37 research outputs found

    Use of Quadrupolar Nuclei for Quantum Information processing by Nuclear Magnetic Resonance: Implementation of a Quantum Algorithm

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    Physical implementation of Quantum Information Processing (QIP) by liquid-state Nuclear Magnetic Resonance (NMR), using weakly coupled spin-1/2 nuclei of a molecule, is well established. Nuclei with spin>>1/2 oriented in liquid crystalline matrices is another possibility. Such systems have multiple qubits per nuclei and large quadrupolar couplings resulting in well separated lines in the spectrum. So far, creation of pseudopure states and logic gates have been demonstrated in such systems using transition selective radio-frequency pulses. In this paper we report two novel developments. First, we implement a quantum algorithm which needs coherent superposition of states. Second, we use evolution under quadrupolar coupling to implement multi qubit gates. We implement Deutsch-Jozsa algorithm on a spin-3/2 (2 qubit) system. The controlled-not operation needed to implement this algorithm has been implemented here by evolution under the quadrupolar Hamiltonian. This method has been implemented for the first time in quadrupolar systems. Since the quadrupolar coupling is several orders of magnitude greater than the coupling in weakly coupled spin-1/2 nuclei, the gate time decreases, increasing the clock speed of the quantum computer.Comment: 16 pages, 3 figure

    Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature

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    Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD.'' All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations.Genetics of disease, diagnosis and treatmen

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    Carbogen breathing differentially enhances blood plasma volume and 5-fluorouracil uptake in two murine colon tumor models with a distinct vascular structure.

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    Contains fulltext : 49878.pdf (publisher's version ) (Open Access)For the systemic treatment of colorectal cancer, 5-fluorouracil (FU)-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2) may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU
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