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CHAPMAN, JEAN PERRY March 11, 1917 to Nov. 27, 2012 FOREVER YOUNG Jean's book, A Miracle a Mile Long, begins with her family's life in Tonopah, Nevada. It then chronicles her growing up in the Wilshire District of LA, meeting Ed Chapman during the Depression, and marrying during WWII. In 1947, Ed's aeronautical engineering talents landed the growing family in San Diego. After Ed's death in 1972, Jean moved from Point Loma to Mission Hills. There she established her legacy as a true artisan, her skills ranging from oils to stained glass, from stone sculpture to bookmaking. She was a member of the SD Sculptors Guild for many decades. Rarely traditional, she favored luminous, abstract themes that captured the unexpected beauty of everyday life. Throughout her 95 years, Jean converted setbacks into challenges to be conquered with resolve, and relished life's simple joys with love, humor, dignity and grace. Jean's spirit continues in her children, Tom Chapman, Billy Chapman, Teri Chapman, Kathy Shaw and Ed Chapman, daughters-in-law Barbra Rhoda, Edie Chapman and Mariko Matsutani, sons-in-law Steve Richman and Peter Shaw, eight grandchildren, two great-grandchildren, extended family, and friends. Memorial Mass: Monday, December 3, 10:30 a.m., St. Vincent de Paul Church, 4080 Hawk St.
Published in U-T San Diego on Dec. 2, 2012


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Publications (29)177.16 Total impact
Article: Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury.[Show abstract] [Hide abstract]
ABSTRACT: Traumatic brain injury (TBI) is an established risk factor for the early development of dementia, including Alzheimer's disease, and the post-traumatic brain frequently exhibits neurofibrillary tangles comprised of aggregates of the protein tau. We have recently defined a brain-wide network of paravascular channels, termed the "glymphatic" pathway, along which CSF moves into and through the brain parenchyma, facilitating the clearance of interstitial solutes, including amyloid-β, from the brain. Here we demonstrate in mice that extracellular tau is cleared from the brain along these paravascular pathways. After TBI, glymphatic pathway function was reduced by ∼60%, with this impairment persisting for at least 1 month post injury. Genetic knock-out of the gene encoding the astroglial water channel aquaporin-4, which is importantly involved in paravascular interstitial solute clearance, exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain. These findings suggest that chronic impairment of glymphatic pathway function after TBI may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration. Copyright © 2014 the authors 0270-6474/14/3416180-14$15.00/0.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 12/2014; 34(49):16180-93. DOI:10.1523/JNEUROSCI.3020-14.2014 · 6.75 Impact Factor
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ABSTRACT: Objective: In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal and interstitial fluids. Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular cerebrospinal fluid (CSF) pathways. The Objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain.Methods: CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy while interstitial solute clearance was evaluated by radio-tracer clearance assays in young (2-3 month), middle age (10-12 month) and old (18-20 month) wild type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function were evaluated by immunofluorescence.Results: Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparechamally injected amyloid β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange.Interpretation: We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of mis-folded protein aggregates. ANN NEUROL 2014. © 2014 American Neurological AssociationAnnals of Neurology 12/2014; 76(6). DOI:10.1002/ana.24271 · 11.91 Impact Factor
Article: Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease[Show abstract] [Hide abstract]
ABSTRACT: Alexander disease (AxD) is the only known human pathology caused by mutations in an astrocyte-specific gene, glial fibrillary acidic protein (GFAP). These mutations result in abnormal GFAP accumulations that promote seizures, motor delays and, ultimately, death. The exact contribution of increased, abnormal levels of astrocytic mutant GFAP in the development and progression of the epileptic phenotype is not clear, and we addressed this question using two mouse models of AxD. Comparison of brain seizure activity spontaneously and after traumatic brain injury (TBI), an effective way to trigger seizures, revealed that abnormal GFAP accumulation contributes to abnormal brain activity (increased interictal discharges) but is not a risk factor for the development of epilepsy after TBI. These data highlight the need to further explore the complex and heterogeneous response of astrocytes towards injury and the involvement of GFAP in the progression of AxD.Brain Research 09/2014; 1582. DOI:10.1016/j.brainres.2014.07.029 · 2.83 Impact Factor
Article: The Spectrum of Neuro-behavioral Sequelae Following Repetitive Mild Traumatic Brain Injury: A Novel Mouse Model of Chronic Traumatic Encephalopathy (CTE).[Show abstract] [Hide abstract]
ABSTRACT: There has been an increased focus on the neurological sequelae of repetitive mild traumatic brain injury (TBI), particularly neurodegenerative syndromes such as chronic traumatic encephalopathy (CTE); however, no animal model exists that captures the behavioral spectrum of this phenomenon. We sought to develop an animal model of CTE. Our novel model is a modification and fusion of two of the most popular models of TBI and allows for controlled closed-head impacts to un-anesthetized mice. Two-hundred and eighty, 12-week old mice were divided into control, single mild-TBI, and repetitive mild-TBI groups. Repetitive mild-TBI mice received six concussive impacts daily, for seven days. Behavior was assessed at various time-points. Neurological severity score (NSS) was computed and vestibulo-motor function tested with the wire grip test (WGT). Cognitive function was assessed with Morris water maze (MWM); anxiety/risk-taking behavior with the elevated-plus-maze (EPM), and depression-like behavior with the forced swim/tail suspension tests. Sleep EEG/EMG studies were performed at one month. NSS was elevated compared to controls in both TBI groups and improved over time. Repetitive mild-TBI mice demonstrated transient vestibulo-motor deficits on WGT. Repetitive mild-TBI mice also demonstrated deficits in MWM testing. Both mild-TBI groups demonstrated increased anxiety at 2-weeks but repetitive mild-TBI mice develop increased risk-taking behaviors at 1-month that persist at 6-months. Repetitive mild-TBI mice exhibit depression-like behavior at 1-month. Both groups demonstrate sleep disturbances. We describe the neurological sequelae of repetitive mild-TBI in a novel mouse model, which resemble several of the neuro-psychiatric behaviors observed clinically in patients sustaining repetitive mild head injury.Journal of neurotrauma 04/2014; DOI:10.1089/neu.2013.3255 · 4.25 Impact Factor
Article: A novel technique for morphometric quantification of subarachnoid hemorrhage-induced microglia activation[Show abstract] [Hide abstract]
