Mutations in Atp2b2, an outer hair cell gene, cause dominant hearing loss in humans. Using a mouse model Atp2b2
, with a dominant hearing loss mutation (Oblivion), we show that liposome-mediated in ...vivo delivery of CRISPR-Cas9 ribonucleoprotein complexes leads to specific editing of the Obl allele. Large deletions encompassing the Obl locus and indels were identified as the result of editing. In vivo genome editing promotes outer hair cell survival and restores their function, leading to hearing recovery. We further show that in a double-dominant mutant mouse model, in which the Tmc1 Beethoven mutation and the Atp2b2 Oblivion mutation cause digenic genetic hearing loss, Cas9/sgRNA delivery targeting both mutations leads to partial hearing recovery. These findings suggest that liposome-RNP delivery can be used as a strategy to recover hearing with dominant mutations in OHC genes and with digenic mutations in the auditory hair cells, potentially expanding therapeutics of gene editing to treat hearing loss.
Lithium is a well-established treatment for bipolar disorders and has been shown to be neuroprotective, and thus low doses might be useful for the treatment of childhood brain injury and neurological ...sequelae. However, pharmacokinetic (PK) data in children are limited. This study was to investigate the PKs after oral administration of low-dose lithium carbonate in young children with intellectual disability.
Fifty-two children with intellectual disability aged 4-10 years old were enrolled. A series of blood samples were collected after a single-dose administration of lithium carbonate. The serum lithium concentration was measured using a validated ion chromatography assay, and the PK concentration data were modeled using a nonlinear mixed effect model in the NONMEM program.
The lithium concentration over time was adequately described by a two-compartment disposition, with a transient absorption and first-order elimination process. The inclusion of body weight as an allometric factor significantly improved the model fit, but age and gender were not associated with the PKs of lithium. The clearance, central volume, inter-compartmental clearance, and peripheral volume estimates from the final population PK model were 0.98 L/h, 13.1 L, 0.84 L/h, and 8.2 L for children with a body weight of 20 kg. The model evaluation suggested that there is no obvious discrepancy between the observations and predictions in the proposed model. A visual predictive check demonstrated the good predictive performance of the final model.
The lithium PK properties in young children were similar to those in older children and adults. The proposed model can be used for further PK/PD analysis to optimize the dosage regimen of lithium in children.
BACKGROUND
At present, non-invasive methods are not comprehensive enough to enable urologists to predict sperm retrieval results accurately in patients with non-obstructive azoospermia (NOA). Our aim ...was to improve the prediction accuracy of sperm retrieval by using leptin and artificial neural networks (ANNs).
METHODS
Data from May 2004 to July 2010 for 280 patients with NOA were reviewed and assigned into the training and testing set for ANNs. All patients underwent standard diagnostic infertility evaluation and testicular sperm extraction (TESE). Twelve factors were recorded as the input variables for ANNs: testicular volume, semen volume, seminal pH, seminal alpha-glucosidase and fructose, serum hormones including FSH, LH, total testosterone (TT), prolactin, estradiol, serum and seminal leptin. Three ANN models were constructed with the following input variables: ANN1-, ANN2- and ANN3-. The prediction accuracy for FSH, leptin and ANN models was compared by receiver operating characteristic (ROC) curve analysis.
RESULTS
All ANN models were better than FSH. ANN1 had the largest area under the curve (AUC =0.83) and demonstrated significant improvement compared with FSH (AUC =0.63, P< 0.01) and leptin (AUC =0.59, P< 0.01).
CONCLUSIONS
ANNs improve the prediction accuracy of sperm retrieval. Although the leptin AUC is low, combined use of leptin and FSH can significantly improve the prediction accuracy for sperm recovery in NOA patients. Leptin may be a good assistant marker for diagnosing NOA. However, studies with larger numbers of patients are required to confirm the improved predictive performance of ANNs.
This article reports viscosity data on a series of colloidal dispersions collected as part of the International Nanofluid Property Benchmark Exercise (INPBE). Data are reported for seven different ...fluids that include dispersions of metal-oxide nanoparticles in water, and in synthetic oil. These fluids, which are also referred to as ‘nanofluids,’ are currently being researched for their potential to function as heat transfer fluids. In a recently published paper from the INPBE study, thermal conductivity data from more than 30 laboratories around the world were reported and analyzed. Here, we examine the influence of particle shape and concentration on the viscosity of these same nanofluids and compare data to predictions from classical theories on suspension rheology.
