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  • 1
    Language: English
    In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, April 2015, Vol.29(4), pp.1136-42
    Description: Interactions between dietary protein and energy balance on the regulation of human skeletal muscle protein turnover are not well described. A dietary protein intake above the recommended dietary allowance during energy balance typically enhances nitrogen retention and up-regulates muscle protein synthesis, which in turn may promote positive protein balance and skeletal muscle accretion. Recent studies show that during energy deficit, muscle protein synthesis is down-regulated with concomitant increases in ubiquitin proteasome-mediated muscle proteolysis and nitrogen excretion, reflecting the loss of skeletal muscle mass. However, consuming high-protein diets (1.6-2.4 g/kg per day), or high-quality, protein-based meals (15-30 g whey) during energy deficit attenuates intracellular proteolysis, restores muscle protein synthesis, and mitigates skeletal muscle loss. These findings are particularly important for physically active, normal-weight individuals because attenuating the extent to which skeletal muscle mass is lost during energy deficit could prevent decrements in performance, reduce injury risk, and facilitate recovery. This article reviews the relationship between energy status, protein intake, and muscle protein turnover, and explores future research directives designed to protect skeletal muscle mass in physically active, normal-weight adults.
    Keywords: Lean Body Mass ; Leucine ; Mtorc1 ; Military ; Diet ; Energy Intake ; Dietary Proteins -- Administration & Dosage ; Muscle, Skeletal -- Anatomy & Histology
    ISSN: 08926638
    E-ISSN: 1530-6860
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  • 2
    Language: English
    In: Diabetes, February 2014, Vol.63(2), pp.421-32
    Description: Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.
    Keywords: Adipose Tissue -- Cytology ; Dietary Fats -- Adverse Effects ; Iron -- Metabolism ; Macrophages -- Metabolism ; Obesity -- Chemically Induced
    ISSN: 00121797
    E-ISSN: 1939-327X
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  • 3
    Language: English
    In: PLoS ONE, 2012, Vol.7(2), p.e31508
    Description: Macrophage inflammatory protein-1α (CCL3) plays a well-known role in infectious and viral diseases; however, its contribution to atherosclerotic lesion formation and lipid metabolism has not been determined. Low density lipoprotein receptor deficient (LDLR −/− ) mice were transplanted with bone marrow from CCL3 −/− or C57BL/6 wild type donors. After 6 and 12 weeks on western diet (WD), recipients of CCL3 −/− marrow demonstrated lower plasma cholesterol and triglyceride concentrations compared to recipients of C57BL/6 marrow. Atherosclerotic lesion area was significantly lower in female CCL3 −/− recipients after 6 weeks and in male CCL3 −/− recipients after 12 weeks of WD feeding ( P 〈0.05). Surprisingly, male CCL3 −/− recipients had a 50% decrease in adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were also significantly lower. These results were specific to CCL3, as LDLR −/− recipients of monocyte chemoattractant protein −/− (CCL2) marrow were not protected from the metabolic consequences of high fat feeding. Despite these improvements in LDLR −/− recipients of CCL3 −/− marrow in the bone marrow transplantation (BMT) model, double knockout mice, globally deficient in both proteins, did not have decreased body weight, plasma lipids, or atherosclerosis compared with LDLR −/− controls. Finally, there were no differences in myeloid progenitors or leukocyte populations, indicating that changes in body weight and plasma lipids in CCL3 −/− recipients was not due to differences in hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid metabolism in hyperlipidemic mice following hematopoietic reconstitution.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Diabetes And Endocrinology
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: Journal of the Franklin Institute, March 2012, Vol.349(2), pp.476-492
    Description: Robust performance of a flight control system in the presence of parametric uncertainty and external disturbances is of paramount importance to a successful planetary exploration program. The present research is concerned with the design of an autopilot that uses high-order sliding mode (HOSM) control principles so as to enhance the robustness properties of a lunar landing vehicle during the approach phase of powered descent. The design technique is applied to a high-fidelity simulation of the Apollo Lunar Module (LM). The design efficiently utilizes both the reaction control system (RCS) actuators and the severely rate-limited gimbal drive actuator (GDA) to effect smooth detection and compensation of sensed angular acceleration disturbances about the vehicle's control axes. The integration of a HOSM control law for the RCS effectors with a HOSM disturbance observer is shown to provide performance comparable to that of the heritage autopilot and may also avoid some difficulties encountered in the Apollo flights. Performance is maintained with the controller implemented in discrete time in the presence of a realistic vehicle and sensor model, demonstrating a unique application of sliding mode control to a complex aerospace system. ► A lunar landing module is robustly controlled by HOSM controller during powered descent. ► The HOSM design technique is applied to a high-fidelity model of Apollo Lunar Module. ► The design utilizes both the reaction control system actuators and the gimbal drive actuator. ► Performance is maintained with the controller and the observer implemented in discrete time. ► The efficacy of the design is confirmed via simulation of the 6 DOF Apollo Lunar Module model.
