126 research outputs found
Assessment of a cost-effective headphone calibration procedure for soundscape evaluations
To increase the availability and adoption of the soundscape standard, a
low-cost calibration procedure for reproduction of audio stimuli over
headphones was proposed as part of the global ``Soundscape Attributes
Translation Project'' (SATP) for validating ISO/TS~12913-2:2018 perceived
affective quality (PAQ) attribute translations. A previous preliminary study
revealed significant deviations from the intended equivalent continuous
A-weighted sound pressure levels () using the open-circuit
voltage (OCV) calibration procedure. For a more holistic human-centric
perspective, the OCV method is further investigated here in terms of
psychoacoustic parameters, including relevant exceedance levels to account for
temporal effects on the same 27 stimuli from the SATP. Moreover, a
within-subjects experiment with 36 participants was conducted to examine the
effects of OCV calibration on the PAQ attributes in ISO/TS~12913-2:2018.
Bland-Altman analysis of the objective indicators revealed large biases in the
OCV method across all weighted sound level and loudness indicators; and
roughness indicators at \SI{5}{\%} and \SI{10}{\%} exceedance levels.
Significant perceptual differences due to the OCV method were observed in about
\SI{20}{\%} of the stimuli, which did not correspond clearly with the biased
acoustic indicators. A cautioned interpretation of the objective and perceptual
differences due to small and unpaired samples nevertheless provide grounds for
further investigation.Comment: For 24th International Congress on Acoustic
Do uHear? Validation of uHear App for Preliminary Screening of Hearing Ability in Soundscape Studies
Studies involving soundscape perception often exclude participants with
hearing loss to prevent impaired perception from affecting experimental
results. Participants are typically screened with pure tone audiometry, the
"gold standard" for identifying and quantifying hearing loss at specific
frequencies, and excluded if a study-dependent threshold is not met. However,
procuring professional audiometric equipment for soundscape studies may be
cost-ineffective, and manually performing audiometric tests is
labour-intensive. Moreover, testing requirements for soundscape studies may not
require sensitivities and specificities as high as that in a medical diagnosis
setting. Hence, in this study, we investigate the effectiveness of the uHear
app, an iOS application, as an affordable and automatic alternative to a
conventional audiometer in screening participants for hearing loss for the
purpose of soundscape studies or listening tests in general. Based on
audiometric comparisons with the audiometer of 163 participants, the uHear app
was found to have high precision (98.04%) when using the World Health
Organization (WHO) grading scheme for assessing normal hearing. Precision is
further improved (98.69%) when all frequencies assessed with the uHear app is
considered in the grading, which lends further support to this cost-effective,
automated alternative to screen for normal hearing.Comment: Full paper submitted to 24th International Congress on Acoustic
Crossing the Linguistic Causeway: Ethnonational Differences on Soundscape Attributes in Bahasa Melayu
Despite being neighbouring countries and sharing the language of Bahasa
Melayu (ISO 639-3:ZSM), cultural and language education policy differences
between Singapore and Malaysia led to differences in the translation of the
"annoying" perceived affective quality (PAQ) attribute from English (ISO
639-3:ENG) to ZSM. This study expands upon the translation of the PAQ
attributes from eng to ZSM in Stage 1 of the Soundscapes Attributes Translation
Project (SATP) initiative, and presents the findings of Stage 2 listening tests
that investigated ethnonational differences in the translated ZSM PAQ
attributes and explored their circumplexity. A cross-cultural listening test
was conducted with 100 ZSM speakers from Malaysia and Singapore using the
common SATP protocol. The analysis revealed that Malaysian participants from
non-native ethnicities (my:o) showed PAQ perceptions more similar to Singapore
(sg) participants than native ethnic Malays (MY:M) in Malaysia. Differences
between Singapore and Malaysian groups were primarily observed in stimuli
related to water features, reflecting cultural and geographical variations.
Besides variations in water source-dominant stimuli perception, disparities
between MY:M and SG could be mainly attributed to vibrant scores. The findings
also suggest that the adoption of region-specific translations, such as
membingitkan in Singapore and menjengkelkan in Malaysia, adequately addressed
differences in the annoying attribute, as significant differences were observed
in one or fewer stimuli across ethnonational groups The circumplexity analysis
indicated that the quasi-circumplex model better fit the data compared to the
assumed equal angle quasi-circumplex model in ISO/TS 12913-3, although
deviations were observed possibly due to respondents' unfamiliarity with the
United Kingdom-centric context of the stimulus dataset...Comment: Preprint submitted to Elsevier for revie
Preliminary investigation of the short-term in situ performance of an automatic masker selection system
Soundscape augmentation or "masking" introduces wanted sounds into the
acoustic environment to improve acoustic comfort. Usually, the masker selection
and playback strategies are either arbitrary or based on simple rules (e.g. -3
dBA), which may lead to sub-optimal increment or even reduction in acoustic
comfort for dynamic acoustic environments. To reduce ambiguity in the selection
of maskers, an automatic masker selection system (AMSS) was recently developed.
