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Haddad, F.

Publications and source records attributed to Haddad, F..

14 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Muon tracking in a LiquidO opaque scintillator detector

LiquidO is an innovative radiation detector concept. The core idea is to exploit stochastic light confinement in a highly scattering medium to self-segment the detector volume. In this paper, we demonstrate event-by-event muon tracking in a LiquidO opaque scintillator detector prototype. The detector consists of a 30 mm cubic scintillator volume instrumented with 64 wavelength-shifting fibres arranged in an 8 × 8 grid with a 3.2 mm pitch and read out by silicon photomultipliers. A wax-based opaque scintillator with a scattering length of approximately 0.5 mm is used. The tracking performance of this LiquidO detector is characterised with cosmic-ray muons and the position resolution is demonstrated to be 450 μm per row of fibres. These results highlight the potential of LiquidO opaque scintillator detectors to achieve fine spatial resolution, enabling precise particle tracking and imaging.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2025

COCOA: A compact Compton camera for astrophysical observation of MeV-scale gamma rays

COCOA (COmpact COmpton cAmera) is a next-generation gamma-ray telescope designed for astrophysical observations in the MeV energy range. The detector comprises a scatterer volume employing the LiquidO detection technology and an array of scintillating crystals acting as absorber. Surrounding plastic scintillator panels serve as a veto system for charged particles. The detector's compact, scalable design enables flexible deployment on microsatellites or high-altitude balloons. Gamma rays at MeV energies have not been well explored historically (the so-called "MeV gap") and COCOA has the potential to improve the sensitivity in this energy band.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2024

Characterization of a radiation detector based on opaque water-based liquid scintillator

Here, we present the characterization of a novel radiation detector based on an opaque water-based liquid scintillator. Opaque scintillators, also known as LiquidO, are made to be highly scattering, such that the scintillation light is effectively confined, and read out through wavelength-shifting fibers. The 1-liter, 32-channel prototype demonstrates the capability for both spectroscopy and topological reconstruction of point-like events. The design, construction, and evaluation of the detector are described, including modeling of the scintillation liquid optical properties and the detector’s response to gamma rays of several energies. A mean position reconstruction error of 4.4 mm for 1.6 MeV-equivalent events and 7.4 mm for 0.8 MeV-equivalent events is demonstrated using a simple reconstruction approach analogous to center-of-mass.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
NASA NTRS2007

The Artificial Gravity Bed Rest Pilot Project: Effects on Knee Extensor and Plantar Flexor Muscle Groups

The goal of this project was to examine the effects of artificial gravity (2.5 g) on skeletal muscle strength and key anabolic/catabolic markers known to regulate muscle mass. Two groups of subjects were selected for study: 1) a 21 day-bed rest (BR) control (C) group (N=7); and 2) an AG group (N=8), which was exposed to 21 days of bed-rest plus daily 1 hr exposures to AG (2.5 g). This particular experiment was part of an integrated AG Pilot Project sponsored by NASA/Johnson Space Center. The in vivo torque-velocity relationships of the knee extensors and plantar flexors of the ankle were determined pre and post treatment. Also, pre- and post treatment biopsy samples were obtained from both the vastus lateralis and soleus muscles and were used, in part, for a series of analyses on gene expression (mRNA abundance) of key factors implicated in the anabolic versus catabolic state of the muscle. Post/Pre toque-velocity determinations revealed greater decrements in knee extensor performance in the C versus AG group (P less than 0.04). The plantar flexor muscle group of the AG subjects actually demonstrated a net gain in torque-velocity relationship; whereas, in the C group the overall post/pre responses declined (AG vs C; P less than 0.001). Measurements of muscle fiber cross-sectional area (for both muscles) demonstrated a loss of approx. 20% in the C group while no losses were evident in the AG group. RT-PCR analyses of muscle biopsy specimens demonstrated that markers of growth and cytoskeletal integrity (IGF-1, IGF-1 BP4, mechano growth factor, total RNA, and pro-collagen 3a) were higher in the AG group, whereas catabolic markers (myostatin and atrogen) were elevated in the C group. Importantly, these patterns were seen in both muscles. Based on these observations we conclude that paradigms of AG have the potential to maintain the functional, biochemical, and structural homeostasis of skeletal muscle in the face of chronic unloading states. These findings also warrant further studies since it is likely that other robust paradigms of AG that employ various exercise strategies may be more effective in counteracting long duration unloading states as anticipated on the platforms of the Moon and Mars.

