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Search Results: 1 - 10 of 218257 matches for " Matthew D Alexander "
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Differential Phagocytosis of White versus Opaque Candida albicans by Drosophila and Mouse Phagocytes
Matthew B. Lohse, Alexander D. Johnson
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001473
Abstract: The human fungal pathogen Candida albicans resides asymptomatically in the gut of most healthy people but causes serious invasive diseases in immunocompromised patients. Many C. albicans strains have the ability to stochastically switch between distinct white and opaque cell types, but it is not known with certainty what role this switching plays in the physiology of the organism. Here, we report a previously undescribed difference between white and opaque cells, namely their interaction with host phagocytic cells. We show that both Drosophila hemocyte-derived S2 cells and mouse macrophage-derived RAW264.7 cells preferentially phagocytose white cells over opaque cells. This difference is seen both in the overall percentage of cultured cells that phagocytose white versus opaque C. albicans and in the average number of C. albicans taken up by each phagocytic cell. We conclude that susceptibility to phagocytosis by cells of the innate immune system is an important distinction between white and opaque C. albicans, and propose that one role of switching from the prevalent white form into the rarer opaque form may be to allow C. albicans to escape phagocytosis.
Galactic Streams of Cosmic-ray Electrons and Positrons
Matthew D. Kistler,Hasan Yuksel,Alexander Friedland
Physics , 2012,
Abstract: Isotropy is a key assumption in many models of cosmic-ray electrons and positrons. We find that simulation results imply a critical energy of ~10-1000 GeV above which electrons and positrons can spend their entire lives in streams threading magnetic fields, due to energy losses. This would restrict the number of electron/positron sources contributing at Earth, likely leading to smooth electron and positron spectra, as is observed. For positrons, this could be as few as one, with an enhanced flux that would ease energetics concerns of a pulsar origin of the positron excess, or even zero, bringing dark matter into play. We conclude that ideas about electron/positron propagation based on either isotropic diffusion or turbulent fields must be changed.
Revisiting normal perfusion pressure breakthrough in light of hemorrhage-induced vasospasm
Matthew D Alexander, E Sander Connolly , Philip M Meyers
World Journal of Radiology , 2010,
Abstract: Cerebral arteriovenous malformations (AVMs) have abnormally enlarged arteries and veins prone to spontaneous hemorrhage. Immediately following surgical excision of a cerebral AVM, even normal brain tissue surrounding the lesion is subject to hemorrhage, a phenomenon termed normal perfusion pressure breakthrough (NPPB) syndrome. According to this theory, arteries supplying cerebral AVMs become dilated and lose their capacity to dilate or constrict to autoregulate pressure. Acutely after removal of a cerebral AVM, excessive blood pressure in these arterial feeders can cause normal brain tissue to bleed. However, this theory remains controversial. We present a patient with a cerebral AVM that demonstrated cerebrovascular reactivity and argues against an assumption underlying the theory of NPPB syndrome.
Systemic panca-associated vasculitis with central nervous involvement causing recurrent myelitis: case report
Alexander J Hamilton, Duncan J Whitehead, Matthew D Bull, Richard J D'Souza
BMC Neurology , 2010, DOI: 10.1186/1471-2377-10-118
Abstract: The patient underwent MRI scanning showing patchy cord enhancement from T10 to the conus, which was suggestive of a cord malignancy. Prior to a cord biopsy, he was treated with steroids and a repeat MRI showed resolution of the original lesion with a new similar lesion from C7 to T3.He made a marked recovery after further treatment with high dose steroids and plasma exchange.This case report highlights a possible presentation of spinal cord inflammation in which imaging initially suggested an alternative pathology to transverse myelitis, such as a spinal cord tumour. In addition it examines recurrent myelitis associated with a systemic pANCA associated vasculitis despite active immunosuppression, in particular the failure of rituximab and the requirement for plasma exchange.There are a handful of reports of central nervous system involvement in patients with vasculitis. Many of these specifically involve Wegener's granulomatosis; López-Rodríguez et al[1] report on a case of Wegener's with a granulomatous mass in the Meckel cavum and diffuse meningeal involvement, treated with steroids and cyclophosphamide. Levin et al[2] report on a case of Wegener's granulomatosis with dural inflammation managed with steroids