Maximizing the biochemical resolving power of fluorescence microscopy.

Most recent advances in fluorescence microscopy have focused on achieving spatial resolutions below the diffraction limit. However, the inherent capability of fluorescence microscopy to non-invasively resolve different biochemical or physical environments in biological samples has not yet been formally described, because an adequate and general theoretical framework is lacking. Here, we develop a mathematical characterization of the biochemical resolution in fluorescence detection with Fisher information analysis. To improve the precision and the resolution of quantitative imaging methods, we demonstrate strategies for the optimization of fluorescence lifetime, fluorescence anisotropy and hyperspectral detection, as well as different multi-dimensional techniques. We describe optimized imaging protocols, provide optimization algorithms and describe precision and resolving power in biochemical imaging thanks to the analysis of the general properties of Fisher information in fluorescence detection. These strategies enable the optimal use of the information content available within the limited photon-budget typically available in fluorescence microscopy. This theoretical foundation leads to a generalized strategy for the optimization of multi-dimensional optical detection, and demonstrates how the parallel detection of all properties of fluorescence can maximize the biochemical resolving power of fluorescence microscopy, an approach we term Hyper Dimensional Imaging Microscopy (HDIM). Our work provides a theoretical framework for the description of the biochemical resolution in fluorescence microscopy, irrespective of spatial resolution, and for the development of a new class of microscopes that exploit multi-parametric detection systems

Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment of solid tumors

[Cu(thp)4][PF6] (HydroCuP) is a phosphino copper(I) complex highly soluble and stable in physiological media that has been developed as a possible viable alternative to platinum-based drugs for anticancer therapy. HydroCuP potently inhibited the growth of human cancer cells derived from solid tumors by inducing endoplasmatic reticulum (ER) stress thus leading to cell death through paraptosis with a preferential efficacy against cancer rather than non-cancer cells. Aim of the present study was to assess the therapeutic potential of HydroCuP in vivo, in syngenic and xenograft murine models of solid tumors by triggering the Unfolded Protein Response (UPR) pathway. With respect to platinum drugs, HydroCuP induced a markedly higher reduction of tumor growth associated with minimal animal toxicity. In human colorectal cancer xenografts, chemotherapy with HydroCuP was extremely effective in both oxaliplatin-sensitive and resistant models. The favorable in vivo tolerability of HydroCuP was also correlated to an encouraging biodistribution profile. Additionally, no signs of drug-related neurotoxicity and nephrotoxicity were observed. Altogether, these results demonstrate that HydroCuP appears worth of further investigation to evaluate its therapeutic activity towards a broad spectrum of solid malignancies

Effects of polluted air-masses advection on atmospheric particles in a semi-rural site in south Italy by SEM-EDX analysis

The variation of aerosol properties under polluted air masses advection was studied in a semi-rural site in South Italy, by means of SEM-EDX analysis performed on particles collected on 13-stages impactor filters. Radiometric measurements, HYSPLIT back-trajectories and NAAPS maps helped to choose four measurement days of polluted air mass circulation, two of them collected in the warm season (31 July 2008, 16 September 2010) and two in the cold one (16 April 2009, 18 March 2010). Polluted aerosol characteristics were compared to those under background (BG) conditions (8 February 2011), highlighting differences in the particles chemical and morphological properties. One of the signatures of the air mass transport in the coarse fraction was the higher content of particles containing S, i.e., S-reacted, (27.5% on average) in comparison with BG conditions (1%). Two main sources of transported aerosols were identified: industrial processes and biomass burning, with fly ash, metal and S-rich particles in the first case, and K-salts and nitrate-coated Ca-bearingparticles in the second. Single particle analysis on the coarse fraction allowed large agglomerates of soot to be identified, with inclusions of silicate particles rich in Cu and Zn, Ca-S, fly ash and metals particles that are a clear indication of extensive modifications of aerosol size, chemical composition and, likely, radiative properties. In finer stages (EAD ≤ 0.94 μm) concurrent collection of organic and inorganic particles originated an agglomerate state matter mainly characterized by K and S for polluted conditions and by K only for BG

Improvements in the processing of Yb:YAG ceramic materials

Laser ceramics can attain a significant role in the frame of the generation of high peak power, high energy laser pulses at high repetition rate, applications where fiber lasers or single crystals undergo fundamental or technological limitations. A ceramic material in order to be used as a laser amplifier, needs to fulfil strict requirements in terms of properties, in particular microstructure, purity level, porosity. The important role played by the production process on the transparency of ceramic materials has been explained elsewhere. The current study focuses on the optimization of the powder processing. An innovative Spray Drying process of solvent-based suspensions has been adopted for the preparation of ready-to-press powders for the reactive sintering of Yb:YAG materials. The influence of the experimental conditions on the morphology of the granulated powders and eventually on the microstructure evolution during sintering and the transparency, is describe

