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Search Results: 1 - 10 of 407600 matches for " Joshua M Miller "
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A case of calciphylaxis and acute myeloid leukemia: A previously unreported association  [PDF]
Joshua D. Rosenberg, Pamela Boswell, William Miller
Case Reports in Clinical Medicine (CRCM) , 2013, DOI: 10.4236/crcm.2013.23061

Calciphylaxis is a condition of induced hypersensitivity in which tissues respond to challenge agents with local calcification. This article reports the first known case of diffuse calciphylaxis associated with acute myeloid leukemia resulting in death from hypoxic respiratory failure and refractory hypotension.

Synthesis of a library of tricyclic azepinoisoindolinones
Bettina Miller,Shuli Mao,Kara M. George Rosenker,Joshua G. Pierce
Beilstein Journal of Organic Chemistry , 2012, DOI: 10.3762/bjoc.8.120
Abstract: Hydrozirconation of 1-hexyne, the addition to in situ prepared N-acyliminium species, and ring-closing metathesis (RCM) were key steps in the preparation of a tricyclic isoindolinone scaffold. An unusual alkene isomerization process during the RCM was identified and studied in some detail. Chemical diversification for library synthesis was achieved by a subsequent alkene epoxidation and zinc-mediated aminolysis reaction. The resulting library products provided selective hits among a large number of high-throughput screens reported in PubChem, thus illustrating the utility of the novel scaffold.
Ghosts of Yellowstone: Multi-Decadal Histories of Wildlife Populations Captured by Bones on a Modern Landscape
Joshua H. Miller
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018057
Abstract: Natural accumulations of skeletal material (death assemblages) have the potential to provide historical data on species diversity and population structure for regions lacking decades of wildlife monitoring, thereby contributing valuable baseline data for conservation and management strategies. Previous studies of the ecological and temporal resolutions of death assemblages from terrestrial large-mammal communities, however, have largely focused on broad patterns of community composition in tropical settings. Here, I expand the environmental sampling of large-mammal death assemblages into a temperate biome and explore more demanding assessments of ecological fidelity by testing their capacity to record past population fluctuations of individual species in the well-studied ungulate community of Yellowstone National Park (Yellowstone). Despite dramatic ecological changes following the 1988 wildfires and 1995 wolf re-introduction, the Yellowstone death assemblage is highly faithful to the living community in species richness and community structure. These results agree with studies of tropical death assemblages and establish the broad capability of vertebrate remains to provide high-quality ecological data from disparate ecosystems and biomes. Importantly, the Yellowstone death assemblage also correctly identifies species that changed significantly in abundance over the last 20 to ~80 years and the directions of those shifts (including local invasions and extinctions). The relative frequency of fresh versus weathered bones for individual species is also consistent with documented trends in living population sizes. Radiocarbon dating verifies the historical source of bones from Equus caballus (horse): a functionally extinct species. Bone surveys are a broadly valuable tool for obtaining population trends and baseline shifts over decadal-to-centennial timescales.
Crashing, Chaos, Culture and Connection
Joshua L. Miller
Religions , 2013, DOI: 10.3390/rel4020186
Abstract: This essay considers the experience of a seasoned disaster responder who encountered a personal disaster while traveling in Thailand. The resulting injury and helplessness led to new insights about mortality, vulnerability, culture and the significance of social trust—echoing lessons gained from professional experiences, but giving them new meaning and resonance.
Population Fluctuation Promotes Cooperation in Networks
Steve Miller,Joshua Knowles
Computer Science , 2014, DOI: 10.1038/srep11054
Abstract: We consider the problem of explaining the emergence and evolution of cooperation in dynamic network-structured populations. Building on seminal work by Poncela et al, which shows how cooperation (in one-shot prisoner's dilemma) is supported in growing populations by an evolutionary preferential attachment (EPA) model, we investigate the effect of fluctuations in the population size. We find that the fluctuating model is more robust than Poncela et al's in that cooperation flourishes for a wide variety of initial conditions. In terms of both the temptation to defect, and the types of strategies present in the founder network, the fluctuating population is found to lead more securely to cooperation. Further, we find that this model will also support the emergence of cooperation from pre-existing non-cooperative random networks. This model, like Poncela et al's, does not require agents to have memory, recognition of other agents, or other cognitive abilities, and so may suggest a more general explanation of the emergence of cooperation in early evolutionary transitions, than mechanisms such as kin selection, direct and indirect reciprocity.
