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Accessibility of 3D Game Environments for People with Aphasia: An Exploratory Study
People with aphasia experience difficulties with all aspects of language and this can mean that their access to technology is substantially reduced. We report a study undertaken to investigate the issues that confront people with aphasia when interacting with technology, specifically 3D game environments. Five people with aphasia were observed and interviewed in twelve workshop sessions. We report the key themes that emerged from the study, such as the importance of direct mappings between usersâ interactions and actions in a virtual environment. The results of the study provide some insight into the challenges, but also the opportunities, these mainstream technologies offer to people with aphasia. We discuss how these technologies could be more supportive and inclusive for people with language and communication difficulties
Targeting trisomic treatments: optimizing Dyrk1a inhibition to improve Down syndrome deficits
Overexpression of Dualâspecificity tyrosineâphosphorylated regulated kinase 1A (DYRK1A), located on human chromosome 21, may alter molecular processes linked to developmental deficits in Down syndrome (DS). Trisomic DYRK1A is a rational therapeutic target, and although reductions in Dyrk1a genetic dosage have shown improvements in trisomic mouse models, attempts to reduce Dyrk1a activity by pharmacological mechanisms and correct these DSâassociated phenotypes have been largely unsuccessful. Epigallocatechinâ3âgallate (EGCG) inhibits DYRK1A activity in vitro and this action has been postulated to account for improvement of some DSâassociated phenotypes that have been reported in preclinical studies and clinical trials. However, the beneficial effects of EGCG are inconsistent and there is no direct evidence that any observed improvement actually occurs through Dyrk1a inhibition. Inconclusive outcomes likely reflect a lack of knowledge about the tissueâspecific patterns of spatial and temporal overexpression and elevated activity of Dyrk1a that may contribute to emerging DS traits during development. Emerging evidence indicates that Dyrk1a expression varies over the life span in DS mouse models, yet preclinical therapeutic treatments targeting Dyrk1a have largely not considered these developmental changes. Therapies intended to improve DS phenotypes through normalizing trisomic Dyrk1a need to optimize the timing and dose of treatment to match the spatiotemporal patterning of excessive Dyrk1a activity in relevant tissues. This will require more precise identification of developmental periods of vulnerability to enduring adverse effects of elevated Dyrk1a, representing the concurrence of increased Dyrk1a expression together with hypothesized tissueâspecificâsensitive periods when Dyrk1a regulates cellular processes that shape the longâterm functional properties of the tissue. Future efforts targeting inhibition of trisomic Dyrk1a should identify these putative spatiotemporally specific developmental sensitive periods and determine whether normalizing Dyrk1a activity then can lead to improved outcomes in DS phenotypes
Neutron-proton analyzing power at 12 MeV and inconsistencies in parametrizations of nucleon-nucleon data
We present the most accurate and complete data set for the analyzing power
Ay(theta) in neutron-proton scattering. The experimental data were corrected
for the effects of multiple scattering, both in the center detector and in the
neutron detectors. The final data at En = 12.0 MeV deviate considerably from
the predictions of nucleon-nucleon phase-shift analyses and potential models.
The impact of the new data on the value of the charged pion-nucleon coupling
constant is discussed in a model study.Comment: Six pages, four figures, one table, to be published in Physics
Letters
HFPK 334: An unusual Supernova Remnant in the Small Magellanic Cloud
We present new Australia Telescope Compact Array (ATCA) radio-continuum and
XMM-Newton/Chandra X-ray Observatory (CXO) observations of the unusual
supernova remnant HFPK 334 in the Small Magellanic Cloud (SMC). The remnant
follows a shell type morphology in the radio-continuum and has a size of
20~pc at the SMC distance. The X-ray morphology is similar, however, we
detect a prominent point source close to the center of the SNR exhibiting a
spectrum with a best fit powerlaw with a photon index of . This central point source is most likely a background object and cannot
be directly associated with the remnant. The high temperature, nonequilibrium
conditions in the diffuse region suggest that this gas has been recently
shocked and point toward a younger SNR with an age of years.