ABSTRACT: Subarachnoid hemorrhage (SAH) is a neurologic catastrophe and poor outcome is typically attributed to vasospasm; however, there is also evidence that SAH causes a pro-inflammatory state and these two phenomena may be interrelated. SAH causes activation of microglia, but the time course and degree of microglial activation after SAH and its link to poor patient outcome and vasospasm remains unknown. Transgenic mice expressing eGFP under the control of the CX3CR1 locus, in which microglia are endogenously fluorescent, were randomly assigned to control or SAH groups. Immunohistochemistry for CD-68 and CD-31 was performed at different time points after SAH. Using confocal microscopy and MatLab software, we have developed a novel technique to detect and quantify the stages of microglial activation and return to quiescence using an automated computerized morphometric analysis. We detected a statistically significant decrease in microglial process complexity 2 and 7 days following SAH. In addition, we detected a statistically significant increase in microglial domain volume 1 day following SAH; however, microglial domain volume returned to baseline by 2 days. Most techniques for microglia assessment are qualitative, not quantitative, and are therefore inadequate to address the effects of anti-inflammatory drug treatment or other therapies after SAH. Using novel image analysis techniques we were able to reproducibly quantify activation of microglia following SAH, which will improve our ability to study the biology of microglial activation, and may ultimately improve management of disease progression and response to therapies directed at microglial activation.Journal of neuroscience methods 04/2014; 229. DOI:10.1016/j.jneumeth.2014.04.001 · 2.30 Impact Factor
Article: The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy.[Show abstract] [Hide abstract]
ABSTRACT: An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.Surgical Neurology International 01/2014; 5:184. DOI:10.4103/2152-7806.147566 · 1.18 Impact Factor
Article: Cerebral Arterial Pulsation Drives Paravascular CSF-Interstitial Fluid Exchange in the Murine Brain[Show abstract] [Hide abstract]
ABSTRACT: CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid β, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ∼50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ∼60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid β, in the aging brain.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 11/2013; 33(46):18190-9. DOI:10.1523/JNEUROSCI.1592-13.2013 · 6.75 Impact Factor
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ABSTRACT: The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.Science 10/2013; 342(6156):373-7. DOI:10.1126/science.1241224 · 31.48 Impact Factor
Article: Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain.[Show abstract] [Hide abstract]
ABSTRACT: In the brain, a paravascular space exists between vascular cells and astroglial end-foot processes, creating a continuous sheath surrounding blood vessels. Using in vivo two-photon imaging we demonstrate that the paravascular circulation facilitates selective transport of small lipophilic molecules, rapid interstitial fluid movement and widespread glial calcium signaling. Depressurizing the paravascular system leads to unselective lipid diffusion, intracellular lipid accumulation and pathological signaling in astrocytes. As the central nervous system is devoid of lymphatic vessels, the paravascular space may serve as a lymphatic equivalent that represents a separate highway for the transport of lipids and signaling molecules.Scientific Reports 09/2013; 3:2582. DOI:10.1038/srep02582 · 5.08 Impact Factor
Article: Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer[Show abstract] [Hide abstract]
ABSTRACT: BackgroundNeurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed.MethodsTime-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30–180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion.ResultsFollowing lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions.ConclusionLumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.Journal of Translational Medicine 05/2013; 11(1):107. DOI:10.1186/1479-5876-11-107 · 3.99 Impact Factor
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ABSTRACT: The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.The Journal of clinical investigation 03/2013; 123(3):1299-309. DOI:10.1172/JCI67677 · 15.39 Impact Factor
Article: 'Hit & Run' model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation.[Show abstract] [Hide abstract]
ABSTRACT: Cerebral edema is a major contributor to morbidity associated with traumatic brain injury (TBI). The methods involved in most rodent models of TBI, including head fixation, opening of the skull, and prolonged anesthesia, likely alter TBI development and reduce secondary injury. We report the development of a closed-skull model of murine TBI, which minimizes time of anesthesia, allows the monitoring of intracranial pressure (ICP), and can be modulated to produce mild and moderate grade TBI. In this model, we characterized changes in aquaporin-4 (AQP4) expression and localization after mild and moderate TBI. We found that global AQP4 expression after TBI was generally increased; however, analysis of AQP4 localization revealed that the most prominent effect of TBI on AQP4 was the loss of polarized localization at endfoot processes of reactive astrocytes. This AQP4 dysregulation peaked at 7 days after injury and was largely indistinguishable between mild and moderate grade TBI for the first 2 weeks after injury. Within the same model, blood-brain barrieranalysis of variance permeability, cerebral edema, and ICP largely normalized within 7 days after moderate TBI. These findings suggest that changes in AQP4 expression and localization may not contribute to cerebral edema formation, but rather may represent a compensatory mechanism to facilitate its resolution.Journal of Cerebral Blood Flow & Metabolism advance online publication, 27 February 2013; doi:10.1038/jcbfm.2013.30.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 02/2013; DOI:10.1038/jcbfm.2013.30 · 5.46 Impact Factor
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ABSTRACT: Microinfarcts are a common clinical feature of the aging brain, particularly in patients with cognitive decline or vascular or Alzheimer's dementia. However, the natural history of these lesions remains largely unexplored. Here we describe a mouse (C57BL/6J) model of multiple diffuse microinfarcts induced by unilateral internal carotid artery injection of cholesterol crystals (40-70 μm). Microinfarcts were spread throughout the deep cortex, subcortical tissue, and hippocampus and were comprised of a core positive for CD68 (a marker for reactive microglia and macrophages), surrounded by large regions of glial fibrillary acidic protein-positive reactive astrogliosis. Widespread reactive gliosis, including mislocalization of the astrocytic water channel aquaporin 4 persisted long after injury, recovering only after 1 month after stroke. Within the cortex, neuronal cell death progressed gradually over the first month, from ∼35% at 3 d to 60% at 28 d after stroke. Delayed demyelination was also observed in lesions, beginning 28 d after stroke. These findings demonstrate that microinfarct development follows a distinct course compared to larger regional infarcts such as those induced by middle cerebral artery occlusion. The long-lasting gliosis, delayed neuronal loss, and demyelination suggest that the therapeutic window for microinfarcts may be much wider (perhaps days to weeks) than for larger strokes.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 12/2012; 32(50):17948-60. DOI:10.1523/JNEUROSCI.1860-12.2012 · 6.75 Impact Factor
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 12/2012; 33(2). DOI:10.1038/jcbfm.2012.182 · 5.46 Impact Factor
Article: A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.[Show abstract] [Hide abstract]
ABSTRACT: Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.Science translational medicine 08/2012; 4(147):147ra111. DOI:10.1126/scitranslmed.3003748 · 14.41 Impact Factor
Article: Epoxyeicosatrienoic acids are endogenous regulators of vasoactive neuropeptide release from trigeminal ganglion neurons.[Show abstract] [Hide abstract]
