140 research outputs found

    Spurious harmonic response of multipulse quantum sensing sequences

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    Multipulse sequences based on Carr-Purcell decoupling are frequently used for narrow-band signal detection in single spin magnetometry. We have analyzed the behavior of multipulse sensing sequences under real-world conditions, including finite pulse durations and the presence of detunings. We find that these non-idealities introduce harmonics to the filter function, allowing additional frequencies to pass the filter. In particular, we find that the XY family of sequences can generate signals at the 2fac, 4fac and 8fac harmonics and their odd subharmonics, where fac is the ac signal frequency. Consideration of the harmonic response is especially important for diamond-based nuclear spin sensing where the NMR frequency is used to identify the nuclear spin species, as it leads to ambiguities when several isotopes are present.Comment: 6 pages, 7 figure

    Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation

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    <p>Abstract</p> <p>Background</p> <p>Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. In murine-to-murine transplantation experiments, CXCR4 expression marks a population of adult murine satellite cells with robust engraftment potential in <it>mdx </it>mice, and CXCR4-positive murine muscle-derived SP cells home more effectively to dystrophic muscle after intra-arterial delivery in <it>mdx<sup>5cv </sup></it>mice. Together, these data suggest that CXCR4 plays an important role in donor cell engraftment. Therefore, we sought to translate these results to a clinically relevant canine-to-canine allogeneic transplant model for Duchenne muscular dystrophy (DMD) and determine if CXCR4 is important for donor cell engraftment.</p> <p>Methods</p> <p>In this study, we used a canine-to-murine xenotransplantation model to quantitatively compare canine muscle cell engraftment, and test the most effective cell population and modulating factor in a canine model of DMD using allogeneic transplantation experiments.</p> <p>Results</p> <p>We show that CXCR4 expressing cells are important for donor muscle cell engraftment, yet FACS sorted CXCR4-positive cells display decreased engraftment efficiency. However, diprotin A, a positive modulator of CXCR4-SDF-1 binding, significantly enhanced engraftment and stimulated sustained proliferation of donor cells <it>in vivo</it>. Furthermore, the canine-to-murine xenotransplantation model accurately predicted results in canine-to-canine muscle cell transplantation.</p> <p>Conclusions</p> <p>Therefore, these results establish the efficacy of diprotin A in stimulating muscle cell engraftment, and highlight the pre-clinical utility of a xenotransplantation model in assessing the relative efficacy of muscle stem cell populations.</p

    Investigation of Surface Magnetic Noise by Shallow Spins in Diamond

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    We present measurements of spin relaxation times (T1, T1ρ, T2) on very shallow (≲5  nm) nitrogen-vacancy centers in high-purity diamond single crystals. We find a reduction of spin relaxation times up to 30 times compared to bulk values, indicating the presence of ubiquitous magnetic impurities associated with the surface. Our measurements yield a density of 0.01–0.1μB/nm2 and a characteristic correlation time of 0.28(3) ns of surface states, with little variation between samples and chemical surface terminations. A low temperature measurement further confirms that fluctuations are thermally activated. The data support the atomistic picture where impurities are associated with the top carbon layers, and not with terminating surface atoms or adsorbate molecules. The low spin density implies that the presence of A single surface impurity is sufficient to cause spin relaxation of a shallow nitrogen-vacancy center

    Design of Polyamine-Grafted Starches for Nucleotide Analogue Delivery: In Vitro Evaluation of the Anticancer Activity

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    Nucleotide analogues are a therapeutic class that is very promising and currently used in clinics, notably against viral infectious diseases and cancer. However, their therapeutic potential is often restricted by a poor stability in vivo, the induction of severe side effects, and limited passive intracellular diffusion due to their hydrophilicity. Polysaccharide-based polymers (e.g., starch) have considerable advantages, including a lack of toxicity and the absence of antigenicity. The aim of this study was to develop new cationic starches able to form complexes with nucleotide analogues, thus protecting them and increasing their cell uptake. At the same time, the material should demonstrate good biocompatibility and low cytotoxicity. Different polyamines, (TREN, TEPA, and spermine) were grafted to starch to evaluate the impact of side-chain properties. The resulting cationic starch derivatives were characterized (e.g., degree of modification) and compared in their ability to form polyplexes with ATP as a model nucleotide. Among the tested candidates, the formulation of starch–TEPA and ATP with an N/P ratio of 2 led to nanoparticles with a size of 429 nm, a PdI of 0.054, and a ζ potential of −9 mV. MTT and LDH assays on A549 cell line showed low toxicity for this polymer. Confocal microscopy study proved that the cell internalization was an incubation-time- and energy-dependent process. Most important, starch–TEPA complexed with ddGTP showed significant biological activity on A549 cancer cells compared to that of plain ddGTP at the same concentration

    Modelling the bronchial barrier in pulmonary drug delivery: A human bronchial epithelial cell line supplemented with human tracheal mucus.