Body Mass and White Matter Integrity: The Influence of Vascular and Inflammatory Markers
Brianne Magouirk Bettcher, Christine M. Walsh, Christa Watson, Joshua W. Miller, Ralph Green, Nihar Patel, Bruce L. Miller, John Neuhaus, Kristine Yaffe, Joel H. Kramer
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077741
Abstract: High adiposity is deleteriously associated with brain health, and may disproportionately affect white matter integrity; however, limited information exists regarding the mechanisms underlying the association between body mass (BMI) and white matter integrity. The present study evaluated whether vascular and inflammatory markers influence the relationship between BMI and white matter in healthy aging. We conducted a cross-sectional evaluation of white matter integrity, BMI, and vascular/inflammatory factors in a cohort of 138 healthy older adults (mean age: 71.3 years). Participants underwent diffusion tensor imaging, provided blood samples, and participated in a health evaluation. Vascular risk factors and vascular/inflammatory blood markers were assessed. The primary outcome measure was fractional anisotropy (FA) of the genu, body, and splenium (corpus callosum); exploratory measures included additional white matter regions, based on significant associations with BMI. Regression analyses indicated that higher BMI was associated with lower FA in the corpus callosum, cingulate, and fornix (p<.001). Vascular and inflammatory factors influenced the association between BMI and FA. Specifically, BMI was independently associated with the genu [β=-.21; B=-.0024; 95% CI, -.0048 to -.0000; p=.05] and cingulate fibers [β=-.39; B=-.0035; 95% CI,-.0056 to -.0015; p<.001], even after controlling for vascular/inflammatory risk factors and blood markers. In contrast, BMI was no longer significantly associated with the fornix and middle/posterior regions of the corpus callosum after controlling for these markers. Results partially support a vascular/inflammatory hypothesis, but also suggest a more complex relationship between BMI and white matter characterized by potentially different neuroanatomic vulnerability.
Requirement of Cognate CD4+ T-Cell Recognition for the Regulation of Allospecific CTL by Human CD4+CD127?CD25+FOXP3+ Cells Generated in MLR
Yuming Yu,Joshua Miller,Joseph R. Leventhal,Anat R. Tambur,Dhivya Chandrasekaran,Josh Levitsky,Xunrong Luo,James M. Mathew
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0022450
Abstract: Although immunoregulation of alloreactive human CTLs has been described, the direct influence of CD4+ Tregs on CD8+ cytotoxicity and the interactive mechanisms have not been well clarified. Therefore, human CD4+CD127?CD25+FOXP3+ Tregs were generated in MLR, immunoselected and their allospecific regulatory functions and associated mechanisms were then tested using modified 51Chromium release assays (Micro-CML), MLRs and CFSE-based multi-fluorochrome flow cytometry proliferation assays. It was observed that increased numbers of CD4+CD127?CD25+FOXP3+ cells were generated after a 7 day MLR. After immunoselection for CD4+CD127?CD25+ cells, they were designated as MLR-Tregs. When added as third component modulators, MLR-Tregs inhibited the alloreactive proliferation of autologous PBMC in a concentration dependent manner. The inhibition was quasi-antigen specific, in that the inhibition was non-specific at higher MLR-Treg modulator doses, but non-specificity disappeared with lower numbers at which specific inhibition was still significant. When tested in micro-CML assays CTL inhibition occurred with PBMC and purified CD8+ responders. However, antigen specificity of CTL inhibition was observed only with unpurified PBMC responders and not with purified CD8+ responders or even with CD8+ responders plus Non-T “APC”. However, allospecificity of CTL regulation was restored when autologous purified CD4+ T cells were added to the CD8+ responders. Proliferation of CD8+ cells was suppressed by MLR-Tregs in the presence or absence of IL-2. Inhibition by MLR-Tregs was mediated through down-regulation of intracellular perforin, granzyme B and membrane-bound CD25 molecules on the responding CD8+ cells. Therefore, it was concluded that human CD4+CD127?CD25+FOXP3+ MLR-Tregs down-regulate alloreactive cytotoxic responses. Regulatory allospecificity, however, requires the presence of cognate responding CD4+ T cells. CD8+ CTL regulatory mechanisms include impaired proliferation, reduced expression of cytolytic molecules and CD25+ activation epitopes.
