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Search Results: 1 - 10 of 84830 matches for " Garrett W. Astary "
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Influence of Neuropathology on Convection-Enhanced Delivery in the Rat Hippocampus
Svetlana Kantorovich, Garrett W. Astary, Michael A. King, Thomas H. Mareci, Malisa Sarntinoranont, Paul R. Carney
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080606
Abstract: Local drug delivery techniques, such as convention-enhanced delivery (CED), are promising novel strategies for delivering therapeutic agents otherwise limited by systemic toxicity and blood-brain-barrier restrictions. CED uses positive pressure to deliver infusate homogeneously into interstitial space, but its distribution is dependent upon appropriate tissue targeting and underlying neuroarchitecture. To investigate effects of local tissue pathology and associated edema on infusate distribution, CED was applied to the hippocampi of rats that underwent electrically-induced, self-sustaining status epilepticus (SE), a prolonged seizure. Infusion occurred 24 hours post-SE, using a macromolecular tracer, the magnetic resonance (MR) contrast agent gadolinium chelated with diethylene triamine penta-acetic acid and covalently attached to albumin (Gd-albumin). High-resolution T1- and T2-relaxation-weighted MR images were acquired at 11.1 Tesla in vivo prior to infusion to generate baseline contrast enhancement images and visualize morphological changes, respectively. T1-weighted imaging was repeated post-infusion to visualize final contrast-agent distribution profiles. Histological analysis was performed following imaging to characterize injury. Infusions of Gd-albumin into injured hippocampi resulted in larger distribution volumes that correlated with increased injury severity, as measured by hyperintense regions seen in T2-weighted images and corresponding histological assessments of neuronal degeneration, myelin degradation, astrocytosis, and microglial activation. Edematous regions included the CA3 hippocampal subfield, ventral subiculum, piriform and entorhinal cortex, amygdalar nuclei, middle and laterodorsal/lateroposterior thalamic nuclei. This study demonstrates MR-visualized injury processes are reflective of cellular alterations that influence local distribution volume, and provides a quantitative basis for the planning of local therapeutic delivery strategies in pathological brain regions.
A Preclinical Assessment of Neural Stem Cells as Delivery Vehicles for Anti-Amyloid Therapeutics
eMalick G. Njie, Svetlana Kantorovich, Garrett W. Astary, Cameron Green, Tong Zheng, Susan L. Semple-Rowland, Dennis A. Steindler, Malisa Sarntinoranont, Wolfgang J. Streit, David R. Borchelt
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034097
Abstract: Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated Aβ peptides that are the major constituents of the senile plaques. Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered. We found that our injection methods led to cells largely distributing to white matter tracts, which are anisotropic conduits for fluids that facilitate rapid distribution within the CNS. Third, with regard to MMP9 as a therapeutic to remove senile plaques, we observed high concentrations of endogenous metalloproteinases around amyloid plaques in the mouse models used for these preclinical tests with no evidence that the NSC-delivered enzymes elevated these activities or had any impact. Interestingly, MMP9-expressing NSCs formed substantially larger grafts. Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.
Globalization and its methodological discontents: Contextualizing globalization through the study of HIV/AIDS
Garrett W Brown, Ronald Labonté
Globalization and Health , 2011, DOI: 10.1186/1744-8603-7-29
Abstract: Academics generally add the suffix 'ization' to a word when they wish to denote that something is a process. When customary law becomes codified positive law, we call this a process of constitutionalization. When pressing issues are increasingly framed in terms of a security threat, we call this a process of securitization. Consequently, when we refer to increasing interconnections between peoples, economies, cultures, governments, environments and other various networks at the global level, we call this a process of globalization. In terms of etymology, globalization literally refers to the idea of 'global process' and the term originally surfaced in the late 1960s as a conceptual device to help us better understand the growing perception that the world was becoming increasingly interconnected economically, financially, technologically, culturally, politically and environmentally. As it is generally defined in any standard dictionary, the term globalization refers to 'an umbrella concept that seeks to capture the growing interconnectedness and integration of human society at the planetary scale [1] [p.112].'However, as with any word ending in 'ization' there remains considerable discontent between globalization scholars about how to conceptualize its meaning and in regards to epistemological and methodological questions concerning how we can come to understand how these processes ultimately operate, intersect and transform our lives. In trying to provide answers to such questions, most scholars have traditionally engaged in the study of globalization from a methodological standpoint that generally relies on two foundational approaches: locating one feature of globalization as representing its defining property [2-4]; and approaching the study of globalization from the assumption that it is an epistemologically understandable phenomenon about which we can reach definite conclusions as to its processes [5,6], its positive or negative effects [7-11], its transformativ
Minding the Gap in Holographic Models of Interacting Fermions
Garrett Vanacore,Philip W. Phillips
Physics , 2014, DOI: 10.1103/PhysRevD.90.044022
Abstract: We study the holographic dual of fermions interacting in a Schwarzschild-AdS$_{d+1}$ background via a dipole (Pauli) coupling sourced by a probe gauge field. We find quite generally that a gap forms in the dual operator spectrum as the Pauli coupling is strengthened. Previous investigations have observed this behavior in analogous constructions with Reissner-Nordstr\"om-AdS (RN-AdS$_4$) backgrounds, but the emergence of log-oscillatory behavior in those models' spectra prevented identification of the underlying gapping mechanism. Our model obviates this issue through its modified geometry and traces the gapping mechanism back to the bulk dynamics. We show in general that there is a duality between zeros for large positive values of the coupling and poles in the spectrum for equivalent couplings but with opposite sign as seen recently in the RN-AdS$_4$ background\cite{alsup}. The duality arises from the two possible quantizations for computing the retarded propagator. Coupled with the earlier string results\cite{gauntlett,gubser2} that Fermi surfaces are generally absent from the spectral function, our finding that the Pauli term engineers the gap suggests that the model examined here offers a way of studying non-perturbative physics in fermionic matter at finite density typified by Mott insulating systems.