ABSTRACT: Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. We previously described the expression of cytochrome P450-2J epoxygenase in rat trigeminal ganglion neurons and that EETs signaling is involved in cerebrovascular dilation resulting from perivascular nerve stimulation. In this study, we evaluate the presence of the EETs signaling pathway in trigeminal ganglion neurons and their role in modulating the release of calcitonin gene-related peptide (CGRP) by trigeminal ganglion neurons. Liquid chromatography tandem mass spectrometry identified the presence of each of the four EETs regio-isomers within primary trigeminal ganglion neurons. Stimulation for 1 h with the transient receptor potential vanilloid-1 channel agonist capsaicin (100 nmol/L) or depolarizing K(+) (60 mmol/L) increased CGRP release as measured by ELISA. Stimulation-evoked CGRP release was attenuated by 30 min pre-treatment with the EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol/L). K(+) stimulation elevated CGRP release 2.9 ± 0.3-fold above control levels, whereas in the presence of 14,15-EEZE K(+)-evoked CGRP release was significantly reduced to 1.1 ± 0.2-fold above control release (p < 0.01 anova, n = 6). 14,15-EEZE likewise attenuated capsaicin-evoked CGRP release from trigeminal ganglion neurons (p < 0.05 anova, n = 6). Similarly, pre-treatment with the cytochrome P450 epoxygenase inhibitor attenuated stimulation-evoked CGRP release. These data demonstrate that EETs are endogenous constituents of rat trigeminal ganglion neurons and suggest that they may act as intracellular regulators of neuropeptide release, which may have important clinical implications for treatment of migraine, stroke and vasospasm after subarachnoid hemorrhage.Journal of Neurochemistry 10/2010; 115(6):1530-42. DOI:10.1111/j.1471-4159.2010.07059.x · 4.24 Impact Factor
Article: Brainstem control of cerebral blood flow and application to acute vasospasm following experimental subarachnoid hemorrhage.[Show abstract] [Hide abstract]
ABSTRACT: Symptomatic ischemia following aneurysmal subarachnoid hemorrhage (SAH) is common but poorly understood and inadequately treated. Severe constriction of the major arteries at the base of the brain, termed vasospasm, traditionally has been thought to be a proximal event underlying these ischemias, although microvascular changes also have been described. The vast majority of studies aimed at understanding the pathogenesis of ischemic deficits, and vasospasm have focused on the interaction of the "spasmogen" of the extravasated blood with the smooth muscle and endothelium of the arteries. This has led to a comparative neglect of the contribution of the CNS to the maintenance of cerebral perfusion. In the present study, we focused on the role of the rostral ventromedial medulla (RVM) in modulating cerebral perfusion at rest and following an experimental SAH in the rat. Changes in cerebral blood flow (CBF) were measured using laser-Doppler flowmetry and three-dimensional optical microangiography. Focal application of a GABA(A) receptor agonist and antagonist was used to respectively inactivate and activate the RVM. We show here that the RVM modulates cerebral blood flow under resting conditions, and further, contributes to restoration of cerebral perfusion following a high-grade SAH. Failure of this brainstem compensatory mechanism could be significant for acute perfusion deficits seen in patients following subarachnoid hemorrhage.Neuroscience 07/2009; 163(2):719-29. DOI:10.1016/j.neuroscience.2009.06.031 · 3.33 Impact Factor
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ABSTRACT: Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites of cytochrome P450 epoxygenase enzymes recognized as key players in vascular function and disease, primarily attributed to their potent vasodilator, anti-inflammatory and pro-angiogenic effects. Although EETs' actions in the central nervous system (CNS) appear to parallel those in peripheral tissue, accumulating evidence suggests that epoxyeicosanoid signaling plays different roles in neural tissue compared to peripheral tissue; roles that reflect distinct CNS functions, cellular makeup and intercellular relationships. This is exhibited at many levels including the expression of EETs-synthetic and -metabolic enzymes in central neurons and glial cells, EETs' role in neuro-glio-vascular coupling during cortical functional activation, the capacity for interaction between epoxyeicosanoid and neuroactive endocannabinoid signaling pathways, and the regulation of neurohormone and neuropeptide release by endogenous EETs. The ability of several CNS cell types to produce and respond to EETs suggests that epoxyeicosanoid signaling is a key integrator of cell-cell communication in the CNS, coordinating cellular responses across different cell types. Under pathophysiological conditions, such as cerebral ischemia, EETs protect neurons, astroglia and vascular endothelium, thus preserving the integrity of cellular networks unique to and essential for proper CNS function. Recognition of EETs' intimate involvement in CNS function in addition to their multi-cellular protective profile has inspired the development of therapeutic strategies against CNS diseases such as cerebral ischemia, tumors, and neural pain and inflammation that are based on targeting the cellular actions of EETs or their biosynthetic and metabolizing enzymes. Based upon the emerging importance of epoxyeicosanoids in cellular function and disease unique to neural systems, we propose that the actions of "neuroactive EETs" are best considered separately, and not in aggregate with all other peripheral EETs functions.Prostaglandins & other lipid mediators 07/2009; 91(3-4):68-84. DOI:10.1016/j.prostaglandins.2009.06.004 · 2.86 Impact Factor
Article: Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia.[Show abstract] [Hide abstract]
ABSTRACT: Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids (EETs), is sexually dimorphic and suppressed by estrogen. We determined if the sex difference in blood flow during focal cerebral ischemia is linked to sEH. Soluble epoxide hydrolase expression in brain, hydrolase activity in cerebral vessels, and plasma 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) were determined in male and female wild-type (WT) and sEH knockout (sEHKO) mice. Male, female, and ovariectomized female WT and sEHKO mice were subjected to 2-h middle cerebral artery occlusion (MCAO) and infarct size was measured at 24 h of reperfusion. Laser-Doppler cortical perfusion during MCAO was compared among groups and differences in cortical blood flow rates were confirmed using in vivo quantitative optical microangiography. Cerebrovascular expression and activity of sEH and plasma 14,15-DHET were lower in WT female than male mice, and blood flow during MCAO was higher and infarct size was smaller in WT female compared with male mice. Sex differences in cerebral blood flow and ischemic damage were abolished after ovariectomy and were absent in sEHKO mice. We conclude that sEH is an important mechanism underlying sex-linked differences in blood flow and brain damage after cerebral ischemia.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 06/2009; 29(8):1475-81. DOI:10.1038/jcbfm.2009.65 · 5.46 Impact Factor
