Kinetic inductance current sensor for visible to near-infrared wavelength transition-edge sensor readout.

Single-photon detectors based on the superconducting transition-edge sensor are used in a number of visible to near-infrared applications, particularly for photon-number-resolving measurements in quantum information science. To be practical for large-scale spectroscopic imaging or photonic quantum computing applications, the size of visible to near-infrared transition-edge sensor arrays and their associated readouts must be increased from a few pixels to many thousands. In this manuscript, we introduce the kinetic inductance current sensor, a scalable readout technology that exploits the nonlinear kinetic inductance in a superconducting resonator to make sensitive current measurements.

Targeting the sphingolipid rheostat in IDH1 glioma alters cholesterol homeostasis and triggers apoptosis via membrane degradation.

The cross-regulation of metabolism and trafficking is not well understood for the vital sphingolipids and cholesterol constituents of cellular compartments. While reports are starting to surface on how sphingolipids like sphingomyelin (SM) dysregulate cholesterol levels in different cellular compartments (Jiang et al., 2022), limited research is available on the mechanisms driving the relationship between sphingolipids and cholesterol homeostasis, or its biological implications.

Raman-based machine-learning platform reveals unique metabolic differences between IDHmut and IDHwt glioma.

Background: Formalin-fixed, paraffin-embedded (FFPE) tissue slides are routinely used in cancer diagnosis, clinical decision-making, and stored in biobanks, but their utilization in Raman spectroscopy-based studies has been limited due to the background coming from embedding media.

Methods: Spontaneous Raman spectroscopy was used for molecular fingerprinting of FFPE tissue from 46 patient samples with known methylation subtypes. Spectra were used to construct tumor/non-tumor, IDH1WT/IDH1mut, and methylation-subtype classifiers.

Metabolic biomarkers of radiotherapy response in plasma and tissue of an IDH1 mutant astrocytoma mouse model.

Astrocytomas are the most common subtype of brain tumors and no curative treatment exist. Longitudinal assessment of patients, usually Magnetic Resonance Imaging (MRI), is crucial since tumor progression may occur earlier than clinical progression. MRI usually provides a means for monitoring the disease, but it only informs about the structural changes of the tumor, while molecular changes can occur as a treatment response without any MRI-visible change.

Probabilistic model checking of cancer metabolism.

Cancer cell metabolism is often deregulated as a result of adaption to meeting energy and biosynthesis demands of rapid growth or direct mutation of key metabolic enzymes. Better understanding of such deregulation can provide new insights on targetable vulnerabilities, but is complicated by the difficulty in probing cell metabolism at different levels of resolution and under different experimental conditions. We construct computational models of glucose and glutamine metabolism with focus on the effect of IDH1/2-mutations in cancer using a combination of experimental metabolic flux data and patient-derived gene expression data.

Advances in measuring cancer cell metabolism with subcellular resolution.

Characterizing metabolism in cancer is crucial for understanding tumor biology and for developing potential therapies. Although most metabolic investigations analyze averaged metabolite levels from all cell compartments, subcellular metabolomics can provide more detailed insight into the biochemical processes associated with the disease. Methodological limitations have historically prevented the wider application of subcellular metabolomics in cancer research.

Large-Area Superconducting Nanowire Single-Photon Detectors for Operation at Wavelengths up to 7.4 μm.

The optimization of superconducting thin-films has pushed the sensitivity of superconducting nanowire single-photon detectors (SNSPDs) to the mid-infrared (mid-IR). Earlier demonstrations have shown that straight tungsten silicide nanowires can achieve unity internal detection efficiency (IDE) up to λ = 10 μm. For a high system detection efficiency (SDE), the active area needs to be increased, but material nonuniformity and nanofabrication-induced constrictions make mid-IR large-area meanders challenging to yield.

Quantum computational advantage with a programmable photonic processor.

A quantum computer attains computational advantage when outperforming the best classical computers running the best-known algorithms on well-defined tasks. No photonic machine offering programmability over all its quantum gates has demonstrated quantum computational advantage: previous machines were largely restricted to static gate sequences. Earlier photonic demonstrations were also vulnerable to spoofing, in which classical heuristics produce samples, without direct simulation, lying closer to the ideal distribution than do samples from the quantum hardware.

Cysteine is a limiting factor for glioma proliferation and survival.

Nutritional intervention is becoming more prevalent as adjuvant therapy for many cancers in view of the tumor dependence on external sources for some nutrients. However, little is known about the mechanisms that make cancer cells require certain nutrients from the microenvironment. Herein, we report the dependence of glioma cells on exogenous cysteine/cystine, despite this amino acid being nonessential.

A Single-Organelle Optical Omics Platform for Cell Science and Biomarker Discovery.

Research in fundamental cell biology and pathology could be revolutionized by developing the capacity for quantitative molecular analysis of subcellular structures. To that end, we introduce the Ramanomics platform, based on confocal Raman microspectrometry coupled to a biomolecular component analysis algorithm, which together enable us to molecularly profile single organelles in a live-cell environment. This emerging omics approach categorizes the entire molecular makeup of a sample into about a dozen of general classes and subclasses of biomolecules and quantifies their amounts in submicrometer volumes.

Quantum circuits with many photons on a programmable nanophotonic chip.

Growing interest in quantum computing for practical applications has led to a surge in the availability of programmable machines for executing quantum algorithms. Present-day photonic quantum computers have been limited either to non-deterministic operation, low photon numbers and rates, or fixed random gate sequences. Here we introduce a full-stack hardware-software system for executing many-photon quantum circuit operations using integrated nanophotonics: a programmable chip, operating at room temperature and interfaced with a fully automated control system.

