Pitch perception at very high frequencies: On psychometric functions and integration of frequency information.

Lau et al. [J. Neurosci. 37, 9013-9021 (2017)] showed that discrimination of the fundamental frequency (F0) of complex tones with components in a high-frequency region was better than predicted from the optimal combination of information from the individual harmonics. The predictions depend on the assumption that psychometric functions for frequency discrimination have a slope of 1 at high frequencies. This was tested by measuring psychometric functions for F0 discrimination and frequency discrimination. Difference limens for F0 (F0DLs) and difference limens for frequency for each frequency component were also measured. Complex tones contained harmonics 6-10 and had F0s of 280 or 1400 Hz. Thresholds were measured using 210-ms tones presented diotically in diotic threshold-equalizing noise (TEN), and 1000-ms tones presented diotically in dichotic TEN. The slopes of the psychometric functions were close to 1 for all frequencies and F0s. The ratio of predicted to observed F0DLs was around 1 or smaller for both F0s, i.e., not super-optimal, and was significantly smaller for the low than for the high F0. The results are consistent with the idea that place information alone can convey pitch, but pitch is more salient when phase-locking information is available

Stretch-Orientation of LaRC(TM) RP 50 Polyimide Film

An addition-curable poly(amic acid) film was subjected to various thermal pretreatments and then to uniaxial or biaxial drawing. Hot-stretching to 300% of the initial length produced better than twofold increases in tensile modulus and strength of partially-cured films. Most of the improvement was maintained upon completion of the curing at constant length

Characterisation and application of a bovine U6 promoter for expression of short hairpin RNAs

BackgroundThe use of small interfering RNA (siRNA) molecules in animals to achieve double-stranded RNA-mediated interference (RNAi) has recently emerged as a powerful method of sequence-specific gene knockdown. As DNA-based expression of short hairpin RNA (shRNA) for RNAi may offer some advantages over chemical and in vitro synthesised siRNA, a number of vectors for expression of shRNA have been developed. These often feature polymerase III (pol. III) promoters of either mouse or human origin.ResultsTo develop a shRNA expression vector specifically for bovine RNAi applications, we identified and characterised a novel bovine U6 small nuclear RNA (snRNA) promoter from bovine sequence data. This promoter is the putative bovine homologue of the human U6-8 snRNA promoter, and features a number of functional sequence elements that are characteristic of these types of pol. III promoters. A PCR based cloning strategy was used to incorporate this promoter sequence into plasmid vectors along with shRNA sequences for RNAi. The promoter was then used to express shRNAs, which resulted in the efficient knockdown of an exogenous reporter gene and an endogenous bovine gene.ConclusionWe have mined data from the bovine genome sequencing project to identify a functional bovine U6 promoter and used the promoter sequence to construct a shRNA expression vector. The use of this native bovine promoter in shRNA expression is an important component of our future development of RNAi therapeutic and transgenic applications in bovine species.<br /

Are Newly Discovered HI High Velocity Clouds Minihalos in the Local Group?

A set of HI sources extracted from the north Galactic polar region by the ongoing ALFALFA survey has properties that are consistent with the interpretation that they are associated with isolated minihalos in the outskirts of the Local Group (LG). Unlike objects detected by previous surveys, such as the Compact High Velocity Clouds of Braun & Burton (1999), the HI clouds found by ALFALFA do not violate any structural requirements or halo scaling laws of the LambdaCDM structure paradigm, nor would they have been detected by extant HI surveys of nearby galaxy groups other than the LG. At a distance of d Mpc, their HI masses range between $5 x 10^4 d^2 and 10^6 d^2 solar and their HI radii between <0.4d and 1.6 d kpc. If they are parts of gravitationally bound halos, the total masses would be on order of 10^8--10^9 solar, their baryonic content would be signifcantly smaller than the cosmic fraction of 0.16 and present in a ionized gas phase of mass well exceeding that of the neutral phase. This study does not however prove that the minihalo interpretation is unique. Among possible alternatives would be that the clouds are shreds of the Leading Arm of the Magellanic Stream.Comment: 4 pages, 3 figures, 1 table; to appear Ap.J. Letter

