The Individual Differences in the Perception of Oral Chemesthesis Are Linked to Taste Sensitivity

Chemesthesis is a part of the flavor experience of foods. Chemesthetic perception is studied to understand its effect on food-related behavior and health. Thus, the objective of this research was to study individual differences in chemesthetic perception. Our study involved sensory tests of three chemesthetic modalities (astringency, pungency, and cooling). Participants (N = 196) evaluated the intensity of samples in different concentrations using a line scale under sensory laboratory conditions. Aluminum ammonium sulfate, capsaicin, and menthol were used as the prototypic chemesthetic compounds. The participants were divided into sensitivity groups in different chemesthetic modalities by hierarchical clustering based on their intensity ratings. In addition, an oral chemesthesis sensitivity score was determined to represent the generalized chemesthesis sensitivity. The results showed that people can perceive chemesthesis on different intensity levels. There were significantly positive correlations between (1) sensitivity scores for oral chemesthesis and taste as well as (2) each chemesthesis and taste modalities. Moreover, based on the multinomial logistic regression model, significant interactions between oral chemesthesis and taste sensitivity were discovered. Our findings showed that people can be classified into different oral chemesthesis sensitivity groups. The methods and results of this study can be utilized to investigate associations with food-related behavior and health

The Individual Differences in the Perception of Oral Chemesthesis Are Linked to Taste Sensitivity

Chemesthesis is a part of the flavor experience of foods. Chemesthetic perception is studied to understand its effect on food-related behavior and health. Thus, the objective of this research was to study individual differences in chemesthetic perception. Our study involved sensory tests of three chemesthetic modalities (astringency, pungency, and cooling). Participants (N = 196) evaluated the intensity of samples in different concentrations using a line scale under sensory laboratory conditions. Aluminum ammonium sulfate, capsaicin, and menthol were used as the prototypic chemesthetic compounds. The participants were divided into sensitivity groups in different chemesthetic modalities by hierarchical clustering based on their intensity ratings. In addition, an oral chemesthesis sensitivity score was determined to represent the generalized chemesthesis sensitivity. The results showed that people can perceive chemesthesis on different intensity levels. There were significantly positive correlations between (1) sensitivity scores for oral chemesthesis and taste as well as (2) each chemesthesis and taste modalities. Moreover, based on the multinomial logistic regression model, significant interactions between oral chemesthesis and taste sensitivity were discovered. Our findings showed that people can be classified into different oral chemesthesis sensitivity groups. The methods and results of this study can be utilized to investigate associations with food-related behavior and health

The Individual Differences in the Perception of Oral Chemesthesis Are Linked to Taste Sensitivity

Chemesthesis is a part of the flavor experience of foods. Chemesthetic perception is studied to understand its effect on food-related behavior and health. Thus, the objective of this research was to study individual differences in chemesthetic perception. Our study involved sensory tests of three chemesthetic modalities (astringency, pungency, and cooling). Participants (N = 196) evaluated the intensity of samples in different concentrations using a line scale under sensory laboratory conditions. Aluminum ammonium sulfate, capsaicin, and menthol were used as the prototypic chemesthetic compounds. The participants were divided into sensitivity groups in different chemesthetic modalities by hierarchical clustering based on their intensity ratings. In addition, an oral chemesthesis sensitivity score was determined to represent the generalized chemesthesis sensitivity. The results showed that people can perceive chemesthesis on different intensity levels. There were significantly positive correlations between (1) sensitivity scores for oral chemesthesis and taste as well as (2) each chemesthesis and taste modalities. Moreover, based on the multinomial logistic regression model, significant interactions between oral chemesthesis and taste sensitivity were discovered. Our findings showed that people can be classified into different oral chemesthesis sensitivity groups. The methods and results of this study can be utilized to investigate associations with food-related behavior and health.</p

