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Search Results: 1 - 10 of 17864 matches for " Mark Hamrick "
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Energy Balance, Myostatin, and GILZ: Factors Regulating Adipocyte Differentiation in Belly and Bone
Xingming Shi,Mark Hamrick,Carlos M. Isales
PPAR Research , 2007, DOI: 10.1155/2007/92501
Abstract: Peroxisome proliferator-activated receptor gamma (PPAR-γ) belongs to the nuclear hormone receptor subfamily of transcription factors. PPARs are expressed in key target tissues such as liver, fat, and muscle and thus they play a major role in the regulation of energy balance. Because of PPAR-γ's role in energy balance, signals originating from the gut (e.g., GIP), fat (e.g., leptin), muscle (e.g., myostatin), or bone (e.g., GILZ) can in turn modulate PPAR expression and/or function. Of the two PPAR-γ isoforms, PPAR-γ2 is the key regulator of adipogenesis and also plays a role in bone development. Activation of this receptor favors adipocyte differentiation of mesenchymal stem cells, while inhibition of PPAR-γ2 expression shifts the commitment towards the osteoblastogenic pathway. Clinically, activation of this receptor by antidiabetic agents of the thiazolidinedione class results in lower bone mass and increased fracture rates. We propose that inhibition of PPAR-γ2 expression in mesenchymal stem cells by use of some of the hormones/factors mentioned above may be a useful therapeutic strategy to favor bone formation.
The Knee Joint Tissues Differ Significantly in TGFβ1 Expression and Its Sensitivity  [PDF]
Sadanand Fulzele, Monte Hunter, Rajnikumar Sangani, Norman Chutkan, Carlos Isales, Mark W. Hamrick
CellBio (CellBio) , 2013, DOI: 10.4236/cellbio.2013.24022
Abstract:

The knee joint is the largest and most complex joint in the human body. In this study, we investigated TGFβ1 expression in the outer meniscus, inner meniscus and articular cartilage of rabbit and human knee tissue (outer and inner menisci) in order to determine the potential role of this factor in normal meniscal function. We also examined the potential of TGF-β1 stimulation to promote tissue regeneration in the two different regions of rabbit knee meniscus tissue. Immunohistochemical investigations of TGF-β1 were performed on rabbit and human knee tissue. The rabbit outer, inner and articular cartilage cells were culture and stimulated with TGF-β1 followed by cell proliferation assay and extracellular matrix analysis. Regulatory studies were performed using TGF-β1 inhibitors SB-431542 and PD98059. Gene expression was analyzed by quantitative polymerase chain reaction. We found marked regional variation in the expression of TGF-β1 in rabbit and human knee. TGF-β1 expressions are relatively greater in the outer meniscus than inner meniscus. Furthermore, we found that exogenous TGF-β1 stimulation increased cell proliferation and aggrecan synthesis more so in the outer than in the inner meniscus. Articular cartilage tissue shows moderate levels of cell proliferation and ECM synthesis when compared with outer and inner meniscus. These findings suggest that growth factors used to enhance the repair and regeneration of meniscal tissue should be tailored to enhance region-specific variation in cell proliferation and extracellular matrix synthesis.

Stromal Cell-Derived Factor-1β Mediates Cell Survival through Enhancing Autophagy in Bone Marrow-Derived Mesenchymal Stem Cells
Samuel Herberg, Xingming Shi, Maribeth H. Johnson, Mark W. Hamrick, Carlos M. Isales, William D. Hill
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058207
Abstract: Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for cell-based therapy, yet the therapeutic efficacy remains uncertain. Transplanted BMSCs often fail to engraft within the bone marrow (BM), in part due to the poor survival of donor cells in response to inflammatory reactions, hypoxia, oxidative stress, or nutrient starvation. Two basic cell processes, apoptosis and autophagy, could potentially be responsible for the impaired survival of transplanted BMSCs. However, the functional relationship between apoptosis and autophagy in BMSC homeostasis is complex and not well understood. The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signaling axis appears to be critical in maintaining proliferation and survival of BM stem cell populations through improving cell proliferation and survival in response to stress; however, the exact mechanisms remain unclear. We recently described novel genetically engineered Tet-Off-SDF-1β BMSCs, which over-express SDF-1β under tight doxycycline-control, thus providing an ideal model system to investigate the isolated effects of SDF-1β. In this study we tested the hypothesis that SDF-1β can mediate cell survival of BMSCs in vitro through increasing autophagy. We found that SDF-1β had no effect on BMSC proliferation; however, SDF-1β significantly protected genetically engineered BMSCs from H2O2-induced cell death through increasing autophagy and decreasing caspase-3-dependent apoptosis. Taken together, we provide novel evidence that the SDF-1/CXCR4 axis, specifically activated by the SDF-1β isoform, plays a critical role in regulating BMSC survival under oxidative stress through increasing autophagy.
