Beam-profile compensation for quantum yield characterisation of Yb-Tm codoped upconverting nanoparticles emitting at 474 nm, 650 nm and 804 nm.

Upconverting nanoparticles (UCNPs) have found widespread applications in biophotonics and energy harvesting due to their unique non-linear optical properties arising from energy transfer upconversion (ETU) mechanisms. However, accurately characterising the power density-dependent efficiency of UCNPs using the internal quantum yield (iQY) is challenging due to the lack of methods that account for excitation beam-profile distortions. This limitation hinders the engineering of optimal UCNPs for diverse applications. To address this, this work present a novel beam profile compensation strategy based on a general analytical rate-equations model, enabling the evaluation of iQY for ETU processes of arbitrary order, such as ETU2, ETU3, and beyond. The method was applied to characterise the ETU2 and ETU3 processes corresponding to the main emission peaks (474 nm, 650 nm, and 804 nm) of a Yb-Tm codoped core-shell ß-UCNP. Through this approach, the transition power density points (which delimit the distinct non-linear regimes of the upconversion luminescence (UCL)), and the saturation iQY values (which are reached at high excitation power densities above the transition points) were determined. The ETU2 process exhibits a single transition power density point, denoted as ρ2, while the ETU3 processes involve two transition points, ρ2 and ρ3. By compensating for the beam profile, we evaluate the iQY of individual lines across a wide dynamic range of excitation power densities (up to 105 W cm-2), encompassing both non-linear and linear regimes of UCL. This study introduces a valuable approach for accurately characterising the iQY of UCNPs, facilitating a deeper understanding of the upconversion and its performance. By addressing excitation beam-profile distortions, this method provides a comprehensive and reliable assessment of the power density-dependent iQY. The results highlight the applicability and effectiveness of this beam profile compensation strategy, which can be employed for a wide range of UCNPs. This advancement opens new avenues for the tailored design and application of UCNPs in various fields, especially for biophotonics.

Generalised analytical model of the transition power densities of the upconversion luminescence and quantum yield.

The quantum yield (QY) evaluation of upconverting nanoparticles (UCNPs) is an essential step in the characterisation of such materials. The QY of UCNPs is governed by competing mechanisms of populating and depopulating the electronic energy levels involved in the upconversion (UC), namely linear decay rates and energy transfer rates. As a consequence, at low excitation, the QY excitation power density (ρ) dependence obeys the power law ρn-1, where n represents the number of absorbed photons required for the emission of a single upconverted photon and determines the order of the energy transfer upconversion (ETU) process. At high power densities, the QY transits to a saturation level independent of the ETU process and the number of excitation photons, as a result of an anomalous power density dependence present in UCNPs. Despite the importance of this non-linear process for several applications (e.g., living tissue imaging and super-resolution-microscopy), little has been reported in the literature regarding theoretical studies to describe the UC QY, especially for ETUs with order higher than two. Therefore, this work presents a simple general analytical model, which introduces the concept of the transition power density points and QY saturation to characterise the QY of an arbitrary ETU process. The transition power density points determine where the power density dependence of the QY and the UC luminescence changes. The results provided in this paper from fitting the model to experimental QY data of a Yb-Tm codoped ß-UCNP for 804 nm and 474 nm emissions (ETU2 and ETU3 processes, respectively) exemplify the application of the model. The common transition points found for both processes were compared to each other showing strong agreement with theory, as well as, compared to previous reports when possible.

Evaluation of relative beam-profile-compensated quantum yield of upconverting nanoparticles over a wide dynamic range of power densities.

