442 research outputs found
Coherent electrical control of a single high-spin nucleus in silicon
Nuclear spins are highly coherent quantum objects. In large ensembles, their control and detection via magnetic resonance is widely exploited, for example, in chemistry, medicine, materials science and mining. Nuclear spins also featured in early proposals for solid-state quantum computers1 and demonstrations of quantum search2 and factoring3 algorithms. Scaling up such concepts requires controlling individual nuclei, which can be detected when coupled to an electron4–6. However, the need to address the nuclei via oscillating magnetic fields complicates their integration in multi-spin nanoscale devices, because the field cannot be localized or screened. Control via electric fields would resolve this problem, but previous methods7–9 relied on transducing electric signals into magnetic fields via the electron–nuclear hyperfine interaction, which severely affects nuclear coherence. Here we demonstrate the coherent quantum control of a single 123Sb (spin-7/2) nucleus using localized electric fields produced within a silicon nanoelectronic device. The method exploits an idea proposed in 196110 but not previously realized experimentally with a single nucleus. Our results are quantitatively supported by a microscopic theoretical model that reveals how the purely electrical modulation of the nuclear electric quadrupole interaction results in coherent nuclear spin transitions that are uniquely addressable owing to lattice strain. The spin dephasing time, 0.1 seconds, is orders of magnitude longer than those obtained by methods that require a coupled electron spin to achieve electrical driving. These results show that high-spin quadrupolar nuclei could be deployed as chaotic models, strain sensors and hybrid spin-mechanical quantum systems using all-electrical controls. Integrating electrically controllable nuclei with quantum dots11,12 could pave the way to scalable, nuclear- and electron-spin-based quantum computers in silicon that operate without the need for oscillating magnetic fields
Reshaping the preterm heart: shifting cardiac renin-angiotensin system towards cardioprotection in rats exposed to neonatal high-oxygen stress
Background:
Approximately 10% of infants are born preterm. Preterm birth leads to short and long-term changes in cardiac shape and function. By using a rat model of neonatal high-oxygen (80%O2) exposure, mimicking the premature hyperoxic transition to the extrauterine environment, we revealed a major role of the renin-angiotensin system peptide Angio II (angiotensin II) and its receptor AT1 (angiotensin receptor type 1) on neonatal O2-induced cardiomyopathy. Here, we tested whether treatment with either orally active compounds of the peptides Angio-(1–7) or alamandine included in cyclodextrin could prevent postnatal cardiac remodeling and the programming of cardiomyopathy induced by neonatal high-O2 exposure.
Methods:
Sprague-Dawley pups were exposed to room air or 80% O2 from postnatal day 3 (P3) to P10. Neonatal rats were treated orally from P3 to P10 and assessed at P10 and P28. Left ventricular (LV) shapes were characterized by tridimensional computational atlases of ultrasound images in addition to histomorphometry.
Results:
At P10, high O2-exposed rats presented a smaller, globular and hypertrophied LV shape versus controls. Treatment with cyclodextrin–Angio-(1–7) significantly improved LV function in the O2-exposed neonatal rats and slightly changed LV shape. Cyclodextrin-alamandine and cyclodextrin–Angio-(1–7) treatments similarly reduced hypertrophy at P10 as well as LV remodeling and dysfunction at P28. Both treatments upregulated cardiac angiotensin-converting enzyme 2 in O2-exposed rats at P10 and P28.
Conclusions:
Our findings demonstrate LV remodeling changes induced by O2-stress and the potential benefits of treatments targeting the cardioprotective renin-angiotensin system axis, supporting the neonatal period as an important window for interventions aiming at preventing cardiomyopathy in people born preterm
Exploring facilitating factors and barriers to the nationwide dissemination of a Dutch school-based obesity prevention program “DOiT”: a study protocol
In Vivo Serial MR Imaging of Magnetically Labeled Endothelial Progenitor Cells Homing to the Endothelium Injured Artery in Mice
Background: Emerging evidence of histopathological analyses suggests that endothelial progenitor cells (EPCs) play an important role in vascular diseases. Neointimal hyperplasia can be reduced by intravenous transfusion of EPCs after vascular injury in mice. Therefore, it would be advantageous to develop an in vivo technique that can explore the temporal and spatial migration of EPCs homing to the damaged endothelium noninvasively. Methodology/Principal Findings: The left carotid common artery (LCCA) was injured by removal of endothelium with a flexible wire in Kunming mice. EPCs were collected by in vitro culture of spleen-derived mouse mononuclear cells (MNCs). EPCs labeling was carried out in vitro using Fe2O3-poly-L-lysine (Fe2O3-PLL). In vivo serial MR imaging was performed to follow-up the injured artery at different time points after intravenous transfusion of EPCs. Vessel wall areas of injured artery were computed on T2WI. Larger MR signal voids of vessel wall on T2WI was revealed in all 6 mice of the labeled EPC transfusion group 15 days after LCCA injury, and it was found only in 1 mouse in the unlabeled EPC transfusion group (p = 0.015). Quantitative analyses of vessel wall areas on T2WI showed that the vessel wall areas of labeled EPC transfusion group were less than those of unlabeled EPC transfusion group and control group fifteen days after artery injury (p,0.05). Histopathological analyses confirmed accumulation and distribution of transfused EPCs at the injury site of LCCA. Conclusions/Significance: These data indicate that MR imaging might be used as an in vivo method for the tracking of EPC
Genetically Engineered Alginate Lyase-PEG Conjugates Exhibit Enhanced Catalytic Function and Reduced Immunoreactivity