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ABSTRACT: Epoxyeicosatrienoic acids (EETs) are potent vasodilators produced from arachidonic acid by cytochrome P-450 (CYP) epoxygenases and metabolized to vicinal diols by soluble epoxide hydrolase (sEH). In the brain, EETs are produced by astrocytes and the vascular endothelium and are involved in the control of cerebral blood flow (CBF). Recent evidence, however, suggests that epoxygenases and sEH are present in perivascular vasodilator nerve fibers innervating the cerebral surface vasculature. In the present study, we tested the hypothesis that EETs are nerve-derived relaxing factors in the cerebral circulation. We first traced these fibers by retrograde labeling in the rat to trigeminal ganglia (TG) and sphenopalatine ganglia (SPG). We then examined the expression of CYP epoxygenases and sEH in these ganglia. RT-PCR and Western blot analysis identified CYP2J3 and CYP2J4 epoxygenase isoforms and sEH in both TG and SPG, and immunofluorescence double labeling identified CYP2J and sEH immunoreactivity in neuronal cell bodies of both ganglia. To evaluate the functional role of EETs in neurogenic vasodilation, we elicited cortical hyperemia by electrically stimulating efferent cerebral perivascular nerve fibers and by chemically stimulating oral trigeminal fibers with capsaicin. Cortical blood flow responses were monitored by laser-Doppler flowmetry. Local administration to the cortical surface of the putative EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (30 mumol/l) attenuated CBF responses to electrical and chemical stimulation. These results suggest that EETs are produced by perivascular nerves and play a role in neurogenic vasodilation of the cerebral vasculature. The findings have important implications to such clinical conditions as migraine, vasospasm after subarachnoid hemorrhage, and stroke.AJP Heart and Circulatory Physiology 04/2009; 296(5):H1352-63. DOI:10.1152/ajpheart.00950.2008 · 4.01 Impact Factor
Top Journals
University Center Rochester
Rochester, Minnesota, United States
- Department of Neurosurgery
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Rochester, New York, United States
- Center for Translational Neuromedicine
Oregon Health and Science University
Portland, Oregon, United States
- • Department of Anesthesiology & Perioperative Medicine
- • Department of Physiology & Pharmacology
University of PortlandPortland, Oregon, United States
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Seattle, Washington, United States
- Department of Neurological Surgery

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The cleaniness
Access to the hotel. Construction
When we came in, the older receptionist was so friendly- he took me out back to show me where to park my large U-haul truck. He also pointed out a back alley to get back on the bridge that goes over the freeway so I could go to a Thai restaurant I wanted to eat at. The reception area was done in marble and just had a feel of majestic places that are no longer built. The room was large, nice paint, and the entire place seemed very clean, unlike some of the reviews I had read. The king bed was very comfortable. I will travel this route just to go back to this hotel.
To get to the entrance of the hotel, you have to take the freeway on-ramp and then turn off before reaching the freeway. A little unusual, but there is also a back entrance that goes between two gas stations and a McDonalds that doesn't use this entrance from the freeway on-ramp.
Friendly service, accommodating when needed help.
I prefer a room 121 because of my disability
I liked the fact my room was beautiful and made me feel at home.
The parking was kind of limited for the amount of rooms they provide. . .
Price; of course.
Not enough lighting in room; particularly at head of bed in order to read. Not enough shelf space either. No towel rack in bathroom and not enough vanity space as well. Bed was somewhat uncomfortable and lock on door not really sufficient.
The staff was very accommodating.
The amenities, especially the laundry rooms!
I wish the pool was indoor. The heating/cooling units in the room did not go with the scheme of the rest of the hotel (they were old fashioned). I would have liked to be able to digitally control the temp via a wall thermostat
Older motel. Nothing special. Decent room for the money if you're just looking for a clean place to sleep for the night.
Right off the freeway. Lots of traffic noise.
Clean room- great price online
Upon checking in - the lady asked for my CC info an wrote on back of a piece of paper- I didn't care for that since I had already paid in advance online! Too much CC scams an I didn't feel it's safe
Microwave and refrigerator cleanliness
No shampoo,conditioner or hairdryer. WiFi only worked in the lobby not in our our rooms
Room was a nice size.
It was somewhat cheap by still too pricey for the crappy stay
Bed was terrible, location was bad, had a strange odor
First impression: the lobby was clean and decorated for Christmas. I got exactly what I'd reserved..non-smoking room w/two beds. Inside and outside doors so smokers could go outside. Parking was within a few feet of outside door.
Nothing to dislike, got exactly what I requested while making reservation.
Things did not work
The staff was really friendly and helpful, the rooms were clean and comfortable, and they allowed our dogs without a ridiculously expensive surcharge
No good parking for trucks/trailers - which we had since we were moving from WA state
The room was clean.
There was a lot of loud noises, no parking area close to room, unable to sleep for the noises, and not enough towels
Voilà pourquoi :
Nous ne sommes pas un site marchand
À KAYAK nous ne fixons pas les prix, il nous est donc impossible de garantir des produits et services vendus par d'autres compagnies.
Nous recueillons des données pour vous
Notre site vous permet de comparer rapidement et facilement des centaines de sites de voyage à la fois. En ce sens, KAYAK est un moteur de recherche et nous ne pouvons garantir les prix que nous trouvons.
Pourquoi les prix ne sont-ils pas exacts à 100% ?
Le prix des billets d'avions, chambres d'hôtels et véhicules de location varie fréquemment. Il est également probable que plusieurs personnes tentent de réserver la même option de voyage en simultané. C'est pourquoi il se peut qu'occasionnellement, certains prix ne soient plus disponibles.
Vous souhaitez plus d'informations ou avez trouvé une différence de prix? Contactez-nous
N'hésitez pas à nous envoyer un
et un membre de notre équipe vous répondra dans les plus brefs délais.


text:
If you and the tea party want to complain about spending Mr. Arn then why not discuss Pentagon spending which is by far the single largest discretionary item in the Federal Budget or the multi-trillion dollar tax cuts of the Bush years. Perhaps it's because both benefit the wealthy which includes David and Charles Koch, the benefactors of your organization. Keep in mind the orginal tea party movement in 1773 was primarily opposed to the relationship between large concentrations of wealth and the government. Time to turn in your pointy hat.
- TRRT April 1-7 | Online Edition
- Guest Commentary: the Rockford Apartment Association
- State Roundup: NIU employee improperly reimbursed $30K
- State Roundup: Governor signs budget fix bills
- Rauner, Democratic leaders shake hands and make law
- State roundup: National guardsman and cousin arrested in terror plot
- Lawmaker says license plate readers a privacy threat
- Bryant not the first to feel impact of free agency rules
- State Roundup: Parents' group calls for standardized test opt-out bill
- Hononegah Mack: 'The best woman in the county'
Throwing away our money on government spending
A $447 billion jobs bill and $787 billion in stimulus has or will be spent to deal with the high unemployment this country faces; that is $1.234 trillion. And what have we gotten for all that spending? Record food stamp use, a rise in the poverty rate, a credit downgrade, 9.1 percent unemployment rate nationwide, 11.6 percent for the Rockford metro area, 16.2 percent underemployment rate and zero net new jobs created across the country in August.