Caiozzo, V. J.↗
NASA NTRS2003

Transcriptional regulation of IGF-I expression in skeletal muscle

The present study investigated the role of transcription in the regulation of insulin-like growth factor (IGF)-I expression in skeletal muscle. RT-PCR was used to determine endogenous expression of IGF-I pre-mRNA and mRNA in control (Con) and functionally overloaded (FO) rat plantaris. The transcriptional activities of five different-length IGF-I promoter fragments controlling transcription of a firefly luciferase (FLuc) reporter gene were tested in vitro by transfection of myoblasts or in vivo during FO by direct gene transfer into the plantaris. Increased endogenous IGF-I gene transcription during 7 days of plantaris FO was evidenced by an approximately 140-160% increase (P < 0.0001) in IGF-I pre-mRNA (a transcriptional marker). IGF-I mRNA expression also increased by approximately 90% (P < 0.0001), and it was correlated (R = 0.93; P < 0.0001) with the pre-mRNA increases. The three longest IGF-I exon 1 promoters induced reporter gene expression in proliferating C2C12 and L6E9 myoblasts. In differentiated L6E9 myotubes, promoter activity increased approximately two- to threefold over myoblasts. Overexpression of calcineurin and MyoD increased the activity of the -852/+192 promoter in C2C12 myotubes by approximately 5- and approximately 18-fold, respectively. However, FO did not induce these exogenous promoter fragments. Nevertheless, the present findings are consistent with the hypothesis that the IGF-I gene is transcriptionally regulated during muscle hypertrophy in vivo as evidenced by the induction of the endogenous IGF-I pre-mRNA during plantaris FO. The exon 1 promoter region of the IGF-I gene is sufficient to direct inducible expression in vitro; however, an in vivo response to FO may require elements outside the -852/+346 region of the exon 1 IGF-I promoter or features inherent to the endogenous IGF-I gene.

Non-NASA Center↗
NASA NTRS2001

Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T(3), 3,5,3'-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T(3)/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T(3) or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T(3) and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.

NASA Discipline Musculoskeletal↗
NASA NTRS2000

In vivo regulation of the beta-myosin heavy chain gene in soleus muscle of suspended and weight-bearing rats

In the weight-bearing hindlimb soleus muscle of the rat, approximately 90% of muscle fibers express the beta-myosin heavy chain (beta-MHC) isoform protein. Hindlimb suspension (HS) causes the MHC isoform population to shift from beta toward the fast MHC isoforms. Our aim was to establish a model to test the hypothesis that this shift in expression is transcriptionally regulated through specific cis elements of the beta-MHC promoter. With the use of a direct gene transfer approach, we determined the activity of different length beta-MHC promoter fragments, linked to a firefly luciferase reporter gene, in soleus muscle of control and HS rats. In weight-bearing rats, the relative luciferase activity of the longest beta-promoter fragment (-3500 bp) was threefold higher than the shorter promoter constructs, which suggests that an enhancer sequence is present in the upstream promoter region. After 1 wk of HS, the reporter activities of the -3500-, -914-, and -408-bp promoter constructs were significantly reduced ( approximately 40%), compared with the control muscles. However, using the -215-bp construct, no differences in promoter activity were observed between HS and control muscles, which indicates that the response to HS in the rodent appears to be regulated within the -408 and -215 bp of the promoter.

Non-NASA Center↗
NASA NTRS1999

Myosin Heavy Chain Gene Expression in Developing Neonatal Skeletal Muscle: Involvement of the Nerve, Gravity, and Thyroid State

The myosin heavy chain (MHC) gene family encodes at least six MHC proteins (herein designated as neonatal, embryonic, slow type I (beta), and fast IIa, IIx, and IIb) that are expressed in skeletal muscle in a muscle-specific and developmentally-regulated fashion. At birth, both antigravity (e.g. soleus) and locomotor (e.g., plantaris) skeletal muscles are undifferentiated relative to the adult MHC phenotype such that the neonatal and embryonic MHC isoforms account for 80 - 90% of the MHC pool in a fast locomotor muscle; whereas, the embryonic and slow, type I isoforms account for approx. 90% of the pool in a typical antigravity muscle. The goal of this study was to investigate the role of an intact nerve, gravity and thyroid hormone (T3), as well as certain interactions of these interventions, on MHC gene expression in developing neonatal skeletal muscles of rodents.

Baldwin, K. M.↗
NASA NTRS1997

Interaction of thyroid state and denervation on skeletal myosin heavy chain expression

The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

NASA Discipline Musculoskeletal↗
NASA NTRS1997

Analysis of myosin heavy chain mRNA expression by RT-PCR

An assay was developed for rapid and sensitive analysis of myosin heavy chain (MHC) mRNA expression in rodent skeletal muscle. Only 2 microg of total RNA were necessary for the simultaneous analysis of relative mRNA expression of six different MHC genes. We designed synthetic DNA fragments as internal standards, which contained the relevant primer sequences for the adult MHC mRNAs type I, IIa, IIx, IIb as well as the embryonic and neonatal MHC mRNAs. A known amount of the synthetic fragment was added to each polymerase chain reaction (PCR) and yielded a product of different size than the amplified MHC mRNA fragment. The ratio of amplified MHC fragment to synthetic fragment allowed us to calculate percentages of the gene expression of the different MHC genes in a given muscle sample. Comparison with the traditional Northern blot analysis demonstrated that our reverse transcriptase-PCR-based assay was reliable, fast, and quantitative over a wide range of relative MHC mRNA expression in a spectrum of adult and neonatal rat skeletal muscles. Furthermore, the high sensitivity of the assay made it very useful when only small quantities of tissue were available. Statistical analysis of the signals for each MHC isoform across the analyzed samples showed a highly significant correlation between the PCR and the Northern signals as Pearson correlation coefficients ranged between 0.77 and 0.96 (P < 0.005). This assay has potential use in analyzing small muscle samples such as biopsies and samples from pre- and/or neonatal stages of development.

Non-NASA Center↗
NASA NTRS1996

The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

NASA Discipline Musculoskeletal↗
NASA NTRS1994

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning

Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

Flight Experiment↗
NASA NTRS1993

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

short duration↗