914 research outputs found
Comparison of adeno-associated virus pseudotype 1, 2, and 8 vectors administered by intramuscular injection in the treatment of murine phenylketonuria
Phenylketonuria (PKU) is caused by hepatic phenylalanine hydroxylase (PAH) deficiency and is associated with systemic accumulation of phenylalanine (Phe). Previously we demonstrated correction of murine PKU after intravenous injection of a recombinant type 2 adeno-associated viral vector pseudotyped with type 8 capsid (rAAV2/8), which successfully directed hepatic transduction and Pah gene expression. Here, we report that liver PAH activity and phenylalanine clearance were also restored in PAH-deficient mice after simple intramuscular injection of either AAV2 pseudotype 1 (rAAV2/1) or rAAV2/8 vectors. Serotype 2 AAV vector (rAAV2/2) was also investigated, but long-term phenylalanine clearance has been observed only for pseudotypes 1 and 8. Therapeutic correction was shown in both male and female mice, albeit more effectively in males, in which correction lasted for the entire period of the experiment (>1 year). Although phenylalanine levels began to rise in female mice at about 8-10 months after rAAV2/8 injection they remained only mildly hyperphenylalaninemic thereafter and subsequent supplementation with synthetic tetrahydrobiopterin resulted in a transient decrease in blood phenylalanine. Alternatively, subsequent administration of a second vector with a different AAV pseudotype to avoid immunity against the previously administrated vector was also successful for long-term treatment of female PKU mice. Overall, this relatively less invasive gene transfer approach completes our previous studies and allows comparison of complementary strategies in the development of efficient PKU gene therapy protocols
Efficient scheme for one-way quantum computing in thermal cavities
We propose a practical scheme for one-way quantum computing based on
efficient generation of 2D cluster state in thermal cavities. We achieve a
controlled-phase gate that is neither sensitive to cavity decay nor to thermal
field by adding a strong classical field to the two-level atoms. We show that a
2D cluster state can be generated directly by making every two atoms collide in
an array of cavities, with numerically calculated parameters and appropriate
operation sequence that can be easily achieved in practical Cavity QED
experiments. Based on a generated cluster state in Box configuration,
we then implement Grover's search algorithm for four database elements in a
very simple way as an example of one-way quantum computing.Comment: 6 pages, 3 figure
River Murray Channel Productivity Monitoring 2020. CSIRO Land & Water, Canberra, ACT 2601
Field-induced single-ion magnetic behaviour in a highly luminescent Er3+ complex
This work is licensed under a Creative Commons Attribution Non-Commercial No Derivatives License
Slater-Pauling Behavior of the Half-Ferromagnetic Full-Heusler Alloys
Using the full-potential screened Korringa-Kohn-Rostoker method we study the
full-Heusler alloys based on Co, Fe, Rh and Ru. We show that many of these
compounds show a half-metallic behavior, however in contrast to the
half-Heusler alloys the energy gap in the minority band is extremely small.
These full-Heusler compounds show a Slater-Pauling behavior and the total
spin-magnetic moment per unit cell (M_t) scales with the total number of
valence electrons (Z_t) following the rule: M_t=Z_t-24. We explain why the
spin-down band contains exactly 12 electrons using arguments based on the group
theory and show that this rule holds also for compounds with less than 24
valence electrons. Finally we discuss the deviations from this rule and the
differences compared to the half-Heusler alloys.Comment: 10 pages, 8 figures, revised figure 3, new text adde
Coherent matter wave inertial sensors for precision measurements in space
We analyze the advantages of using ultra-cold coherent sources of atoms for
matter-wave interferometry in space. We present a proof-of-principle experiment
that is based on an analysis of the results previously published in [Richard et
al., Phys. Rev. Lett., 91, 010405 (2003)] from which we extract the ratio h/m
for 87Rb. This measurement shows that a limitation in accuracy arises due to
atomic interactions within the Bose-Einstein condensate
Tight-binding parameters for charge transfer along DNA
We systematically examine all the tight-binding parameters pertinent to
charge transfer along DNA. The molecular structure of the four DNA bases
(adenine, thymine, cytosine, and guanine) is investigated by using the linear
combination of atomic orbitals method with a recently introduced
parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are
discussed and then used for calculating the corresponding wavefunctions of the
two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO
and LUMO energies of the bases are in good agreement with available
experimental values. Our results are then used for estimating the complete set
of charge transfer parameters between neighboring bases and also between
successive base-pairs, considering all possible combinations between them, for