How much more of our money is going to be thrown away before Keynesian economic-loving Democrats admit their philosophy, their agenda, their policies are complete and total unmitigated disasters? Probably never; therefore, we will just have to give every big government spending-addicted Democrat who is allergic to fiscal responsibility the pink slip.
Ulysses S. Arn
Ashton, Ill.
From the Oct. 12-18, 2011, issue


text:
Hotel Amazon
Mon 10|9c
Breaking Borders
Sun 9|8c
Expedition Unknown
Thurs 9|8c
If These Walls Could Talk 02:04
Travel's Best Family Adventures 2015 02:45
Tony Bourdain finds himself in San Francisco, a city known by vegan and vegetarian lovers alike. Tony discovers that San Francisco is a "bare-knuckled, 2-fisted drinking town.
Anthony Bourdain: No Reservations:Philippines
Anthony Bourdain: No Reservations:Sardinia
Mysteries at the Castle:Making of an Artist, Secret Sonar, Fairy Flag
Mysteries at the Museum:Baseball Stalker, Peggy Shippen and Moon Hoax
Mysteries at the Museum:Strangers on a Train, Madame Tussaud, WD-40
Mysteries at the Museum:Margery the Medium, Everest Ascent, The Pastor and the Choir Singer
Mysteries at the Museum:Squeaky Fromme, Hodag, Typhoid Mary
Expedition Unknown:Code to Gold
Man v. Food:Las Vegas
Man v. Food:Syracuse
Bizarre Foods:Hawaii's Big Island: Eyeballs and Abalone
Man v. Food:Oklahoma City
Man v. Food:Springfield
Expedition Unknown:Secrets of the Nazca
Expedition Unknown:Samurai Sword of Power
The Layover:New Orleans
Anthony Bourdain: No Reservations:Japan: Hokkaido


text:
New 2015 Ford Mustang Test 'n Tune Drag Racing
A mixture of different 2015 Ford Mustangs from the folks at AmericanMuscle.com and Revolution Automotive along with a few others head out for a little test n tune! All of the cars are bone...
Turbo & Nitrous Ford Mustangs drag racing Edgewater 2012
All Ford Mustang & Outlaw Mustang Test & Tune, all Turbo, Supercharged and Nitous Ford Mustangs drag racing, filmed 8-10-12 at Edgewater drag strip for the 2012 season. This video features...
Fox Body Ford Mustang Drag Racing Racelegal.com 8-10-2012
Drag race your ride at qualcomm stadium this red fox body ford mustang manual transmission car making passes on the 1/8 mile drag strip the day after the chargers played the green bay packers...
Ford vs. Ford: Cobra Jet versus GRC Fiesta ST
On one side, you have a 2013 Cobra Jet -- a 5.0L V8 powerplant with a Ford Racing-built Whipple 2.9L Supercharger. On the other is a Ford Fiesta ST Competition Car -- a 2.0L, 550+ horsepower...
Flat Black Nissan GTR vs 2013 Ford Mustang GT Drag Race
FACEBOOK: http://facebook.com/612to303 TWITTER: http://twitter.com/612to303 SUBSCRIBE IF YOU CAN HANDLE THIS AWESOMENESS Sweet Murdered out nissan gtr vs 2013 ford mustang gt ...
1969 Chevy Camaro vs Ford Mustang Shelby GT500 - Drag Race
1969 Chevy Camaro vs Ford Mustang Shelby GT500 tags: drag race, drag race crash, drag race 2014, drag racing, drag racing 2014, drag racing videos, drag race muscle car, muscle...
1970 Ford Mustang 428 Mach 1 Cobra Jet (Drag racing edition)
I would definitely recommend listening to this with decent speakers or headphones, otherwise you won't really be able to hear the car that well since the music was so loud!
1966 blown ford mustang drag car 11/2012
1969 Mustang vs Ford Focus DRAG RACE
A vintage 1969 Ford Mustang Mach 1 lines up against a new FORD Focus for a 1/4 Mile Race at Toronto Motorsports Park, May 15, 2013. TMP Drag Racing.
Ford Mustang GT500 vs Corvette Drag Race
FACEBOOK: http://facebook.com/612to303 TWITTER: http://twitter.com/612to303 SUBSCRIBE IF YOU CAN HANDLE THIS AWESOMENESS This was filmed at Bandimere Speedway in Morrison ...
SRT Viper vs Ford Mustang Shelby GT 500 Drag Race Viertelmeile Rennen Acceleration Sound + Burnout
1/4 Mile Run - Audi R8 V10 get destroyed : http://youtu.be/nZ1ku_MZQc4 Audi S8 V10 Acceleration Sound : http://youtu.be/vSxq3waCJKA SRT10 vs SRT10 Roadster Race : http://youtu.be/JsLakxyyrgU.
2015 Ford Mustang GT vs. 2014 Ford Mustang GT Drag Race
Lined up a new 2015 Ford Mustang GT Premium against a 2014 Ford Mustang GT with the optional Track Package. The 2015 had Pirelli all-season tires working against it, while the 2014 had stickier...
Ferrari LaFerrari vs Bugatti Veyron 16.4 Super Sport
Dodge Ram Crushes GT-R in 1/4-Mile Pass
Drag Racing Down Under — 1500HP VW
Wheelstand Wednesday — Compilation Video
©2015 DragTimes - Disclaimer - Contact Us


text:
DAM! that's really good dodek, excellent job!!
This member has provided no bio about themself...
DAM! that's really good dodek, excellent job!!
Get Temuera Morrison he's looking for work :P
Name sounds familiar, is it from bf2 MC?
Haha, I remember this thing! :D
That's nice :)
Keep back you weak-minded fool! Avert your gaze, or you'll go cryyystal craaazy!
I love it, think it suits the game very well.
HKM4-L w/ M203 :)
We have our ways *muhahaha*
New collision meshes by moi :)
Indeed More sunshine preferable! Its just concept art though :P
Very awesome! I do love it
Interesting! you've gotten rid of the sights without it looking ugly
Best mod for Jedi Knight Jedi Academy, though i do suggest some new sounds! :P
Very cool idea there! I think in Crash Bandicoot 2: Cortex Boss you actually chase him with a Jetpack, so racing against bosses is certainly something unheard of!
yea, they're just placeholders i assume
It looks more like the original good work!
Love it!
Close! Just need to change the materials to the same model, its currently using the texture of the sa80.
I should look into clothes modeling :D Make some 3d clothes
Many memories, i look forward to this!