Secrecy, Computational Loads and Rates in Practical Quantum Cryptography
G. Gilbert,M. Hamrick
Physics , 2001,
Abstract: A number of questions associated with practical implementations of quantum cryptography systems having to do with unconditional secrecy, computational loads and effective secrecy rates in the presence of perfect and imperfect sources are discussed. The different types of unconditional secrecy, and their relationship to general communications security, are discussed in the context of quantum cryptography. In order to actually carry out a quantum cryptography protocol it is necessary that sufficient computational resources be available to perform the various processing steps, such as sifting, error correction, privacy amplification and authentication. We display the full computer machine instruction requirements needed to support a practical quantum cryptography implementation. We carry out a numerical comparison of system performance characteristics for implementations that make use of either weak coherent sources of light or perfect single photon sources, for eavesdroppers making individual attacks on the quantum channel characterized by different levels of technological capability. We find that, while in some circumstances it is best to employ perfect single photon sources, in other situations it is preferable to utilize weak coherent sources. In either case the secrecy level of the final shared cipher is identical, with the relevant distinguishing figure-of-merit being the effective throughput rate.
Constraints on Eavesdropping on the BB84 Protocol
G. Gilbert,M. Hamrick
Physics , 2001,
Abstract: An undetected eavesdropping attack must produce count rate statistics that are indistinguishable from those that would arise in the absence of such an attack. In principle this constraint should force a reduction in the amount of information available to the eavesdropper. In this paper we illustrate, by considering a particular class of eavesdropping attacks, how the general analysis of this problem may proceed.
The Secrecy Capacity of Practical Quantum Cryptography
G. Gilbert,M. Hamrick
Physics , 2001,
Abstract: Quantum cryptography has attracted much recent attention due to its potential for providing secret communications that cannot be decrypted by any amount of computational effort. This is the first analysis of the secrecy of a practical implementation of the BB84 protocol that simultaneously takes into account and presents the {\it full} set of complete analytical expressions for effects due to the presence of pulses containing multiple photons in the attenuated output of the laser, the finite length of individual blocks of key material, losses due to error correction, privacy amplification, continuous authentication, errors in polarization detection, the efficiency of the detectors, and attenuation processes in the transmission medium. The analysis addresses eavesdropping attacks on individual photons rather than collective attacks in general. Of particular importance is the first derivation of the necessary and sufficient amount of privacy amplification compression to ensure secrecy against the loss of key material which occurs when an eavesdropper makes optimized individual attacks on pulses containing multiple photons. It is shown that only a fraction of the information in the multiple photon pulses is actually lost to the eavesdropper.
Practical Quantum Cryptography: A Comprehensive Analysis (Part One)
G. Gilbert,M. Hamrick
Physics , 2000,
Abstract: We perform a comprehensive analysis of practical quantum cryptography (QC) systems implemented in actual physical environments via either free-space or fiber-optic cable quantum channels for ground-ground, ground-satellite, air-satellite and satellite-satellite links. (1) We obtain universal expressions for the effective secrecy capacity and rate for QC systems taking into account three important attacks on individual quantum bits, including explicit closed-form expressions for the requisite amount of privacy amplification. Our analysis also includes the explicit calculation in detail of the total cost in bits of continuous authentication, thereby obtaining new results for actual ciphers of finite length. (2) We perform for the first time a detailed, explicit analysis of all systems losses due to propagation, errors, noise, etc. as appropriate to both optical fiber cable- and satellite communications-based implementations of QC. (3) We calculate for the first time all system load costs associated to classical communication and computational constraints that are ancillary to, but essential for carrying out, the pure QC protocol itself. (4) We introduce an extended family of generalizations of the Bennett-Brassard (BB84) QC protocol that equally provide unconditional secrecy but allow for the possibility of optimizing throughput rates against specific cryptanalytic attacks. (5) We obtain universal predictions for maximal rates that can be achieved with practical system designs under realistic environmental conditions. (6) We propose a specific QC system design that includes the use of a novel method of high-speed photon detection that may be able to achieve very high throughput rates for actual implementations in realistic environments.
