Microscopy with undetected photons in the mid-infrared

Owing to its capacity for unique (bio)-chemical specificity, microscopy withmid-IR illumination holds tremendous promise for a wide range of biomedical and industrial applications. The primary limitation, however, remains detection; with current mid-IR detection technology often marrying inferior technical capabilities with prohibitive costs. This has lead to approaches that shift detection towavelengths into the visible regime, where vastly superior silicon-based cameratechnology is available. Here, we experimentally show how nonlinear interferometry with entangled light can provide a powerful tool for mid-IR microscopy, while only requiring near-infrared detection with a standard CMOS camera. In this proof-of-principle implementation, we demonstrate intensity imaging overa broad wavelength range covering 3.4-4.3um and demonstrate a spatial resolution of 35um for images containing 650 resolved elements. Moreover, we demonstrate our technique is fit for purpose, acquiring microscopic images of biological tissue samples in the mid-IR. These results open a new perspective for potential relevance of quantum imaging techniques in the life sciences.Comment: back-to-back submission with arXiv:2002.05956, Anna V. Paterova, Sivakumar M. Maniam, Hongzhi Yang, Gianluca Grenci, and Leonid A. Krivitsky, "Hyperspectral Infrared Microscopy With Visible Light

Charged black holes: Wave equations for gravitational and electromagnetic perturbations

A pair of wave equations for the electromagnetic and gravitational perturbations of the charged Kerr black hole are derived. The perturbed Einstein-Maxwell equations in a new gauge are employed in the derivation. The wave equations refer to the perturbed Maxwell spinor $\Phi_0$ and to the shear $\sigma$ of a principal null direction of the Weyl curvature. The whole construction rests on the tripod of three distinct derivatives of the first curvature $\kappa$ of a principal null direction.Comment: 12 pages, to appear in Ap.

In vitro biocompatibility and mechanical performance of titanium doped high calcium oxide metaphosphate-based glasses

This study challenged to produce phosphate-based glasses (PBG) for the treatment of osseous defects. The glasses contained, among other components, 40 mol% CaO and 1-5 mol% TiO(2). The mechanical performance and in vitro biocompatibility using both human osteosarcoma and primary osteoblasts were carried out. Incorporation of TiO(2) into PBG had no significant effect on strength and modulus. These glasses encouraged attachment and maintained high viability of osteosarcoma cells similar to the positive control surface. Cells grown directly (on glasses) or indirectly (in the presence of glass extracts) showed similar proliferation pattern to the positive control cells with no significant effect of TiO(2) detected. Increasing TiO(2) content, however, has a profound effect on cytoskeleton organization and spreading and maturation of primary osteoblasts. It is believed that TiO(2) might have acted as a chemical cue-modulating cells response, and hence the substrates supported maturation/mineralization of the primary osteoblasts

Quantum Dot Nanomedicine Formulations Dramatically Improve Pharmacological Properties and Alter Uptake Pathways of Metformin and Nicotinamide Mononucleotide in Aging Mice

Orally administered Ag2S quantum dots (QDs) rapidly cross the small intestine and are taken up by the liver. Metformin and nicotinamide mononucleotide (NMN) target metabolic and aging processes within the liver. This study examined the pharmacology and toxicology of QD-based nanomedicines as carriers of metformin and NMN in young and old mice, determining if their therapeutic potency and reduced effects associated with aging could be improved. Pharmacokinetic studies demonstrated that QD-conjugated metformin and NMN have greater bioavailability, with selective accumulation in the liver following oral administration compared to unconjugated formulations. Pharmacodynamic data showed that the QD-conjugated medicines had increased physiological, metabolic, and cellular potency compared to unconjugated formulations (25× metformin; 100× NMN) and highlighted a shift in the peak induction of, and greater metabolic response to, glucose tolerance testing. Two weeks of treatment with low-dose QD-NMN (0.8 mg/kg/day) improved glucose tolerance tests in young (3 months) mice, whereas old (18 and 24 months) mice demonstrated improved fasting and fed insulin levels and insulin resistance. High-dose unconjugated NMN (80 mg/kg/day) demonstrated improvements in young mice but not in old mice. After 100 days of QD (320 μg/kg/day) treatment, there was no evidence of cellular necrosis, fibrosis, inflammation, or accumulation. Ag2S QD nanomedicines improved the pharmacokinetic and pharmacodynamic properties of metformin and NMN by increasing their therapeutic potency, bypassing classical cellular uptake pathways, and demonstrated efficacy when drug alone was ineffective in aging mice

Metabolic control level and glucose variability in adolescents with type 1 diabetes during low and high-intensity exercise