and cyclophosphamide. Their case highlights periaortitis as a particular feature. Nagashima et al[3] report on a case of pANCA Wegener's with hypertrophic pachymeningitis and multiple cranial neuropathies, this case similarly presented with an initial diagnosis suggesting malignancy that was disproved at biopsy.Morinaga et al[4] report on a case of pANCA positivity associated with cerebellar dural enhancement as well as temporal arteritis. This patient had multiple cranial neuropathies.The imaging features initially supporting a diagnosis of a cord tumour have been documented in the literature by Rourke et al[5]. In this case the abnormal area was macroscopically normal and intraoperative specimens did not show neoplastic cells, and the patient recovered with
Candida albicans White and Opaque Cells Undergo Distinct Programs of Filamentous Growth
Haoyu Si,Aaron D. Hernday,Matthew P. Hirakawa,Alexander D. Johnson,Richard J. Bennett
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003210
Abstract: The ability to switch between yeast and filamentous forms is central to Candida albicans biology. The yeast-hyphal transition is implicated in adherence, tissue invasion, biofilm formation, phagocyte escape, and pathogenesis. A second form of morphological plasticity in C. albicans involves epigenetic switching between white and opaque forms, and these two states exhibit marked differences in their ability to undergo filamentation. In particular, filamentous growth in white cells occurs in response to a number of environmental conditions, including serum, high temperature, neutral pH, and nutrient starvation, whereas none of these stimuli induce opaque filamentation. Significantly, however, we demonstrate that opaque cells can undergo efficient filamentation but do so in response to distinct environmental cues from those that elicit filamentous growth in white cells. Growth of opaque cells in several environments, including low phosphate medium and sorbitol medium, induced extensive filamentous growth, while white cells did not form filaments under these conditions. Furthermore, while white cell filamentation is often enhanced at elevated temperatures such as 37°C, opaque cell filamentation was optimal at 25°C and was inhibited by higher temperatures. Genetic dissection of the opaque filamentation pathway revealed overlapping regulation with the filamentous program in white cells, including key roles for the transcription factors EFG1, UME6, NRG1 and RFG1. Gene expression profiles of filamentous white and opaque cells were also compared and revealed only limited overlap between these programs, although UME6 was induced in both white and opaque cells consistent with its role as master regulator of filamentation. Taken together, these studies establish that a program of filamentation exists in opaque cells. Furthermore, this program regulates a distinct set of genes and is under different environmental controls from those operating in white cells.
The Evolution of Inner Disk Gas in Transition Disks
Keri Hoadley,Kevin France,Richard D Alexander,Matthew McJunkin,Christian Schneider
Physics , 2015, DOI: 10.1088/0004-637X/812/1/41
Abstract: Investigating the molecular gas in the inner regions of protoplanetary disks provides insight into how the molecular disk environment changes during the transition from primordial to debris disk systems. We conduct a small survey of molecular hydrogen (H$_2$) fluorescent emission, using 14 well-studied Classical T Tauri stars at two distinct dust disk evolutionary stages, to explore how the structure of the inner molecular disk changes as the optically thick warm dust dissipates. We simulate the observed HI-Lyman $\alpha$-pumped H$_2$ disk fluorescence by creating a 2D radiative transfer model that describes the radial distributions of H$_{2}$ emission in the disk atmosphere and compare these to observations from the Hubble Space Telescope. We find the radial distributions that best describe the observed H$_2$ FUV emission arising in primordial disk targets (full dust disk) are demonstrably different than those of transition disks (little-to-no warm dust observed). For each best-fit model, we estimate inner and outer disk emission boundaries (r$_{in}$ and r$_{out}$), describing where the bulk of the observed H$_2$ emission arises in each disk, and we examine correlations between these and several observational disk evolution indicators, such as n$_{13-31}$, r$_{in,CO}$, and the mass accretion rate. We find strong, positive correlations between the H$_2$ radial distributions and the slope of the dust SED, implying the behavior of the molecular disk atmosphere changes as the inner dust clears in evolving protoplanetary disks. Overall, we find that H$_2$ inner radii are $\sim$4 times larger in transition systems, while the bulk of the H$_2$ emission originates inside the dust gap radius for all transitional sources.
