Adeno-associated virus (AAV) vectors are showing promise in gene therapy trials and have proven to be extremely efficient biological tools in basic neuroscience research. One major limitation to ...their widespread use in the neuroscience laboratory is the cost, labor, skill and time-intense purification process of AAV. We have recently shown that AAV can associate with exosomes (exo-AAV) when the vector is isolated from conditioned media of producer cells, and the exo-AAV is more resistant to neutralizing anti-AAV antibodies compared with standard AAV. Here, we demonstrate that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice. We observed that exo-AAV is more efficient at gene delivery to the brain at low vector doses relative to conventional AAV, even when derived from a serotype that does not normally efficiently cross the blood-brain barrier. Similar cell types were transduced by exo-AAV and conventionally purified vector. Importantly, no cellular toxicity was noted in exo-AAV-transduced cells. We demonstrated the utility and robustness of exo-AAV-mediated gene delivery by detecting direct GFP fluorescence after systemic injection, allowing three-dimensional reconstruction of transduced Purkinje cells in the cerebellum using ex vivo serial two-photon tomography. The ease of isolation combined with the high efficiency of transgene expression in the CNS, may enable the widespread use of exo-AAV as a neuroscience research tool. Furthermore, the ability of exo-AAV to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant.
Potential differences between primary progressive and relapsing remitting multiple sclerosis are the subject of ongoing controversial discussions. The aim of this work was to determine whether and ...how primary-progressive and relapsing-remitting multiple sclerosis subtypes differ regarding conventional MR imaging parameters, cerebral iron deposits, and their association with clinical status.
We analyzed 24 patients with primary-progressive MS, 80 with relapsing-remitting MS, and 20 healthy controls with 1.5T MR imaging for assessment of the conventional quantitative parameters: T2 lesion load, T1 lesion load, brain parenchymal fraction, and corpus callosum volume. Quantitative susceptibility mapping was performed to estimate iron concentration in the deep gray matter.
Decreased susceptibility within the thalamus in relapsing-remitting MS compared with primary-progressive MS was the only significant MR imaging difference between these MS subtypes. In the relapsing-remitting MS subgroup, the Expanded Disability Status Scale score was positively associated with conventional parameters reflecting white matter lesions and brain atrophy and with iron in the putamen and caudate nucleus. A positive association with putaminal iron and the Expanded Disability Status Scale score was found in primary-progressive MS.
Susceptibility in the thalamus might provide additional support for the differentiation between primary-progressive and relapsing-remitting MS. That the Expanded Disability Status Scale score was associated with conventional MR imaging parameters and iron concentrations in several deep gray matter regions in relapsing-remitting MS, while only a weak association with putaminal iron was observed in primary-progressive MS suggests different driving forces of disability in these MS subtypes.
ABSTRACT Analyzing the available photometry from the Kepler satellite and other databases, we performed detailed light curve modeling of 10 eclipsing binary systems that were found to exhibit a ...periodic modulation of their orbital periods. All of the selected systems are detached Algol type, with orbital periods from 0.9 to 2.9 days. In total, 9448 times of minimum for these binaries were analyzed in an attempt to identify the period variations caused by the third bodies in these systems. The well-known method of the light-travel time effect was used for the analysis. The orbital periods of the outer bodies were found to be between 1 and 14 years. This hypothesis makes such systems interesting for future prospective detections of these components, despite their low predicted masses. Considering the dynamical interaction between the orbits, the system KIC 3440230 seems to be the most interesting, in which one would expect the detection of some effects (i.e., changing the inclination) even after a few years or decades of observations.
Concepts from the Australian mathematics curriculum on fractions were used as core elements to design three computer games. In each game, the concepts were presented in the form of tangible puzzles, ...customized to a difficulty level based on student capability. The games were integrated into a single virtual game world, and a fantasy story was used to help build a compelling experience. Five Year 6 classes were used to evaluate the game over four weeks. Three of the classes were provided with the games, and two served as a control. Both the intervention and control groups also covered fractions in class as part of the regular teaching program, consisting of instructor led content combined with access to online resources and activities. Participants completed a diagnostic test before the trial, and again at the end, designed to assess competence in the fractions concepts targeted by the game. Results show that on average students who had access to the game in addition to the regular teaching scored higher than control group students. In particular, looking at just students who started with a lower level of fractions skills, greater improvement was seen in those that had access to the game.
Lay description
What is already known about this topic:
Fractions is considered both a challenge to teach, as well as a challenge for most students to learn.
There is a lack of studies evaluating game‐based fractions learning in terms of its impact on improving skills.
What this paper adds:
We have created a set of fractions games which cover several fractions concepts from year four to seven in the Australian curriculum.
The integration of the games into a standard year six fractions teaching program for four weeks was evaluated against the teaching program without the game.
Prior to the game being introduced, a targeted fractions test showed no significant difference between the average score of students who were to be exposed to the game and students in the control group.
After the four‐week intervention, students who had access to the game achieved on average higher scores on a targeted fractions test as compared to students in the control group.