Nickel catalyst supported on honeycomb cinder (Ni/HC) was prepared by a homogeneous precipitation method. The catalyst was applied to produce hydrogen-rich combustible gas by catalytic pyrolysis of ...soybean straw and plastic (PE) mixture. The straw and plastic materials were analyzed by elemental analysis and industrial analysis. The support and catalyst were characterized by X-ray fluorescence (XRF), X-ray diffraction (XRD), scanning electron microscopy (SEM), and N2 adsorption-desorption isotherm (BET). The analysis showed that NiO was well loaded on the surface of honeycomb coal slag carrier. The effects of Ni loading, pyrolysis temperature, holding time, and calcination temperature on the experimental results were studied. The results showed that the preparation of the catalyst was feasible and that it had a good catalytic effect. When Ni loading was 15 wt.%, catalytic pyrolysis temperature was 700 °C, holding time was 20 min, and calcination temperature of catalyst was 400 °C, H2 concentration increased from 20.6 to 52.8 vol.%, and while H2 yield was 302 mL/g, CH4 concentration decreased from 51.1 to 22.6 vol.% and CO concentration increased from 10.8 to 17.8 vol.%. After the catalyst was regenerated 6 times, the H2 concentration still reached 40 vol.% and the combustible gas concentration was still above 80 vol.%. The catalyst still had good catalytic activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A large body of knowledge about magnetism is attained from models of interacting spins, which usually reside on magnetic ions. Proposals beyond the ionic picture are uncommon and seldom verified by ...direct observations in conjunction with microscopic theory. Here, using inelastic neutron scattering to study the itinerant near-ferromagnet MnSi, we find that the system's fundamental magnetic units are interconnected, extended molecular orbitals consisting of three Mn atoms each rather than individual Mn atoms. This result is further corroborated by magnetic Wannier orbitals obtained by ab initio calculations. It contrasts the ionic picture with a concrete example and presents an unexplored regime of the spin waves where the wavelength is comparable to the spatial extent of the molecular orbitals. Our discovery brings important insights into not only the magnetism of MnSi but also a broad range of magnetic quantum materials where structural symmetry, electron itinerancy, and correlations act in concert.
Topological invariants in the band structure, such as Chern numbers, are important for the understanding and classification of the topological properties of matter and dictate the occurrence of ...exotic behaviors, yet their direct spectroscopic determination has been largely limited to electronic bands. Here, we use inelastic neutron scattering in conjunction with ab initio calculations to identify a variety of topological phonon band crossings in MnSi and CoSi single crystals. We find a distinct relation between the Chern numbers of a band-crossing node and the scattering intensity modulation in momentum space around the node. Given sufficiently high resolution, our method can be used to determine arbitrarily large Chern numbers of topological phonon band-crossing nodes.
Graphene's original promise to succeed silicon faltered due to pervasive edge disorder in lithographically patterned deposited graphene and the lack of a new electronics paradigm. Here we demonstrate ...that the annealed edges in conventionally patterned graphene epitaxially grown on a silicon carbide substrate (epigraphene) are stabilized by the substrate and support a protected edge state. The edge state has a mean free path that is greater than 50 microns, 5000 times greater that the bulk states and involves a theoretically unexpected Majorana-like zero-energy non-degenerate quasiparticle that does not produce a Hall voltage. In seamless integrated structures, the edge state forms a zero-energy one-dimensional ballistic network with essentially dissipationless nodes at ribbon-ribbon junctions. Seamless device structures offer a variety of switching possibilities including quantum coherent devices at low temperatures. This makes epigraphene a technologically viable graphene nanoelectronics platform that has the potential to succeed silicon nanoelectronics.
A large body of knowledge about magnetism is attained from models of interacting spins, which usually reside on magnetic ions. Proposals beyond the ionic picture are uncommon and seldom verified by ...direct observations in conjunction with microscopic theory. Here, using inelastic neutron scattering to study the itinerant near-ferromagnet MnSi, we find that the system's fundamental magnetic units are interconnected, extended molecular orbitals consisting of three Mn atoms each, rather than individual Mn atoms. This result is further corroborated by magnetic Wannier orbitals obtained by ab initio calculations. It contrasts the ionic picture with a concrete example, and presents a novel regime of the spin waves where the wavelength is comparable to the spatial extent of the molecular orbitals. Our discovery brings important insights into not only the magnetism of MnSi, but also a broad range of magnetic quantum materials where structural symmetry, electron itinerancy and correlations act in concert.
Topological invariants in the band structure, such as Chern numbers, are crucial for the classification of topological matters and dictate the occurrence of exotic properties, yet their direct ...spectroscopic determination has been largely limited to electronic bands. Here, we use inelastic neutron scattering in conjunction with ab initio calculations to identify a variety of topological phonon band crossings in MnSi and CoSi single crystals. We find a distinct relation between the Chern numbers of a band-crossing node and the scattering intensity modulation in momentum space around the node. Given sufficiently high resolution, our method can be used to determine arbitrarily large Chern numbers of topological phonon band-crossing nodes.
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