With an average radio spectral index of we find that an
equipartition magnetic field for the remnant is 90~G, a value
typical of younger SNRs in low-density environments. Also, we report detection
of scattered radio polarisation across the remnant at 20~cm, with a peak
fractional polarisation level of 255\%.Comment: 19 pages, 6-figures, submitted to A
Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model
Down syndrome (DS) or Trisomy 21 causes intellectual disabilities in humans and the Ts65Dn DS mouse model is deficient in learning and memory tasks. DYRK1A is triplicated in DS and Ts65Dn mice. Ts65Dn mice were given up to ~ 20 mg/kg/day epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, or water beginning on postnatal day 24 and continuing for three or seven weeks, and were tested on a series of behavioral and learning tasks, including a novel balance beam test. Ts65Dn as compared to control mice exhibited higher locomotor activity, impaired novel object recognition, impaired balance beam and decreased spatial learning and memory. Neither EGCG treatment improved performance of the Ts65Dn mice on these tasks. Ts65Dn mice had a non-significant increase in Dyrk1a activity in the hippocampus and cerebellum. Given the translational value of the Ts65Dn mouse model, further studies will be needed to identify the EGCG doses (and mechanisms) that may improve cognitive function
Silicon photomultiplier arrays - a novel photon detector for a high resolution tracker produced at FBK-irst, Italy
A silicon photomultiplier (SiPM) array has been developed at FBK-irst having
32 channels and a dimension of 8.0 x 1.1 mm^2. Each 250 um wide channel is
subdivided into 5 x 22 rectangularly arranged pixels. These sensors are
developed to read out a modular high resolution scintillating fiber tracker.
Key properties like breakdown voltage, gain and photon detection efficiency
(PDE) are found to be homogeneous over all 32 channels of an SiPM array. This
could make scintillating fiber trackers with SiPM array readout a promising
alternative to available tracker technologies, if noise properties and the PDE
are improved
Multivariate Concentric Square Field unveils behavioral exploratory categories of locomotor activity in mouse model of Down syndrome
poster abstractDown Syndrome (DS), trisomy 21(Ts21), is a genetic condition in which a third copy of chromosome 21 is present, and results in neurodevelopmental deficits including intellectual disability. DS has been modeled in mice; Ts65Dn mouse model displays many of the phenotypes associated with DS, including cognitive deficits. We previously studied behavioral phenotypes of Ts65Dn mice and observed significantly increased locomotor activity in a novel arena (an âopen fieldâ). In those studies, treatment of the Ts65Dn mice with ~10 mg/kg/day of epigallocatechin-3-gallate (EGCG), a selective inhibitor of the DYRK1A kinase (one of the genes implicated in the neurodevelopmental deficits in DS and in Ts65Dn mice), failed to attenuate hyperactivity. Locomotor activity in an open field is a basic measure of general exploration in a simple environment, and was only moderately sensitive to the hyperactivity of the Ts65Dn mice. The aim of the current study was to use a more advanced analysis of behavioral patterns of exploration in a more complex, multi-partitioned arena, termed the Multivariate Concentric Square Field (MCSF). The advantage of MCSF is that it provides more elaborate measures of exploratory behavior by examining different categories of exploration: general activity, exploratory activity, risk assessment, risk taking and shelter seeking behavior. Trisomic mice and euploid littermates were treated with a continuous high dose (~100 mg/kg/day) of EGCG or water (controls) beginning at weaning. At seven weeks of age, they were tested in the MCSF on two consecutive days. Our current results indicate that Ts65Dn mice displayed more exploratory behavior compared to controls, and the EGCG treatment may have normalized exploratory behavior toward that of controls. Identifying altered patterns of exploratory behavior in the Ts65Dn mouse and the normalizing effects of EGCG treatment may help provide a therapeutic approach to DS
Effects of EGCG Treatment of Ts65Dn Down Syndrome Mice on a Balance Beam Task
poster abstractDown syndrome (DS) is caused by trisomy of chromosome 21, and affects 1/700 live births. DS results in about 80 clinical phenotypes, including cognitive impairment. DYRK1A, a chromosome 21 gene, has been linked to alterations in morphology and function of the brain resulting in cognitive impairment. Epigallocatechin-3-gallate (EGCG), an inhibitor of DYRK1A activity, has been proposed as a possible treatment for cognitive deficits seen in individuals with DS. Using the Ts65Dn DS mouse model, we examined the effects of EGCG treatment on cerebellum dependent tasks using a balance beam test. We hypothesized that treatment with EGCG would improve Ts65Dn performance on the balance beam. In a first experiment, mice were given a dose of ~30 mg/kg/day EGCG, which showed no significant improvement in the balance beam task. In a second experiment, mice were given a dose of 100 mg/kg/day EGCG or water (control) starting at 3 weeks of age. The mice were handled two days before testing and then underwent a series of behavioral tasks including the balance beam test. The mice traversed three beams of differing widths (12, 9 and 6 mm), and three consecutive trials for each were recorded for further analysis. The balance beam recordings were scored by three independent scorers, blind to genotype and treatment, and the number of hind paw slips for each trial were scored. Our preliminary results indicate that the Ts65Dn mice are impaired at this task and have more hind paw slips compared to euploid controls. A larger number of animals should help to distinguish any differences in Ts65Dn mice due to EGCG treatment
Can Epigallocatechin gallate (EGCG) Treatment Rescue Hippocampal-Dependent Cognitive Function in a Down Syndrome Mouse Model?
poster abstractDown Syndrome (DS) is caused by the trisomy of human chromosome 21 (Hsa21).