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    The airway epithelium together with the mucus layer coating it forms a protective system that efficiently filters and removes potentially harmful particles contained in inhaled air. The same mechanism, however, serves to entrap particulate drug carriers, precluding their interaction with their target. The mucus barrier is often neglected in in vitro testing setups employed for the assessment of pulmonary drug delivery strategies. Therefore, our aim was to more accurately model the bronchial barrier, by developing an in vitro system comprising a tight epithelial cell layer which may be optionally supplemented with a layer of human tracheal mucus. To form the epithelium in vitro, we used the cystic fibrosis cell line CFBE41o-, which can be grown as monolayers on Transwell® supports, expressing tight junctions as well as relevant transport proteins. In contrast to the cell line Calu-3, however, CFBE41o- does not produce mucus. Therefore, native human mucus, obtained from tracheal tubes of patients undergoing elective surgery, was used as a supplement. The compatibility of CFBE41o- cells with the human mucus was addressed with the MTT assay, and confirmed by fluorescein diacetate/propidium iodide live/dead staining. Moreover, the CFBE41o- cells retained their epithelial barrier properties after being supplemented with mucus, as evidenced by the high trans-epithelial electrical resistance values (∼1000Ωcm(2)) together with a continued low level of paracellular transport of sodium fluorescein. Fluorescently-labeled chitosan-coated PLGA nanoparticles (NP, ∼168nm) were used as a model drug delivery system to evaluate the suitability of this in vitro model for studying mucus permeation and cell uptake. Comparing CFBE41o- cell monolayers with and without mucus, resp., showed that the NP uptake was dramatically reduced in the presence of mucus. This model may therefore be used as a tool to study potential mucus interactions of aerosolized drugs, and more specifically NP-based drug delivery systems designed to exert their effect in the bronchial region

    Design of polyamines-grafted starches for nucleotide analogues delivery: in vitro evaluation of the anticancer activity

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    Nucleotide analogues are a therapeutic class really promising and currently used in clinic notably against viral infectious diseases and cancer. However, their therapeutic potential is often restricted by a poor stability in vivo, the induction of severe side effects and a limited passive intracellular diffusion due to their hydrophilicity. Polysaccharide-based polymers (e. g. starch) have considerable advantages including a lack of toxicity and absence of antigenicity. The aim of this study was to develop new cationic starches able to form complexes with nucleotide analogues: to protect them and increase their cell uptake. The material should demonstrate good biocompatibility and low cytotoxicity. Different oligoamines, (TREN, TEPA and spermine) were covalently grafted to starch: the resulting cationic starch derivatives were characterized (e.g. degree of modification) and compared in their properties to form polyplexes with ATP as a model nucleotide. Among the tested candidates, the formulation of starch-TEPA and ATP with a N/P ratio = 2 led to nanoparticles with a size of 429 nm, a PdI of 0.054 and a zeta potential of -9 mV. MTT and LDH assays on A549 cell line showed a low toxicity of this cationic starch. Confocal microscopy studies proved that the cell internalization was an incubation time and energy dependent process. Most important, starch-TEPA complexes with ddGTP (0.3 mg/mL) showed a significant biological activity on A549 cancer cells (&gt; 90 %) compared to plain ddGTP (~ 21 %) at the same concentration, revealing a real promising system to deliver intracellularly nucleotide analogues

    The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine

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    BACKGROUND: Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline. METHODS: The committee made specific practice recommendations using the Grades of Recommendation Assessment, Development, and Evaluation system. This was based on five systematic reviews of the literature. Specific areas of focus included (1) prevention of diabetic foot ulceration, (2) off-loading, (3) diagnosis of osteomyelitis, (4) wound care, and (5) peripheral arterial disease. RESULTS: Although we identified only limited high-quality evidence for many of the critical questions, we used the best available evidence and considered the patients' values and preferences and the clinical context to develop these guidelines. We include preventive recommendations such as those for adequate glycemic control, periodic foot inspection, and patient and family education. We recommend using custom therapeutic footwear in high-risk diabetic patients, including those with significant neuropathy, foot deformities, or previous amputation. In patients with plantar diabetic foot ulcer (DFU), we recommend off-loading with a total contact cast or irremovable fixed ankle walking boot. In patients with a new DFU, we recommend probe to bone test and plain films to be followed by magnetic resonance imaging if a soft tissue abscess or osteomyelitis is suspected. We provide recommendations on comprehensive wound care and various débridement methods. For DFUs that fail to improve (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, we recommend adjunctive wound therapy options. In patients with DFU who have peripheral arterial disease, we recommend revascularization by either surgical bypass or endovascular therapy. CONCLUSIONS: Whereas these guidelines have addressed five key areas in the care of DFUs, they do not cover all the aspects of this complex condition. Going forward as future evidence accumulates, we plan to update our recommendations accordingly

    Investigation of Surface Magnetic Noise by Shallow Spins in Diamond

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    We present measurements of spin relaxation times (T1, T1ρ, T2) on very shallow (≲5  nm) nitrogen-vacancy centers in high-purity diamond single crystals. We find a reduction of spin relaxation times up to 30 times compared to bulk values, indicating the presence of ubiquitous magnetic impurities associated with the surface. Our measurements yield a density of 0.01–0.1μB/nm2 and a characteristic correlation time of 0.28(3) ns of surface states, with little variation between samples and chemical surface terminations. A low temperature measurement further confirms that fluctuations are thermally activated. The data support the atomistic picture where impurities are associated with the top carbon layers, and not with terminating surface atoms or adsorbate molecules. The low spin density implies that the presence of A single surface impurity is sufficient to cause spin relaxation of a shallow nitrogen-vacancy center
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