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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Proteomic Tissue-Based Classifier for Early Prediction of Prostate Cancer Progression

Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes, we used targeted mass spectrometry to quantify proteins that significantly differed in primary tumors from PCa patients treated with radical prostatectomy (RP) across three study outcomes: (i) metastasis ≥1-year post-RP, (ii) biochemical recurrence ≥1-year post-RP, and (iii) no progression after ≥10 years post-RP. Sixteen proteins that differed significantly in an initial set of 105 samples were evaluated in the entire cohort (n = 338). A five-protein classifier which combined FOLH1, KLK3, TGFB1, SPARC, and CAMKK2 with existing clinical and pathological standard of care variables demonstrated significant improvement in predicting distant metastasis, achieving an area under the receiver-operating characteristic curve of 0.92 (0.86, 0.99, p = 0.001) and a negative predictive value of 92% in the training/testing analysis. This classifier has the potential to stratify patients based on risk of aggressive, metastatic PCa that will require early intervention compared to low risk patients who could be managed through active surveillance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Analyzing BMP2, FGFR, and TGF Beta Expressions in High-Grade Osteosarcoma Untreated and Treated Autografts Using Proteomic Analysis

In the last few decades, biological reconstruction techniques have improved greatly for treating high-grade osteosarcoma patients. To conserve the limb, and its function the affected tumor-bearing bones have been treated using liquid nitrogen and irradiation processes that enable the removal of entire tumors from the bone, and these treated autografts can be reconstructed for the patients. Here, we focus on the expressions of the growth factor family proteins from the untreated and treated autografts that play a crucial role in bone union, remodeling, and regeneration. In this proteomic study, we identify several important cytoskeletal, transcriptional, and growth factor family proteins that showed substantially low levels in untreated autografts. Interestingly, these protein expressions were elevated after treating the tumor-bearing bones using liquid nitrogen and irradiation. Therefore, from our preliminary findings, we chose to determine the expressions of BMP2, TGF-Beta, and FGFR proteins by the target proteomics approach. Using a newly recruited validation set, we successfully validate the expressions of the selected proteins. Furthermore, the increased growth factor protein expression after treatment with liquid nitrogen may contribute to bone regeneration healing, assist in faster recovery, and reduce local recurrence and metastatic spread in high-grade sarcoma patients.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1994

Hemodynamic Responses to Head and Neck Cooling

Personal thermoregulatory systems which provide head and neck cooling are used in the industrial and aerospace environments to alleviate thermal stress. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objective of this study was to measure the scalp temperature and circulatory responses during use of one commercially available thermal control system. The Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used in this study. Two EEG electrodes and one skin temperature transducer were placed on the anterior midline of the scalp to measure the scalp blood and temperature. Blood flow was measured using a bipolar impedance rheograph. Ten subjects, seated in an upright position at normal room temperature, were tested at high, medium, moderate, moderate-low and low coolant temperatures. Scalp blood flow was recorded continuously using a computer data acquisition system with a sampling frequency of 200 Hz. Scalp temperature and cooling helmet Inlet temperature was logged periodically during the test period. This study quantifies the effect of head cooling upon scalp temperature and blood flow. These data may also be used to select operational specifications of the head cooling system for biomedical applications such as the treatment of migraine headaches, scalp cooling during chemotherapy, and cooling of multiple sclerosis patients.

Ku, Yu-Tsuan E.↗
NASA NTRS1999

Otolith and Vertical Canal Contributions to Dynamic Postural Control

The objective of this project is to determine: 1) how do normal subjects adjust postural movements in response to changing or altered otolith input, for example, due to aging? and 2) how do patients adapt postural control after altered unilateral or bilateral vestibular sensory inputs such as ablative inner ear surgery or ototoxicity, respectively? The following hypotheses are under investigation: 1) selective alteration of otolith input or abnormalities of otolith receptor function will result in distinctive spatial, frequency, and temporal patterns of head movements and body postural sway dynamics. 2) subjects with reduced, altered, or absent vertical semicircular canal receptor sensitivity but normal otolith receptor function or vice versa, should show predictable alterations of body and head movement strategies essential for the control of postural sway and movement. The effect of altered postural movement control upon compensation and/or adaptation will be determined. These experiments provide data for the development of computational models of postural control in normals, vestibular deficient subjects and normal humans exposed to unusual force environments, including orbital space flight.