Genetic linkage map of a wild genome: genomic structure, recombination and sexual dimorphism in bighorn sheep
Jocelyn Poissant, John T Hogg, Corey S Davis, Joshua M Miller, Jillian F Maddox, David W Coltman
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-524
Abstract: Bighorn sheep population-specific maps differed slightly in contiguity but were otherwise very similar in terms of genomic structure and recombination rates. The joint analysis of the two pedigrees resulted in a highly contiguous map composed of 247 microsatellite markers distributed along all 26 autosomes and the X chromosome. The map is estimated to cover about 84% of the bighorn sheep genome and contains 240 unique positions spanning a sex-averaged distance of 3051 cM with an average inter-marker distance of 14.3 cM. Marker synteny, order, sex-averaged interval lengths and sex-averaged total map lengths were all very similar between sheep species. However, in contrast to domestic sheep, but consistent with the usual pattern for a placental mammal, recombination rates in bighorn sheep were significantly greater in females than in males (~12% difference), resulting in an autosomal female map of 3166 cM and an autosomal male map of 2831 cM. Despite differing genome-wide patterns of heterochiasmy between the sheep species, sexual dimorphism in recombination rates was correlated between orthologous intervals.We have developed a first-generation bighorn sheep linkage map that will facilitate future studies of the genetic architecture of trait variation in this species. While domestication has been hypothesized to be responsible for the elevated mean recombination rate observed in domestic sheep, our results suggest that it is a characteristic of Ovis species. However, domestication may have played a role in altering patterns of heterochiasmy. Finally, we found that interval-specific patterns of sexual dimorphism were preserved among closely related Ovis species, possibly due to the conserved position of these intervals relative to the centromeres and telomeres. This study exemplifies how transferring genomic resources from domesticated species to close wild relative can benefit evolutionary ecologists while providing insights into the evolution of genomic structure and
Quantifying the Value of Open Source Hard-ware Development  [PDF]
Joshua M. Pearce
Modern Economy (ME) , 2015, DOI: 10.4236/me.2015.61001
Abstract: With the maturation of digital manufacturing technologies like 3-D printing, a new paradigm is emerging of distributed manufacturing in both scientific equipment and consumer goods. Hardware released under free licenses is known as free and open source hardware (FOSH). The availability of these FOSH designs has a large value to those with access to digital manufacturing methods and particularly for scientists with needs for highly-customized low-volume production products. It is challenging to use traditional funding models to support the necessary investment of resources in FOSH development because of the difficulty in quantifying the value of the result. In order to overcome that challenge and harvest the current opportunity in both low-cost scientific equipment and consumer products, this article evaluates the following methods to quantify the value of FOSH design including: 1) downloaded substitution valuation; 2) avoided reproduction valuation and 3) market savings valuation along with additional benefits related to market expansion, scientific innovation acceleration, educational enhancement and medical care improvement. The strengths and weaknesses of these methods are analyzed and the results show that the methods are relatively straight-forward to institute, based on reliable freely-available data, and that they minimize assumptions. A case study of a syringe pump with numerous scientific and medical applications is presented. The results found millions of dollars of economic value from a relatively simple scientific device being released under open-licenses representing orders of magnitude increase in value from conventional proprietary development. The inescapable conclusion of this study is that FOSH development should be funded by organizations interested in maximizing return on public investments particularly in technologies associated with science, medicine and education.
A first look at transition amplitudes in (2+1)-dimensional causal dynamical triangulations
Joshua H. Cooperman,Jonah Miller
Physics , 2013, DOI: 10.1088/0264-9381/31/3/035012
Abstract: We study a lattice regularization of the gravitational path integral--causal dynamical triangulations--for (2+1)-dimensional Einstein gravity with positive cosmological constant in the presence of past and future spacelike boundaries of fixed intrinsic geometries. For spatial topology of a 2-sphere, we determine the form of the Einstein-Hilbert action supplemented by the Gibbons-Hawking-York boundary terms within the Regge calculus of causal triangulations. Employing this action we numerically simulate a variety of transition amplitudes from the past boundary to the future boundary. To the extent that we have so far investigated them, these transition amplitudes appear consistent with the gravitational effective action previously found to characterize the ground state of quantum spacetime geometry within the Euclidean de Sitter-like phase. Certain of these transition amplitudes convincingly demonstrate that the so-called stalks present in this phase are numerical artifacts of the lattice regularization, seemingly indicate that the quantization technique of causal dynamical triangulations differs in detail from that of the no-boundary proposal of Hartle and Hawking, and possibly represent the first numerical simulations of portions of temporally unbounded quantum spacetime geometry within the causal dynamical triangulations approach. We also uncover tantalizing evidence suggesting that Lorentzian not Euclidean de Sitter spacetime dominates the ground state on sufficiently large scales.
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