Metasurfaces with strongly anisotropic optical properties can support deep subwavelength-scale confined electromagnetic waves (polaritons), which promise opportunities for controlling light in ...photonic and optoelectronic applications. We developed a mid-infrared hyperbolic metasurface by nanostructuring a thin layer of hexagonal boron nitride that supports deep subwavelength-scale phonon polaritons that propagate with in-plane hyperbolic dispersion. By applying an infrared nanoimaging technique, we visualize the concave (anomalous) wavefronts of a diverging polariton beam, which represent a landmark feature of hyperbolic polaritons. The results illustrate how near-field microscopy can be applied to reveal the exotic wavefronts of polaritons in anisotropic materials and demonstrate that nanostructured van der Waals materials can form a highly variable and compact platform for hyperbolic infrared metasurface devices and circuits.
Optical nanoantennas are of great importance for photonic devices and spectroscopy due to their capability of squeezing light at the nanoscale and enhancing light–matter interactions. Among them, ...nanoantennas made of polar crystals supporting phonon polaritons (phononic nanoantennas) exhibit the highest quality factors. This is due to the low optical losses inherent in these materials, which, however, hinder the spectral tuning of the nanoantennas due to their dielectric nature. Here, active and passive tuning of ultranarrow resonances in phononic nanoantennas is realized over a wide spectral range (≈35 cm−1, being the resonance linewidth ≈9 cm−1), monitored by near‐field nanoscopy. To do that, the local environment of a single nanoantenna made of hexagonal boron nitride is modified by placing it on different polar substrates, such as quartz and 4H‐silicon carbide, or covering it with layers of a high‐refractive‐index van der Waals crystal (WSe2). Importantly, active tuning of the nanoantenna polaritonic resonances is demonstrated by placing it on top of a gated graphene monolayer in which the Fermi energy is varied. This work presents the realization of tunable polaritonic nanoantennas with ultranarrow resonances, which can find applications in active nanooptics and (bio)sensing.
Near‐field nanoscopy monitors active and passive tuning of ultranarrow resonances in phononic nanoantennas over a wide spectral range (−35 cm−1, being the resonance linewidth ≈9 cm−1). Passive tunability can be realized by tailoring the dielectric environment of nanoantennas made of boron nitride, while reversible in situ tuning of narrow resonances is realized by placing nanoantennas on top of a graphene layer.
The complexities of tumor genomes are rapidly being uncovered, but how they are regulated into functional proteomes remains poorly understood. Standard proteomics workflows use databases of known ...proteins, but these databases do not capture the uniqueness of the cancer transcriptome, with its point mutations, unusual splice variants and gene fusions. Onco-proteogenomics integrates mass spectrometry-generated data with genomic information to identify tumor-specific peptides. Linking tumor-derived DNA, RNA and protein measurements into a central-dogma perspective has the potential to improve our understanding of cancer biology.
DNA sequencing has identified recurrent mutations that drive the aggressiveness of prostate cancers. Surprisingly, the influence of genomic, epigenomic, and transcriptomic dysregulation on the tumor ...proteome remains poorly understood. We profiled the genomes, epigenomes, transcriptomes, and proteomes of 76 localized, intermediate-risk prostate cancers. We discovered that the genomic subtypes of prostate cancer converge on five proteomic subtypes, with distinct clinical trajectories. ETS fusions, the most common alteration in prostate tumors, affect different genes and pathways in the proteome and transcriptome. Globally, mRNA abundance changes explain only ∼10% of protein abundance variability. As a result, prognostic biomarkers combining genomic or epigenomic features with proteomic ones significantly outperform biomarkers comprised of a single data type.
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•A comprehensive proteomic analyses of localized prostate cancers•Integration of all levels of the central dogma (DNA → RNA → protein)•ETS fusions have divergent effects on transcriptome and proteome•Combining genomics and proteomics improves biomarker performance
Sinha et al. determine the proteogenomic landscape of localized, intermediate-risk prostate cancers and show that the presence of ETS gene fusions has one of the strongest effects on the proteome. Prognostic biomarkers that integrate multi-omics significantly outperform those comprised of a single data type.
Abstract
Polaritons – coupled excitations of photons and dipolar matter excitations – can propagate along anisotropic metasurfaces with either hyperbolic or elliptical dispersion. At the transition ...from hyperbolic to elliptical dispersion (corresponding to a topological transition), various intriguing phenomena are found, such as an enhancement of the photonic density of states, polariton canalization and hyperlensing. Here, we investigate theoretically and experimentally the topological transition, the polaritonic coupling and the strong nonlocal response in a uniaxial infrared-phononic metasurface, a grating of hexagonal boron nitride (hBN) nanoribbons. By hyperspectral infrared nanoimaging, we observe a synthetic transverse optical phonon resonance (strong collective near-field coupling of the nanoribbons) in the middle of the hBN Reststrahlen band, yielding a topological transition from hyperbolic to elliptical dispersion. We further visualize and characterize the spatial evolution of a deeply subwavelength canalization mode near the transition frequency, which is a collimated polariton that is the basis for hyperlensing and diffraction-less propagation.