Alginate lyase enzymes represent prospective biotherapeutic agents for treating bacterial infections, particularly in the cystic fibrosis airway. To effectively deimmunize one therapeutic candidate while maintaining high level catalytic proficiency, a combined genetic engineering-PEGylation strategy was implemented. Rationally designed, site-specific PEGylation variants were constructed by orthogonal maleimide-thiol coupling chemistry. In contrast to random PEGylation of the enzyme by NHS-ester mediated chemistry, controlled mono-PEGylation of A1-III alginate lyase produced a conjugate that maintained wild type levels of activity towards a model substrate. Significantly, the PEGylated variant exhibited enhanced solution phase kinetics with bacterial alginate, the ultimate therapeutic target. The immunoreactivity of the PEGylated enzyme was compared to a wild type control using in vitro binding studies with both enzyme-specific antibodies, from immunized New Zealand white rabbits, and a single chain antibody library, derived from a human volunteer. In both cases, the PEGylated enzyme was found to be substantially less immunoreactive. Underscoring the enzyme's potential for practical utility, >90% of adherent, mucoid, Pseudomonas aeruginosa biofilms were removed from abiotic surfaces following a one hour treatment with the PEGylated variant, whereas the wild type enzyme removed only 75% of biofilms in parallel studies. In aggregate, these results demonstrate that site-specific mono-PEGylation of genetically engineered A1-III alginate lyase yielded an enzyme with enhanced performance relative to therapeutically relevant metrics.Cystic Fibrosis Foundation (Research Development Program)National Center for Research Resources (U.S.) (P20RR018787-06
Expression of IMP1 Enhances Production of Murine Leukemia Virus Vector by Facilitating Viral Genomic RNA Packaging
Murine leukemia virus (MLV)-based retroviral vector is widely used for gene transfer. Efficient packaging of the genomic RNA is critical for production of high-titer virus. Here, we report that expression of the insulin-like growth factor II mRNA binding protein 1 (IMP1) enhanced the production of infectious MLV vector. Overexpression of IMP1 increased the stability of viral genomic RNA in virus producer cells and packaging of the RNA into progeny virus in a dose-dependent manner. Downregulation of IMP1 in virus producer cells resulted in reduced production of the retroviral vector. These results indicate that IMP1 plays a role in regulating the packaging of MLV genomic RNA and can be used for improving production of retroviral vectors
EuropeaN Energy balance Research to prevent excessive weight Gain among Youth (ENERGY) project: Design and methodology of the ENERGY cross-sectional survey
Background: Obesity treatment is by large ineffective long term, and more emphasis on the prevention of excessive weight gain in childhood and adolescence is warranted. To inform energy balance related behaviour (EBRB) change interventions, insight in the potential personal, family and school environmental correlates of these behaviours is needed. Studies on such multilevel correlates of EBRB among schoolchildren in Europe are lacking. The ENERGY survey aims to (1) provide up-to-date prevalence rates of measured overweight, obesity, self-reported engagement in EBRBs, and objective accelerometer-based assessment of physical activity and sedentary behaviour and blood-sample biomarkers of metabolic function in countries in different regions of Europe, (2) to identify personal, family and school environmental correlates of these EBRBs. This paper describes the design, methodology and protocol of the survey. Method/Design: A school-based cross-sectional survey was carried out in 2010 in seven different European countries; Belgium, Greece, Hungary, the Netherlands, Norway, Slovenia, and Spain. The survey included measurements of anthropometrics, child, parent and school-staff questionnaires, and school observations to measure and assess outcomes (i.e. height, weight, and waist circumference), EBRBs and potential personal, family and school environmental correlates of these behaviours including the social-cultural, physical, political, and economic environmental factors. In addition, a selection of countries conducted accelerometer measurements to objectively assess physical activity and sedentary behaviour, and collected blood samples to assess several biomarkers of metabolic function. Discussion: The ENERGY survey is a comprehensive cross-sectional study measuring anthropometrics and biomarkers as well as assessing a range of EBRBs and their potential correlates at the personal, family and school level, among 10-12 year old children in seven European countries. This study will result in a unique dataset, enabling cross country comparisons in overweight, obesity, risk behaviours for these conditions as well as the correlates of engagement in these risk behaviours
Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma : preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates
Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D (KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.Peer reviewe
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Medium-term seed storage of 50 genera of forage legumes and evidence-based genebank monitoring intervals
Genebanks maintaining seeds for long-term genetic resources conservation monitor seed lots to detect early loss in viability. Monitoring is costly and depletes valuable seed. Three decades of genebank seed germination test results of diverse forage species from 50 legume genera in the International Livestock Research Institute’s medium-term store (circa 8° C with 5 % moisture content) were analysed to determine whether advice on seed monitoring intervals could be derived. Cumulative normal distributions were fitted by probit analysis for each seed lot and compared within each genus. Six patterns of within-genus variation were identified: no detectable trend in germination test results during storage (4 genera); detectable trends, but variable (positive to negative) amongst lots (5); consistent slope of loss in viability amongst lots (17); consistent slope of increase in ability to germinate amongst lots (21); common loss in viability amongst lots (2); common increase in ability to germinate amongst lots (1). Seed lot monitoring intervals for the medium-term store were derived for each of 19 genera with consistent loss in viability across seed lots: three genera provided comparatively rapid deterioration, five met the general expectations for a medium-term store (2-10 years’ maintenance of high viability), whilst 11 provided much better survival. Moreover, 26 further genera provided no evidence as yet of seed deterioration; of these, 22 improved in ability to germinate during storage indicating confounding of hardseededness with viability in germination tests
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