The relationship between the L1 and L2 domains of the insulin and epidermal growth factor receptors and leucine-rich repeat modules
Colin W Ward, Thomas PJ Garrett
BMC Bioinformatics , 2001, DOI: 10.1186/1471-2105-2-4
Abstract: Here we have used profile searches and multiple sequence alignments to identify the repeat motif Ixx-LxIxx-Nx-Lxx-Lxx-Lxx-Lxx- in the L1 and L2 domains of the insulin receptor and epidermal growth factor receptors. These analyses were aided by reference to the known three dimensional structures of the insulin-like growth factor type I receptor L domains and two members of the leucine rich repeat family, porcine ribonuclease inhibitor and internalin 1B. Pectate lyase, another beta helix protein, can also be seen to contain the sequence motif and much of the structural features characteristic of leucine-rich repeat proteins, despite the existence of major insertions in some of its repeats.Multiple sequence alignments and comparisons of the 3D structures has shown that right-handed beta helix proteins such as pectate lyase and the L domains of members of the insulin receptor and epidermal growth factor receptor families, are members of the leucine-rich repeat superfamily.Many proteins have a modular architecture and are composed of a number of different, sometimes repeated structural units [1,2]. The four most common modules found in the extracellular regions of proteins are immunoglobulin (Ig) domains, epidermal growth factor (EGF)-like repeats, fibronectin type 3 (Fn3) modules and leucine-rich repeats [2]. Two of these, Fn3 modules [3-6] and EGF-like repeats [7-10], have been identified in members of the insulin receptor (IR) family.There is some evidence to suggest that the L domains of the IR and EGFR families are leucine-rich repeats. At 10–16%, leucine is the most common residue in these domains. Furthermore, the 3D structure of the L1/cys-rich/L2 fragment of the IGF-1R showed that the L domains were single-stranded right-handed β-helices [8] with structural similarities to pectate lyase, a right-handed beta helix protein [11,12] and the ribonuclease inhibitor, a right-handed beta-alpha superhelix protein [13]. Ribonuclease inhibitor (RI) is recognised as a membe
The "movement" of mixed methods research and the role of educators
John W. Creswell,Amanda L. Garrett
South African Journal of Education , 2008,
Abstract: The landscape of research is continually evolving, enabling researchers to study increasingly complex phenomena. Educational researchers have propelled much of this forward progress and have developed novel methodologies to provide increasingly sound and complete evidence. Mixed methods research has emerged alongside quantitative and qualitative approaches as an important tool for researchers. In this article our overall aim is to better acquaint educational scholars with the mixed methods field by articulating the development of the mixed methods field and by citing current trends and issues. The role of educational researchers in the evolution of mixed methods research is high-lighted. The early and ongoing dialogue of mixed methods research is multi-disciplinary in nature with current writings across fields. The current debate over key aspects of mixed methods research is now in progress and is ripe for future contributions. Even the very nature of what constitutes mixed methods research is being discussed among scholars. Understanding and advancing the mixed methods field is an important goal for methodologists and researchers. With the increased interest and enthusiasm for mixed methods research, it is likely that the dialogue surrounding mixed methods approaches will thrive, continuing the movement of the field.
