Recent developments have enabled the practical realization of optical elements in which the polarization of light may vary spatially. We present an extension of Fourier optics-matrix Fourier ...optics-for understanding these devices and apply it to the design and realization of metasurface gratings implementing arbitrary, parallel polarization analysis. We show how these gratings enable a compact, full-Stokes polarization camera without standard polarization optics. Our single-shot polarization camera requires no moving parts, specially patterned pixels, or conventional polarization optics and may enable the widespread adoption of polarization imaging in machine vision, remote sensing, and other areas.
Introduction
Electrocardiographic characteristics in COVID‐19‐related mortality have not yet been reported, particularly in racial/ethnic minorities.
Methods and Results
We reviewed demographics, ...laboratory and cardiac tests, medications, and cardiac rhythm proximate to death or initiation of comfort care for patients hospitalized with a positive SARS‐CoV‐2 reverse‐transcriptase polymerase chain reaction in three New York City hospitals between March 1 and April 3, 2020 who died. We described clinical characteristics and compared factors contributing toward arrhythmic versus nonarrhythmic death. Of 1258 patients screened, 133 died and were enrolled. Of these, 55.6% (74/133) were male, 69.9% (93/133) were racial/ethnic minorities, and 88.0% (117/133) had cardiovascular disease. The last cardiac rhythm recorded was VT or fibrillation in 5.3% (7/133), pulseless electrical activity in 7.5% (10/133), unspecified bradycardia in 0.8% (1/133), and asystole in 26.3% (35/133). Most 74.4% (99/133) died receiving comfort measures only. The most common abnormalities on admission electrocardiogram included abnormal QRS axis (25.8%), atrial fibrillation/flutter (14.3%), atrial ectopy (12.0%), and right bundle branch block (11.9%). During hospitalization, an additional 17.6% developed atrial ectopy, 14.7% ventricular ectopy, 10.1% atrial fibrillation/flutter, and 7.8% a right ventricular abnormality. Arrhythmic death was confirmed or suspected in 8.3% (11/133) associated with age, coronary artery disease, asthma, vasopressor use, longer admission corrected QT interval, and left bundle branch block (LBBB).
Conclusions
Conduction, rhythm, and electrocardiographic abnormalities were common during COVID‐19‐related hospitalization. Arrhythmic death was associated with age, coronary artery disease, asthma, longer admission corrected QT interval, LBBB, ventricular ectopy, and usage of vasopressors. Most died receiving comfort measures.
Optical elements that convert the spin angular momentum (SAM) of light into vortex beams have found applications in classical and quantum optics. These elements—SAM-to–orbital angular momentum (OAM) ...converters—are based on the geometric phase and only permit the conversion of left- and right-circular polarizations (spin states) into states with opposite OAM. We present a method for converting arbitrary SAM states into total angular momentum states characterized by a superposition of independent OAM. We designed a metasurface that converts left- and right-circular polarizations into states with independent values of OAM and designed another device that performs this operation for elliptically polarized states. These results illustrate a general material-mediated connection between SAM and OAM of light and may find applications in producing complex structured light and in optical communication.
We present a method allowing for the imposition of two independent and arbitrary phase profiles on any pair of orthogonal states of polarization-linear, circular, or elliptical-relying only on ...simple, linearly birefringent wave plate elements arranged into metasurfaces. This stands in contrast to previous designs which could only address orthogonal linear, and to a limited extent, circular polarizations. Using this approach, we demonstrate chiral holograms characterized by fully independent far fields for each circular polarization and elliptical polarization beam splitters, both in the visible. This approach significantly expands the scope of metasurface polarization optics.
The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) has emerged as an important mechanism of treatment resistance. NEPC is associated with ...overexpression and gene amplification of MYCN (encoding N-Myc). N-Myc is an established oncogene in several rare pediatric tumors, but its role in prostate cancer progression is not well established. Integrating a genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc overexpression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC. This includes an abrogation of androgen receptor signaling and induction of Polycomb Repressive Complex 2 signaling. Altogether, our data establishes N-Myc as an oncogenic driver of NEPC.
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•N-Myc drives the NEPC phenotype and associated molecular program•N-Myc abrogates AR signaling, which results in enhanced AKT activity•N-Myc redirects EZH2 activity and sensitizes cells to EZH2 inhibitors•N-Myc interacts with Aurora-A, which facilitates N-Myc target gene expression
Dardenne et al. demonstrate that N-Myc overexpression in pre-clinical models drives aggressive prostate cancer that mimics human neuroendocrine prostate cancer, including reduced AR signaling and enhanced PRC2 target gene repression, and sensitizes cells to an Aurora-A inhibitor and EZH2 SET domain inhibitors.
