Polydimethylsiloxane (PDMS) elastomers are extensively used for soft lithographic replication of microstructures in microfluidic and micro-engineering applications. Elastomeric microstructures are ...commonly required to fulfil an explicit mechanical role and accordingly their mechanical properties can critically affect device performance. The mechanical properties of elastomers are known to vary with both curing and operational temperatures. However, even for the elastomer most commonly employed in microfluidic applications, Sylgard 184, only a very limited range of data exists regarding the variation in mechanical properties of bulk PDMS with curing temperature. We report an investigation of the variation in the mechanical properties of bulk Sylgard 184 with curing temperature, over the range 25 °C to 200 °C. PDMS samples for tensile and compressive testing were fabricated according to ASTM standards. Data obtained indicates variation in mechanical properties due to curing temperature for Young's modulus of 1.32-2.97 MPa, ultimate tensile strength of 3.51-7.65 MPa, compressive modulus of 117.8-186.9 MPa and ultimate compressive strength of 28.4-51.7 GPa in a range up to 40% strain and hardness of 44-54 ShA.
Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural ...substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer‐reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single‐photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal−limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre‐processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra‐nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.
The extension of in vivo optical imaging for disease screening and image-guided surgical interventions requires brightly emitting, tissue-specific materials that optically transmit through living ...tissue and can be imaged with portable systems that display data in real-time. Recent work suggests that a new window across the short-wavelength infrared region can improve in vivo imaging sensitivity over near infrared light. Here we report on the first evidence of multispectral, real-time short-wavelength infrared imaging offering anatomical resolution using brightly emitting rare-earth nanomaterials and demonstrate their applicability toward disease-targeted imaging. Inorganic-protein nanocomposites of rare-earth nanomaterials with human serum albumin facilitated systemic biodistribution of the rare-earth nanomaterials resulting in the increased accumulation and retention in tumour tissue that was visualized by the localized enhancement of infrared signal intensity. Our findings lay the groundwork for a new generation of versatile, biomedical nanomaterials that can advance disease monitoring based on a pioneering infrared imaging technique.
Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to ...conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.
MicroRNAs are tiny RNA molecules which serve as important post‐transcriptional regulators of gene expression. Dysregulated expression of microRNAs has been observed in human cancers, indicating that ...microRNAs may function as oncogenes or as tumor suppressors. To date, the microRNAs encoded by the oncogenic miR‐17‐92 cluster, and its paralog the miR‐106b‐25 cluster, are among those which are differentially expressed in human cancers. In this study, we examined and confirmed the over‐expression of these clusters in hepatocellular carcinoma and in hepatoma‐derived cells. At least 50% of the tumor samples showed a greater than two‐fold increase in the expression for miR‐18 and for the miR‐106b‐25 cluster when compared with the corresponding paired non‐tumor samples. Knock‐down studies for the miR‐106b‐25 cluster, which includes miR‐106b, miR‐93 and miR‐25, showed that the expression of the cluster is necessary for cell proliferation and for anchorage‐independent growth. In tumors with high expression of this cluster, reduced expression of the BH3‐only protein Bim, a miR‐25 target, was observed. We further identified the transcription factor E2F1 as a target gene for miR‐106b and miR‐93 and it is likely that one of the roles of the miR‐106b‐25 cluster is to prevent excessively high E2F1 expression, which may then cause apoptosis. We conclude that there is aberrant expression of microRNAs encoded by the oncogenic miR‐17‐92 cluster and the miR‐106b‐25 cluster in hepatocellular carcinoma. The consistent overexpression of the miR‐106b‐25 cluster and its role in cell proliferation and anchorage‐independent growth points to the oncogenic potential of this cluster. (Cancer Sci 2009; 100: 1234–1242)
Background and purpose
This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson’s disease (PD) and explored their ...associations with cardiovascular risk factors and cognitive performance.
Methods
A total of 175 non‐demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD‐MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10‐year cardiovascular risk score (mFRS).
Results
A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD‐MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P = 0.015) and periventricular WMH (P = 0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD‐MCI (P = 0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD‐MCI compared with patients in the 1st quintile of periventricular WMH burden (P = 0.004). However, total brain WMH burden was not associated with PD‐MCI (P = 0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors.
Conclusion
Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD.