Black, F. Owen↗
DOE OSTI2022

Development of a prediction model for radiotherapy response among patients with head and neck squamous cell carcinoma based on the tumor immune microenvironment and hypoxia signature

Abstract Introduction The immune system and hypoxia are major factors influencing radiosensitivity in patients with different cancer types. This study aimed at developing a model to predict radiotherapy response in patients with head and neck squamous cell carcinoma (HNSCC) based on the tumor immune microenvironment and hypoxia signature. Materials and Methods We first evaluated the hypoxia status and tumor immune microenvironment in the Cancer Genome Atlas (TCGA) cohort by using transcriptomic data. Differentially expressed genes (DEGs) were identified between the “high immunity and low hypoxia” and “low immunity and high hypoxia” groups and those DEGs significantly associated with disease‐specific survival in the univariate Cox regression analysis were selected as the prognostic DEGs. We selected the immune hypoxia–related genes (IHRGs) by intersecting prognostic DEGs with immune and hypoxia gene sets. We used the IHRGs to train a multivariate Cox regression model in the TCGA cohort, based on which we calculated the IHRG prognostic index (IHRGPI) for each patient and validated its efficacy in predicting radiotherapy response in the Gene Expression Omnibus cohorts. Furthermore, we explored potential mechanisms and effective combinational treatment strategies for different IHRGPI groups. Results Five IHRGs were used to construct the IHRGPI, which was used to dichotomize the cohorts. The patients with lower IHRGPI showed a better radiotherapy response across different cohorts and endpoints, including overall survival, progression‐free survival, and recurrence‐free survival ( p < 0.05). Patients with higher IHRGPI showed greater hypoxia and lesser immune cell infiltration. A lower IHRGPI indicated a better immunotherapy response, while a higher IHRGPI indicated a better chemotherapy response. Conclusions IHRGPI is promising for predicting radiotherapy response and guiding combinational treatment strategies in patients with HNSCC.

Zhu, Guang‐Li↗
DOE OSTI2021

Surfactant-assisted one-pot sample preparation for label-free single-cell proteomics

Large numbers of cells are generally required for quantitative global proteome profiling due to surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs)). Here we report a surfactant-assisted one-pot sample preparation coupled with mass spectrometry (MS) method termed SOP-MS for label-free global single-cell proteomics. SOP-MS capitalizes on the combination of a MS-compatible nonionic surfactant, n-Dodecyl-β-D-maltoside, and hydrophobic surface-based low-bind tubes or multi-well plates for ‘all-in-one’ one-pot sample preparation. This ‘all-in-one’ method including elimination of all sample transfer steps maximally reduces surface adsorption losses for effective processing of single cells, thus improving detection sensitivity for single-cell proteomics. This method allows convenient label-free quantification of hundreds of proteins from single human cells and ~1200 proteins from small tissue sections (close to ~20 cells). When applied to a patient CTC-derived xenograft (PCDX) model at the single-cell resolution, SOP-MS can reveal distinct protein signatures between primary tumor cells and early metastatic lung cells, which are related to the selection pressure of anti-tumor immunity during breast cancer metastasis. The approach paves the way for routine, precise, quantitative single-cell proteomics.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Host cell and viral protease targets of human SERPINs identified by in silico docking

Serine protease inhibitors (SERPINs) are involved in various physiological processes and diseases, such as inflammation, cancer metastasis, and neurodegeneration. Their role in viral infections is poorly understood, as their expression patterns during infection and the range of proteases they target have yet to be fully characterized. Here, we show widespread expression of human SERPINs in response to respiratory virus infections, both in bronchioalveolar lavages from COVID-19 patients and in polarized human airway epithelial cultures. Using in silico docking of 10 SERPINs to 48 host proteases, we confirm known targets and predict new interactions. Protease activity assays validated selected interactions, confirming the newly predicted host targets for PAI-1 (SERPINE1) and PAI-2 (SERPINB2). PAI-1 inhibits cathepsin L, essential for SARS-CoV-2 maturation, and suppresses multi-cycle replication of both ancestral SARS-CoV-2 WA-1 and its variant Omicron BA.1. In addition, we identify PAI-2 as an antiviral SERPIN that reduces infectivity of human adenovirus 5 by directly inhibiting the adenoviral protease. Our study leverages in silico docking using full-length 3D protein structures to uncover new SERPIN targets, offering a range of candidate targets for therapeutic interventions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms

Determinants for molecular and structural instability, that is, impending growth or rupture, of intracranial aneurysms (IAs) remain uncertain. To elucidate this, we endeavored to estimate the actual turnover rates of the main molecular constituent in human IA (collagen) on the basis of radiocarbon ( 14 C) birth dating in relation to IA hemodynamics. Collagen turnover rates in excised human IA samples were calculated using mathematical modeling of 14 C birth dating data of collagen in relation to risk factors and histological markers for collagen maturity/turnover in selected IA. Hemodynamics were simulated using image-based computational fluid dynamics. Correlation, logistic regression, and receiver operating characteristic analyses were performed. Collagen turnover rates were estimated in 46 IA (43 patients); computational fluid dynamics could be performed in 20 IA (20 patients). The mean collagen turnover rate (γ) constituted 126% (±1% error) per year. For patients with arterial hypertension, γ was greater than 2600% annually, whereas γ was distinctly lower with 32% (±1% error) per year for patients without risk factors, such as smoking and hypertension. There was a distinct association between histological presence of rather immature collagen in human IA and the presence of modifiable risk factors. Spatial-temporal averaged wall shear stress predicted rapid collagen turnover (odds ratio, 1.6 [95% CI, 1.0–2.7]). Receiver operating characteristic analysis demonstrated a good test accuracy (area under the curve, 0.798 [95% CI, 0.598–0.998]) for average wall shear stress with a threshold ≥4.9 Pa for rapid collagen turnover. Our data indicate that turnover rates and stability of collagen in human IA are strongly associated with the presence of modifiable risk factors and aneurysmal hemodynamics. Finally, these findings underline the importance of strict risk factor modification in patients with unruptured IA. Future should include more detailed risk factor data to establish a more causal understanding of hemodynamics and the rupture risk of individual IA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients’ platelets

Highlights: • 4996 mRNAs and 2942 circRNAs were identified differentially expressed in platelets of AS patients. • Several platelet-derived immune mediators were upregulated to regulate the interaction between platelets and immune cells. • Two downregulated circRNA were identified, and the corresponding circRNA-miRNA-mRNA regulatory network was constructed. • mRNAs and circRNAs found herein could be used as diagnostic biomarkers or new therapeutic targets. Ankylosing spondylitis (AS) is a chronic inflammatory disease significantly decreasing the quality of life. Platelets play an important and active role in the development of AS. Accumulating evidence demonstrated platelets contain diverse RNA repository inherited from megakaryocytes or microvesicles. Platelet RNAs are dynamically affected by pathological conditions and could be used as diagnostic or prognostic biomarkers. However, the role of the platelet RNAs in AS is elusive. In this study, we compared mRNA and circRNA profiles in platelets between AS patients and healthy controls using RNA sequencing and bioinformatic analysis, and found 4996 mRNAs and 2942 circRNAs were differently expressed. The significantly over-expressed mRNAs in AS patients are involved in platelet activity, gap junction, focal adhesion, rap1 and toll and Imd signaling pathway. The previous identified platelet-derived immune mediators such as P2Y1, P2Y12, PF4, GPIbα, CD40L, ICAM2, CCL5 (RANTES), TGF-β (TGF-β1 and TGF-β2) and PDGF (PDGFB and PDGFA) are also included in these over expressed mRNAs, implying these factors may trigger inflammatory cascades and promote the development of AS. Additionally, we found two down-regulated circRNA (circPTPN22 and circFCHSD2) from the intersection analyses of platelets and spinal ligament tissues of AS patients. The circRNA-miRNA-mRNA regulatory network of these two circRNAs was constructed, and the target mRNAs were enriched in Th17 cell differentiation, inflammatory bowel disease, cell adhesion molecules, cytokine-cytokine receptor interaction, Jak-STAT and Wnt signaling pathway, all these pathways participate in the bone remodeling and pro/anti-inflammatory immune regulation in AS. Then, qRT-PCR was performed to validate the expression of selected key mRNAs and circRNAs and the results demonstrated that the expression levels of P2Y12, GPIbα, circPTPN22 and circFCHSD2 were consistent with the sequencing analysis. In addition, the high expression of five predicted miRNAs interacting with circPTPN22 and circFCHSD2 were also detected in AS by qRT-PCR. Taken together, our study presents a comprehensive overview of mRNAs and circRNAs in platelets in AS patients and offers new insight into the mechanisms of platelet involving in the pathogenesis of AS. The mRNAs and circRNAs identified in this study may serve as candidates for diagnosis and targeted treatment of AS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Overexpression and surface localization of HPRT in prostate cancer provides a potential target for cancer specific antibody mediated cellular cytotoxicity