Haters, what haters? :PP
Love this mod project, campaign is so unique!
Nope, you need to get a computer! :D
I gave you the fix for it though.
Its in 1on1
But, skull needs to decide if it would suit SOF.
its going to be to-scale, the soldier fit in the sink :D cause it was scaled incorrectly. The house level will be 1 storey and if it turns out succesful, i'll make a sequel map :P
Haha thats great!
Hmmm i have to agree, the other 2 look nice and artistic, but as stated before don't suit the mod as much. Thanks anyway!
I did make a lightsaber ages ago, but i didn't place it on any of the maps. 2.0 didn't have the lightsaber so i have no idea how you got that :D
It's just a test and incredibly buggy, have fun with it anyway haha.
I just think of band of brothers when i see this, good work!
Perhaps, someone should do a band of brothers machinima using FH2?
It's ok, this is just a test project and an intresting one as well. I think this mod should be labeled as "Non-Release" for obvious reasons.
Finally, this goes so well with the animation. Default M4 reload, so overused haha :)
Almost the same gun
FH2 and PR are still updating though, not as fast.
2 Pictures to compare
COD4: Farm4.static.flickr.com
Real Life??: 50magnum.com
Well, this mod has been, by the most of it, created by me. I have had Skull help out with a couple of animations and Shamrok, doing music and graphics. We have tried recruiting a number of times, but it seems bf2 modders are just to busy now.
tritium sights i'm fairly sure.
Nice work Shamrok3, i agree the current logo is a glitch i had with bfeditor and took a screenshot of :P, this is getting much nicer!
Soon, a new menu!!
I like "recycling" parts from other guns, but on this instance the only "fold-stock" i could find was from the AK74U, G36 and PP-19 Bizon. Each stock did not suit this gun and just didn't look right, so i just placed the MP5 knob thing at the back.
:P Thanks, supprisingly it worked with default animations too :D
Thanks, will be added :)
Yep, live in Brisbane :D
Wow awesome!
It will be a hidden vehicle...
But im trying to find air physics coders cause it difficult to control.
Never was lol, only Ghillie in 3p.
I think 7game should make the sights look similar to BC2's AUG.
I don't think zmoderler is good for bf2, gmax would be a better free version. I am using 3ds max and imported the bf2 scar l. No photoshop was needed for this one, no BF editor either. Just import, recreate the scope using more polygones on the cylinder. Then UVW mapped it to the original SCAR texture.
I have the time. Plenty of time lol
Thanks. Sorry about low quality graphics though lol
Uhm if you want to see what the difference is, check out the Scar Video and you will see what the scope used to look like before it had to be reconstructed.
That is fantastic! Glad this mod is active, can't wait for release
DOH! we got to get back onto this! How did you do the M9? looks nice
Yeah it is a WIP but just edit the last part cause its a little jerky
I like it. How do u do filters, is it just a hud blend node? Looks hd-like :)
Thats only if we release the mod which we are only using to make the film. If we did release the mod u would have to download bf xpack to play. That would be perfectly legal
You do great at camos Very well done!
DID U MAKE THAT YOURSELF!? not airone!?
Well it is the magazine from the M4 Carbine, retextured to be white. If you look close enough you will see the reciver is actually a barrel :) Im going to hopefully animate it today and record a vid
PSP? its for PC look at the platform. 1on1 would be cool for psp though :)
Yeah, I would love to like Print it off and give it to a friend!
Wait, thats the nanjing XD
I usually put them at 0.1 cause then its more fun when they are stupid :D, besides i tried 1.0 and they just spawn camp, those noobs :O
Thanks for comment please submit feedback i would like to know about how downloaders think of the mod. any changes ect. Oh I forgot about forums any suggestions you can post on the new forums
I like the concept of it. Well done with that! I hope this project will be do-able by recycling bf2 parts!
Your reloads are definitely getting better!
Likes this. :)
You've given me an interesting idea. Perhaps adding a 3p chase camera to the "duck" cam could work! It won't look perfect, but it's a nice concept.
Nah, we'll stick with unlimited ammo for now lol, but it isn't using an animated system, its all just a trick, 1p hands attatched to the weapon's 1p model. The HMG turned out to have a 3p model, which saved lots of effort there, however it didn't have an ironsight, so I got the ironsight i made for the M249 SAW and placed it on there so it would line up correctly, then attatched the hands after weighting them to the 1p hands setup.
Oooo, i wasn't aware what that was, thanks for the info i'll look into that!
Thank you, believe it or not it's just hands attached to the HMG 1p model, then the Hmmwv model edited so that it has a 1p. Nothing animated here, but at least the hands move with the 'recoil'.
I thought about that, but it looks pretty gross, i've done some tests with cars in 3p where you can see the full body, its a nice feature but its too unstable i'd say and there are only 2 bones per hand pretty much
I just hope they go the way Unreal and Crysis are going with their mod tools. Releasing the engine for public education
It might be more clearer than the first one, but you can see the soldier finger in the bottom left corner, i'll try extend the scope so you can't see that, or we'll have to fix with animations.
Mods are not as confined to the legalities of full-production games :)
I've been thinking of that, and if the zoom time is short, i don't think it will be too noticable. It could also give more freedom for moving it about (sort of)
Haha airone website was done yesterday, got scared! :O
Hmmm the aiming still doesn't look as straight, do you think we should move it more forward/back until it lines up Jones?
Ohhh sorry to say, gravity should be adjusted, and jump height higher instead of gravity reduced. Also, it seems crash takes a while to get up to speed, perhaps make his 'acceleration' higher and 'top speed' lower (lol)
Yea, don't worry got some cool stuff comming your way :)
I definitely like this HD recreation! Good job with everything done here!
Love it, see your reloads are good! Sounds are always good too!
Great job, really like all the effect improvements. Checkpoint effect, so brilliant! I can see the resemblence with the old level as well, so well done on that! The Hud is very nice, good job coding it correct, can't wait to see more progress!
Very very very cool! I'm most enthusiastic about this mod. Few suggetions (sorry if they're obvious)
- Shadows on Hud is a nice concept, but it looks sort of glitchy when it colides through rocks, ect
- I know you're using bones/animations from another crysis character, but at least the running animation should look a little less hunched :P
- Original music please, the snow music should suit the snow level (haha)
- Spin effects
- Less buggy wampa harvesting.
Then, its pretty much perfected!
Looks very nice, i found two possible colour combinatins see if you like em.
So good to see the fun brought back into bf2, excellent work so far ;)
Had some fun on the beta, no online servers i can see of but i like the concept of a vehicle-only mod. Could be intresting.