The presented work uses a discrete strategy of beam profile compensation to evaluate the local internal quantum yield (iQY) of upconverting nanoparticles (UCNPs) at the pixel level of the beam profile using a compact CMOS camera. The two-photon process of upconversion with a central emission peak at 804 nm was studied for a ß-phase core-shell Tm-codoped UCNP under 976 nm excitation. At the balancing power density point, ρb, found to be 44 ± 3 W cm-2, the iQY, ηb, was obtained as 2.3 ± 0.1%. Combining the power density dynamic range provided by the pixel depth of the camera with the dynamic range achieved using two distinct beam profiles to excite the UCNPs, the iQY was evaluated throughout a range of 104 in the iQY scale (from 0.0003% to 4.6%) and 106 in power densities of excitation (from 0.003 W cm-2 to 1050 W cm-2). To the best of our knowledge, these are the lowest values ever obtained as QY results have never been reported under 0.02% or at excitation power densities below 0.01 W cm-2.

Structural Insights to Human Immunodeficiency Virus (HIV-1) Targets and Their Inhibition.

Human immunodeficiency virus (HIV) is a deadly virus that attacks the body's immune system, subsequently leading to AIDS (acquired immunodeficiency syndrome) and ultimately death. Currently, there is no vaccine or effective cure for this infection; however, antiretrovirals that act at various phases of the virus life cycle have been useful to control the viral load in patients. One of the major problems with antiretroviral therapies involves drug resistance. The three-dimensional structure from crystallography studies are instrumental in understanding the structural basis of drug binding to various targets. This chapter provides key insights into different targets and drugs used in the treatment from a structural perspective. Specifically, an insight into the binding characteristics of drugs at the active and allosteric sites of different targets and the importance of targeting allosteric sites for design of new-generation antiretrovirals to overcome complex and resistant forms of the virus has been reviewed.

Historical atmospheric pollution trends in Southeast Asia inferred from lake sediment records.

Fossil fuel combustion leads to increased levels of air pollution, which negatively affects human health as well as the environment. Documented data for Southeast Asia (SEA) show a strong increase in fossil fuel consumption since 1980, but information on coal and oil combustion before 1980 is not widely available. Spheroidal carbonaceous particles (SCPs) and heavy metals, such as mercury (Hg), are emitted as by-products of fossil fuel combustion and may accumulate in sediments following atmospheric fallout. Here we use sediment SCP and Hg records from several freshwater lentic ecosystems in SEA (Malaysia, Philippines, Singapore) to reconstruct long-term, region-wide variations in levels of these two key atmospheric pollution indicators. The age-depth models of Philippine sediment cores do not reach back far enough to date first SCP presence, but single SCP occurrences are first observed between 1925 and 1950 for a Malaysian site. Increasing SCP flux is observed at our sites from 1960 onward, although individual sites show minor differences in trends. SCP fluxes show a general decline after 2000 at each of our study sites. While the records show broadly similar temporal trends across SEA, absolute SCP fluxes differ between sites, with a record from Malaysia showing SCP fluxes that are two orders of magnitude lower than records from the Philippines. Similar trends in records from China and Japan represent the emergence of atmospheric pollution as a broadly-based inter-region environmental problem during the 20th century. Hg fluxes were relatively stable from the second half of the 20th century onward. As catchment soils are also contaminated with atmospheric Hg, future soil erosion can be expected to lead to enhanced Hg flux into surface waters.

Size quantization of Dirac fermions in graphene constrictions.

Quantum point contacts are cornerstones of mesoscopic physics and central building blocks for quantum electronics. Although the Fermi wavelength in high-quality bulk graphene can be tuned up to hundreds of nanometres, the observation of quantum confinement of Dirac electrons in nanostructured graphene has proven surprisingly challenging. Here we show ballistic transport and quantized conductance of size-confined Dirac fermions in lithographically defined graphene constrictions. At high carrier densities, the observed conductance agrees excellently with the Landauer theory of ballistic transport without any adjustable parameter. Experimental data and simulations for the evolution of the conductance with magnetic field unambiguously confirm the identification of size quantization in the constriction. Close to the charge neutrality point, bias voltage spectroscopy reveals a renormalized Fermi velocity of ∼1.5 × 10(6) m s(-1) in our constrictions. Moreover, at low carrier density transport measurements allow probing the density of localized states at edges, thus offering a unique handle on edge physics in graphene devices.

