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At least 145 records · Page 8

XPCA - R Implementation

Principal component analysis (PCA) is arguably the most popular tool in multivariate exploratory data analysis. We consider the question of how to handle heterogeneous variables that include continuous, binary, and ordinal. In the probabilistic interpretation of low-rank PCA, the data has a normal multivariate distribution and, therefore, normal marginal distributions for each column. If some marginals are continuous but not normal, the semiparametric copula-based principal component analysis (COCA) method is an alternative to PCA that combines a Gaussian copula with nonparametric marginals. If some marginals are discrete or semi-continuous, we present a new extended PCA (XPCA) method that also uses a Gaussian copula and nonparametric marginals and accounts for discrete variables in the likelihood calculation by integrating over appropriate intervals. Like PCA, the factors produced by XPCA can be used to find latent structure in data, build predictive models, and perform dimensionality reduction. We implement the new model, XPCA, and its ancestors PCA and COCA in both R and Python. This software provides implementations of XPCA, COCA, and probabilistic PCA in both R and Python. XPCA is written in arXiv report https://arxiv.org/abs/1808.07510. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA0003525. SAND2019-10591 M

Kincher-Winoto, Kina↗

XPCA -Python Implementation

Principal component analysis (PCA) is arguably the most popular tool in multivariate exploratory data analysis. We consider the question of how to handle heterogeneous variables that include continuous, binary, and ordinal. In the probabilistic interpretation of low-rank PCA, the data has a normal multivariate distribution and, therefore, normal marginal distributions for each column. If some marginals are continuous but not normal, the semiparametric copula-based principal component analysis (COCA) method is an alternative to PCA that combines a Gaussian copula with nonparametric marginals. If some marginals are discrete or semi-continuous, we present a new extended PCA (XPCA) method that also uses a Gaussian copula and nonparametric marginals and accounts for discrete variables in the likelihood calculation by integrating over appropriate intervals. Like PCA, the factors produced by XPCA can be used to find latent structure in data, build predictive models, and perform dimensionality reduction. We implement the new model, XPCA, and its ancestors PCA and COCA in both R and Python. This software provides implementations of XPCA, COCA, and probabilistic PCA in both R and Python. XPCA is written in arXiv report https://arxiv.org/abs/1808.07510. SAND2019-10591 M Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Kincher-Winoto, Kina↗

The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30–84

Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30–84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surfaceattached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30–84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conducted comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30–84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage- derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30–84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities.

59 BASIC BIOLOGICAL SCIENCES↗

Simulator Evaluation of Simplified Propulsion-Only Emergency Flight Control Systems on Transport Aircraft

With the advent of digital engine control systems, considering the use of engine thrust for emergency flight control has become feasible. Many incidents have occurred in which engine thrust supplemented or replaced normal aircraft flight controls. In most of these cases, a crash has resulted, and more than 1100 lives have been lost. The NASA Dryden Flight Research Center has developed a propulsion-controlled aircraft (PCA) system in which computer-controlled engine thrust provides emergency flight control capability. Using this PCA system, an F-15 and an MD-11 airplane have been landed without using any flight controls. In simulations, C-17, B-757, and B-747 PCA systems have also been evaluated successfully. These tests used full-authority digital electronic control systems on the engines. Developing simpler PCA systems that can operate without full-authority engine control, thus allowing PCA technology to be installed on less capable airplanes or at lower cost, is also a desire. Studies have examined simplified ?PCA Ultralite? concepts in which thrust control is provided using an autothrottle system supplemented by manual differential throttle control. Some of these concepts have worked well. The PCA Ultralite study results are presented for simulation tests of MD-11, B-757, C-17, and B-747 aircraft.

Burcham, Frank W., Jr.↗

The Application of Infrared Thermographic Inspection Techniques to the Space Shuttle Thermal Protection System