Highlights: • HPRT is heterogeneously expressed in prostate cancer cells, with surface HPRT being expressed in a p53-dependent fashion. • HPRT is localized to the surface of DU145 prostate cancer cells and is targeted specifically to induce anti-tumor efficacy. • Reductions in p53 expression correspond to reductions in HPRT internal and surface expression within mutant p53 cell lines. We chose to evaluate Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) as a possible biomarker for prostate cancer due to its involvement in nucleotide synthesis and cell cycle progression. We utilized two prostate cancer cell lines (PC3 and DU145) along with patient tissue and knockdowns to evaluate overall HPRT expression. The surface localization of HPRT was determined utilizing flow cytometry, confocal microscopy, and scanning electron microscopy followed by ADCC to evaluate targeting potential. We found significant upregulation of HPRT within malignant samples with approximately 47% of patients had elevated levels of HPRT compared to normal controls. We also observed a significant association between HPRT and the plasma membrane of DU145 cells (p = 0.0004), but found no presence on PC3 cells (p = 0.14). This was confirmed with scanning electron microscopy and confocal microscopy. ADCC experiments were performed to determine whether HPRT could be used as a target antigen for selective cell-mediated killing. We found that DU145 cells treated with HPRT antibodies had a significantly higher incidence of cell death than both isotype treated samples and PC3 cells treated with the same concentrations of HPRT antibody. Finally, we determined that p53 had a significant impact on HPRT expression both internally and on the surface of cancer cells. These results suggest HPRT as a possible biomarker target for the treatment of patients with prostate cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Patient mutations in human ATP:cob(I)alamin adenosyltransferase differentially affect its catalytic versus chaperone functions

Human ATP:cob(I)alamin adenosyltransferase (ATR) is a mitochondrial enzyme that catalyzes an adenosyl transfer to cob(I)alamin, synthesizing 5'-deoxyadenosylcobalamin (AdoCbl) or coenzyme B 12 . ATR is also a chaperone that escorts AdoCbl, transferring it to methylmalonyl-CoA mutase, which is important in propionate metabolism. Mutations in ATR lead to methylmalonic aciduria type B, an inborn error of B12 metabolism. Our previous studies have furnished insights into how ATR protein dynamics influence redox-linked cobalt coordination chemistry, controlling its catalytic versus chaperone functions. In this study, we have characterized three patient mutations at two conserved active site residues in human ATR, R190C/H, and E193K and obtained crystal structures of R190C and E193K variants, which display only subtle structural changes. All three mutations were found to weaken affinities for the cob(II)alamin substrate and the AdoCbl product and increase K M(ATP) . 31 P NMR studies show that binding of the triphosphate product, formed during the adenosylation reaction, is also weakened. However, although the k cat of this reaction is significantly diminished for the R190C/H mutants, it is comparable with the WT enzyme for the E193K variant, revealing the catalytic importance of Arg-190. Furthermore, although the E193K mutation selectively impairs the chaperone function by promoting product release into solution, its catalytic function might be unaffected at physiological ATP concentrations. In contrast, the R190C/H mutations affect both the catalytic and chaperoning activities of ATR. Because the E193K mutation spares the catalytic activity of ATR, our data suggest that the patients carrying this mutation are more likely to be responsive to cobalamin therapy.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Kinetic analysis of Cas12a and Cas13a RNA-Guided nucleases for development of improved CRISPR-Based diagnostics