Limitations to carrier mobility and phase-coherent transport in bilayer graphene.

We present transport measurements on high-mobility bilayer graphene fully encapsulated in hexagonal boron nitride. We show two terminal quantum Hall effect measurements which exhibit full symmetry broken Landau levels at low magnetic fields. From weak localization measurements, we extract gate-tunable phase-coherence times τϕ as well as the inter- and intravalley scattering times τi and τ*, respectively. While τϕ is in qualitative agreement with an electron-electron interaction-mediated dephasing mechanism, electron spin-flip scattering processes are limiting τϕ at low temperatures. The analysis of τi and τ* points to local strain fluctuation as the most probable mechanism for limiting the mobility in high-quality bilayer graphene.

Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink.

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.

Graphene-based charge sensors.

We discuss graphene nanoribbon-based charge sensors and focus on their functionality in the presence of external magnetic fields and high frequency pulses applied to a nearby gate electrode. The charge detectors work well with in-plane magnetic fields of up to 7 T and pulse frequencies of up to 20 MHz. By analyzing the step height in the charge detector's current at individual charging events in a nearby quantum dot, we determine the ideal operation conditions with respect to the applied charge detector bias. Average charge sensitivities of 1.3 × 10(-3)e Hz(-1/2) can be achieved. Additionally, we investigate the back action of the charge detector current on the quantum transport through a nearby quantum dot. By varying the charge detector bias from 0 to 4.5 mV, we can increase the Coulomb peak currents measured at the quantum dot by a factor of around 400. Furthermore, we can completely lift the Coulomb blockade in the quantum dot.

Fabrication of coupled graphene-nanotube quantum devices.

We report on the fabrication and characterization of all-carbon hybrid quantum devices based on graphene and single-walled carbon nanotubes. We discuss both carbon nanotube quantum dot devices with graphene charge detectors and nanotube quantum dots with graphene leads. The devices are fabricated by chemical vapor deposition growth of carbon nanotubes and subsequent structuring of mechanically exfoliated graphene. We study the detection of individual charging events in the carbon nanotube quantum dot by a nearby graphene nanoribbon and show that they lead to changes of up to 20% of the conductance maxima in the graphene nanoribbon, acting as a well performing charge detector. Moreover, we discuss an electrically coupled graphene-nanotube junction, which exhibits a tunneling barrier with tunneling rates in the low GHz regime. This allows us to observe Coulomb blockade on a carbon nanotube quantum dot with graphene source and drain leads.

Electronic excited states in bilayer graphene double quantum dots.

We report tunneling spectroscopy experiments on a bilayer graphene double quantum dot device that can be tuned by all-graphene lateral gates. The diameter of the two quantum dots are around 50 nm and the constrictions acting as tunneling barriers are 30 nm in width. The double quantum dot features additional energies on the order of 20 meV. Charge stability diagrams allow us to study the tunable interdot coupling energy as well as the spectrum of the electronic excited states on a number of individual triple points over a large energy range. The obtained constant level spacing of 1.75 meV over a wide energy range is in good agreement with the expected single-particle energy spacing in bilayer graphene quantum dots. Finally, we investigate the evolution of the electronic excited states in a parallel magnetic field.

Steady-state analysis of polymer adsorption at and transport across an interface between two polymer phases.