Experimental features affecting the transparency of YAG materials

The important role played by the processing on the transparency of ceramic materials is often underestimated. In the literature a high level of transparency has been reported by many authors that for years focused their research on the development of polycrystalline YAG for laser applications,but the description of the experimental process is seldom thoroughly described. A detailed description of the powder treatment and shaping and of other important information that are necessary to reproduce the described results, is often missing. In order to be transparent a ceramic material must exhibit a very low concentration of defects such as secondary or grain boundary phases and residual pores. In order to fulfill this requirement specific experimental conditions must be combined together. Powders need to be nanometric or at least sub-micrometric and extremely pure. On the other hand, nanometric powders aggregate easily and the poor packing that may derived can lead to residual porosity. In addition, very fine powders are difficult to handle and tend to absorb water on the surface. Finally, the powder manipulation (weighting operations, solvent removal, spray drying, shaping, etc), easily introduces impurities. In case of transparent materials all these features must be controlled because they lead to the formation of defects that works as light scattering sources thus decreasing the transparency. This work describes the results obtained with YAG based ceramics under different experimental conditions of powder treatment and shaping. Commercial powders are used for the reactive sintering in a clean atmosphere and under high vacuum of YAG materials doped with Nd, Yb or Er. These dopants have been selected as the more appropriate for high power lasers. The powder treatment (ball milling duration and speed, suspension concentration, solvent/powder ratio, type and amount of dispersant) the solvent removal technique (spray drying conditions, rotavapor temperature, etc.) are described in detail as well as the conditions adopted during shaping. The influence of the powder process on the powder packing during shaping by pressing is also reported. Finally, the influence of the pre-sintering and sintering cycles is also described

Hyperfunctioning Parathyroid Giant Adenoma

Purpose: The objective of this paper is to report the management and treatment of a 47-year-old patient admitted with multiple problems including asthenia, nausea and bradycardia, and was diagnosed with a giant parathyroid adenoma. Case report: A 47-year-old man was admitted to the Department of General Surgery for acute and worsening asthenia, nausea and bradycardia. Blood tests showed hypercalcemia, hypophosporemia, very high serum parathormone level, so that he was diagnosed with primary hyperparathyroidism. Cervical ultrasonography and scintigraphy with technetium 99 mTc Methoxyisobutylisonitrile (99 mTc-MIBI) showed the presence of positive nodule at the isthmus of the thyroid gland. The patient underwent neck exploration. Intra-operative iPTH essay was measured. A giant parathyroid adenoma was identified and excised, with no macroscopic signs of malignancy. Discussion and conclusion: Hyper functioning parathyroid giant adenoma can present with typical symptoms of hypercalcemic crisis: ECG alterations, kidney failure, emotional lability, confusion, delirium, psychosis, asthenia, epilepsy. Elective treatment is the excission. The surgical technique contemplates neck exploration and to ensure the finding of the adenoma, previously identified with imaging tests. It is necessary to measure intra-operative iPTH assay

DNA-based technologies for grapevine biodiversity exploitation: state of the art and future perspectives

The cultivated grapevine, Vitis vinifera subsp. vinifera L., is represented by an enormous population of varieties and clones. They arise from the accumulation of gametic and somatic mutations during centuries of sexual and asexual propagation. These varieties represent a vast reservoir of traits/alleles that could be useful in improving the berry quality as well as against environmental stresses. However, most of them are still unexploited. For this reason, an efficient characterization system is essential to define the varietal identity, avoid cases of synonymy (identical genotypes but different names) and homonymy (same names but different genotypes) and deepen our understanding of the existing diversity within the grape germplasm. The plethora of DNA-based high-throughput technologies currently available provides promising tools for the analysis of diversity, overcoming many of the limitations of phenotypic-based diversity analyses. However, the analysis of intra-varietal diversity remains challenging. In this scenario, after summarizing the causes and consequences of grapevine genetic inter- and intra-varietal diversity, we review the DNA-based technologies used for varietal genotyping, emphasizing those able to distinguish clones within a variety. This review provides an update on the technologies used to explore grapevine diversity, the knowledge of which is necessary for an efficient exploitation and conservation of the grapevine germplasm

Pertussis-associated persistent cough in previously vaccinated children

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