Absence of Functional Leptin Receptor Isoforms in the POUND (Leprdb/lb) Mouse Is Associated with Muscle Atrophy and Altered Myoblast Proliferation and Differentiation
Phonepasong Arounleut, Matthew Bowser, Sunil Upadhyay, Xing-Ming Shi, Sadanand Fulzele, Maribeth H. Johnson, Alexis M. Stranahan, William D. Hill, Carlos M. Isales, Mark W. Hamrick
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072330
Abstract: Objective Leptin receptors are abundant in human skeletal muscle, but the role of leptin in muscle growth, development and aging is not well understood. Here we utilized a novel mouse model lacking all functional leptin receptor isoforms (POUND mouse, Leprdb/lb) to determine the role of leptin in skeletal muscle. Methods and Findings Skeletal muscle mass and fiber diameters were examined in POUND mice, and primary myoblast cultures were used to determine the effects of altered leptin signaling on myoblast proliferation and differentiation. ELISA assays, integrated pathway analysis of mRNA microarrays, and reverse phase protein analysis were performed to identify signaling pathways impacted by leptin receptor deficiency. Results show that skeletal muscle mass and fiber diameter are reduced 30–40% in POUND mice relative to wild-type controls. Primary myoblast cultures demonstrate decreased proliferation and decreased expression of both MyoD and myogenin in POUND mice compared to normal mice. Leptin treatment increased proliferation in primary myoblasts from muscles of both adult (12 months) and aged (24 months) wild-type mice, and leptin increased expression of MyoD and myogenin in aged primary myoblasts. ELISA assays and protein arrays revealed altered expression of molecules associated with the IGF-1/Akt and MAPK/MEK signaling pathways in muscle from the hindlimbs of mice lacking functional leptin receptors. Conclusion These data support the hypothesis that the adipokine leptin is a key factor important for the regulation of skeletal muscle mass, and that leptin can act directly on its receptors in peripheral tissues to regulate cell proliferation and differentiation.
Aromatic Amino Acid Activation of Signaling Pathways in Bone Marrow Mesenchymal Stem Cells Depends on Oxygen Tension
Mona El Refaey, Qing Zhong, William D. Hill, Xing-Ming Shi, Mark W. Hamrick, Lakiea Bailey, Maribeth Johnson, Jianrui Xu, Wendy B. Bollag, Norman Chutkan, Carlos M. Isales
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091108
Abstract: The physiologic oxygen pressures inside the bone marrow environment are much lower than what is present in the peripheral circulation, ranging from 1–7%, compared to values as high as 10–13% in the arteries, lungs and liver. Thus, experiments done with bone marrow mesenchymal stem cells (BMMSCs) using standard culture conditions may not accurately reflect the true hypoxic bone marrow microenvironment. However, since aging is associated with an increased generation of reactive oxygen species, experiments done under 21%O2 conditions may actually more closely resemble that of the aging bone marrow environment. Aromatic amino acids are known to be natural anti-oxidants. We have previously reported that aromatic amino acids are potent agonists for stimulating increases in intracellular calcium and phospho-c-Raf and in promoting BMMSC differentiation down the osteogenic pathway. Our previous experiments were performed under normoxic conditions. Thus, we next decided to compare a normoxic (21% O2) vs. a hypoxic environment (3% O2) alone or after treatment with aromatic amino acids. Reverse-phase protein arrays showed that 3% O2 itself up-regulated proliferative pathways. Aromatic amino acids had no additional effect on signaling pathways under these conditions. However, under 21%O2 conditions, aromatic amino acids could now significantly increase these proliferative pathways over this “normoxic” baseline. Pharmacologic studies are consistent with the aromatic amino acids activating the extracellular calcium-sensing receptor. The effects of aromatic amino acids on BMMSC function in the 21% O2 environment is consistent with a potential role for these amino acids in an aging environment as functional anti oxidants.
Efficient Construction of Photonic Quantum Computational Clusters
Gerald Gilbert,Michael Hamrick,Yaakov S. Weinstein
Physics , 2005, DOI: 10.1103/PhysRevA.73.064303
Abstract: We demonstrate a method of creating photonic two-dimensional cluster states that is considerably more efficient than previously proposed approaches. Our method uses only local unitaries and type-I fusion operations. The increased efficiency of our method compared to previously proposed constructions is obtained by identifying and exploiting local equivalence properties inherent in cluster states.
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