391 research outputs found
The role of hand size in body representation:a developmental investigation
Knowledge of one’s own body size is a crucial facet of body representation, both for acting on the environment and perhaps also for constraining body ownership. However, representations of body size may be somewhat plastic, particularly to allow for physical growth in childhood. Here we report a developmental investigation into the role of hand size in body representation (the sense of body ownership, perception of hand position, and perception of own-hand size). Using the rubber hand illusion paradigm, this study used different fake hand sizes (60%, 80%, 100%, 120% or 140% of typical size) in three age groups (6- to 7-year-olds, 12- to 13-year-olds, and adults; N = 229). We found no evidence that hand size constrains ownership or position: participants embodied hands which were both larger and smaller than their own, and indeed judged their own hands to have changed size following the illusion. Children and adolescents embodied the fake hands more than adults, with a greater tendency to feel their own hand had changed size. Adolescents were particularly sensitive to multisensory information. In sum, we found substantial plasticity in the representation of own-body size, with partial support for the hypothesis that children have looser representations than adults.</p
Questions to Ask Before You Join a Club
Despite the recent flurry of large transactions in which a consortium of private equity firms have teamed up to make joint bids and acquisitions, “club deals” themselves are not breaking news. In fact, they have been a staple of small- and middle-sized private equity M&A transactions for years. Recently, however, there has been a growing trend toward large club deals with enterprise values over $1 billion.1 Due to their size, complexity and, often, international dimension, these transactions have generated considerable attention in the business press and have prompted much discussion among private equity professionals and the limited partners whose money they manage
Questions to Ask Before You Join a Club
Despite the recent flurry of large transactions in which a consortium of private equity firms have teamed up to make joint bids and acquisitions, “club deals” themselves are not breaking news. In fact, they have been a staple of small- and middle-sized private equity M&A transactions for years. Recently, however, there has been a growing trend toward large club deals with enterprise values over $1 billion.1 Due to their size, complexity and, often, international dimension, these transactions have generated considerable attention in the business press and have prompted much discussion among private equity professionals and the limited partners whose money they manage
The detection of flaws in austenitic welds using the decomposition of the time reversal operator
The non-destructive testing of austenitic welds using ultrasound plays an important role in the assessment of the structural integrity of safety critical structures. The internal microstructure of these welds is highly scattering and can lead to the obscuration of defects when investigated by traditional imaging algorithms. This paper proposes an alternative objective method for the detection of flaws embedded in austenitic welds based on the singular value decomposition of the time-frequency domain response matrices. The distribution of the singular values is examined in the cases where a flaw exists and where there is no flaw present. A lower threshold on the singular values, specific to austenitic welds, is derived which, when exceeded, indicates the presence of a flaw. The detection criterion is successfully implemented on both synthetic and experimental data. The datasets arising from welds containing a flaw, are further interrogated using the decomposition of the time reversal operator (DORT) method and the total focussing method (TFM) and it is shown that images constructed via the DORT algorithm typically exhibit a higher signal to noise ratio than those constructed by the TFM algorithm
A Maximum Eigenvalue Approximation for Crack-Sizing Using Ultrasonic Arrays
Ultrasonic phased array systems are becoming increasingly popular as tools for the inspection of safety-critical structures with in the non-destructive testing industry. The datasets captured by these arrays can be used to image the internal microstructure of individual components, all owing the location and nature of any defects to be deduced. Unfortunately, many of the current imaging algorithms require an arbitrary threshold at which the defect measurements can be taken and this aspect of subjectivity can lead to varying characterisations of a flaw between different operators. This paper puts forward an objective approach based on the Kirchoff scattering model and the approximation of the resulting scattering matrices by Toeplitz matrices. A mathematical expression relating the crack size to the maximum eigenvalue of the associated scattering matrix is thus derived. The formula is analysed numerically to assess its sensitivity to the system parameters and it is shown that the method is most effective for sizing defects that are commensurate with the wavelength of the ultrasonic wave (or just smaller than. The method is applied to simulated FMC data arising from finite element calculations where the crack length to wavelength ratios range between 0.6 and 1.8. The recovered objective crack size exhibits an error of 12%
Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration
BACKGROUND:
Progressive neuron loss in the frontal and temporal lobes of the cerebral cortex typifies frontotemporal lobar degeneration (FTLD). FTLD sub types are classified on the basis of neuronal aggregated protein deposits, typically containing either aberrantly phosphorylated TDP-43 or tau. Our recent work demonstrated that tau tubulin kinases 1 and 2 (TTBK1/2) robustly phosphorylate TDP-43 and co-localize with phosphorylated TDP-43 in human postmortem neurons from FTLD patients. Both TTBK1 and TTBK2 were initially identified as tau kinases and TTBK1 has been shown to phosphorylate tau epitopes commonly observed in Alzheimer's disease and other tauopathies.
METHODS:
To further elucidate how TTBK1/2 activity contributes to both TDP-43 and tau phosphorylation in the context of the neurodegeneration seen in FTLD, we examined the consequences of elevated human TTBK1/2 kinase expression in transgenic animal models of disease.
RESULTS:
We show that C. elegans co-expressing tau/TTBK1 tau/TTBK2, or TDP-43/TTBK1 transgenes in combination exhibit synergistic exacerbation of behavioral abnormalities and increased pathological protein phosphorylation. We also show that C. elegans co-expressing tau/TTBK1 or tau/TTBK2 transgenes in combination exhibit aberrant neuronal architecture and neuron loss. Surprisingly, the TTBK2/TDP-43 transgenic combination showed no exacerbation of TDP-43 proteinopathy related phenotypes. Additionally, we observed elevated TTBK1/2 protein expression in cortical and hippocampal neurons of FTLD-tau and FTLD-TDP cases relative to normal controls.