The Nondestructive Evaluation Sciences Branch at NASA s Langley Research Center has been actively involved in the development of thermographic inspection techniques for more than 15 years. Since the Space Shuttle Columbia accident, NASA has focused on the improvement of advanced NDE techniques for the Reinforced Carbon-Carbon (RCC) panels that comprise the orbiter s wing leading edge. Various nondestructive inspection techniques have been used in the examination of the RCC, but thermography has emerged as an effective inspection alternative to more traditional methods. Thermography is a non-contact inspection method as compared to ultrasonic techniques which typically require the use of a coupling medium between the transducer and material. Like radiographic techniques, thermography can be used to inspect large areas, but has the advantage of minimal safety concerns and the ability for single-sided measurements. Principal Component Analysis (PCA) has been shown effective for reducing thermographic NDE data. A typical implementation of PCA is when the eigenvectors are generated from the data set being analyzed. Although it is a powerful tool for enhancing the visibility of defects in thermal data, PCA can be computationally intense and time consuming when applied to the large data sets typical in thermography. Additionally, PCA can experience problems when very large defects are present (defects that dominate the field-of-view), since the calculation of the eigenvectors is now governed by the presence of the defect, not the "good" material. To increase the processing speed and to minimize the negative effects of large defects, an alternative method of PCA is being pursued where a fixed set of eigenvectors, generated from an analytic model of the thermal response of the material under examination, is used to process the thermal data from the RCC materials. Details of a one-dimensional analytic model and a two-dimensional finite-element model will be presented. An overview of the PCA process as well as a quantitative signal-to-noise comparison of the results of performing both embodiments of PCA on thermographic data from various RCC specimens will be shown. Finally, a number of different applications of this technology to various RCC components will be presented.

Cramer, K. E.↗

The Application of Principal Component Analysis Using Fixed Eigenvectors to the Infrared Thermographic Inspection of the Space Shuttle Thermal Protection System

The Nondestructive Evaluation Sciences Branch at NASA s Langley Research Center has been actively involved in the development of thermographic inspection techniques for more than 15 years. Since the Space Shuttle Columbia accident, NASA has focused on the improvement of advanced NDE techniques for the Reinforced Carbon-Carbon (RCC) panels that comprise the orbiter s wing leading edge. Various nondestructive inspection techniques have been used in the examination of the RCC, but thermography has emerged as an effective inspection alternative to more traditional methods. Thermography is a non-contact inspection method as compared to ultrasonic techniques which typically require the use of a coupling medium between the transducer and material. Like radiographic techniques, thermography can be used to inspect large areas, but has the advantage of minimal safety concerns and the ability for single-sided measurements. Principal Component Analysis (PCA) has been shown effective for reducing thermographic NDE data. A typical implementation of PCA is when the eigenvectors are generated from the data set being analyzed. Although it is a powerful tool for enhancing the visibility of defects in thermal data, PCA can be computationally intense and time consuming when applied to the large data sets typical in thermography. Additionally, PCA can experience problems when very large defects are present (defects that dominate the field-of-view), since the calculation of the eigenvectors is now governed by the presence of the defect, not the good material. To increase the processing speed and to minimize the negative effects of large defects, an alternative method of PCA is being pursued when a fixed set of eigenvectors is used to process the thermal data from the RCC materials. These eigen vectors can be generated either from an analytic model of the thermal response of the material under examination, or from a large cross section of experimental data. This paper will provide the details of the analytic model; an overview of the PCA process; as well as a quantitative signal-to-noise comparison of the results of performing both embodiments of PCA on thermographic data from various RCC specimens. Details of a system that has been developed to allow insitu inspection of a majority of shuttle RCC components will be presented along with the acceptance test results for this system. Additionally, the results of applying this technology to the Space Shuttle Discovery after its return from flight will be presented.

Cramer, K. Elliott↗

Epidural Analgesia Versus Patient-Controlled Analgesia for Pain Relief in Uterine Artery Embolization for Uterine Fibroids: A Decision Analysis

Purpose: This study was designed to compare the costs and effects of epidural analgesia (EDA) to those of patient-controlled intravenous analgesia (PCA) for postintervention pain relief in women having uterine artery embolization (UAE) for systematic uterine fibroids. Methods: Cost-effectiveness analysis (CEA) based on data from the literature by constructing a decision tree to model the clinical pathways for estimating the effects and costs of treatment with EDA and PCA. Literature on EDA for pain-relief after UAE was missing, and therefore, data on EDA for abdominal surgery were used. Outcome measures were compared costs to reduce one point in visual analogue score (VAS) or numeric rating scale (NRS) for pain 6 and 24 h after UAE and risk for complications. Results: Six hours after the intervention, the VAS was 3.56 when using PCA and 2.0 when using EDA. The costs for pain relief in women undergoing UAE with PCA and EDA were Euro-Sign 191 and Euro-Sign 355, respectively. The costs for EDA to reduce the VAS score 6 h after the intervention with one point compared with PCA were Euro-Sign 105 and Euro-Sign 179 after 24 h. The risk of having a complication was 2.45 times higher when using EDA. Conclusions: The results of this indirect comparison of EDA for abdominal surgery with PCA for UAE show that EDA would provide superior analgesia for post UAE pain at 6 and 24 h but with higher costs and an increased risk of complications.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Fenofibrate inhibits the growth of prostate cancer through regulating autophagy and endoplasmic reticulum stress