both electrons and holes. The calculated microscopic quantities can be used in
mesoscopic theoretical models of electron or hole transfer along the DNA double
helix, as they provide the necessary parameters for a tight-binding
phenomenological description based on the molecular overlap. We find that
usually the hopping parameters for holes are higher in magnitude compared to
the ones for electrons, which probably indicates that hole transport along DNA
is more favorable than electron transport. Our findings are also compared with
existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table
Transverse Momentum Dependent Parton Distribution/Fragmentation Functions at an Electron-Ion Collider
We present a summary of a recent workshop held at Duke University on Partonic
Transverse Momentum in Hadrons: Quark Spin-Orbit Correlations and Quark-Gluon
Interactions. The transverse momentum dependent parton distribution functions
(TMDs), parton-to-hadron fragmentation functions, and multi-parton correlation
functions, were discussed extensively at the Duke workshop. In this paper, we
summarize first the theoretical issues concerning the study of partonic
structure of hadrons at a future electron-ion collider (EIC) with emphasis on
the TMDs. We then present simulation results on experimental studies of TMDs
through measurements of single spin asymmetries (SSA) from semi-inclusive
deep-inelastic scattering (SIDIS) processes with an EIC, and discuss the
requirement of the detector for SIDIS measurements. The dynamics of parton
correlations in the nucleon is further explored via a study of SSA in D (`D)
production at large transverse momenta with the aim of accessing the unexplored
tri-gluon correlation functions. The workshop participants identified the SSA
measurements in SIDIS as a golden program to study TMDs in both the sea and
valence quark regions and to study the role of gluons, with the Sivers
asymmetry measurements as examples. Such measurements will lead to major
advancement in our understanding of TMDs in the valence quark region, and more
importantly also allow for the investigation of TMDs in the sea quark region
along with a study of their evolution.Comment: 44 pages 23 figures, summary of Duke EIC workshop on TMDs accepted by
EPJ
Computer modeling of diabetes and Its transparency: a report on the Eighth Mount Hood Challenge
Objectives
The Eighth Mount Hood Challenge (held in St. Gallen, Switzerland, in September 2016) evaluated the transparency of model input documentation from two published health economics studies and developed guidelines for improving transparency in the reporting of input data underlying model-based economic analyses in diabetes.
Methods
Participating modeling groups were asked to reproduce the results of two published studies using the input data described in those articles. Gaps in input data were filled with assumptions reported by the modeling groups. Goodness of fit between the results reported in the target studies and the groups’ replicated outputs was evaluated using the slope of linear regression line and the coefficient of determination (R2). After a general discussion of the results, a diabetes-specific checklist for the transparency of model input was developed.
Results
Seven groups participated in the transparency challenge. The reporting of key model input parameters in the two studies, including the baseline characteristics of simulated patients, treatment effect and treatment intensification threshold assumptions, treatment effect evolution, prediction of complications and costs data, was inadequately transparent (and often missing altogether). Not surprisingly, goodness of fit was better for the study that reported its input data with more transparency. To improve the transparency in diabetes modeling, the Diabetes Modeling Input Checklist listing the minimal input data required for reproducibility in most diabetes modeling applications was developed.
Conclusions
Transparency of diabetes model inputs is important to the reproducibility and credibility of simulation results. In the Eighth Mount Hood Challenge, the Diabetes Modeling Input Checklist was developed with the goal of improving the transparency of input data reporting and reproducibility of diabetes simulation model results
Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy
Heart failure (HF) is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ) (70 mg /kg). Riboflavin (20 mg/kg) was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), the level of malondialdehyde (MDA) as well as heme oxygenase-1 (HO-1) protein level. Myocardial connective tissue growth factor (CTGF) level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP) rate of pressure rose (+dp/dt), and rate of pressure decay (−dp/dt) were depressed while left ventricular end-diastolic pressure (LVEDP) was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest that riboflavin treatment ameliorates myocardial function and improves heart oxidant status, whereas raising myocardial HO-1 and decreasing myocardial CTGF levels have beneficial effects on diabetic cardiomyopathy
- …