Determination of epithelial tissue scattering coefficient using confocal microscopy

Most models of light propagation through tissue assume the scattering properties of the various tissue layers are the same. The authors present evidence that the scattering coefficient of normal cervical epithelium is significantly lower than values previously reported for bulk epithelial tissue. They estimated the scattering coefficient of normal and precancerous cervical epithelium using measurements of the reflectance as a function of depth from confocal images. Reflectance measurements were taken from ex vivo cervical biopsies and fit to an exponential function based upon Beer's law attenuation. The mean scattering coefficients derived were 22 cm/sup -1/ for normal tissue and 69 cm/sup -1/ for precancerous tissue. These values are significantly lower than previously reported for bulk epithelial tissues and suggest that scattering of bulk tissue is dominated by the stroma. They also suggest that computational models to describe light propagation in epithelial tissue must incorporate different scattering coefficients for the epithelium and stroma. Further, the lower scattering of the epithelium suggests greater probing depths for fiber optic probes used by optical diagnostic devices which measure reflectance and fluorescence in epithelial tissue. The difference in scattering between normal and precancerous tissue is attributed to increased nuclear size, optical density, and chromatin texture. The scattering coefficients measured here are consistent with predictions of numerical solutions to Maxwell's equations for epithelial cell scattering.     

Development of α-Tocopherol Acetate Nanoparticles: Influence of Preparative Processes

We studied different methods of preparing α-tocopherol acetate (ATA) nanoparticles, which are to be used in targeting the lungs as aerosols in order to prevent cigarette smoke toxicity. Poly-(lactide) nanoparticles were prepared using nanoprecipitation and solvent evaporation techniques, which produced, respectively, too small and too large nanoparticles to be aerosolized. The emulsification-diffusion method produced 2 months stable nanoparticles with a size between (500–700 nm). Increasing ATA concentration (1–7 mg/mL) induced a decrease in the association rate (97–93%) and in the adsorbed ATA rate (7–4.5%), which was associated with variations of Zeta potentials (?27.5 to ?24.3 mV) and decrease in polymeric wall thickness and density.     

A broadband multimedia collaborative system for advancedteleradiology and medical imaging diagnosis

This paper presents a new telemedicine system currently in routine clinical usage, developed within the European Union (EU) ACTS BONAPARTE project. The telemedicine system is developed on an asynchronous transfer mode (ATM) multimedia hardware/software platform comprising the following set of telemedicine services: synchronous cooperative work, high-quality video conference, multimedia mail, medical image digitizing, processing, storing and printing, and local and remote transparent database access. The medical information handled by the platform conforms to the Digital Imaging and Communications in Medicine (DICOM) 3.0 medical imaging standard. The telemedicine system has been installed for clinical routines in three Spanish hospitals since November 1997 and has been used in an average of one/two clinical sessions per week. At each clinical session, a usability and clinical evaluation of the system was carried out. Evaluation is carried out through direct observation of interactions and questionnaire-based subjective data. The usability evaluation methodology and the results of the system usability study are also presented in this article. The experience gained from the design, development, and evaluation of the telemedicine system is providing an indepth knowledge of the benefits and difficulties involved in the installation and clinical usage of this type of high-usability and advanced multimedia telemedicine system in the field of teleradiology and collaborative medical imaging diagnosis     

A century of tobamovirus evolution in an Australian population of Nicotiana glauca

The evolution over the past century of two tobamoviruses infecting populations of the immigrant plant Nicotiana glauca in New South Wales (NSW), Australia, has been studied. This plant species probably entered Australia in the 1870s. Isolates of the viruses were obtained from N. glauca specimens deposited in the NSW Herbarium between 1899 and 1972, and others were obtained from living plants in 1985 and 1993. It was found that the NSW N. glauca population was infected with tobacco mosaic tobamovirus (TMV) and tobacco mild green mosaic tobamovirus (TMGMV) before 1950 but only with TMGMV after that date. Half the pre-1950 infections were mixtures of the two viruses, and one was a recombinant. Remarkably, sequence analyses showed no increase in the genetic diversity among the TMGMV isolates over the period. However, for TMV, the genetic diversity of synonymous (but not of nonsynonymous) differences between isolates varied and was correlated with their time of isolation. TMV accumulated to smaller concentrations than TMGMV in N. glauca plants, and in mixed experimental infections, the accumulation of TMV, but not of TMGMV, was around 1/10 that in single infections. However, no evidence was found of isolate-specific interaction between the viruses. We conclude that although TMV may have colonized N. glauca in NSW earlier or faster than TMGMV, the latter virus caused a decrease of the TMV population below a threshold at which deleterious mutations were eliminated. This phenomenon, called Muller's ratchet, or a "mutational meltdown," probably caused the disappearance of TMV from the niche.     

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. These novel mAbs are currently under investigation for use as monotherapy or in combination with hypomethylating agents, BCL2 inhibitors, and chemotherapy in various clinical trials at different phases of development. Here, we review the main molecular targets and modes of action of novel mAb-based immunotherapies, which can represent the future of AML and higher risk MDS treatment.     

On-line analysis of urban particulate matter focusing on elevated wintertime aerosol concentrations

A 10-day winter sampling campaign was conducted in downtown Toronto for particulate matter (PM) air pollution in the fine (<2.5 microm) size range. An aerosol laser ablation mass spectrometer (LAMS), a tapered-element oscillating microbalance (TEOM), and an aerodynamic particle sizer (APS) were operated in parallel to characterize the PM on-line. In this study, the LAMS observed differences in the chemical composition between three separate episodes with higher PM2.5 mass and APS counts. LAMS results showed that in one instance of elevated PM, organic amines were present in the particulates. Temporal analyses of this episode revealed chemical transformations as the amines, characterized by m/z peaks 58(C3HeN)+, 86(C5H2N)+, and nitrates, increased in number concentration while Ca and hydrocarbon particle classes concurrently decreased. On another day, sulfates were found to have increased significantly. The third event was only 4 h in duration and exhibited an increase in the number of submicron-sized K/hydrocarbons and sulfate-containing particles. In this last event, the hydrocarbons and a K to Fe ratio enrichment indicated there was likely a contribution from a combustion source. This work offers some of the first insights into single particle size and chemistry in a cold winter climate.     

On the effective conductivity and the apparent viscosity of a thin rough polymer interface using PGD-based separated representations

Composite manufacturing processes usually proceed from preimpregnated preforms that are consolidated by simultaneously applying heat and pressure, so as to ensure a perfect contact compulsory for making molecular diffusion possible. However, in practice, the contact is rarely perfect. This results in a rough interface where air could remain entrapped, thus affecting the effective thermal conductivity. Moreover, the interfacial melted polymer is squeezed flowing in the rough gap created by the fibers located on the prepreg surfaces. Because of the typical dimensions of a composite prepreg, with thickness orders of magnitude smaller than its other in-plane dimensions, and its surface roughness having a characteristic size orders of magnitude smaller than the prepreg thickness, high-fidelity numerical simulations for elucidating the impact of surface and interface roughness remain today, despite the impressive advances in computational availabilities, unattainable. This work aims at elucidating roughness impact on heat conduction and the effective viscosity of the interfacial polymer squeeze flow by using an advanced numerical strategy able to reach resolutions never attained until now, a sort of numerical microscope able to attain the scale of the smallest geometrical detail.