The AMSS uses a deep-learning model trained on a large-scale dataset of
subjective responses to maximize the derived ISO pleasantness (ISO 12913-2).
Hence, this study investigates the short-term in situ performance of the AMSS
implemented in a gazebo in an urban park. Firstly, the predicted ISO
pleasantness from the AMSS is evaluated in comparison to the in situ subjective
evaluation scores. Secondly, the effect of various masker selection schemes on
the perceived affective quality and appropriateness would be evaluated. In
total, each participant evaluated 6 conditions: (1) ambient environment with no
maskers; (2) AMSS; (3) bird and (4) water masker from prior art; (5) random
selection from same pool of maskers used to train the AMSS; and (6) selection
of best-performing maskers based on the analysis of the dataset used to train
the AMSS.Comment: paper submitted to the 52nd International Congress and Exposition on
Noise Control Engineering held in Chiba, Greater Tokyo, Japan, on 20-23
August 2023 (Inter-Noise 2023
Molecular determinants of plaque size as an indicator of dengue virus attenuation
The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients, and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines
Microenvironmental Influence on Pre-Clinical Activity of Polo-Like Kinase Inhibition in Multiple Myeloma: Implications for Clinical Translation
Polo-like kinases (PLKs) play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM). We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM) and rapid (commitment to cell death <24 hrs) in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM and other cancers
A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings
Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation).In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented.We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes
Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer
BACKGROUND: Although the nuclear factor-erythroid 2-related factor 2 (NRF2) pathway is one of the most frequently dysregulated in cancer, it is not clear whether mutational status is a good predictor of NRF2 activity. Here we utilise four members of the aldo-keto reductase (AKR) superfamily as biomarkers to address this question. METHODS: Twenty-three cell lines of diverse origin and NRF2-pathway mutational status were used to determine the relationship between AKR expression and NRF2 activity. AKR expression was evaluated in lung cancer biopsies and Cancer Genome Atlas (TCGA) and Oncomine data sets. RESULTS: AKRs were expressed at a high basal level in cell lines carrying mutations in the NRF2 pathway. In non-mutant cell lines, co-ordinate induction of AKRs was consistently observed following activation of NRF2. Immunohistochemical analysis of lung tumour biopsies and interrogation of TCGA data revealed that AKRs are enriched in both squamous cell carcinomas (SCCs) and adenocarcinomas that contain somatic alterations in the NRF2 pathway but, in the case of SCC, AKRs were also enriched in most other tumours. CONCLUSIONS: An AKR biomarker panel can be used to determine NRF2 status in tumours. Hyperactivation of the NRF2 pathway is far more prevalent in lung SCC than previously predicted by genomic analyses
Identification of Genes with Allelic Imbalance on 6p Associated with Nasopharyngeal Carcinoma in Southern Chinese
Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC. In total, 360 subjects and 360 healthy controls were included, and 233 single nucleotide polymorphisms (SNPs) on 6p were examined. Significant single-marker associations were found for SNPs rs2267633 (p = 4.49×10−5), rs2076483 (most significant, p = 3.36×10−5), and rs29230 (p = 1.43×10−4). The highly associated genes were the gamma-amino butyric acid B receptor 1 (GABBR1), human leukocyte antigen (HLA-A), and HLA complex group 9 (HCG9). Haplotypic associations were found for haplotypes AAA (located within GABBR1, p-value = 6.46×10−5) and TT (located within HLA-A, p = 0.0014). Further investigation of the homozygous genotype frequencies between cases and controls suggested that micro-deletion regions occur in GABBR1 and neural precursor cell expressed developmentally down-regulated 9 (NEDD9). Quantitative real-time polymerase chain reaction (qPCR) using 11 pairs of NPC biopsy samples confirmed the significant decline in GABBR1 and NEDD9 mRNA expression in the cancer tissues compared to the adjacent non-tumor tissue (p<0.05). Our study demonstrates that multiple chromosome 6p susceptibility loci contribute to the risk of NPC, possibly though GABBR1 and NEDD9 loss of function
- …