Field Performance of Quercus bicolor Established as Repeatedly Air-Root-Pruned Container and Bareroot Planting Stock  [PDF]
J. W. Van Sambeek, Larry D. Godsey, William D. Walter, Harold E. Garrett, John P. Dwyer
Open Journal of Forestry (OJF) , 2016, DOI: 10.4236/ojf.2016.63014
Abstract: Benefits of repeated air-root-pruning of seedlings when stepping up to progressively larger containers include excellent lateral root distribution immediately below the root collar and an exceptionally fibrous root ball. To evaluate long-term field performance of repeatedly air-root-pruned container stock, three plantings of swamp white oak (Quercus bicolor Willd.) 10 to 13 years old were located that also included bareroot planting stock. Initial and final stem diameter and height and above-ground green weights were determined on randomly selected trees at each site. On a site with a sandy, excessively drained, high pH soil, trees (age 10) from container stock were 1.5 times taller, 2.3 times larger in dbh, and 2.8 times greater in green weight than trees from bareroot stock which averaged only 2.9 m tall, 3.9 cm dbh, and 16.3 kg green weight. On a site with high clay, poor internal drainage, and frequent flooding, trees (age 12) from container stock were 1.4 times taller, 1.8 times larger in dbh, and 4.1 times greater in green weight than trees from bareroot stock which averaged 4 m tall, 7.3 cm dbh, and 28 kg green weight. On an upland site with deep loess soils, there was a trend for trees (age 13) from container stock to be only slightly larger than trees from bareroot stock with each stock type averaging 9.6 m tall, 20 cm dbh, and 177 kg green weight. Repeated air-root pruning produced lateral roots immediately below the root collar that resulted in large container stock with large well-balanced root systems that were competitive on harsh or less than ideal oak sites. Although the process is relatively labor intensive, propagation of repeatedly air-root-pruned container stock is readily adaptable internationally to locally available sources of organic matter and open-bottom containers.
Absence of Power-Law Mid-Infrared Conductivity in Gravitational Crystals
Brandon W. Langley,Garrett Vanacore,Philip W. Phillips
Physics , 2015, DOI: 10.1007/JHEP10(2015)163
Abstract: We compute conductivities of strongly-interacting and non-uniform charge densities dual to inhomogeneous anti-de Sitter--black hole spacetimes. Backreacting bulk scalars with periodic boundary profiles, we construct generalizations of Reissner-Nordstr\"om-AdS that interpolate between those used in two previous studies --- one that reports power-law scaling for the boundary optical conductivity and one that does not. We find no evidence for power-law scaling of the conductivity, thereby corroborating the previous negative result that gravitational crystals are insufficient to generate the power-law mid-infrared conductivity observed in cuprate superconductors.
MYEOV (myeloma overexpressed gene) drives colon cancer cell migration and is regulated by PGE2
Garrett Lawlor, Peter P Doran, Padraic MacMathuna, David W Murray
Journal of Experimental & Clinical Cancer Research , 2010, DOI: 10.1186/1756-9966-29-81
Abstract: To assess the role of Myeov expression in CRC cell migration and to evaluate the role of PGE 2 in Myeov bioactivity.siRNA mediated Myeov knockdown was achieved in T84 CRC cells. Knockdown was assessed using quantitative real time PCR. The effect of knockdown on CRC cell migration was assessed using a scratch wound healing assay. Separately, T84 cells were treated with PGE 2 (0.00025 μ M, 0.1 μ M and 1 μ M) from 30 min to 3 hours and the effect on Myeov gene expression was assessed using real time PCR.Myeov knockdown resulted in a significant reduction in CRC cell migration, observable as early as 12 hours (P < 0.05) with a 39% reduction compared to control at 36 hours (p < 0.01). Myeov expression was enhanced after treatment with PGE 2, with the greatest effect seen at 60 mins for all 3 PGE 2 doses. This response was dose dependent with a 290%, 550% & 1,000% increase in Myeov expression for 0.00025 μ M, 0.1 μ M and 1 μ M PGE 2 respectively.In addition to promoting CRC proliferation and invasion, our findings indicate that Myeov stimulates CRC cell migration, and its expression may be PGE 2 dependant.Colorectal cancer is a heterogeneous disease arising from a complex series of molecular changes [1]. In 1990, Fearon and Vogelstein described the molecular basis of colorectal cancer as a multi-step model of carcinogenesis [2]. The model describes the accumulation of genetic events, each conferring a selective growth advantage to an affected colon cell, including inactivation of tumour suppressor genes and activation of oncogenes.Using a bioinformatics approach we have identified genes with enhanced expression in colorectal cancer tissue [3,4]. Myeov, (MYEloma OVerexpressed gene) was initially noted for its association with a subset of multiple myeloma cell lines [4,5] and it has also been implicated in oesophageal squamous cell carcinomas [6] and breast cancer [7]. Myeov is co-amplified with cyclin D1, a known oncogene [5]. We have previously shown Myeov to play a role
Update on Robotic Laparoscopic Radical Prostatectomy
Garrett S. Matsunaga,Thomas E. Ahlering,Douglas W. Skarecky
The Scientific World Journal , 2006, DOI: 10.1100/tsw.2006.394
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