We consider a mutually incompatible polymer mixture composed of two major components AN and BN and a third minority component C(N). The interactions, parameterized by short-range Flory-Huggins interaction parameters, are chosen such that C wets the A/B interface completely at three-phase coexistence. At sub-saturated conditions the adsorption of C remains necessarily microscopic. We study such a system in a stationary off-equilibrium state: due to imposed chemical potential gradients, polymer AN diffuses from the A-rich bulk phase through the interface to the A-poor bulk phase. Polymer BN travels in the opposite direction. Symmetric conditions are selected for which the polymer CN that accumulates at the A/B-interface has no net flux in the stationary state. This system is described by the Mean Field Stationary Diffusion (MFSD) model, an approach that solves the Scheutjens Fleer self-consistent-field (SF-SCF) equations with the boundary condition that the chemical potentials in the two bulk phases are different (but constant) so that a stationary state can be described. When the chemical potentials in the two bulk phases are the same, MFSD reduces to the equilibrium SF-SCF results. From the MFSD method we obtain the stationary volume fraction profiles and segmental fluxes. By forcing the system further from three-phase coexistence, i.e. by imposing larger concentration gradients, the adsorption of C goes unexpectedly from a thin adsorption layer to a thick adsorption film. The susceptibility partial differential J(A)/partial differential Delta(phi)A of the flux of A (equal to minus the flux of B) with respect to the imposed concentration gradient changes abruptly at the transition in adsorption behaviour. Interestingly, upon variation of the concentration gradients, the fluxes of A and B are enhanced by the accumulation of C at the interface. This means that the adsorbed C-film does not behave as an inert barrier.

In vitro measurements of optical properties of porcine brain using a novel compact device.

Knowledge of the optical properties of tissues can be applied in numerous medical and scientific fields, including cancer diagnostics and therapy. There are many different ways of determining the optical properties of turbid media. The paper describes measurements of the optical properties of porcine brain tissue using novel instrumentation for simultaneous absorption and scattering characterisation of small turbid samples. Integrating sphere measurements are widely used as a reference method for determination of the optical properties of relatively thin turbid samples. However, this technique is associated with bulky equipment, complicated measuring techniques, interference compensation techniques and inconvenient sample handling. It is believed that the sphere for some applications can be replaced by a new, compact device, called the combined angular and spatially resolved head sensor, to measure the optical properties of thin turbid samples. The results compare very well with data obtained with an integrating sphere for well-defined samples. The instrument was shown to be accurate to within 12% for microa and 1% for micro's in measurements of intralipid-ink samples. The corresponding variations of data were 17% and 2%, respectively. The reduced scattering coefficient for porcine white matter was measured to be 100 cm(-1) at 633 nm, and the value for coagulated brain tissue was 65 cm(-1). The corresponding absorption coefficients were 2 and 3 cm(-1), respectively.

MADSTRESS: a linear approach for evaluating scattering and absorption coefficients of samples measured using time-resolved spectroscopy in reflection.

Time-resolved spectroscopy is a powerful technique permitting the separation of the scattering properties from the chemical absorption properties of a sample. The reduced scattering coefficient and the absorption coefficient are usually obtained by fitting diffusion or Monte Carlo models to the measured data using numerical optimization techniques. However, these methods do not take the spectral dimension of the data into account during the evaluation procedure, but evaluate each wavelength separately. A procedure involving multivariate methods may seem more appealing for people used to handling conventional near-infrared data. In this study we present a new method for processing TRS spectra in order to compute the absorption and reduced scattering coefficients. This approach, MADSTRESS, is based on linear regression and a two-dimensional (2D) interpolation procedure. The method has allowed us to calculate absorption and scattering coefficients of apples and fructose powder. The accuracy of the method was good enough to provide the identification of fructose absorption peaks in apple absorption spectra and the construction of a calibration model predicting the sugar content of apples.

Stationary dynamics approach to analytical approximations for polymer coexistence curves.

Phase separation in polymer blends is an important process. However, the compositions of the coexisting phases can only be predicted by numerical methods. We provide simple analytical expressions which serve as good approximations for the compositions after phase separation of binary homopolymer blends. These approximations are obtained by a stationary dynamics approach: we calculate the compositions of two polymer mixtures such that the stationary diffusion between these distinguishable mixtures vanishes. For the diffusion equations we employ composition-dependent diffusion coefficients, as derived according to the slow- and fast-mode theory from the Flory-Huggins free energy. The analytical results are in good agreement with exact (numerically calculated) binodal compositions. Our coexistence curves are more accurate than some conventional approximations. Another advantage of the stationary dynamics approach is that it is not only applicable to binary polymer blends or polymer solutions, but also to symmetrical multicomponent blends. The same diffusion coefficients may be used to obtain the exact spinodal compositions in multicomponent systems.