Love it! reminds me of my M4 Drum mag :D
Yeah yeah, I'm getting to the last few weeks until my classes are finally finished :D
Awesome! Good to see how Alpha Project is progressing. Can't wait to get back on the scene and join the team again :)
I like it, a scary map is a good map :)
Loving the UFO's!!
Lets just hope it will work as good as the M16A4 ;)
Sigh, this isn't the Sir. mod
It would be interesting to get some new posters haha :P
More or less inspired by this
Oh no i spot a texture issue! On the handguard one of the "lines" is black, should fix asap before it irritates me too much!
Need for Speed Karkand anyone?
Silencer, M16A4 HandGuard (m203), M4 Stock, Eotech
I sure do think this will be the best mod ever, I will buy crysis just for this mod!
Woah woah woah! Brings back the memories of paying the old games. New ones can never ever beat the originals!
Google Translate :\
wow wow wow! Ramène les souvenirs de payer les anciens jeux. De nouveaux ne peuvent jamais battu les originaux!
woah woah woah slow down, this mod is getting to awesome!


text:
Ryan Britt has written for The New York Times, Electric Literature, The Awl, VICE Motherboard, Clarkesworld Magazine, and is a consulting editor for Story Magazine. He was the staff writer for the Hugo-Award winning web magazine Tor.com, where he remains a contributor. He lives in New York City.
Wanna contact a writer or editor? Email email@example.com.


text:
The breakfast, the decor and the location were all fantastic.The parking facilities were excellent (own private garage for 10 euros a day) also. - Katy
estrema gentilezza e disponibilità nelle informazioni del luogo, camere calde e ben pulite - Mauro
La reception e l'arredamento della camera - Anonymous
posizione ottima, albergo molto carino e camere confortevoli - Fabio
Convenient. Happy to provide free coffee in morning even though we did not have breakfast. - Anonymous
Superb Rooms. Renovated Chateau only recently opened, but friendly and welcoming Owners and staff. Quiet situation, but beautiful grounds. Very impressive interior and good French breakfast. Close to St Malo giving easy access by car, but set in peaceful countryside, away from the busy town. - Stephen
Questo hotel è semplicemente incantevole, non solo per la posizione ma per l'atmosfera e la gentilezza della signora. - Luisa
this hotel is beyond my expectation with good location and friendly stuff. I do not feel any noise as described by other comment. It is a good choice to stay in St Malo. - Anonymous
la cordialita', la gentilezza e la simpatia delle persone che lo gestiscono - Aligi
il panorama sull'oceano e la vicinanza al centro di s. malo - Anonymous
la simpatia, cordialità e disponibilità dei gestori dell'hotel. la bellezza e tranquillità dell'hotel - Roberta
The room - very nice, clean, we got the view to he castle, but it was also good. The hotel has old style and looks wondefull.We were with the small baby, and it was were comfortable to drive in the hotel with the stroller.
Stuff - friendly,helpfull.
Location - can imagine the best. Just outside the oldtown wall it's already the beach. You can easy also visit oldtown. Parking is outside the oldtown walls. But the hotel can sell you special card for parking, it costs 5 eur for 24 hours.
Resta - Anonymous


text:
- Like
- Thanks for voting!
- Download
- Collection
hubbahubba July 20, 2010
after all that fucking, and thats how much he comes? "/
slutcassie July 21, 2010
i love sucking dicks when my bf got with me he knew i was a ho. i use to suck the football players cocks after school.by the time i was 17 i suck 59 dick must black because i want to a mostly black school but there cum is better. i told my bf i would not fuck anyone but if someone wants a bj that i would give them one he use to get so mad but now dont care
10inchBliss December 7, 2010
@slutcassie - you can suck my dick...if you can get to fit in your mouth!
DeeMak May 14, 2013
I chose a good day to be black
YouDub July 20, 2010
I always wondered what Bonnie Langford was up to now.
li July 20, 2010
very good
bouba July 20, 2010
what a breast !
Stefeen July 20, 2010
;o P'tin comme elle jouie c'te meuf sa fait peur !!!
sex July 20, 2010
Jameson July 20, 2010
I'd love to fuck Annie Body. Her hairy pussy and her very long hair make me wanna cum
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Vikings sign Babatunde Aiyegbusi, a ginormous Polish-born tackle (pics/vid)
The Minnesota Vikings on Thursday went well outside the typical free agent search radius by signing Babatunde Aiyegbusi, an absolutely massive Polish-born offensive tackle who most previously played for the German Football League's Dresden Monarchs, according to a Vikings.com report. Standing at 6-foot-9 and weighing in at a whopping 351 pounds, even the behemoth that…Read More
Dwight Howard willing to make 'ultimate sacrifice' to help Rockets
Dwight Howard returned to the Houston Rockets lineup Wednesday night for a tilt against the New Orleans Pelicans after missing the team's previous 26 games due to a troublesome right knee. In his first game back on the court since Jan. 23, Howard logged 16 minutes, scored four points and pulled down seven rebounds as…Read More
David Ortiz slams Boston 'reporter with the red jheri curl' in fiery steroid essay
Boston Red Sox slugger David Ortiz penned a fiery essay for "The Players' Tribune" in which he defiantly defends his integrity in the face of the steroid accusations that have been thrown at him during his career. Ortiz saves his most vitriolic comments in the essay for Dan Shaughnessy, a columnist for the Boston Globe…Read More
Butch Harmon concerned Rory McIlroy may be bulking up too much
Butch Harmon recently expressed concern that Rory McIlroy's intensely focused dedication to reshaping his body could have an adverse effect on the golfer down the road. The renowned golf coach believes bulking up to a such a degree could have similar consequences to how it is speculated that Tiger Woods' obsession with pumping iron earlier…Read More
Habs fan in Carey Price photobomb pic sends thank you note to his 'hero'
A photograph went viral earlier this week that featured Montreal Canadiens netminder Carey Price photobombing a young fan who was taking a selfie by the glass during stoppage in the team's game on Saturday against the New York Islanders. The fan, a nine-year-old Justin, was so appreciative of Price's impromptu participation in his selfie actually…Read More


text:
Our Pink Himalayan Salt is hand-mined from ancient salt beds within the Himalayan Mountains. Protected from pollution and impurites since their formation 200 million years ago, Pink Himalayan salt is believed to be the purest form of salt available. This sea salt is known for it's stimulating and soothing properties. We love it in salt bars for it's exfoliating and moisturizing abilities, with the course size sprinkled on top for a wow factor. Color ranges from white to deep pink.