Nonsense-mediated messenger RNA (mRNA) decay (NMD) is a surveillance pathway used by cells to control the quality mRNAs and to fine-tune transcript abundance. NMD plays an important role in cell ...cycle regulation, cell viability, DNA damage response, while also serving as a barrier to virus infection. Disturbance of this control mechanism caused by genetic mutations or dys-regulation of the NMD pathway can lead to pathologies, including neurological disorders, immune diseases and cancers. The role of NMD in cancer development is complex, acting as both a promoter and a barrier to tumour progression. Cancer cells can exploit NMD for the downregulation of key tumour suppressor genes, or tumours adjust NMD activity to adapt to an aggressive immune microenvironment. The latter case might provide an avenue for therapeutic intervention as NMD inhibition has been shown to lead to the production of neoantigens that stimulate an immune system attack on tumours. For this reason, understanding the biology and co-option pathways of NMD is important for the development of novel therapeutic agents. Inhibitors, whose design can make use of the many structures available for NMD study, will play a crucial role in characterizing and providing diverse therapeutic options for this pathway in cancer and other diseases.
Recent interest in targeted therapies has been sparked by the study of MHC-associated peptides (MAPs) that undergo post-translational modifications (PTMs), particularly glycosylation. In this study, ...we introduce a fast computational workflow that merges the MSFragger-Glyco search algorithm with a false discovery rate control for glycopeptide analysis from mass spectrometry-based immunopeptidome data. By analyzing eight large-scale publicly available studies, we find that glycosylated MAPs are predominantly presented by MHC class II. Here, we present HLA-Glyco, a comprehensive resource containing over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. This resource provides valuable insights, including high levels of truncated glycans, conserved HLA-binding cores, and differences in glycosylation positional specificity between HLA allele groups. We integrate the workflow within the FragPipe computational platform and provide HLA-Glyco as a free web resource. Overall, our work provides a valuable tool and resource to aid the nascent field of glyco-immunopeptidomics.
Van der Waals (vdW) materials host a variety of polaritons, which make them an emerging material platform for manipulating light at the nanoscale. Due to the layered structure of vdW materials, the ...polaritons can exhibit a hyperbolic dispersion and propagate as nanoscale‐confined volume modes in thin flakes. On the other hand, surface‐confined modes can be found at the flake edges. Surprisingly, the guiding of these modes in ribbons—representing typical linear waveguide structures—is widely unexplored. Here, a detailed study of hyperbolic phonon polaritons propagating in hexagonal boron nitride ribbons is reported. Employing infrared nanoimaging, a variety of modes are observed. Particularly, the fundamental volume waveguide mode that exhibits a cutoff width is identified, which, interestingly, can be lowered by reducing the waveguide thickness. Further, hybridization of the surface modes and their evolution with varying frequency and waveguide width are observed. Most importantly, it is demonstrated that the symmetrically hybridized surface mode does not exhibit a cutoff width, and thus enables linear waveguiding of the polaritons in arbitrarily narrow ribbons. The experimental data, supported by simulations, establish a solid basis for the understanding of hyperbolic polaritons in linear waveguides, which is of critical importance for their application in future photonic devices.
Infrared nanoimaging and theoretical simulations are applied to study phonon polariton waveguide modes in nanoscale hexagonal boron nitride ribbons. Fundamental volume and hybridized surface modes are identified. Most importantly, the symmetrically hybridized surface mode does not exhibit a cutoff width, and thus allows for linear waveguiding of infrared energy in the narrowest ribbons that can be fabricated.
Onco-proteogenomics aims to understand how changes in a cancer's genome influences its proteome. One challenge in integrating these molecular data is the identification of aberrant protein products ...from mass-spectrometry (MS) datasets, as traditional proteomic analyses only identify proteins from a reference sequence database.
We established proteomic workflows to detect peptide variants within MS datasets. We used a combination of publicly available population variants (dbSNP and UniProt) and somatic variations in cancer (COSMIC) along with sample-specific genomic and transcriptomic data to examine proteome variation within and across 59 cancer cell-lines.
We developed a set of recommendations for the detection of variants using three search algorithms, a split target-decoy approach for FDR estimation, and multiple post-search filters. We examined 7.3 million unique variant tryptic peptides not found within any reference proteome and identified 4771 mutations corresponding to somatic and germline deviations from reference proteomes in 2200 genes among the NCI60 cell-line proteomes.
We discuss in detail the technical and computational challenges in identifying variant peptides by MS and show that uncovering these variants allows the identification of druggable mutations within important cancer genes.
Novice runners are at significantly greater risk of running-related injuries than experienced recreational runners. To develop prevention strategies for this population, it is important to identify ...predisposing factors that contribute to the incidence of these injuries. This study aims to assess the relationship between running-related injuries, foot posture and other factors in novice runners.
Case-control study in 600 novice runners, classified as cases or controls based on incidence of running-related injuries. Participants' foot posture was measured using the Foot Posture Index, and we performed a descriptive analysis of the explanatory variables, comparing cases and controls. To assess the association between the injury and the presence of exposure and other explanatory variables, we performed a simple logistic regression for each variable and then fit a multivariable regression model.
Our regression model showed that high supination was associated with 76.8 times higher odds of injury than a neutral Foot Posture Index score (P < 0.001). High pronation was associated with 20-fold higher odds of injury than neutral foot posture (P < 0.001). Other variables such as running surface, number of shoes used, and body mass index were also associated with injury. The model showed an acceptable predictive capacity, with an area under the ROC curve of 0.7753.
If the association between Foot Posture Index and running-related injury is confirmed in large prospective studies, running programs for beginners should consider foot posture in efforts to prevent running-related injuries.
•There is a significant association between running-related injury and foot posture.•Running surface type might be associated with injury in novice runners.•The use of one pair of shoes might be associated with injury in novice runners.•Body mass index might be associated with the presence of injury in novice runners.•Running experience might be associated with injury in novice runners.
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