Bacterial CRISPR systems provide acquired immunity against invading nucleic acids by activating RNA-programmable RNases and DNases. Cas13a and Cas12a enzymes bound to CRISPR RNA (crRNA) recognize specific nucleic acid targets, initiating cleavage of the targets as well as non-target (trans) nucleic acids. Here, we examine the kinetics of single-turnover target and multi-turnover trans-nuclease activities of both enzymes. High-turnover, non-specific Cas13a trans-RNase activity is coupled to rapid binding of target RNA. By contrast, low-turnover Cas12a trans-nuclease activity is coupled to relatively slow cleavage of target DNA, selective for DNA over RNA, indifferent to base identity, and preferential for single-stranded substrates. Combining multiple crRNA increases detection sensitivity of targets, an approach we use to quantify pathogen DNA in samples from patients suspected of Buruli ulcer disease. Results reveal that these enzymes are kinetically adapted to play distinct roles in bacterial adaptive immunity and show how kinetic analysis can be applied to CRISPR-based diagnostics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Carbapenems drive the collateral resistance to ceftaroline in cystic fibrosis patients with MRSA

Chronic airways infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with worse respiratory disease cystic fibrosis (CF) patients. Ceftaroline is a cephalosporin that inhibits the penicillin-binding protein (PBP2a) uniquely produced by MRSA. We analyzed 335 S. aureus isolates from CF sputum samples collected at three US centers between 2015–2018. Molecular relationships demonstrated that high-level resistance of preceding isolates to carbapenems were associated with subsequent isolation of ceftaroline resistant CF MRSA. In vitro evolution experiments showed that pre-exposure of CF MRSA to meropenem with further selection with ceftaroline implied mutations in mecA and additional mutations in pbp1 and pbp2 , targets of carbapenems; no effects were achieved by other β-lactams. An in vivo pneumonia mouse model showed the potential therapeutic efficacy of ceftaroline/meropenem combination against ceftaroline-resistant CF MRSA infections. Thus, the present findings highlight risk factors and potential therapeutic strategies offering an opportunity to both prevent and address antibiotic resistance in this patient population.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Pressured cytotoxic T cell epitope strength among SARS-CoV-2 variants correlates with COVID-19 severity

Heterogeneity in susceptibility among individuals to COVID-19 has been evident through the pandemic worldwide. Cytotoxic T lymphocyte (CTL) responses generated against pathogens in certain individuals are known to impose selection pressure on the pathogen, thus driving emergence of new variants. In this study, we probe the role played by host genetic heterogeneity in terms of HLA-genotypes in determining differential COVID-19 severity in patients. We use bioinformatic tools for CTL epitope prediction to identify epitopes under immune pressure. Using HLA-genotype data of COVID-19 patients from a local cohort, we observe that the recognition of pressured epitopes from the parent strain Wuhan-Hu-1 correlates with COVID-19 severity. We also identify and rank list HLA-alleles and epitopes that offer protectivity against severe disease in infected individuals. Finally, we shortlist a set of 6 pressured and protective epitopes that represent regions in the viral proteome that are under high immune pressure across SARS-CoV-2 variants. In conclusion, identification of such epitopes, defined by the distribution of HLA-genotypes among members of a population, could potentially aid in prediction of indigenous variants of SARS-CoV-2 and other pathogens.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Emergence of nosocomial associated opportunistic pathogens in the gut microbiome after antibiotic treatment