CONCLUSIONS:
Our findings suggest a possible etiology for the two most common FTLD subtypes through a kinase activation driven mechanism of neurodegeneration
Enhancing learning through the use of animals in undergraduate biology teaching: the student voice
The way in which society views the use of animals in university learning and teaching has changed dramatically in the last 30 years. A review of the literature shows that those who support the use of animals in teaching and learning counter arguments for effective alternative teaching strategies on the basis that in some situations there are no alternatives which provide the same skills and experiences. Debate by teachers and animal welfare advocates about the pros and cons of using animals in learning and teaching is widespread in the published literature, nationally and internationally, but rarely gives the students themselves a voice.
A case study, based on a survey of students at three Australian universities, explored student perspectives on the use of animals in learning and teaching. The results show that biology students appreciate the authenticity of such experiences and the consolidation of theoretical learning, and the chance to tap into multiple learning modes using hands on experiences. In particular, students see the benefits of such experiences improving not only their understanding of biological concepts and opportunities for future employment, but also their awareness of the ethics of working with animals, which has direct relevance to Science Threshold Learning Outcome 5
Applicant Reactions to the AAMC Standardized Video Interview During the 2018 Application Cycle
PURPOSE: This study examined applicant reactions to the Association of American Medical Colleges (AAMC) Standardized Video Interview (SVI) during its first year of operational use in emergency medicine (EM) residency program selection in order to identify strategies to improve applicants\u27 SVI experience and attitudes.
METHOD: Individuals who self-classified as EM applicants applying in the Electronic Residency Application Service 2018 cycle and completed the SVI in summer 2017 were invited to participate in two surveys. Survey 1, which focused on procedural issues, was administered immediately after SVI completion. Survey 2, which focused on applicants\u27 SVI experience, was administered in fall 2017, after SVI scores were released.
RESULTS: The response rates for surveys 1 and 2 were 82.3% (2,906/3,532) and 58.7% (2,074/3,532), respectively. Applicant reactions varied by aspect of the SVI studied and their SVI total scores. Most applicants were satisfied with most procedural aspects of the SVI, but most applicants were not satisfied with the SVI overall or with their total SVI scores. About 20-30% of applicants had neutral opinions about most aspects of the SVI. Negative reactions to the SVI were stronger for applicants who scored lower on the SVI.
CONCLUSIONS: Applicants had generally negative reactions to the SVI. Most were skeptical of its ability to assess the target competencies and its potential to add value to the selection process. Applicant acceptance and appreciation of the SVI will be critical to the SVI\u27s acceptance by the graduate medical education community
The AAMC Standardized Video Interview: Reactions and Use by Residency Programs During the 2018 Application Cycle
PURPOSE: To evaluate how emergency medicine (EM) residency programs perceived and used Association of American Medical Colleges (AAMC) SVI total scores and videos during the Electronic Residency Application Service (ERAS) 2018 cycle.
METHOD: Study 1 (November 2017) used a program director survey to evaluate user reactions to the SVI following the first year of operational use. Study 2 (January 2018) analyzed program usage of SVI video responses using data collected through the AAMC Program Director\u27s Workstation.
RESULTS: Results from the survey (125/175 programs, 71% response rate) and video usage analysis suggested programs viewed videos out of curiosity and to understand the range of SVI total scores. Programs were more likely to view videos for attendees of U.S. MD-granting medical schools and applicants with higher United States Medical Licensing Examination Step 1 scores, but there were no differences by gender or race/ethnicity. More than half of programs that did not use SVI total scores in their selection processes were unsure of how to incorporate them (36/58, 62%) and wanted additional research on utility (33/58, 57%). More than half of programs indicated being at least somewhat likely to use SVI total scores (55/97; 57%) and videos (52/99; 53%) in the future.
CONCLUSIONS: Program reactions on the utility and ease of use of SVI total scores were mixed. Survey results indicate programs used the SVI cautiously in their selection processes, consistent with AAMC recommendations. Future surveys of SVI users will help the AAMC gauge improvements in user acceptance and familiarity with the SVI
The phosphatase calcineurin regulates pathological TDP-43 phosphorylation
Detergent insoluble inclusions of TDP-43 protein are hallmarks of the neuropathology in over 90% of amyotrophic lateral sclerosis (ALS) cases and approximately half of frontotemporal dementia (FTLD-TDP) cases. In TDP-43 proteinopathy disorders, lesions containing aggregated TDP-43 protein are extensively post-translationally modified, with phosphorylated TDP-43 (pTDP) being the most consistent and robust marker of pathological TDP-43 deposition. Abnormally phosphorylated TDP-43 has been hypothesized to mediate TDP-43 toxicity in many neurodegenerative disease models. To date several different kinases have been implicated in the genesis of pTDP, but no phosphatases have been shown to reverse pathological TDP-43 phosphorylation. We have identified the phosphatase calcineurin as an enzyme binding to and catalyzing the removal of pathological C-terminal phosphorylation of TDP-43 in vitro. In C. elegans models of TDP-43 proteinopathy, genetic elimination of calcineurin results in accumulation of excess pTDP, exacerbated motor dysfunction, and accelerated neurodegenerative changes. In cultured human cells, treatment with FK506 (tacrolimus), a calcineurin inhibitor, results in accumulation of pTDP species. Lastly, calcineurin co-localizes with pTDP in degenerating areas of the central nervous system in subjects with FTLD-TDP and ALS. Taken together these findings suggest calcineurin acts on pTDP as a phosphatase in neurons. Furthermore, patient treatment with calcineurin inhibitors may have unappreciated adverse neuropathological consequences
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