IDH1 mutations induce organelle defects via dysregulated phospholipids.

Infiltrating gliomas are devastating and incurable tumors. Amongst all gliomas, those harboring a mutation in isocitrate dehydrogenase 1 mutation (IDH1) acquire a different tumor biology and clinical manifestation from those that are IDH1. Understanding the unique metabolic profile reprogrammed by IDH1 mutation has the potential to identify new molecular targets for glioma therapy.

Single-photon detection in the mid-infrared up to 10 m wavelength using tungsten silicide superconducting nanowire detectors.

We developed superconducting nanowire single-photon detectors based on tungsten silicide, which show saturated internal detection efficiency up to a wavelength of 10 m. These detectors are promising for applications in the mid-infrared requiring sub-nanosecond timing, ultra-high gain stability, low dark counts, and high efficiency, such as chemical sensing, LIDAR, dark matter searches, and exoplanet spectroscopy.

Metabolic plasticity of IDH1 glioma cell lines is responsible for low sensitivity to glutaminase inhibition.

Background: Targeting glutamine metabolism in cancer has become an increasingly vibrant area of research. Mutant IDH1 (IDH1 ) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate (2HG).

Methods: We have employed a combination of C tracers including glutamine and glucose for investigating the metabolism of patient-derived IDH1 glioma cell lines through NMR and LC/MS.

Sphingolipid Pathway as a Source of Vulnerability in IDH1 Glioma.

In addition to providing integrity to cellular structure, the various classes of lipids participate in a multitude of functions including secondary messengers, receptor stimulation, lymphocyte trafficking, inflammation, angiogenesis, cell migration, proliferation, necrosis and apoptosis, thus highlighting the importance of understanding their role in the tumor phenotype. In the context of IDH1 glioma, investigations focused on metabolic alterations involving lipidomics' present potential to uncover novel vulnerabilities. Herein, a detailed lipidomic analysis of the sphingolipid metabolism was conducted in patient-derived IDH1 glioma cell lines, as well as model systems, with the of identifying points of metabolic vulnerability.

Broadband quadrature-squeezed vacuum and nonclassical photon number correlations from a nanophotonic device.

We report demonstrations of both quadrature-squeezed vacuum and photon number difference squeezing generated in an integrated nanophotonic device. Squeezed light is generated via strongly driven spontaneous four-wave mixing below threshold in silicon nitride microring resonators. The generated light is characterized with both homodyne detection and direct measurements of photon statistics using photon number-resolving transition-edge sensors.

Metabolic Landscape of a Genetically Engineered Mouse Model of IDH1 Mutant Glioma.

Understanding the metabolic reprogramming of aggressive brain tumors has potential applications for therapeutics as well as imaging biomarkers. However, little is known about the nutrient requirements of isocitrate dehydrogenase 1 (IDH1) mutant gliomas. The IDH1 mutation involves the acquisition of a neomorphic enzymatic activity which generates D-2-hydroxyglutarate from α-ketoglutarate.

Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma.

Background: Osteosarcoma (OS) is a malignant bone tumor that often develops during the period of rapid growth associated with adolescence. Despite successful primary tumor control accompanied by adjuvant chemotherapy, death from pulmonary metastases occurs in approximately 30% of patients within 5 years. As overall survival in patients remains unchanged over the last 30 years, urgent needs for novel therapeutic strategies exist.

Detector-Agnostic Phase-Space Distributions.

The representation of quantum states via phase-space functions constitutes an intuitive technique to characterize light. However, the reconstruction of such distributions is challenging as it demands specific types of detectors and detailed models thereof to account for their particular properties and imperfections. To overcome these obstacles, we derive and implement a measurement scheme that enables a reconstruction of phase-space distributions for arbitrary states whose functionality does not depend on the knowledge of the detectors, thus defining the notion of detector-agnostic phase-space distributions.

Quantum-enhanced interferometry with large heralded photon-number states.

Quantum phenomena such as entanglement can improve fundamental limits on the sensitivity of a measurement probe. In optical interferometry, a probe consisting of entangled photons provides up to a enhancement in phase sensitivity compared to a classical probe of the same energy. Here, we employ high-gain parametric down-conversion sources and photon-number-resolving detectors to perform interferometry with heralded quantum probes of sizes up to = 8 (i.

Kilopixel array of superconducting nanowire single-photon detectors.

We present a 1024-element near-infrared imaging array of superconducting nanowire single photon detectors (SNSPDs) using a 32×32 row-column multiplexing architecture. The array has an active area of 0.96 × 0.

Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma.

Altered cellular metabolism, including an increased dependence on aerobic glycolysis, is a hallmark of cancer. Despite the fact that this observation was first made nearly a century ago, effective therapeutic targeting of glycolysis in cancer has remained elusive. One potentially promising approach involves targeting the glycolytic enzyme lactate dehydrogenase (LDH), which is overexpressed and plays a critical role in several cancers.

Toward Single-Organelle Lipidomics in Live Cells.

Detailed studies of lipids in biological systems, including their role in cellular structure, metabolism, and disease development, comprise an increasingly prominent discipline called lipidomics. However, the conventional lipidomics tools, such as mass spectrometry, cannot investigate lipidomes until they are extracted, and thus they cannot be used for probing the lipid distribution nor for studying in live cells. Furthermore, conventional techniques rely on the lipid extraction from relatively large samples, which averages the data across the cellular populations and masks essential cell-to-cell variations.