Introduction: According to the Centers for Disease Control’s 2015 Hospital Acquired Infection Hospital Prevalence Survey, 1 in 31 hospital patients was infected with at least one nosocomial pathogen while being treated for unrelated issues. Many studies associate antibiotic administration with nosocomial infection occurrence. However, to our knowledge, there is little to no direct evidence of antibiotic administration selecting for nosocomial opportunistic pathogens. Aim: This study aims to confirm gut microbiota shifts in an animal model of antibiotic treatment to determine whether antibiotic use favors pathogenic bacteria. Methodology: We utilized next-generation sequencing and in-house metagenomic assembly and taxonomic assignment pipelines on the fecal microbiota of a urinary tract infection mouse model with and without antibiotic treatment. Results: Antibiotic therapy decreased the number of detectable species of bacteria by at least 20-fold. Furthermore, the gut microbiota of antibiotic treated mice had a significant increase of opportunistic pathogens that have been implicated in nosocomial infections, like Acinetobacter calcoaceticus/baumannii complex, Chlamydia abortus, Bacteroides fragilis, and Bacteroides thetaiotaomicron. Moreover, antibiotic treatment selected for antibiotic resistant gene enriched subpopulations for many of these opportunistic pathogens. Conclusions: Oral antibiotic therapy may select for common opportunistic pathogens responsible for nosocomial infections. In this study opportunistic pathogens present after antibiotic therapy harbored more antibiotic resistant genes than populations of opportunistic pathogens before treatment. Our results demonstrate the effects of antibiotic therapy on induced dysbiosis and expansion of opportunistic pathogen populations and antibiotic resistant subpopulations of those pathogens. Follow-up studies with larger samples sizes and potentially controlled clinical investigations should be performed to confirm our findings.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Capability: Selective Endotoxin Uptake

Researchers at Los Alamos National Lab are developing a new capability to selectively absorb lipopolysaccharide, also known as endotoxin. Current sepsis treatment technologies generally target the bacteria causing the infection, but do not mitigate the host response that causes sickness. This disruptive capability could enable the removal of endotoxin from patient blood adding a much needed tool to the toolkit of sepsis treatments. We are seeking a CRADA partner with the desire to develop sepsis treatments and collaborate on the next steps.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1993

Rehabilitation Tool

Biotran, or Fastex as named by Cybex, the company that manufactures it, is a force sensing system that helps physicians and physical therapists treat people with movement deficiencies. Based on NASA sensor technology, it also has applications in sports training and evaluation. Biotran provides a means of testing weight-bearing capabilities that may have been compromised by injury or disease. It also assists in the rehabilitation process by putting patients through a course of computer-directed exercises designed to improve strength and balance reaction time. The system tests and documents progress until maximum medical improvement is achieved. Lewis Research Center also assisted the company in the selection of the material used in the Biotran force sensing platforms. Biotran is currently manufactured by Cybex under the name Fastex.

Source record↗
NASA NTRS1995

Rheoencephalographic (REG) Assessment of Head and Neck Cooling for use with Multiple Sclerosis Patients

We have prepared a computer program (RHEOSYS:RHEOencephalographic impedance trace scanning SyStem) that can be used to automate the analysis of segmental impedance blood flow waveforms. This program was developed to assist in the post test analysis of recorded impedance traces from multiple segments of the body. It incorporates many of the blood flow, segmental volume, and vascular state indices reported in the world literature. As it is currently programmed, seven points are selected from each blood flow pulse and associated ECG waveforrn: 1. peak of the first ECG QRS complex, 2. start of systolic slope on the blood flow trace, 3. maximum amplitude of the impedance pulse, 4. position of the dicrotic notch, 5. maximum amplitude of the postdicrotic segment, 6. peak of the second ECG QRS complex, and 7. start of the next blood flow pulse. These points we used to calculate various geometric, area, and time-related values associated with the impedance pulse morphology. RHEOSYS then calculates a series of 34 impedance and cardiac cycle parameters which include pulse amplitudes; areas; pulse propagation times; cardiac cycle times; and various measures of arterial and various tone, contractility, and pulse volume. We used this program to calculate the scalp and intracranial blood flow responses to head and neck cooling as it may be applied to lower the body temperatures of multiple sclerosis patients. Twelve women and twelve men were tested using a commercially available head and neck cooling system operated at its maximum cooling capacity for a period of 30 minutes. Head and neck cooling produced a transient change in scalp blood flow and a significant, (P<0.05) decrease of approx. 30% in intracranial blood flow. Results of this experiment will illustrate how REG and RHEOSYS can be used in biomedical applications.

Montogomery, Leslie D.↗