Implications for practice and/or policy:
Including the developed set of games in a normal classroom teaching program can help increase the skills of the students.
Traditional lessons on fractions can be augmented with computer games that pose the concepts in a concrete setting rather than replicate the traditional pen and paper testing instrument format.
Eclipsing binaries remain crucial objects for our understanding of the universe. In particular, those that are components of multiple systems can help us solve the problem of the formation of these ...systems. Analysis of the radial velocities together with the light curve produced for the first time precise physical parameters of the components of the multiple systems V773 Cas, QS Aql, and BR Ind. Their visual orbits were also analyzed, which resulted in slightly improved orbital elements. What is typical for all these systems is that their most dominant source is the third distant component. The system V773 Cas consists of two similar G1-2V stars revolving in a circular orbit and a more distant component of the A3V type. Additionally, the improved value of parallax was calculated to be 17.6 mas. Analysis of QS Aql resulted in the following: the inner eclipsing pair is composed of B6V and F1V stars, and the third component is of about the B6 spectral type. The outer orbit has high eccentricity of about 0.95, and observations near its upcoming periastron passage between the years 2038 and 2040 are of high importance. Also, the parallax of the system was derived to be about 2.89 mas, moving the star much closer to the Sun than originally assumed. The system BR Ind was found to be a quadruple star consisting of two eclipsing K dwarfs orbiting each other with a period of 1.786 days; the distant component is a single-lined spectroscopic binary with an orbital period of about 6 days. Both pairs are moving around each other on their 148 year orbit.
We present a catalogue of the Transiting Exoplanet Survey Satellite (TESS) targets that show multiple eclipses. In all of these stars, we detected two sets of eclipses, for which their two ...distinctive periods can be derived. These multiple stellar systems could either be doubly eclipsing quadruples or triple-star coplanar systems showing eclipses on the outer orbit in addition to the inner eclipses. In total, 116 systems were found to be doubly eclipsing, while 25 stars were identified as triply eclipsing triples. Several confirmed blends of two close sources were not included in our analysis. All these systems were identified by scanning the known eclipsing systems taken from the Variable Star Index database and checking their TESS light curves. The average period of the dominant pair, pair A, is 2.7 days in our sample, while for the second pair, pair B, the average period is 5.3 days. Several systems show evident eclipse timing variation (ETV) changes even from the short interval of the TESS data, indicating possible period changes and short mutual orbit. We also present evidence that the system V0871 Cen is probably a septuple-star system of architecture (Aa-Ab)-B-C-D. Most of the presented systems are adequately bright and show deep enough eclipses for observing, and therefore we call for new ground-based observations for these extremely interesting multiples. Owing to this motivation, we have included also the ephemerides for both pairs of each system, our catalogue also contains their depths of eclipses and the light-curve shapes as extracted from the TESS data. These new ground-based observations would be very useful for further derivation of the mutual movement of both pairs on their orbit via detection of the ETVs of both pairs for example.
We report the very first analysis of 27 eclipsing binary systems with high eccentricities that sometimes reach up to 0.8. The orbital periods for these systems range from 1.4 to 37 days, and the ...median of the sample is 10.3 days. Star CzeV3392 (= UCAC4 623 022784), for example, currently is the eclipsing system with the highest eccentricity (
e
= 0.22) of stars with a period shorter than 1.5 days. We analysed the light curves of all 27 systems and obtained the physical parameters of both components, such as relative radii, inclinations, or relative luminosities. The most important parameters appear to be the derived periods and eccentricities. They allow constructing the period–eccentricity diagram. This eccentricity distribution is used to study the tidal circularisation theories. Many systems have detected third-light contributions, which means that the Kozai-Lidov cycles might also be responsible for the high eccentricities in some of the binaries.
Background
The presence of myocardial fibrosis is associated with adverse outcome in dilated cardiomyopathy (DCM). Delayed contrast-enhanced cardiac magnetic resonance (DE-CMR) currently represents ...the gold standard in noninvasive evaluation of myocardial scarring. However, a significant number of patients are unable to undergo DE-CMR study for various reasons. We sought to determine the diagnostic accuracy of cardiac CT (CCT) compared with CMR in the investigation of the presence of delayed contrast enhancement (DCE) in subjects with DCM.
Methods
We prospectively enrolled 17 consecutive patients with DCM, who were initially referred to our institution because of recently manifested heart failure due to unexplained left ventricular systolic dysfunction. In all subjects, CCT and DE-CMR were performed within 1 week.
Results
CCT and DE-CMR showed satisfactory agreement in detecting DCE (agreement in 82% cases, κ = 0.56) with 50% sensitivity, 100% specificity, and a positive predictive value of 100%.
Conclusion
CCT may be a valuable method for detecting DCE in patients with DCM. CCT thus might be considered as an alternative method to DE-CMR in the assessment of the presence and extent of myocardial fibrosis in subjects who are not suitable for DE-CMR examination.
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