Highlights: • Fenofibrate induces cell apoptosis in prostate cancer. • Fenofibrate blocks complete autophagy flux via regulating AMPK-mTOR pathway. • Fenofibrate stimulates endoplasmic reticulum stress. • Fenofibrate inhibits in vivo growth of prostate cancer in mice. Fenofibrate is a fibric acid derivative which exhibits a role of peroxisome proliferator-activated receptor-alpha agonist. It is widely utilized in therapy of hyperlipidemia and hypercholesterolemia. Its anticancer function is discovered in recent years. However, the role of fenofibrate in prostate cancer (PCa) is poorly understood. In this study, we investigated the function and mechanism of fenofibrate in PCa cells. Firstly, fenofibrate treated PCa cells showed more apoptosis compared with the control group. Further, we found that fenofibrate induced autophagy but finally blocked its complete flux in PCa cells through regulating AMPK-mTOR pathway. The intermediate metabolite from uncompleted autophagy induced endoplasmic reticulum stress (ER stress) via PERK and IRE1 signalings. In vivo mice model confirmed that fenofibrate inhibited the growth of PCa. This study suggests that fenofibrate is an effective inhibitor of PCa by regulating autophagy and ER stress.

60 APPLIED LIFE SCIENCES↗

LINC00992 exerts oncogenic activities in prostate cancer via regulation of SOX4

Highlights: • LNC992 is significantly overexpressed in PCa and is associated with poor prognosis. • LNC992 is associated with the malignant biological behavior of PCa cells. • LNC992 can positively regulate the expression of SOX4. • LNC992 binds to EIF4A3. • SOX4 abrogates the repressive effects of sh-LNC992 on the PCa cell viability. The critical role of long non-coding RNAs (lncRNAs) has been implicated in prostate cancer (PCa). As one of them, LINC00992 (LNC992) has been revealed by bioinformatics prediction to be significantly overexpressed in PCa. However, the underlying mechanism of LNC992 in PCa has not been well investigated.

60 APPLIED LIFE SCIENCES↗

Contact- and distance-based principal component analysis of protein dynamics

To interpret molecular dynamics simulations of complex systems, systematic dimensionality reduction methods such as principal component analysis (PCA) represent a well-established and popular approach. Apart from Cartesian coordinates, internal coordinates, e.g., backbone dihedral angles or various kinds of distances, may be used as input data in a PCA. Adopting two well-known model problems, folding of villin headpiece and the functional dynamics of BPTI, a systematic study of PCA using distance-based measures is presented which employs distances between C{sub α}-atoms as well as distances between inter-residue contacts including side chains. While this approach seems prohibitive for larger systems due to the quadratic scaling of the number of distances with the size of the molecule, it is shown that it is sufficient (and sometimes even better) to include only relatively few selected distances in the analysis. The quality of the PCA is assessed by considering the resolution of the resulting free energy landscape (to identify metastable conformational states and barriers) and the decay behavior of the corresponding autocorrelation functions (to test the time scale separation of the PCA). By comparing results obtained with distance-based, dihedral angle, and Cartesian coordinates, the study shows that the choice of input variables may drastically influence the outcome of a PCA.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Principal component analysis of computed emission lines from protostellar jets

