Publications by authors named "Timothy J Miller"

This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown.

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Exploring the tumour microenvironment provides insight into the unique interaction between the host and tumour. Ultimately, its study improves understanding of how an individual mounts and achieves an anti-tumour immune response. In the context of colorectal cancer, immune biomarkers within the tumour microenvironment outperform traditional histopathological staging in predicting disease recurrence.

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Background: The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c DC co-expressing the immunoinhibitory molecule PD-L1 and their spatial relationship with CD8 T-cells in patients treated for stage III colon cancer.

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The use of multi-colour immunofluorescence (IF) for immunophenotyping in formalin-fixed paraffin-embedded tissue sections is gaining popularity worldwide. This technique allows for the simultaneous detection of multiple markers on the same tissue section, thereby yielding more complex information than is possible by chromogenic immunohistochemistry (IHC). However, many commercially-available multiplex IF kits are designed for use in conjunction with a multispectral imaging system, to which many research groups have limited access.

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Premise Of The Study: Wildfire changes the demography, morphology, and behavior of plants, and may alter the pollinator community. Such trait changes may drastically alter the outcome of pollination mutualisms on plants; however, the direct role of fire on these mutualisms is poorly known.

Methods: Following a pair of fires in the northern California coast range chaparral, we censused floral visitor communities of Trichostema laxum (Lamiaceae), quantified visiting bee behavior, and estimated outcrossing rates using a widespread Mendelian recessive floral polymorphism across a matrix of populations in burned and unburned sites.

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Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy.

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This paper establishes a strategy for chemical deposition of functionalized nanoparticles onto solid substrates in a layer-by-layer process based on self-limiting surface chemical reactions leading to monolayer formation within the multilayer system without any additional intermediate layers - nanoparticle layer deposition (NPLD). This approach is fundamentally different from previously established traditional layer-by-layer deposition techniques and is conceptually more similar to well-known atomic and molecular - layer deposition processes. The NPLD approach uses efficient chemical functionalization of the solid substrate material and complementary functionalization of nanoparticles to produce a nearly of these nanoparticles with the use of "click chemistry".

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Background: Implementation of highly active antiretroviral therapy (HAART) significantly increased the life expectancy of those living with human immunodeficiency virus (HIV). Except for prevalence, scientific reports regarding clinical manifestations of plantar verrucae in the post-HAART era are lacking. The objective of this study was to compare clinical manifestations of plantar verrucae between HIV-infected and noninfected individuals and then to compare these findings with those observed before the implementation of HAART.

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Background: Patients with calcaneus fractures often exhibit settling of the posterior facet with a corresponding decrease in Bohler's angle (BA) following either operative or nonoperative treatment. Both injury BA and postoperative BA have been shown to be prognostic for outcomes; however, the demographic and surgeon-specific factors that may contribute to settling have not been critically examined in the literature. The purpose of this study was to identify these causative factors.

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Background: The study by Lauge-Hansen published in the Archives of Surgery in 1950 still stands as the seminal work for our understanding of the pathomechanics of ankle fractures. The purpose of the present study was to recreate Lauge-Hansen's experiments for the supination-external rotation (SER) fracture mechanism and to determine whether the predicted sequence of osseous and soft-tissue injury is reproducible on the basis of his originally described methodology.

Methods: Ten fresh-frozen cadaver specimens amputated above the knee were utilized.

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Premise Of The Study: Ultraviolet (UV) floral patterns are common in angiosperms and mediate pollinator attraction, efficiency, and constancy. UV patterns may vary within species, yet are cryptic to human observers. Thus, few studies have explicitly described the distribution or ecological significance of intraspecific variation in UV floral patterning.

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Unlabelled: Calcaneus fractures are the most commonly fractured tarsal bone with approximately 75% being intra-articular in nature. Böhler's angle has been found to be reliable and prognostic, and it has been used as a proxy for joint depression and articular involvement. It often guides the need for advanced imaging and/or operative intervention.

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Leatherback sea turtles, Dermochelys coriacea, are highly migratory predators that feed exclusively on gelatinous zooplankton, thus playing a unique role in coastal and pelagic food webs. From 2007 to 2010, we used satellite telemetry to monitor the movements and dive behavior of nine adult and eleven subadult leatherbacks captured on the Northeast USA shelf and tracked throughout the Northwest Atlantic. Leatherback movements and environmental associations varied by oceanographic region, with slow, sinuous, area-restricted search behavior and shorter, shallower dives occurring in cool (median sea surface temperature: 18.