    Keywords: Engineering
    ISSN: 0016-0032
    E-ISSN: 1879-2693
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  • 5
    Language: English
    In: Diabetes, November 2011, Vol.60(11), pp.2820-9
    Description: Mice with CCR2 deficiency are protected from insulin resistance but only after long periods of high-fat diet (HFD) feeding, despite the virtual absence of circulating inflammatory monocytes. We performed a time course study in mice with hematopoietic and global CCR2 deficiency to determine adipose tissue-specific mechanisms for the delayed impact of CCR2 deficiency on insulin resistance. Mice with global or hematopoietic CCR2 deficiency (CCR2(-/-) and BM-CCR2(-/-), respectively) and wild-type controls (CCR2(+/+) and BM-CCR2(+/+), respectively) were placed on an HFD for 6, 12, and 20 weeks. Adipose tissue myeloid populations, degree of inflammation, glucose tolerance, and insulin sensitivity were assessed. Flow cytometry analysis showed that two different populations of F4/80(+) myeloid cells (CD11b(lo)F4/80(lo) and CD11b(hi)F4/80(hi)) accumulated in the adipose tissue of CCR2(-/-) and BM-CCR2(-/-) mice after 6 and 12 weeks of HFD feeding, whereas only the CD11b(hi)F4/80(hi) population was detected in the CCR2(+/+) and BM-CCR2(+/+) controls. After 20 weeks of HFD feeding, the CD11b(lo)F4/80(lo) cells were no longer present in the adipose tissue of CCR2(-/-) mice, and only then were improvements in adipose tissue inflammation detected. Gene expression and histological analysis of the CD11b(lo)F4/80(lo) cells indicated that they are a unique undifferentiated monocytic inflammatory population. The CD11b(lo)F4/80(lo) cells are transiently found in wild-type mice, but CCR2 deficiency leads to the aberrant accumulation of these cells in adipose tissue. The discovery of this novel adipose tissue monocytic cell population provides advances toward understanding the pleiotropic role of CCR2 in monocyte/macrophage accumulation and regulation of adipose tissue inflammation.
    Keywords: Insulin Resistance ; Adipose Tissue -- Pathology ; Myeloid Cells -- Pathology ; Obesity -- Metabolism ; Receptors, Ccr2 -- Physiology
    ISSN: 00121797
    E-ISSN: 1939-327X
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  • 6
    Language: English
    In: Neuroscience and Biobehavioral Reviews, 2009, Vol.33(2), pp.116-124
    Description: The sympathetic nervous system (SNS) plays an essential role in the regulation of metabolic and cardiovascular homeostasis. Low SNS activity has been suggested to be a risk factor for weight gain and obesity development. In contrast, SNS activation is characteristic of a number of metabolic and cardiovascular diseases that occur more frequently in obese individuals. Until recently, the relation between obesity and SNS behavior has been controversial because previous approaches for assessing SNS activity in humans have produced inconsistent findings. Beginning in the early 1990s, many studies using state of the art neurochemical and neurophysiological techniques have provided important insight. The purpose of the present review is to provide an overview of our current understanding of the region specific alterations in SNS behavior in human obesity. We will discuss findings from our own laboratory which implicate visceral fat as an important depot linking obesity with skeletal muscle SNS activation. The influence of weight change on SNS behavior and the potential mechanisms and consequences of region specific SNS activation in obesity will also be considered.