Sequential Electronic and Structural Transitions in VO2 Observed Using X-ray Absorption Spectromicroscopy
Suhas Kumar,John Paul Strachan,Matthew D. Pickett,Alexander Bratkovsky,Yoshio Nishi,R. Stanley Williams
Physics , 2015, DOI: 10.1002/adma.201402404
Abstract: The popular dual electronic (Mott) and structural (Peierls) transitions in VO2 are explored using x-ray absorption spectromicroscopy with high spatial and spectral resolutions. It is found that during both heating and cooling, the electronic transition always precedes the structural Peierls transition. Between the two transitions, there are intermediate states that are spectrally isolated here.
The Market Effects of Patent Litigation  [PDF]
Matthew D. Henry
Technology and Investment (TI) , 2013, DOI: 10.4236/ti.2013.41007

This study measures the value of patents to firms and identifies factors that contribute to that value by observing the abnormal change in firms stock market values following court decisions. Firms lose 0.85% (about $19 million) of their value following a decision that one of their patents is “Invalid”, but only gain about 0.7% following a Valid & Infringed decision. The factors that that affect the expectations of investors as to the enforceability of patent rights are at least as important in determining the contribution of the patent to the firms market value as are characteristics of the patent. Most prominently, this confirms the substantial impact that the creation of the Court of Appeals for the Federal Circuit (CAFC) had on the value of patents. After the creation of the CAFC, “Invalid” decisions resulted in a 0.7% (about $15.5 million) greater loss of firm value. Clearly, patents are more valuable because of this change in the legal landscape.

Characterization of Rabensburg Virus, a Flavivirus Closely Related to West Nile Virus of the Japanese Encephalitis Antigenic Group
Matthew T. Aliota, Susan A. Jones, Alan P. Dupuis, Alexander T. Ciota, Zdenek Hubalek, Laura D. Kramer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039387
Abstract: Rabensburg virus (RABV), a Flavivirus with ~76% nucleotide and 90% amino acid identity with representative members of lineage one and two West Nile virus (WNV), previously was isolated from Culex pipiens and Aedes rossicus mosquitoes in the Czech Republic, and phylogenetic and serologic analyses demonstrated that it was likely a new lineage of WNV. However, no direct link between RABV and human disease has been definitively established and the extent to which RABV utilizes the typical WNV transmission cycle is unknown. Herein, we evaluated vector competence and capacity for vertical transmission (VT) in Cx. pipiens; in vitro growth on avian, mammalian, and mosquito cells; and infectivity and viremia production in birds. RABV infection and replication only were detected on mosquito cells. Experimentally inoculated birds did not become infected. Cx. pipiens had poor peroral vector competence and a higher VT rate as compared to US-WNV in Cx. pipiens. As a result, we postulate that RABV is an intermediate between the mosquito-specific and horizontally transmitted flaviviruses.
An Allosteric Regulator of R7-RGS Proteins Influences Light-Evoked Activity and Glutamatergic Waves in the Inner Retina
Matthew D. Cain, Bradly Q. Vo, Alexander V. Kolesnikov, Vladimir J. Kefalov, Susan M. Culican, Daniel Kerschensteiner, Kendall J. Blumer
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082276
Abstract: In the outer retina, G protein-coupled receptor (GPCR) signaling mediates phototransduction and synaptic transmission between photoreceptors and ON bipolar cells. In contrast, the functions of modulatory GPCR signaling networks in the inner retina are less well understood. We addressed this question by determining the consequences of augmenting modulatory Gi/o signaling driven by endogenous transmitters. This was done by analyzing the effects of genetically ablating the R7 RGS-binding protein (R7BP), a membrane-targeting protein and positive allosteric modulator of R7-RGS (regulator of the G protein signaling 7) family that deactivates Gi/oα subunits. We found that R7BP is expressed highly in starburst amacrine cells and retinal ganglion cells (RGCs). As indicated by electroretinography and multielectrode array recordings of adult retina, ablation of R7BP preserved outer retina function, but altered the firing rate and latency of ON RGCs driven by rods and cones but not rods alone. In developing retina, R7BP ablation increased the burst duration of glutamatergic waves whereas cholinergic waves were unaffected. This effect on glutamatergic waves did not result in impaired segregation of RGC projections to eye-specific domains of the dorsal lateral geniculate nucleus. R7BP knockout mice exhibited normal spatial contrast sensitivity and visual acuity as assessed by optomotor reflexes. Taken together these findings indicate that R7BP-dependent regulation of R7-RGS proteins shapes specific aspects of light-evoked and spontaneous activity of RGCs in mature and developing retina.
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