2,819 research outputs found
A Human Islet Cell-Culture System for High-Throuput screening.
A small-molecule inducer of beta-cell proliferation in human islets represents a potential regeneration strategy for treating type 1 diabetes. However, the lack of suitable human beta cell lines makes such a discovery a challenge. Here, we adapted an islet cell culture system to high-throughput screening to identify such small molecules. We prepared microtiter plates containing extracellular matrix from a human bladder carcinoma cell line. Dissociated human islets were seeded onto these plates, cultured for up to 7 days, and assessed for proliferation by simultaneous Ki67 and C-peptide immunofluorescence. Importantly, this environment preserved beta-cell physiological function, as measured by glucose-stimulated insulin secretion. Adenoviral overexpression of cdk-6 and cyclin D(1), known inducers of human beta cell proliferation, was used as a positive control in our assay. This induction was inhibited by cotreatment with rapamycin, an immunosuppressant often used in islet transplantation. We then performed a pilot screen of 1280 compounds, observing some phenotypic effects on cells. This high-throughput human islet cell culture method can be used to assess various aspects of beta-cell biology on a relatively large number of compounds
Single and two-particle energy gaps across the disorder-driven superconductor-insulator transition
The competition between superconductivity and localization raises profound
questions in condensed matter physics. In spite of decades of research, the
mechanism of the superconductor-insulator transition (SIT) and the nature of
the insulator are not understood. We use quantum Monte Carlo simulations that
treat, on an equal footing, inhomogeneous amplitude variations and phase
fluctuations, a major advance over previous theories. We gain new microscopic
insights and make testable predictions for local spectroscopic probes. The
energy gap in the density of states survives across the transition, but
coherence peaks exist only in the superconductor. A characteristic pseudogap
persists above the critical disorder and critical temperature, in contrast to
conventional theories. Surprisingly, the insulator has a two-particle gap scale
that vanishes at the SIT, despite a robust single-particle gap.Comment: 7 pages, 5 figures (plus supplement with 4 pages, 5 figures
Vibrotactile pedals : provision of haptic feedback to support economical driving
The use of haptic feedback is currently an underused modality in the driving environment, especially with respect to vehicle manufacturers. This exploratory study evaluates the effects of a vibrotactile (or haptic) accelerator pedal on car driving performance and perceived workload using a driving simulator. A stimulus was triggered when the driver exceeded a 50% throttle threshold, past which is deemed excessive for economical driving. Results showed significant decreases in mean acceleration values, and maximum and excess throttle use when the haptic pedal was active as compared to a baseline condition. As well as the positive changes to driver behaviour, subjective workload decreased when driving with the haptic pedal as compared to when drivers were simply asked to drive economically. The literature suggests that the haptic processing channel offers a largely untapped resource in the driving environment, and could provide information without overloading the other attentional resource pools used in driving
Spontaneous retropharyngeal haematoma: a case report
<p>Abstract</p> <p>Introduction</p> <p>Spontaneous retropharyngeal haematoma is an unusual condition. It has multiple aetiological factors and can present to a number of specialists including the otolaryngologist.</p> <p>Case presentation</p> <p>We describe a case of spontaneous retropharyngeal haematoma which demonstrates the dramatic presentation and emphasises the need for a conservative approach.</p> <p>Conclusion</p> <p>It is important to be aware of this unusual condition with its distinct presentation. Surgical intervention should be resisted unless a treatable aetiological factor is found or airway compromise occurs. Most cases will resolve with conservative management.</p
Phonon-assisted radiofrequency absorption by gold nanoparticles resulting in hyperthermia
It is suggested that in gold nanoparticles (GNPs) of about 5 nm sizes used in
the radiofrequency (RF) hyperthermia, an absorption of the RF photon by the
Fermi electron occurs with involvement of the longitudinal acoustic vibrational
mode (LAVM), the dominating one in the distribution of vibrational density of
states (VDOS). This physical mechanism helps to explain two observed phenomena:
the size dependence of the heating rate (HR) in GNPs and reduced heat
production in aggregated GNPs. The argumentation proceeds within the
one-electron approximation, taking into account the discretenesses of energies
and momenta of both electrons and LAVMs. The heating of GNPs is thought to
consist of two consecutive processes: first, the Fermi electron absorbs
simultaneously the RF photon and the LAVM available in the GNP; hereafter the
excited electron gets relaxed within the GNP's boundary, exciting a LAVM with
the energy higher than that of the previously absorbed LAVM. GNPs containing
the Ta and/or Fe impurities are proposed for the RF hyperthermia as promising
heaters with enhanced HRs, and GNPs with rare-earth impurity atoms are also
brought into consideration. It is shown why the maximum HR values should be
expected in GNPs with about 5-7 nm size.Comment: proceedings at the NATO Advanced Research workshop FANEM-2015 (Minsk,
May 25-27, 2015). To be published in the final form in: "Fundamental and
Applied NanoElectroMagnetics" (Springer Science + Business Media B.V.