A very important issue concerning protostellar jets is the mechanism behind their formation. Obtaining information on the region at the base of a jet can shed light on the subject, and some years ago this was done through a search for a rotational signature in the jet line spectrum. The existence of such signatures, however, remains controversial. In order to contribute to the clarification of this issue, in this paper we show that principal component analysis (PCA) can potentially help to distinguish between rotation and precession effects in protostellar jet images. This method reduces the dimensions of the data, facilitating the efficient extraction of information from large data sets such as those arising from integral field spectroscopy. PCA transforms the system of correlated coordinates into a system of uncorrelated coordinates, the eigenvectors, ordered by principal components of decreasing variance. The projection of the data on these coordinates produces images called tomograms, while eigenvectors can be displayed as eigenspectra. The combined analysis of both can allow the identification of patterns correlated to a particular physical property that would otherwise remain hidden, and can help to separate the effects of physically uncorrelated phenomena in the data. These are, for example, rotation and precession in the kinematics of a stellar jet. In order to show the potential of PCA analysis, we apply it to synthetic spectro-imaging datacubes generated as an output of numerical simulations of protostellar jets. In this way we generate a benchmark with which a PCA diagnostics of real observations can be confronted. Using the computed emission line profiles for [O i]λ6300 and [S ii]λ6716, we recover and analyze the effects of rotation and precession in tomograms generated by PCA. We show that different combinations of the eigenvectors can be used to enhance and to identify the rotation features present in the data. Our results indicate that PCA can be useful for disentangling rotation from precession in jets with an inclination of the jet with respect to the plane of the sky as high as 45°. We have been able to recover the initially imposed rotation jet profile for models at a moderate inclination angle (ϕ≪15°) and without precession.

79 ASTRONOMY AND ASTROPHYSICS↗

Modelling baryonic physics in future weak lensing surveys

Modifications of the matter power spectrum due to baryonic physics are one of the major theoretical uncertainties in cosmological weak lensing measurements. Developing robust mitigation schemes for this source of systematic uncertainty increases the robustness of cosmological constraints, and may increase their precision if they enable the use of information from smaller scales. Here we explore the performance of two mitigation schemes for baryonic effects in weak lensing cosmic shear: the principal component analysis (PCA) method and the halo-model approach in hmcode. We construct mock tomographic shear power spectra from four hydrodynamical simulations, and run simulated likelihood analyses with cosmolike assuming LSST-like survey statistics. With an angular scale cut of ℓmax < 2000, both methods successfully remove the biases in cosmological parameters due to the various baryonic physics scenarios, with the PCA method causing less degradation in the parameter constraints than hmcode. For a more aggressive ℓmax = 5000, the PCA method performs well for all but one baryonic physics scenario, requiring additional training simulations to account for the extreme baryonic physics scenario of Illustris; hmcode exhibits tensions in the 2D posterior distributions of cosmological parameters due to lack of freedom in describing the power spectrum for $k \gt 10\ h^{-1}\, \mathrm{Mpc}$. We investigate variants of the PCA method and improve the bias mitigation through PCA by accounting for the noise properties in the data via Cholesky decomposition of the covariance matrix. Our improved PCA method allows us to retain more statistical constraining power while effectively mitigating baryonic uncertainties even for a broad range of baryonic physics scenarios.

79 ASTRONOMY AND ASTROPHYSICS↗

Lignin structural changes and high p -coumaroylation in incipient lignification in moso bamboo

Lignification is a crucial process for strengthening plant tissues, facilitating water transport, and providing defense against pathogens. In the Poaceae family, p-hydroxycinnamic acids are commonly incorporated into lignin, with acylation by p-coumarate (pCA) occurring during lignification. In this study, we performed DFRC and 2D HSQC-NMR analyses to investigate changes in lignin substructures and the degree of lignin pCA-acylation throughout bamboo stem development. Furthermore, immunohistochemical analysis was conducted to elucidate the spatial distribution of lignin substructures within different cell types. Our results revealed that, in young tissues, β–O–4-linked lignin units are predominantly derived from monolignol-pCA conjugates, specifically coniferyl- and sinapyl-pCA. Both lignin structure and the pattern of pCA acylation varied depending on the stage of cell wall formation and the cell type, particularly between vascular fiber cells and parenchyma cells. Based on our results, moso bamboo culms exhibit a distinctive feature during incipient lignification, in which monolignols are predominantly acylated with pCA. As a result, this feature has not been reported in other grasses, suggesting that extensive p-coumaroylation of monolignols plays an important role in the rapid elongation of bamboo culms.