Neuroendocrine (NE) cancers are a diverse group of neoplasms typically diagnosed and treated on the basis of their site of origin. This Perspective focuses on advances in our understanding of the ...tumorigenesis and treatment of poorly differentiated neuroendocrine tumors. Recent evidence from sequencing indicates that, although neuroendocrine tumors can arise de novo, they can also develop as a result of lineage plasticity in response to pressure from targeted therapies. We discuss the shared genomic alterations of these tumors independently of their site of origin, and we explore potential therapeutic strategies on the basis of recent biological findings.
Abstract
Recent advances in wavefront shaping have enabled complex classes of Structured Light which carry spin and orbital angular momentum, offering new tools for light-matter interaction, ...communications, and imaging. Controlling both components of angular momentum along the propagation direction can potentially extend such applications to 3D. However, beams of this kind have previously been realized using bench-top setups, requiring multiple interaction with light of a fixed input polarization, thus impeding their widespread applications. Here, we introduce two classes of metasurfaces that lift these constraints, namely: i) polarization-switchable plates that couple any pair of orthogonal polarizations to two vortices in which the magnitude and/or sense of vorticity vary locally with propagation, and ii) versatile plates that can structure both components of angular momentum, spin and orbital, independently, along the optical path while operating on incident light of any polarization. Compact and integrated devices of this type can advance light-matter interaction and imaging and may enable applications that are not accessible via other wavefront shaping tools.
Mutations in PIK3CA, which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN, which encodes a phosphatase that degrades ...the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers
. However, pharmacological inhibition of PI3K has resulted in variable clinical responses, raising the possibility of an inherent mechanism of resistance to treatment. As p110α mediates virtually all cellular responses to insulin, targeted inhibition of this enzyme disrupts glucose metabolism in multiple tissues. For example, blocking insulin signalling promotes glycogen breakdown in the liver and prevents glucose uptake in the skeletal muscle and adipose tissue, resulting in transient hyperglycaemia within a few hours of PI3K inhibition. The effect is usually transient because compensatory insulin release from the pancreas (insulin feedback) restores normal glucose homeostasis
. However, the hyperglycaemia may be exacerbated or prolonged in patients with any degree of insulin resistance and, in these cases, necessitates discontinuation of therapy
. We hypothesized that insulin feedback induced by PI3K inhibitors may reactivate the PI3K-mTOR signalling axis in tumours, thereby compromising treatment effectiveness
. Here we show, in several model tumours in mice, that systemic glucose-insulin feedback caused by targeted inhibition of this pathway is sufficient to activate PI3K signalling, even in the presence of PI3K inhibitors. This insulin feedback can be prevented using dietary or pharmaceutical approaches, which greatly enhance the efficacy/toxicity ratios of PI3K inhibitors. These findings have direct clinical implications for the multiple p110α inhibitors that are in clinical trials and provide a way to increase treatment efficacy for patients with many types of tumour.
Targeting the androgen receptor (AR) signaling axis has been, over decades, the mainstay of prostate cancer therapy. More potent inhibitors of androgen synthesis and antiandrogens have emerged and ...have been successfully implemented in clinical practice. That said, the stronger inhibition of the AR signaling axis has led in recent years to an increase of prostate cancers that de-differentiate into AR-negative disease. Unfortunately, this process is intimately linked with a poor prognosis. Here, we review the molecular mechanisms that enable cancer cells to switch from an AR-positive to an AR-negative disease and efforts to prevent/revert this process and thereby maintain/restore AR-dependence.
In metabolism, available free energy is limited and must be divided across pathway steps to maintain a negative ΔG throughout. For each reaction, ΔG is log proportional both to a concentration ratio ...(reaction quotient to equilibrium constant) and to a flux ratio (backward to forward flux). Here we use isotope labeling to measure absolute metabolite concentrations and fluxes in Escherichia coli, yeast and a mammalian cell line. We then integrate this information to obtain a unified set of concentrations and ΔG for each organism. In glycolysis, we find that free energy is partitioned so as to mitigate unproductive backward fluxes associated with ΔG near zero. Across metabolism, we observe that absolute metabolite concentrations and ΔG are substantially conserved and that most substrate (but not inhibitor) concentrations exceed the associated enzyme binding site dissociation constant (Km or Ki). The observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints.
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