Lattice mean-field method for stationary polymer diffusion.

We present a method to study mean-field stationary diffusion (MFSD) in polymer systems. When gradients in chemical potentials vanish, our method reduces to the Scheutjens-Fleer self-consistent field (SF-SCF) method for inhomogeneous polymer systems in equilibrium. To illustrate the concept of our MFSD method, we studied stationary diffusion between two different bulk mixtures, containing, for simplicity, noninteracting homopolymers. Four alternatives for the diffusion equation are implemented. These alternatives are based on two different theories for polymer diffusion (the slow- and fast-mode theories) and on two different ways to evaluate the driving forces for diffusion, one of which is in the spirit of the SF-SCF method. The diffusion profiles are primarily determined by the diffusion theory and they are less sensitive to the evaluation of the driving forces. The numerical stationary state results are in excellent agreement with analytical results, in spite of a minor inconsistency at the system boundaries in the numerical method. Our extension of the equilibrium SF method might be useful for the study of fluxes, steady state profiles and chain conformations in membranes (e.g., during drug delivery), and for many other systems for which simulation techniques are too time consuming.

Changes in tissue optical properties due to radio-frequency ablation of myocardium.

The optical properties of pig heart tissue were measured after in vivo ablation therapy had been performed during open-heart surgery. In vitro samples of normal and ablated tissue were subjected to measurements with an optically integrating sphere set-up in the region 470-900 nm. Three independent measurements were made: total transmittance, total reflectance and collimated transmittance, which made it possible to extract the absorption and scattering coefficients and the scattering anisotropy factor g, using an inverse Monte Carlo model. Between 470 and 700 nm, only the reduced scattering coefficient and absorption could be evaluated. The absorption spectra were fitted to known tissue chromophore spectra, so that the concentrations of haemoglobin and myoglobin could be estimated. The reduced scattering coefficient was compared with Mie computations to provide Mie equivalent average radii. Most of the absorption was from myoglobin, whereas haemoglobin absorption was negligible. Metmyoglobin was formed in the ablated tissue, which could yield a spectral signature to distinguish the ablated tissue with a simple optical probe to monitor the ablation therapy. The reduced scattering coefficient increased by, on average, 50% in the ablated tissue, which corresponded to a slight decrease in the Mie equivalent radius.

Kinetics of the superficial perfusion and temperature in connection with photodynamic therapy of basal cell carcinomas using esterified and non-esterified 5-aminolaevulinic acid.

BACKGROUND: Photodynamic therapy (PDT) is a local treatment modality with increasing indications for various malignant and non malignant diseases. The treatment parameters have not yet been optimized as there is a need for a better understanding of the process. The skin is an important target and serves as a good model for monitoring and evaluating the interaction of light with biological tissue. OBJECTIVES: The tissue perfusion and the temperature of basal cell carcinomas were measured in connection with PDT in order to investigate the biological mechanisms involved. METHODS: An infrared camera was used during the treatment to measure skin temperature and a laser Doppler perfusion imaging device was used to image the superficial perfusion before and after treatment. Six hours after topical application of 5-aminolaevulinic acid (ALA) or methyl esterified ALA (ALA-ME), 38 basal cell carcinomas were treated using light from a diode laser at 633 nm. RESULTS: In the lesions, the perfusion immediately after PDT was similar to that before PDT. One hour after the treatment the perfusion in the lesion was increased 50% compared with before PDT. However, in the skin surrounding the lesions the perfusion was doubled immediately after PDT and was still increasing 1 h after treatment. A temperature increase in the lesions of about 1-3 degrees C was observed for light fluence rates of 100-150 mW cm-2. In all patients treated, a diffuse temperature increase was visible outside the lesions. In some of the patients, the outlines of the blood vessels surrounding the treated lesions became visible in the thermal images. Measurements of temperature on healthy volunteers not administered photosensitizer, but illuminated with light of the same fluence rate, showed a similar increase in temperature in the illuminated spots. However, no temperature increase was observed outside the illuminated area. No statistically significant differences were found between the measurements on patients treated with ALA and ALA-ME. CONCLUSIONS: The increased perfusion in the area surrounding the lesions after PDT, as seen by perfusion and temperature measurements, is the result of an inflammatory reaction to the PDT process. However, directly after PDT the perfusion in the lesions was the same as before irradiation. The combination of these observations suggests the presence of local blood stasis during and immediately after the treatment. The temperature measurements showed that the increased temperature was well below the temperature limit of hyperthermal damage. Furthermore, the measurements indicate that the increase in temperature was primarily a consequence of the heat absorbed in the tissue.

Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism: correlation with clinical and neuropsychological data.

BACKGROUND AND PURPOSE: Chronic alcohol abuse may cause neuropsychological disorders and result in brain atrophy. The purpose of this study was to evaluate the metabolic, morphologic, and functional cerebral changes in the early stage of abstinence from chronic alcoholism. METHODS: Seventeen alcohol-dependent patients underwent MR imaging and MR spectroscopy on days 1 through 3 and days 36 through 39 of abstinence. In addition, psychological performance measures testing intelligence, concentration, attention, and memory were applied. Neuropsychological data were correlated with spectroscopic and volumetric results by using a Pearson's product moment correlation. The same measurements were also performed in 12 healthy, age-matched control subjects. Peak integral values for N-acetylaspartate (NAA) and choline (Cho) were referred to the peak integral value of creatine (Cr) as the internal reference. RESULTS: NAA/Cr was decreased in the patients in both the frontal lobes and cerebellum immediately after cessation of drinking (days 1 through 3). After 36 to 39 days of abstinence, NAA/Cr had significantly increased in the patients and corresponded to performance on psychological tests. The Cho/Cr ratio was decreased in the cerebellum during early abstinence but was recovered on days 36 through 39. The patients had enlarged CSF spaces 1 to 3 days after detoxification, which decreased during sobriety. The extent of brain atrophy did not correspond to performance on psychological performance tests. CONCLUSION: Regression of brain atrophy and metabolic recovery occurs at an early stage after abstinence from chronic alcohol abuse. MR spectroscopy findings return to normal metabolic levels within weeks after detoxification. The recovery of NAA/Cr is associated with improved performance on neuropsychological tests.

Multivariate analysis of laryngeal fluorescence spectra recorded in vivo.

BACKGROUND AND OBJECTIVE: The potential of using various multivariate analysis methods for classification of fluorescence spectra acquired in vivo from laryngeal tissues in Patients was investigated. STUDY DESIGN/MATERIALS AND METHODS: Autofluorescence spectra were measured on 29 normal tissue sites and 25 laryngeal lesions using 337-nm excitation. Four different multivariate analysis schemes were applied. Laryngeal fluorescence spectra from patients who had been administered delta-aminolevulinic acid (ALA) were obtained using 405-nm excitation and were classified using partial least squares discriminant analysis (PLS-DA). RESULTS: For autofluorescence spectra, logistic regression based on principal component analysis (PCA) or PLS, or PLS-DA all resulted in sensitivities and specificities around 90% for lesion vs. normal. Using ALA and 405-nm excitation gave a sensitivity of 100% and a specificity of 69%. CONCLUSION: Multivariate analysis of fluorescence spectra could allow classification of laryngeal lesions in vivo with high sensitivity and specificity. PLS performs at least as well as PCA, and PLS-DA performs as well as logistic regression techniques on these data.