomimetics and molecular machines and devices. The bibliography includes 1714 references.

Development and large volume production of extremely high current density YBa2Cu3O7 superconducting wires for fusion.

Abstract: The fusion power density produced in a tokamak is proportional to its magnetic field strength to the fourth power Second-generation high temperature superconductor (2G HTS) wires demonstrate remarkable engineering current density (averaged over the full wire), JE, at very high magnetic fields, driving progress in fusion and other applications The key challenge for HTS wires has been to offer an acceptable combination of high and consistent superconducting performance in high magnetic fields, high volume supply, and low price Here we report a very high and reproducible JE in practical HTS wires based on a simple YBa2Cu3O7 (YBCO) superconductor formulation with Y2O3 nanoparticles, which have been delivered in just nine months to a commercial fusion customer in the largest-volume order the HTS industry has seen to date We demonstrate a novel YBCO superconductor formulation without the c-axis correlated nano-columnar defects that are widely believed to be prerequisite for high in-field performance The simplicity of this new formulation allows robust and scalable manufacturing, providing, for the first time, large volumes of consistently high performance wire, and the economies of scale necessary to lower HTS wire prices to a level acceptable for fusion and ultimately for the widespread commercial adoption of HTS

Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel.

Abstract: Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing. Cryo-EM structures of the heat-activated TRP channel TRPV3 in lipid nanodiscs at different temperatures reveal a conformational wave involved in the gating process.

FDA-Approved and Emerging Next Generation Predictive Biomarkers for Immune Checkpoint Inhibitors in Cancer Patients

Abstract: A patient's response to immune checkpoint inhibitors (ICIs) is a complex quantitative trait, and determined by multiple intrinsic and extrinsic factors. Three currently FDA-approved predictive biomarkers (progra1mmed cell death ligand-1 (PD-L1); microsatellite instability (MSI); tumor mutational burden (TMB)) are routinely used for patient selection for ICI response in clinical practice. Although clinical utility of these biomarkers has been demonstrated in ample clinical trials, many variables involved in using these biomarkers have poised serious challenges in daily practice. Furthermore, the predicted responders by these three biomarkers only have a small percentage of overlap, suggesting that each biomarker captures different contributing factors to ICI response. Optimized use of currently FDA-approved biomarkers and development of a new generation of predictive biomarkers are urgently needed. In this review, we will first discuss three widely used FDA-approved predictive biomarkers and their optimal use. Secondly, we will review four novel gene signature biomarkers: T-cell inflamed gene expression profile (GEP), T-cell dysfunction and exclusion gene signature (TIDE), melanocytic plasticity signature (MPS) and B-cell focused gene signature. The GEP and TIDE have shown better predictive performance than PD-L1, and PD-L1 or TMB, respectively. The MPS is superior to PD-L1, TMB, and TIDE. The B-cell focused gene signature represents a previously unexplored predictive biomarker to ICI response. Thirdly, we will highlight two combined predictive biomarkers: TMB+GEP and MPS+TIDE. These integrated biomarkers showed improved predictive outcomes compared to a single predictor. Finally, we will present a potential nucleic acid biomarker signature, allowing DNA and RNA biomarkers to be analyzed in one assay. This comprehensive signature could represent a future direction of developing robust predictive biomarkers, particularly for the cold tumors, for ICI response.

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

Abstract: Background Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.

Dynamics of soliton self-injection locking in optical microresonators

Abstract: Soliton microcombs constitute chip-scale optical frequency combs, and have the potential to impact a myriad of applications from frequency synthesis and telecommunications to astronomy. The demonstration of soliton formation via self-injection locking of the pump laser to the microresonator has significantly relaxed the requirement on the external driving lasers. Yet to date, the nonlinear dynamics of this process has not been fully understood. Here, we develop an original theoretical model of the laser self-injection locking to a nonlinear microresonator, i.e., nonlinear self-injection locking, and construct state-of-the-art hybrid integrated soliton microcombs with electronically detectable repetition rate of 30 GHz and 35 GHz, consisting of a DFB laser butt-coupled to a silicon nitride microresonator chip. We reveal that the microresonator's Kerr nonlinearity significantly modifies the laser diode behavior and the locking dynamics, forcing laser emission frequency to be red-detuned. A novel technique to study the soliton formation dynamics as well as the repetition rate evolution in real-time uncover non-trivial features of the soliton self-injection locking, including soliton generation at both directions of the diode current sweep. Our findings provide the guidelines to build electrically driven integrated microcomb devices that employ full control of the rich dynamics of laser self-injection locking, key for future deployment of microcombs for system applications.