Munekata, Noriaki [Kyoto University (Japan); Unive↗

Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cells (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between benign and malignant origin. Validation showed a preferential abundance of PDCD6IP, FASN and XPO1. Cytoplasmic XPO1 is the most promising candidate biomarker.

biomarkers↗

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↗

Solar cosmic ray effects in the lower ionosphere

The polar cap absorption (PCA) events are the most remarkable geophysical phenomena in the high latitude ionosphere. Their effects are extended on the whole polar region in both hemispheres. The PCA events are caused by the intense fluxes of the solar cosmic rays (SCR) which are generated by the solar proton flares. Entering into the Earth's magnetosphere and ionosphere the SCR fluxes create excessive anomal ionization at the ionospheric heights of 50 to 100 km which exceeds usual undisturbed level of ionization in several orders of magnitude. The PCA events can be considered as catastrophic in relation to the polar ionosphere because all radio systems using ionospheric radio channels ceased to operate during these events. On the other hand the abnormally high level of ionization in the ionospheric D region during the PCA events create excellent opportunities to conduct fruitful aeronomical research for the lower ionosphere. Obvious scientific and practical importance of the PCA events leads to publishing of special PCA catalogues. The ionospheric effects caused by the SCR fluxes were profoundly described in the classical paper (Bailey, 1964). Nevertheless several aspects of this problem were not studied properly. An attempt is made to clarify these questions.

Shirochkov, A. V.↗

Development and Flight Evaluation of an Emergency Digital Flight Control System Using Only Engine Thrust on an F-15 Airplane

A propulsion-controlled aircraft (PCA) system for emergency flight control of aircraft with no flight controls was developed and flight tested on an F-15 aircraft at the NASA Dryden Flight Research Center. The airplane has been flown in a throttles-only manual mode and with an augmented system called PCA in which pilot thumbwheel commands and aircraft feedback parameters were used to drive the throttles. Results from a 36-flight evaluation showed that the PCA system can be used to safety land an airplane that has suffered a major flight control system failure. The PCA system was used to recover from a severe upset condition, descend, and land. Guest pilots have also evaluated the PCA system. This paper describes the principles of throttles-only flight control; a history of loss-of-control accidents; a description of the F-15 aircraft; the PCA system operation, simulation, and flight testing; and the pilot comments.

Burcham, Frank W., Jr.↗

Effect of Hindlimb Unloading on Rat Soleus Fiber Force, Stiffness, and Calcium Sensitivity

The purpose of this study was to examine the time course of change in soleus muscle fiber peak force (N), tension (P(sub 0), kN/sq m), elastic modulus (E(sub 0)), and force-pCa and stiffness - pCa relationships. After 1, 2, or 3 wk of Hindlimb Unloading (HU), single fibers were isolated and placed between a motor arm and a transducer, and fiber diameter, peak absolute force, P(sub 0), E(sub 0), and force-pCa and stiffness-pca relationships were characterized. One week of HU resulted in a significant reduction in fiber diameter (68 +/- 2 vs. 57 +/- 1 micrometer), force (3.59 +/- 0.15 vs. 2.19 +/- 0.12 x 10(exp -4) N), P(sub 0) (102 +/- 4 vs. 85 +/- 2 kN/sq m), and E(sub 0) (1.96 +/- 0.12 vs. 1.37 +/- 0.13 X 10(exp 7) N/sq m) and 2 wk of HU caused a further decline in fiber diameter (45 +/- 1 micrometer), force (1.31 +/- 0.06 x 10(exp -4) N), and E(sub 0)(0.96 +/- 0.09 x 10(exp 7) N/sq m). Although the mean fiber diameter and absolute force continued to decline through 3 wk of HU, P(sub 0) recovered to values not significantly different from control. The P(sub 0)/E(sub 0) ratio was significantly increased after 1 (5.5 +/- 0.3 to 7.1 +/- 0.6), 2, and 3 wk of HU, and the 2-wk (9.5 +/- 0.4) and 3-wk (9.4 +/- 0.8) values were significantly greater than the 1-wk values. The force-pCa and stiffness-pCa curves were shifted right- ward after 1, 2, and 3 wk of HU. At 1 wk of HU, the Ca(2+) sensitivity of isometric force, assessed by Ca(2+) concentration required for half-maximal force, was increased from the control value of 1.83 +/- 0.12 to 2.30 +/- 0.10 micrometers. In conclusion, after HU, the decrease in soleus fiber P(sub 0) can be explained by a reduction in the number of myofibrillar cross bridges per cross-sectional area. Our working hypothesis is that the loss of contractile protein reduces the number of cross bridges per cross-sectional area and increases the filament lattice spacing. The increased spacing reduces cross-bridge force and stiffness, but P(sub 0)/E(sub 0) increases because of a quantitatively greater effect on stiffness.

McDonald Kerry S.↗