NEMESIS setup for Indirect Detection of WIMPs

We summarize the evidence for DM-like anomalies in neutron multiplicity spectra collected underground with Pb targets by three independent experiments: NEMESIS (at 210 m.w.e.) NMDS (at 583 m.w.e.), and ZEPLIN-II (at 2850 m.w.e.). A new analysis shows small but persistent anomalies at high neutron multiplicities. Adjusted for differences in detection efficiencies, the positions of the anomalies are consistent between the three systems. Also, the intensities match when corrected for the acquisition time and estimated detection efficiency. While the three measurements are inconclusive when analyzed separately, together, they exclude a statistical fluke to better than one in a million. To prove the existence of the anomalies above the 5-sigma discovery threshold, we propose to upgrade the current NEMESIS setup. The upgrade concept and the critical components of the new experiment are described. The upgraded setup would already acquire the needed data sample during the first year of operation. Additional information, vital for the physics interpretation of the analysis, will be obtained with a Cu target.Peer reviewe

New NEMESIS Results

Funding Information: This work has been supported in part by the EU INTERREG for the Baltic Sea programme within the BSUIN project, and by the Polish Ministry of Science and Higher Education (Grant no. Funding Information: This work has been supported in part by the EU INTERREG for the Baltic Sea programme within the BSUIN project, and by the Polish Ministry of Science and Higher Education (Grant no. 3988/INTERREG BSR/2018/2). Publisher Copyright: © Copyright owned by the author(s) under the terms of the Creative Commons.Preliminary results from a 349-day run (live time) with a 565 kg Pb target and a 166-day background measurement are presented. Three minor anomalies were detected in muon-suppressed neutron multiplicity spectra. The multiplicities of these small excesses match the outcome of an earlier, similar but independent measurement. The nature of the anomalies remains unclear, but, in principle, they may be a signature of self-annihilation of a Weakly Interacting Massive Particle (WIMP) with a mass around 10 GeV/c2. If our interpretation is correct, the expected cross section would be of the order of 10-42 cm2 for Spin Dependent and 10-46 cm2 for Spin Independent interactions. Analysis of the event rate, based on the statistical uncertainty, indicates that cross-section limits for Dark Matter (DM) mass range of approximately 3-40 GeV/c2 can be investigated with an upgraded NEMESIS setup.Peer reviewe

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&amp;Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings

Specific Visualization of Glioma Cells in Living Low-Grade Tumor Tissue

BACKGROUND: The current therapy of malignant gliomas is based on surgical resection, radio-chemotherapy and chemotherapy. Recent retrospective case-series have highlighted the significance of the extent of resection as a prognostic factor predicting the course of the disease. Complete resection in low-grade gliomas that show no MRI-enhanced images are especially difficult. The aim in this study was to develop a robust, specific, new fluorescent probe for glioma cells that is easy to apply to live tumor biopsies and could identify tumor cells from normal brain cells at all levels of magnification. METHODOLOGY/PRINCIPAL FINDINGS: In this investigation we employed brightly fluorescent, photostable quantum dots (QDs) to specifically target epidermal growth factor receptor (EGFR) that is upregulated in many gliomas. Living glioma and normal cells or tissue biopsies were incubated with QDs coupled to EGF and/or monoclonal antibodies against EGFR for 30 minutes, washed and imaged. The data include results from cell-culture, animal model and ex vivo human tumor biopsies of both low-grade and high-grade gliomas and show high probe specificity. Tumor cells could be visualized from the macroscopic to single cell level with contrast ratios as high as 1000: 1 compared to normal brain tissue. CONCLUSIONS/SIGNIFICANCE: The ability of the targeted probes to clearly distinguish tumor cells in low-grade tumor biopsies, where no enhanced MRI image was obtained, demonstrates the great potential of the method. We propose that future application of specifically targeted fluorescent particles during surgery could allow intraoperative guidance for the removal of residual tumor cells from the resection cavity and thus increase patient survival

Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas

BACKGROUND: Malignant gliomas are the most prevalent type of primary brain tumours but the therapeutic armamentarium for these tumours is limited. Platelet-derived growth factor (PDGF) signalling has been shown to be a key regulator of glioma development. Clinical trials evaluating the efficacy of anti-PDGFRA therapies on gliomas are ongoing. In this study, we intended to analyse the expression of PDGFA and its receptor PDGFRA, as well as the underlying genetic (mutations and amplification) mechanisms driving their expression in a large series of human gliomas. METHODS: PDGFA and PDGFRA expression was evaluated by immunohistochemistry in a series of 160 gliomas of distinct World Health Organization (WHO) malignancy grade. PDGFRA-activating gene mutations (exons 12, 18 and 23) were assessed in a subset of 86 cases by PCR-single-strand conformational polymorphism (PCR-SSCP), followed by direct sequencing. PDGFRA gene amplification analysis was performed in 57 cases by quantitative real-time PCR (QPCR) and further validated in a subset of cases by chromogenic in situ hybridisation (CISH) and microarray-based comparative genomic hybridisation (aCGH). RESULTS: PDGFA and PDGFRA expression was found in 81.2% (130 out of 160) and 29.6% (48 out of 160) of gliomas, respectively. Its expression was significantly correlated with histological type of the tumours; however, no significant association between the expression of the ligand and its receptor was observed. The absence of PDGFA expression was significantly associated with the age of patients and with poor prognosis. Although PDGFRA gene-activating mutations were not found, PDGFRA gene amplification was observed in 21.1% (12 out of 57) of gliomas. No association was found between the presence of PDGFRA gene amplification and expression, excepting for grade II diffuse astrocytomas. CONCLUSION: The concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas. Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas

SAQC: SNP Array Quality Control

<p>Abstract</p> <p>Background</p> <p>Genome-wide single-nucleotide polymorphism (SNP) arrays containing hundreds of thousands of SNPs from the human genome have proven useful for studying important human genome questions. Data quality of SNP arrays plays a key role in the accuracy and precision of downstream data analyses. However, good indices for assessing data quality of SNP arrays have not yet been developed.</p> <p>Results</p> <p>We developed new quality indices to measure the quality of SNP arrays and/or DNA samples and investigated their statistical properties. The indices quantify a departure of estimated individual-level allele frequencies (AFs) from expected frequencies via standardized distances. The proposed quality indices followed lognormal distributions in several large genomic studies that we empirically evaluated. AF reference data and quality index reference data for different SNP array platforms were established based on samples from various reference populations. Furthermore, a confidence interval method based on the underlying empirical distributions of quality indices was developed to identify poor-quality SNP arrays and/or DNA samples. Analyses of authentic biological data and simulated data show that this new method is sensitive and specific for the detection of poor-quality SNP arrays and/or DNA samples.</p> <p>Conclusions</p> <p>This study introduces new quality indices, establishes references for AFs and quality indices, and develops a detection method for poor-quality SNP arrays and/or DNA samples. We have developed a new computer program that utilizes these methods called SNP Array Quality Control (SAQC). SAQC software is written in R and R-GUI and was developed as a user-friendly tool for the visualization and evaluation of data quality of genome-wide SNP arrays. The program is available online (<url>http://www.stat.sinica.edu.tw/hsinchou/genetics/quality/SAQC.htm</url>).</p

Autocrine PDGF stimulation in malignancies

Platelet-derived growth factor (PDGF) isoforms are important mitogens for different types of mesenchymal cells, which have important functions during the embryonal development and in the adult during wound healing and tissue homeostasis. In tumors, PDGF isoforms are often over-expressed and contribute to the growth of both normal and malignant cells. This review focuses on tumors expressing PDGF isoforms together with their tyrosine kinase receptors, thus resulting in autocrine stimulation of growth and survival. Patients with such tumors could benefit from treatment with inhibitors of either PDGF or PDGF receptors