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Background And Aims: Plant populations experiencing divergent pollination environments may be under selection to modify floral traits in ways that increase both attractiveness to and efficiency of novel pollinators. These changes may come at the cost of reducing overall effectiveness of other pollinators. The goal of this study was to examine differences in attractiveness and efficiency between Clarkia concinna and C.

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Metacommunity theory allows predictions about the dynamics of potentially interacting species' assemblages that are linked by dispersal, but strong empirical tests of the theory are rare. We analyzed the metacommunity dynamics of Florida rosemary scrub, a patchily distributed pyrogenic community, to test predictions about turnover rates, community nestedness, and responses to patch size, arrangement, and quality. We collected occurrence data for 45 plant species from 88 rosemary scrub patches in 1989 and 2005 and used growth form, mechanism of regeneration after fire, and degree of habitat specialization to categorize species by life history.

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The FXYD family, which contains seven members, are tissue specific regulators of the Na,K-ATPase. Increased expression of FXYD5, a cancer-cell-associated membrane glycoprotein, has been associated with increased cell motility and metastatic potential. To better understand how FXYD5 may modulate cell motility, we analyzed S163, a conserved residue in all FXYD family members located in the C-terminus.

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1. Lipids have more negative delta(13)C values relative to other major biochemical compounds in plant and animal tissues. Although variable lipid content in biological tissues alters results and conclusions of delta(13)C analyses in aquatic food web and migration studies, no standard correction protocol exists.

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Spatially structured population dynamics models are important management tools for harvested, highly mobile species and although conventional tag recovery experiments remain useful for estimation of various demographic parameters of these models, archival tagging experiments are becoming an important data source for analyzing migratory behavior of mobile marine species. We provide a likelihood-based approach for estimating the regional migration and mortality rate parameters intrinsic to these models that may use information obtained from conventional tag recovery and archival tagging experiments. Specifically, we assume that the regional location and survival of animals through time is a finite-state continuous-time stochastic process.

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FXYD5, also known as dysadherin, belongs to a family of tissue-specific regulators of the Na(+)-K(+)-ATPase. We determined the kinetic effects of FXYD5 on Na(+)-K(+)-ATPase pump activity in stably transfected Madin-Darby canine kidney cells. FXYD5 significantly increased the apparent affinity for Na(+) twofold and decreased the apparent affinity for K(+) by 60% with a twofold increase in V(max) of K(+), a pattern that would increase activity and Na(+) removal from the cell.

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The National Institutes of Health (NIH) rabies vaccine potency test is used internationally for evaluating the efficacy of inactivated rabies vaccines, despite concerns about its methods. An alternative test has been developed, using a simplified in vivo method for rabies vaccine testing which has several advantages over the currently recommended method of efficacy testing. The rabies peripheral challenge test more closely models practical vaccine application in target species; decreases the observed effect of vaccine virus strain in testing results and allows sensitive analysis of vaccine and production lot testing.

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Objective: We sought to calculate the sensitivity, specificity, negative predictive value, and positive predictive value of a limited sinus computed tomographic (CT) scan for sinus disease.

Methods: We conducted a retrospective case series. Inclusion criteria included a sinus CT scan obtained between April 1999 and November 2000.

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Charge-neutral DNA nanoparticles have been developed in which single molecules of DNA are compacted to their minimal possible size. We speculated that the small size of these DNA nanoparticles may facilitate gene transfer in postmitotic cells, permitting nuclear uptake across the 25-nm nuclear membrane pore. To determine whether DNA nanoparticles can transfect nondividing cells, growth-arrested neuroblastoma and hepatoma cells were transfected with DNA/liposome mixtures encoding luciferase.

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Objective: To determine effect of route of challenge and strain of rabies virus on efficacy of inactivated rabies vaccines in mice.

Animals: 3,056 mice.

Procedure: Challenge was performed with fixed and street rabies virus strains by use of footpad and intracerebral routes as well as IM injection into the hip, shoulder, neck, and masseter muscles.

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Objective: To evaluate the effect of various routes of administration and number of doses of 3 commercially produced rabies vaccines on serum antibody responses and protection in mice challenged by intracerebral injection with fixed-strain rabies virus.

Animals: 2,213 mice.

Procedure: Inactivated, adjuvanted rabies vaccines were administered to mice in either 2, 1, or 0 (control) doses via IP, IM, and SC routes, and mice were challenged intracerebrally with fixed-strain rabies virus.

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