Nitric oxide (NO) and nitrous oxide (N2O) emissions from nitrifying ecosystems are a serious threat to the environment. The factors influencing the emission and the responsible microorganisms and ...pathways were studied using a laboratory-scale nitrifying reactor system. The nitrifying culture was established at growth rates relevant to wastewater treatment plants (WWTPs). During stable ammonia oxidation, 0.03% of ammonium was emitted as NO and 2.8% was emitted as N2O. Although mixed cultures were used, clear responses in emission of ammonia oxidizing bacteria (AOB) could be detected and it was concluded that the denitrification pathway of AOB was the main source of the emissions. Emissions of nitrogen oxides in the system were strongly influenced by oxygen, nitrite, and ammonium concentrations. Steady state emission levels greatly underestimate the total emission, because changes in oxygen, nitrite, and ammonium concentrations induced a dramatic rise in NO and N2O emission. The data presented can be used as an indication for NO and N2O emission by AOB in plug-flow activated sludge systems, which is highly relevant because of the atmospheric impact and potential health risk of these compounds.
Aims/hypothesis Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic ...events associated with IR, while controlling for obesity. Methods We selected 263 non-obese (BMI approximately 24 kg/m²) Asian-Indian and Chinese men from a large cross-sectional study carried out in Singapore. Individuals taking medication for diabetes or hyperlipidaemia were excluded. Participants were separated into lower and upper tertiles of IR based on HOMA indices of ≤1.06 or ≥1.93, respectively. MS-based metabolic profiling of acylcarnitines, amino acids and organic acids was combined with hormonal and cytokine profiling in all participants. Results After controlling for BMI, commonly accepted risk factors for IR, including circulating fatty acids and inflammatory cytokines, did not discriminate the upper and lower quartiles of insulin sensitivity in either Asian-Indian or Chinese men. Instead, IR was correlated with increased levels of alanine, proline, valine, leucine/isoleucine, phenylalanine, tyrosine, glutamate/glutamine and ornithine, and a cluster of branched-chain and related amino acids identified by principal components analysis. These changes were not due to increased protein intake by individuals in the upper quartile of IR. Increased abdominal adiposity and leptin, and decreased adiponectin and IGF-binding protein 1 were also correlated with IR. Conclusions/interpretation These findings demonstrate that perturbations in amino acid homeostasis, but not inflammatory markers or NEFAs, are associated with IR in individuals of relatively low body mass.
The COVID-19 pandemic has caused unexpected disruption to the operation of many museums. However, the disruption also presents an opportunity for local museums to explore new modes of audience ...engagement that could also help to mitigate the negative health impact of COVID-19 through the imaginative use of technology. This article provides a snapshot of the various digital initiatives that were developed by museums in Singapore during the most challenging time of COVID-19 to exemplify the expanded role of museums as a public health resource. It will also offer a brief reflection on the challenges and benefits of curating wellbeing with digital technologies.
A review of creative responses to COVID-19 by museums in Singapore.
Scoping search.
Several local museums have stepped up efforts to support the wellbeing of people by exploring possibilities with digital virtual platforms. Their swift response to develop online contents following an abrupt closure due to the pandemic exemplifies the caring role of museums in offering people a much-needed respite from social isolation by connecting and interacting with others from a safe distance. Moving forward, it is also important for the museums to be mindful of the barriers that digital virtual platforms might present; since access to technology differs amongst population groups, as do digital competency, and literacy. Museums can benefit from further partnerships with sector experts and organisations to learn about the needs and challenges of different groups in future planning and design. This will help them to gather a holistic overview and help ensure inclusionary strategy and practice.
COVID-19 has challenged museums to adapt their programme and keep the public engaged through virtual programmes on online spaces. Online initiatives have offered opportunities for people to remain socially active and meaningfully engaged despite the stringent measures imposed in response to the viral situation. Postpandemic, we can continue to anticipate a highly connected and inclusive society brought together by virtual technologies.
•COVID-19 pandemic and mandatory closures have left museums in a difficult position.•Digital transformation presents museums with possibilities to resolve long-standing limitations.•This article provides an overview of digital initiatives developed by museums in Singapore.•Reflection on some of the challenges and benefits of curating wellbeing with digital technologies.
It is widely accepted that the familial Parkinson's disease (PD)-linked gene product, parkin, functions as a ubiquitin ligase involved in protein turnover via the ubiquitin-proteasome system. ...Substrates ubiquitinated by parkin are hence thought to be destined for proteasomal degradation. Because we demonstrated previously that parkin interacts with and ubiquitinates synphilin-1, we initially expected synphilin-1 degradation to be enhanced in the presence of parkin. Contrary to our expectation, we found that synphilin-1 is normally ubiquitinated by parkin in a nonclassical, proteasomal-independent manner that involves lysine 63 (K63)-linked polyubiquitin chain formation. Parkin-mediated degradation of synphilin-1 occurs appreciably only at an unusually high parkin to synphilin-1 expression ratio or when primed for lysine 48 (K48)-linked ubiquitination. In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. Our results suggest that parkin is a dual-function ubiquitin ligase and that K63-linked ubiquitination of synphilin-1 by parkin may be involved in the formation of Lewy body inclusions associated with PD.