    Keywords: Adiposity ; Autonomic Nervous System ; Muscle Sympathetic Nerve Activity ; Anatomy & Physiology
    ISSN: 0149-7634
    E-ISSN: 1873-7528
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  • 7
    Language: English
    In: Journal of visualized experiments : JoVE, 22 May 2013(75), pp.e50707
    Description: The discovery of increased macrophage infiltration in the adipose tissue (AT) of obese rodents and humans has led to an intensification of interest in immune cell contribution to local and systemic insulin resistance. Isolation and quantification of different immune cell populations in lean and obese AT is now a commonly utilized technique in immunometabolism laboratories; yet extreme care must be taken both in stromal vascular cell isolation and in the flow cytometry analysis so that the data obtained is reliable and interpretable. In this video we demonstrate how to mince, digest, and isolate the immune cell-enriched stromal vascular fraction. Subsequently, we show how to antibody label macrophages and T lymphocytes and how to properly gate on them in flow cytometry experiments. Representative flow cytometry plots from low fat-fed lean and high fat-fed obese mice are provided. A critical element of this analysis is the use of antibodies that do not fluoresce in channels where AT macrophages are naturally autofluorescent, as well as the use of proper compensation controls.
    Keywords: Adipose Tissue -- Cytology ; Flow Cytometry -- Methods ; Macrophages -- Cytology ; T-Lymphocytes -- Cytology
    E-ISSN: 1940-087X
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  • 8
    Language: English
    In: Journal of Aircraft, 2017, Vol.54(1), p.135(14)
    Description: A brief history of the X-15-3 adaptive control system and an analysis of the destructive limit-cycle oscillation that occurred during its final November 1967 flight are presented. The X-15 was a piloted single-seat rocket-propelled hypersonic research aircraft operated by the NASA Flight Research Center from 1959 until 1968. Due to the limited information previously available in the public domain and the 1968 decision by the accident investigation board to forego detailed analysis of the adaptive control system's role in the accident, it was widely assumed in the adaptive controls community that an anomalous behavior of the adaptive component caused the loss of control. Notwithstanding the complex human factors and subsystem failures that contributed to the accident, it is shown that the adaptation dynamics were not a causal factor. The limit cycle observed in the flight data is reproduced in a nonlinear time-domain simulation. Describing function analysis reveals that the instability was caused by a latent design error in the inner-loop structural filters that did not account for the nonlinear behavior of the X-15 servoactuator under rate saturation when coupled with the lightly damped aircraft longitudinal mode at high Mach numbers. DOI: 10.2514/1.C033703
    Keywords: Oscillations – Models ; Aircraft Piloting – Models ; Engineering Models – Usage
    ISSN: 0021-8669
    E-ISSN: 15333868
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  • 9
    Language: English
    In: Journal of Guidance, Control, and Dynamics, 03/2014, Vol.37(2), pp.374-382
    Description: A generalized approach to the allocation of redundant thrust vector slew commands for multi-actuated launch vehicles is presented, where deflection constraints are expressed as omniaxial or elliptical deflection limits in gimbal axes. More importantly than in the aircraft control...
    Keywords: Boosters ; Thrust ; Control Equipment ; Redundant ; Algorithms ; Deflection ; Linear Transformations ; Allocations ; Aerospace Engineering (General) (Mt) ; Guidance Systems (Ea) ; Information Storage, Retrieval, and Analysis (Ci) ; General (Ah);
    ISSN: 0731-5090
    E-ISSN: 1533-3884
    Source: American Institute of Aeronautics and Astronautics (via CrossRef)
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  • 10
    Language: English
    Description: The November 15, 1967, loss of X-15 Flight 3-65-97 (hereafter referred to as Flight 3-65) was a unique incident in that it was the first and only aerospace flight accident involving loss of crew on a vehicle with an adaptive flight control system (AFCS). In addition, Flight 3-65 remains the only incidence of a single-pilot departure from controlled flight of a manned entry vehicle in a hypersonic flight regime. To mitigate risk to emerging aerospace systems, the NASA Engineering and Safety Center (NESC) proposed a comprehensive review of this accident. The goal of the assessment was to resolve lingering questions regarding the failure modes of the aircraft systems (including the AFCS) and thoroughly analyze the interactions among the human agents and autonomous systems that contributed to the loss of the pilot and aircraft. This document contains the outcome of the accident review.
    Keywords: Space Transportation And Safety
    Source: NASA Center for AeroSpace Information (CASI)
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