Trisomy 21 can cause various behavioral, cognitive, learning and memory deficits.
Deficits in hippocampal structure and function have been identified in mouse
models of DS and are implicated in cognitive and learning impairments. Mouse
models have suggested that deficits in cognitive function are associated with
overexpression of Dyrk1a, a gene on Hsa21 found in three copies of individuals with
DS. Dyrk1a is a gene that is involved in brain development and function. Ts65Dn DS
model mice exhibit trisomy for approximately half of the genes on Hsa21 including
Dyrk1a and exhibit cognitive and learning impairments. We are using Ts65Dn mice
to test the effects of Epigallocatechin gallate (EGCG), a Dyrk1a inhibitor, on Dyrk1a
activity and cognitive function. We hypothesize that EGCG will reduce Dyrk1a
activity in the hippocampus and improve hippocampal-dependent spatial learning
and memory in the Morris water maze place learning task in Ts65Dn mice. The mice
were given daily EGCG treatment (200 mg/kg per day) by means of oral gavage
beginning on postnatal day 54 and continuing throughout water maze testing
(postnatal days 67-74). Measures of spatial learning included latency and path
length to find a submerged platform during acquisition trials (postnatal days 67-73).
Memory for the previously learned location of the platform was assessed on a probe
trial (postnatal day 74) in which the platform was removed and the amount of time
spent swimming in the area of the tank previously containing the platform was
measured. These measures allowed us to analyze the miceâs ability to learn and
remember the position of the platform and to spatially orient themselves.
Preliminary data indicates that EGCG treatment may not be an effective treatment
for the spatial learning and memory deficits evident in this mouse model of DS
Correction of cerebellar movement related deficits by normalizing Dyrk1a copy number in the Ts65Dn mouse model for Down syndrome
poster abstractElucidation of the underlying mechanisms involved in brain related deficits of
Down syndrome (DS) would be useful for consideration of therapeutic interventions.
Several DSspecific phenotypes have been hypothesized to be linked to altered
expression or function of specific trisomic genes. One such gene of interest is D YRK1A ,
which has been implicated in behavioral functions of the hippocampus and cerebellum.
The Ts65Dn mouse model for DS includes a triplication of D yrk1a in addition to a
triplication of >100 other human chromosome 21 mouse orthologs. To evaluate the role
of D yrk1a in cerebellar function, we have genetically normalized the D yrk1a copy
number in otherwise trisomicTs65Dn mice and reduced D yrk1a copy number in
otherwise euploid mice (2N) for a total of 3 alternative genetic doses of D yrk1a:
EuploidDyrk1a +/+ , EuploidDyrk1a +/, Ts65DnDyrk1a +/+/+ , and Ts65DnDyrk1a +/+/. Cerebellar movementrelated function in these knockdown models is being assessed through a novel behavioral balance beam task. Additionally, levels of D yrk1a activity in the cerebellum for all genotypes were analyzed by HPLC. We have previously demonstrated that Ts65DnDyrk1a +/+/+ mice perform worse in the balance beam task in comparison to EuploidDyrk1a +/+ mice. Preliminary results of the current study do not indicate such a difference among Ts65DnDyrk1a +/+/+ mice in comparison to EuploidDyrk1a +/+ mice. We hypothesize that the lack of replication of the previous findings may be due to differences in postweaning housing environments. Mice in the previous study were singlehoused, whereas mice in the present study were grouphoused, which may help mitigate motor deficits in the trisomic mice. Additionally, current trends display a deficit in balance beam performance of both the EuploidDyrk1a +/and the Ts65DnDyrk1a +/+/groups, which suggests that reducing the copy number of D yrk1a by one may have detrimental effects on motor coordination.
Concomitant analysis of the balance beam performances and Dyrk1a activity levels may
indicate the sensitivity of the balance beam task to assess the role Dyrk1a activity in
cerebellar function
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