OBJECTIVE The main purpose of this study was to characterize the determinants of metabolic changes in young type 1 diabetes (T1DM) and to determine glycemic variability during low and high-intensity exercise. PATIENTS AND METHODS 20 young male T1DM patients were divided into two subgroups characterized by levels of glycated hemoglobin (HbA1c): HbA1c7.3% (worse HbA1c subgroup, n=10). All participants performed a maximal oxygen uptake test and two efforts of various intensities (45 minutes of aerobic exercise and 30 minutes of mixed aerobic-anaerobic intensity exercise). Continuous glucose monitors (CGM) were used to control the glucose concentration. RESULTS Changes in biomarkers describing the metabolic response were similar in both groups. A comparison of applied efforts exhibited that maximal capacity effort resulted in the highest values of blood glucose (BG) at the end (150.9-160.6 mg/dl) and 1 hour after the exercise (140.2-161.3 mg/dl). BG concentration before, during, 1 hour, and 24 hours after each exercise was insignificantly higher in the worse Hb1Ac group. CONCLUSIONS HbA1c levels are insufficient to confirm whether the applied effort is performed in acceptable glycemic values. The CGM monitors allow for precise control of BG variations and accurate planning of physical activity by adjusting the insulin and carbohydrate consumption dose

The protein corona determines the cytotoxicity of nanodiamonds: implications of corona formation and its remodelling on nanodiamond applications in biomedical imaging and drug delivery

The use of nanodiamonds for biomedical and consumer applications is growing rapidly. As their use becomes more widespread, so too do concerns around their cytotoxicity. The cytotoxicity of nanodiamonds correlates with their cellular internalisation and circulation time in the body. Both internalisation and circulation time are influenced by the formation of a protein corona on the nanodiamond surface. However, a precise understanding of both how the corona forms and evolves and its influence on cytotoxicity is lacking. Here, we investigated protein corona formation and evolution in response to two classes of nanodiamonds, pristine and aminated, and two types of proteins, bovine serum albumin and fibronectin. Specifically, we found that a corona made of bovine serum albumin (BSA), which represents the most abundant protein in blood plasma, reduced nanodiamond agglomeration. Fibronectin (FN9-10), the second most abundant protein found in the plasma, exhibited a significantly higher nanodiamond binding affinity than BSA, irrespective of the nanodiamond surface charge. Finally, nanodiamonds with a BSA corona displayed less cytotoxicity towards nonphagocytic liver cells. However, regardless of the type of corona (FN9-10 or BSA), both classes of nanodiamonds induced substantial phagocytic cell death. Our results emphasise that a precise understanding of the corona composition is fundamental to determining the fate of nanoparticles in the body

Kerr-AdS and its Near-horizon Geometry: Perturbations and the Kerr/CFT Correspondence

We investigate linear perturbations of spin-s fields in the Kerr-AdS black hole and in its near-horizon geometry (NHEK-AdS), using the Teukolsky master equation and the Hertz potential. In the NHEK-AdS geometry we solve the associated angular equation numerically and the radial equation exactly. Having these explicit solutions at hand, we search for linear mode instabilities. We do not find any (non-)axisymmetric instabilities with outgoing boundary conditions. This is in agreement with a recent conjecture relating the linearized stability properties of the full geometry with those of its near-horizon geometry. Moreover, we find that the asymptotic behaviour of the metric perturbations in NHEK-AdS violates the fall-off conditions imposed in the formulation of the Kerr/CFT correspondence (the only exception being the axisymmetric sector of perturbations).Comment: 26 pages. 4 figures. v2: references added. matches published versio

One-loop Quantum Gravity in Schwarzschild Spacetime

The quantum theory of linearized perturbations of the gravitational field of a Schwarzschild black hole is presented. The fundamental operators are seen to be the perturbed Weyl scalars $\dot\Psi_0$ and $\dot\Psi_4$ associated with the Newman-Penrose description of the classical theory. Formulae are obtained for the expectation values of the modulus squared of these operators in the Boulware, Unruh and Hartle-Hawking quantum states. Differences between the renormalized expectation values of both $\bigl| \dot\Psi_0 \bigr|^2$ and $\bigl| \dot\Psi_4 \bigr|^2$ in the three quantum states are evaluated numerically.Comment: 39 pages, 11 Postscript figures, using revte

Biological impact of nanodiamond particles – label free, high-resolution methods for nanotoxicity assessment

Current methods for the assessment of nanoparticle safety that are based on 2D cell culture models and fluorescence-based assays show limited sensitivity and they lack biomimicry. Consequently, the health risks associated with the use of many nanoparticles have not yet been established. There is a need to develop in vitro models that mimic physiology more accurately and enable high throughput assessment. There is also a need to set up new assays that offer high sensitivity and are label-free. Here we developed ‘mini-liver’ models using scaffold-free bioprinting and used these models together with label-free nanoscale techniques for the assessment of toxicity of nanodiamond produced by laser-assisted technology. Results showed that NDs induced cytotoxicity in a concentration and exposure-time dependent manner. The loss of cell function was confirmed by increased cell stiffness, decreased cell membrane barrier integrity and reduced cells mobility. We further showed that NDs elevated the production of reactive oxygen species and reduced cell viability. Our approach that combined mini-liver models with label-free high-resolution techniques showed improved sensitivity in toxicity assessment. Notably, this approach allowed for label-free semi-high throughput measurements of nanoparticle-cell interactions, thus could be considered as a complementary approach to currently used methods