INCI: Sodium Chloride
Reply from Bramble Berry
Hi Delinda! We've found this salt creates gentle exfoliation, as seen in this Pretty in Pink: Salty Cold Process Tutorial. You can also use it in a lot of other recipes, such as these Bath Truffles or Show Your Love: Pink Salt Foot Scrub. Because all our products are processed in a warehouse that isn't set up for food safety, we recommend using our products only for cosmetics, not for cooking. I'll be emailing you personally to resolve this issue!
"Thank you for your prompt response. Bramble Berry has the best customer service of any company I know of. Pass the word!" -Rene
Kevin of Devinely Designed creates beautiful soap and shares his creations via his YouTube channel, Devinely Designed. With over 100 videos, Kevin has made a name for himself in the community for providing creative and educational soap making videos. From a Dandelion Zebra Swirl Tutorial to his first experience making liquid soap, Kevin's videos are fun and […]
The post Interview with Kevin of Devinely Designed appeared first on Soap Queen.


text:
Please note that as of October 24, 2014, the Nokia Developer Wiki will no longer be accepting user contributions, including new entries, edits and comments, as we begin transitioning to our new home, in the Windows Phone Development Wiki. We plan to move over the majority of the existing entries. Thanks for all your past and future contributions.
Pages that link to "How do I use the same pkg file for debug and release builds?"
The following pages link to How do I use the same pkg file for debug and release builds?:View (previous 50 | next 50) (20 | 50 | 100 | 250 | 500)
- How to guide for creating/signing sis files (← links)
- Portal:Tools and SDK (← links)
- SIS File Production (← links)


text:
Money manager performance
Watch breaking news videos and read news updates about Money Manager Performance on pionline.com
Casey Quirk: Global public money managers see 13% revenue growth in 2014
truePublicly traded fund management firms globally delivered median revenue growth of 13% in 2014 and a median profit margin level of 33% — the highest in five years, analysis by money manager consultant Casey, Quirk & Associates shows.
New York state comptroller: Wall Street bonus pool jumped by 3% in 2014
trueWall Street's bonus pool rose 3% to $28.5 billion in 2014, according to estimates by New York state Comptroller Thomas DiNapoli.
OM Asset Management's AUM up 3.3% in quarter, 11.1% for year
trueOM Asset Management reported $220.8 billion in assets under management as of Dec. 31, up 3.3% from Sept. 30 and up 11.1% from Dec. 31, 2013.
Fortress Investment Group reports 2.2% AUM gain in fourth quarter
trueFortress Investment Group reported $67.5 billion in assets under management as of Dec. 31, up 2.2% from three months earlier and up 9.4% from a year earlier.
Allianz reports 144.8 billion euros in net outflows at PIMCO in fourth quarter
trueAssets under management at Allianz's money management arm decreased 3.8% to €1.8 trillion ($2 trillion) in the quarter ended Dec. 31, but were up 1.8% for the year, despite continued outflows following former PIMCO Chief Investment Officer William H. Gross' September departure.
AllianceBernstein's assets flat in fourth quarter, up 5.2% for year
trueAllianceBernstein reported $474 billion in assets under management as of Dec. 31, which is flat from Sept. 30 but up 5.2%, from a year earlier.
Voya AUM flat in quarter, up 1.8% for year
trueoya Financial's assets under management as of Dec. 31 totaled $279 billion, the same as the previous quarter, and up 1.8% from the year before, its earnings report released Wednesday said.
Oaktree AUM dips in quarter, up for year
trueOaktree Capital Group reported $90.8 billion in assets under management as of Dec. 31, down 2.6% from three months earlier, but up 8.6% from a year earlier, the firm said in its quarterly report released Monday.
Managers with good returns, outperformance charge lower fees — bfinance study
trueMoney managers that achieve consistent returns and outperformance tend to adopt a below-average fees, said a new study by consultant bfinance.
Aberdeen AUM flat in quarter after outflows across all strategies
trueAberdeen Asset Management reported assets under management of £323.3 billion ($486.6 billion), as of Dec. 31, a 0.34% drop from three months earlier, with outflows across all four parts of the business.
Artisan Partners AUM inches up 2.3% for the year
trueArtisan Partners Asset Management saw assets under management increase slightly in the fourth quarter of 2014 to $107.9 billion, capping what President and CEO Eric Colson said in an earnings release were "mixed results" for the company last year.
Franklin Resources' AUM and net income drop in fourth quarter
trueFranklin Resources reported declines in assets under management, profit and revenue for the quarter ended Dec. 31.
Legg Mason's AUM flat in quarter; liquidity outflows cancel strong fixed-income growth
trueLegg Mason reported $709.1 billion in assets under management as of Dec. 31, flat from three months earlier up 4% from a year earlier.
Blackstone Group's AUM climbs 9% for year to record $290 billion
trueBlackstone Group reported a record $290 billion in assets under management as of Dec. 31, up 2% from Sept. 30 and up 9% from Dec. 31, 2013.
Invesco's AUM flat from prior quarter, up 2% for year
trueInvesco on Thursday reported $792.4 billion in assets under management of as of Dec. 31, flat from the end of the previous quarter and up 2% from a year earlier.


text:
South Plains College Workforce Development, Texas Tech and the Bridge of Lubbock will offer an Adult Education Resource Fair from 10 a.m. to 1 p.m. Feb. 28 at 1301 Redbud.
The event is free and open to the public.
Researchers at Texas Tech's National Wind Institute will take part in a $2.5 million government research project to improve short-term wind forecasting capabilities in mountainous terrain to help enhance wind-energy creation.
Three of Lubbock Independent School District's five high school academic decathlon teams qualified for state at Jan. 31 regional decathlon competitions.
The coach who inspired the Disney movie "McFarland USA" being released this week will be at Lubbock Christian University today.
Officials from the Talkington School for Young Women Leaders said while 75 percent of students there are from economically disadvantaged homes and 85 percent will be first-generation college students, the emphasis at the school is college readiness and leadership development.
Berta Fogerson, principal at Talkington, gave a report on her school to the Lubbock Independent School District Board of Trustees Thursday morning.
Frenship High School College Readiness Coordinator Bonnie Thompson was selected by Texas A&M University as a 2015 Very Important Counselor.
Recipients of the annual Chancellor's Council distinguished faculty awards at Texas Tech University were announced by Chancellor Robert Duncan on Wednesday.
Marvin L. Baker, retired president emeritus of South Plains College, died Feb. 5 at the age of 88.
Baker served 33 years as the second president of SPC from 1961 to 1994. He died in Weatherford.
A memorial service has been scheduled for 2 p.m. Feb.
Shallowater Middle School students are headed to San Antonio to perform Friday at the Texas Music Educators Association conference as the 2015 Texas Honor Band for class 1C junior highs.
Lubbock Christian University's enrollment is down by 13 students from last spring at 1,763.
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