Early cell loss associated with mesenchymal stem cell cardiomyoplasty

Background: Human mesenchymal stem cells (hMSCs) show potential for therapeutic cellular cardiomyoplasty. However, a range of delivery methods, including direct intramyocardial injection, have resulted in poor engraftment in vivo. We used the in vivo rat heart model to study hMSC engraftment and retention in a normal beating heart. Materials and Methods: HMSCs transfected with green fluorescent protein were injected into the left ventricle (LV) of immunocompetent rats. Hearts were cryopreserved 30 minutes (Group A), 24 hours (Group B), and 5 days (Group C) post hMSC delivery. HMSC retention was estimated using confocal fluorescence microscopy and immunohistochemistry. Measured values were compared to projected GFP-positive cellular volumes. Immunohistochemical analyses probed for the presence of human cells with human prolyl hydroxylase beta (p4hβ) and an immune response with murine monocyte/macrophage antigen (CD68). Results: HMSC retention decreased significantly from 30 minutes to 5 days (p<0.05). In Group A the projected GFP positive cellular volume of 31% correlated with measured values and was significantly greater than the 1% predicted cellular volume in Group C. Moreover, human p4hβ was detected in Groups A and B, and not in Group C. Conversely, CD68 was detected in Groups B and C and not in Group A. Conclusions: In immunocompetent rats, engraftment and retention of hMSCs delivered intramyocardially significantly declines over a five day period. The influx of monocytes/macrophages suggests an unfavorable micro-environment for exogenous stem cell survival, confirmed by the absence of human cells detected five days post injection

Duplex ultrasound in aneurysm surveillance following endovascular aneurysm repair: a comparison with computed tomography aortography

ObjectivesCumulative radiation dose, cost, and increased demand for computed tomography aortography (CTA) suggest that duplex ultrasonography (DU) may be an alternative to CTA-based surveillance. We compared CTA with DU during endovascular aneurysm repair (EVAR) follow-up.MethodsPatients undergoing EVAR had clinical and radiological follow-up data entered in a prospectively maintained database. For the purpose of this study, the gold standard test for endoleak detection was CTA, and an endoleak detected on DU alone was assumed to be a false positive result. DU interpretation was performed independently of CTA and vice versa.ResultsOne hundred thirty-two patients underwent EVAR, of whom 117 attended for follow-up ranging from six months to nine years (mean, 32 months). Adequate aneurysm sac visualisation on DU was not possible in 1.7% of patients, predominantly due to obesity. Twenty-eight endoleaks were detected in 28 patients during follow-up. Of these, 24 were initially identified on DU (four false negative DU examinations), and eight had at least one negative CTA with a positive DU prior to diagnosis. Twenty-three endoleaks were type II in nature and three of these patients had increased sac size. There was one type I and four type III endoleaks. Two of these (both type III) had an increased sac size. Of 12 patients with increased aneurysm size of 5 mm or more at follow-up, five had an endoleak visible on DU, yet negative CTA and a further five had endoleak visualisation on both DU and CTA. Of six endoleaks which underwent re-intervention, all were initially picked up on DU. One of these endoleaks was never demonstrated on CTA and a further two had at least one negative CTA prior to endoleak confirmation. Positive predictive value for DU was 45% and negative predictive value 94%. Specificity of DU for endoleak detection was 67% when compared with CTA, because of the large number of false positive DU results. Sensitivity for DU was 86%, with all clinically significant endoleaks demonstrated on CTA also detected on DU.ConclusionDespite its low positive predictive value, we found DU to be a sensitive test for the detection of clinically significant endoleaks. Given concerns about cumulative radiation exposure and cost, and the surprisingly low sensitivity of CTA for endoleak detection in this series, selective CTA based on DU surveillance may be a more appropriate long-term strategy

An Intron 7 Polymorphism in APP Affects the Age of Onset of Dementia in Down Syndrome

People with Down syndrome (DS) develop Alzheimer's disease (AD) with an early age of onset. A tetranucleotide repeat, attt5−8, in intron 7 of the amyloid precursor protein has been associated with the age of onset of AD in DS in a preliminary study. The authors examine the impact of this polymorphism in a larger cohort of individuals with DS. Adults with DS were genotyped for attt5−8 and APOE. The results were analysed with respect to the age of onset of dementia. The presence of three copies of the six-repeat allele resulted in onset of dementia seven years earlier than in the presence of other genotypes. Further study is essential to elucidate the mechanism by which this polymorphism functions, with an exciting opportunity to identify novel treatment targets relevant for people with DS and AD