Interpretation of the ion mass spectra in the mass range 25-35 obtained in the inner coma of Halley's comet by the HIS-sensor of the Giotto IMS Experiment

The IMS-HIS double-focussing mass spectrometer that flew on the Giotto spacecraft covered the mass per charge range from 12 to 56 (AMU/e). By comparing flight data, calibration data, and results of model calculations of the ion population in the inner coma, the absolute mass scale is established, and ions in the mass range 25 to 35 are identified. Ions resulting from protonation of molecules with high proton affinity are relatively abundant, enabling us to estimate relative source strengths for H2CO, CH3OH, HCN, and H2S, providing for the first time a positive in situ measurement of methanol. Also, upper limits for NO and some hydrocarbons are derived

Dynamics Explorer 1: Energetic Ion Composition Spectrometer (EICS)

The Energetic Ion Composition Spectrometer (EICS) experiment was selected as part of the Dynamics Explorer (DE) Program. One of the primary goals of the DE program was to investigate in detail the plasma physics processes responsible for energizing thermal (approximately 1 eV) ionospheric ions and transporting them to the earth's plasma sheet and distant polar cap. The results of the EICS data analysis (including support of other investigators) and of the archiving efforts supported by this contract are summarized in this document. Also reported are some aspects of our operational support activities

Measuring Venous Oxygen Saturation Using the Photoplethysmograph Waveform

The pulse oximeter is now a standard-of-care monitor. In its most basic form it measures the arterial oxygenation saturation. It accomplishes this through the use of the photoplethysmograph waveform (PPG) at two or more wavelengths. Advances in digital signal processing are allowing for a re-examination of these waveforms. It has been recognized for some time that the movement of venous blood can be detected (1, 2) using the PPG. For the most part, this phenomenon has been seen as a source of artifact which interferes with calculation of arterial saturation. On the other hand, if venous saturation can be reliably measured, interesting new possibilities are opened. We hypothesize that the PPG waveform, obtained non-invasively by modern pulse oximeters, can be analyzed via digital signal processing to infer the venous oxygen saturation

Modulation of finger photoplethysmographic traces during forced respiration: venous blood in motion?

Photoplethysmographic (PPG) signals were recorded from the fingers of 10 healthy volunteers during forced respiratory inspiration. The aim of this pilot study was to assess the effect of negative airway pressure on the blood volumes within the tissue bed of the finger, and the resultant modulation of PPG signals. The acquired signals were analysed and oxygen saturations estimated from the frequency spectra in the cardiac and respiratory frequency ranges. Assuming that respiratory modulation affects blood volumes in veins to a greater extent than in arteries, the local venous oxygen saturation was estimated. Estimated venous oxygen saturation was found to be 3.1% (±4.2%) lower than the estimated arterial saturation

Measuring venous oxygenation using the photoplethysmograph waveform

OBJECTIVE: We investigate the hypothesis that the photoplethysmograph (PPG) waveform can be analyzed to infer regional venous oxygen saturation. METHODS: Fundamental to the successful isolation of the venous saturation is the identification of PPG characteristics that are unique to the peripheral venous system. Two such characteristics have been identified. First, the peripheral venous waveform tends to reflect atrial contraction. Second, ventilation tends to move venous blood preferentially due to the low pressure and high compliance of the venous system. Red (660 nm) and IR (940 nm) PPG waveforms were collected from 10 cardiac surgery patients using an esophageal PPG probe. These waveforms were analyzed using algorithms written in Mathematica. Four time-domain saturation algorithms (ArtSat, VenSat, ArtInstSat, VenInstSat) and four frequency-domain saturation algorithms (RespDC, RespAC, Cardiac, and Harmonic) were applied to the data set. RESULTS: Three of the algorithms for calculating venous saturation (VenSat, VenInstSat, and RespDC) demonstrate significant difference from ArtSat (the conventional time-domain algorithm for measuring arterial saturation) using the Wilcoxon signed-rank test with Bonferroni correction (p < 0.0071). CONCLUSIONS: This work introduces new algorithms for PPG analysis. Three algorithms (VenSat, VenInstSat, and RespDC) succeed in detecting lower saturation blood. The next step is to confirm the accuracy of the measurement by comparing them to a gold standard (i.e., venous blood gas)

Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>A critical therapeutic challenge in epithelial ovarian carcinoma is the development of chemoresistance among tumor cells following exposure to first line chemotherapeutics. The molecular and genetic changes that drive the development of chemoresistance are unknown, and this lack of mechanistic insight is a major obstacle in preventing and predicting the occurrence of refractory disease. We have recently shown that Regulators of G-protein Signaling (RGS) proteins negatively regulate signaling by lysophosphatidic acid (LPA), a growth factor elevated in malignant ascites fluid that triggers oncogenic growth and survival signaling in ovarian cancer cells. The goal of this study was to determine the role of RGS protein expression in ovarian cancer chemoresistance.</p> <p>Results</p> <p>In this study, we find that RGS2, RGS5, RGS10 and RGS17 transcripts are expressed at significantly lower levels in cells resistant to chemotherapy compared with parental, chemo-sensitive cells in gene expression datasets of multiple models of chemoresistance. Further, exposure of SKOV-3 cells to cytotoxic chemotherapy causes acute, persistent downregulation of RGS10 and RGS17 transcript expression. Direct inhibition of RGS10 or RGS17 expression using siRNA knock-down significantly reduces chemotherapy-induced cell toxicity. The effects of cisplatin, vincristine, and docetaxel are inhibited following RGS10 and RGS17 knock-down in cell viability assays and phosphatidyl serine externalization assays in SKOV-3 cells and MDR-HeyA8 cells. We further show that AKT activation is higher following RGS10 knock-down and RGS 10 and RGS17 overexpression blocked LPA mediated activation of AKT, suggesting that RGS proteins may blunt AKT survival pathways.</p> <p>Conclusions</p> <p>Taken together, our data suggest that chemotherapy exposure triggers loss of RGS10 and RGS17 expression in ovarian cancer cells, and that loss of expression contributes to the development of chemoresistance, possibly through amplification of endogenous AKT signals. Our results establish RGS10 and RGS17 as novel regulators of cell survival and chemoresistance in ovarian cancer cells and suggest that their reduced expression may be diagnostic of chemoresistance.</p

Instantaneous venous oxygenation estimation using the Photoplethysmograph (PPG) waveform

In this study oesophageal photoplethysmograph data from eight patients under positive pressure ventilation were analysed in order to test the hypothesis that the modulations created by the ventilation in the AC Photoplethysmograph (PPG) signal could be used to estimate venous oxygen saturation. In order to estimate the instantaneous arterial and venous oxygen saturation Smoothed-pseudo Wigner-Ville Distribution (SPWVD) was utilised. The result from this study showed that there was no significant different in the conventional (time domain) arterial saturation and the instantaneous arterial saturation. However, the instantaneous venous oxygen saturation estimated with the ventilator modulation were significantly lower then the conventional arterial saturation (P=0.008) and also from the instantaneous arterial saturation (P=0.008)

Addressing Personal Barriers to Advance Care Planning: Qualitative Investigation of a Mindfulness-Based Intervention for Adults with Cancer and Their Family Caregivers

Objective Advance care planning (ACP) increases quality of life and satisfaction with care for those with cancer and their families, yet these important conversations often do not occur. Barriers include patients’ and families’ emotional responses to cancer, such as anxiety and sadness, which can lead to avoidance of discussing illness-related topics such as ACP. Interventions that address psychological barriers to ACP are needed. The purpose of this study was to explore the effects of a mindfulness intervention designed to cultivate patient and caregiver emotional and relational capacity to respond to the challenges of cancer with greater ease, potentially decreasing psychological barriers to ACP and enhancing ACP engagement. Method The Mindfully Optimizing Delivery of End-of-Life (MODEL) Care intervention provided 12 hours of experiential training to two cohorts of six to seven adults with advanced-stage cancer and their family caregivers (n = 13 dyads). Training included mindfulness practices, mindful communication skills development, and information about ACP. Patient and caregiver experiences of the MODEL Care program were assessed using semistructured interviews administered immediately postintervention and open-ended survey questions delivered immediately and at 4 weeks postintervention. Responses were analyzed using qualitative methods. Result Four salient themes were identified. Patients and caregivers reported the intervention (1) enhanced adaptive coping practices, (2) lowered emotional reactivity, (3) strengthened relationships, and (4) improved communication, including communication about their disease. Significance of results The MODEL Care intervention enhanced patient and caregiver capacity to respond to the emotional challenges that often accompany advanced cancer and decreased patient and caregiver psychological barriers to ACP

Palmitate and thapsigargin have contrasting effects on ER membrane lipid composition and ER proteostasis in neuronal cells

The endoplasmic reticulum (ER) is an organelle that performs several key functions such as protein synthesis and folding, lipid metabolism and calcium homeostasis. When these functions are disrupted, such as upon protein misfolding, ER stress occurs. ER stress can trigger adaptive responses to restore proper functioning such as activation of the unfolded protein response (UPR). In certain cells, the free fatty acid palmitate has been shown to induce the UPR. Here, we examined the effects of palmitate on UPR gene expression in a human neuronal cell line and compared it with thapsigargin, a known depletor of ER calcium and trigger of the UPR. We used a Gaussia luciferase-based reporter to assess how palmitate treatment affects ER proteostasis and calcium ho-meostasis in the cells. We also investigated how ER calcium depletion by thapsigargin affects lipid membrane composition by performing mass spectrometry on subcellular fractions and compared this to palmitate. Sur-prisingly, palmitate treatment did not activate UPR despite prominent changes to membrane phospholipids. Conversely, thapsigargin induced a strong UPR, but did not significantly change the membrane lipid composition in subcellular fractions. In summary, our data demonstrate that changes in membrane lipid composition and disturbances in ER calcium homeostasis have a minimal influence on each other in neuronal cells. These data provide new insight into the adaptive interplay of lipid homeostasis and proteostasis in the cell.Peer reviewe