Positive psychology of Malaysian students: impacts of engagement, motivation, self-compassion and wellbeing on mental health
Malaysia plays a key role in education of the Asia Pacific, expanding its scholarly output rapidly. However, mental health of Malaysian students is challenging, and their help-seeking is low because of stigma. This study explored the relationships between mental health and positive psychological constructs (academic engagement, motivation, self-compassion, and wellbeing), and evaluated the relative contribution of each positive psychological construct to mental health in Malaysian students. An opportunity sample of 153 students completed the measures regarding these constructs. Correlation, regression, and mediation analyses were conducted. Engagement, amotivation, self-compassion, and wellbeing were associated with, and predicted large variance in mental health. Self-compassion was the strongest independent predictor of mental health among all the positive psychological constructs. Findings can imply the strong links between mental health and positive psychology, especially selfcompassion. Moreover, intervention studies to examine the effects of self-compassion training on mental health of Malaysian students appear to be warranted.N/
The association between subjective memory complaint and objective cognitive function in older people with previous major depression
The goal of this study is to investigate associations between subjective memory complaint and objective cognitive performance in older people with previous major depression-a high-risk sample for cognitive impairment and later dementia. A cross-sectional study was carried out in people aged 60 or over with previous major depression but not fulfilling current major depression criteria according to DSM-IV-TR. People with dementia or Mini-Mental State Examination score less than 17 were excluded. Subjective memory complaint was defined on the basis of a score ≧4 on the subscale of Geriatric Mental State schedule, a maximum score of 8. Older people aged equal or over 60 without any psychiatric diagnosis were enrolled as healthy controls. Cognitive function was evaluated using a series of cognitive tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility in all participants. One hundred and thirteen older people with previous major depression and forty-six healthy controls were enrolled. Subjective memory complaint was present in more than half of the participants with depression history (55.8%). Among those with major depression history, subjective memory complaint was associated with lower total immediate recall and delayed verbal recall scores after adjustment. The associations between subjective memory complaint and worse memory performance were stronger in participants with lower depressive symptoms (Hamilton Depression Rating Scale score<7). The results suggest subjective memory complaint may be a valid appraisal of memory performance in older people with previous major depression and consideration should be given to more proactive assessment and follow-up in these clinical samples
4-Phenylbutyric acid treatment rescues trafficking and processing of a mutant surfactant protein C
Mutations in the SFTPC gene, encoding surfactant protein–C (SP-C), are associated with interstitial lung disease (ILD). Knowledge of the intracellular fate of mutant SP-C is essential in the design of therapies to correct trafficking/processing of the proprotein, and to prevent the formation of cytotoxic aggregates. We assessed the potential of a chemical chaperone to correct the trafficking and processing of three disease-associated mutant SP-C proteins. HEK293 cells were stably transfected with wild-type (SP-C(WT)) or mutant (SP-C(L188Q), SP-C(Δexon4), or SP-C(I73T)) SP-C, and cell lines with a similar expression of SP-C mRNA were identified. The effects of the chemical chaperone 4-phenylbutyric acid (PBA) and lysosomotropic drugs on intracellular trafficking to the endolysosomal pathway and the subsequent conversion of SP-C proprotein to mature peptide were assessed. Despite comparable SP-C mRNA expression, proprotein concentrations varied greatly: SP-C(I73T) was more abundant than SP-C(WT) and was localized to the cell surface, whereas SP-C(Δexon4) was barely detectable. In contrast, SP-C(L188Q) and SP-C(WT) proprotein concentrations were comparable, and a small amount of SP-C(L188Q) was localized to the endolysosomal pathway. PBA treatment restored the trafficking and processing of SP-C(L188Q) to SP-C(WT) concentrations, but did not correct the mistrafficking of SP-C(I73T) or rescue SP-C(Δexon4). PBA treatment also promoted the aggregation of SP-C proproteins, including SP-C(L188Q). This study provides proof of the principle that a chemical chaperone can correct the mistrafficking and processing of a disease-associated mutant SP-C proprotein
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