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Sample records for early diffuse murine

  1. Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy

    PubMed Central

    Ramirez, Gabriel; Proctor, Ashley R.; Jung, Ki Won; Wu, Tong Tong; Han, Songfeng; Adams, Russell R.; Ren, Jingxuan; Byun, Daniel K.; Madden, Kelley S.; Brown, Edward B.; Foster, Thomas H.; Farzam, Parisa; Durduran, Turgut; Choe, Regine

    2016-01-01

    The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide increased blood flow as early as 3 days after administration, whereas paclitaxel induced a transient blood flow decrease at 1 day after administration. Early blood flow changes correlated strongly with the treatment outcome and distinguished treated from untreated mice individually for effective treatments. PMID:27699124

  2. Establishment of a Novel Murine Model of Ischemic Cardiomyopathy with Multiple Diffuse Coronary Lesions

    PubMed Central

    Nakaoka, Hajime; Nakagawa-Toyama, Yumiko; Nishida, Makoto; Okada, Takeshi; Kawase, Ryota; Yamashita, Taiji; Yuasa-Kawase, Miyako; Nakatani, Kazuhiro; Masuda, Daisaku; Ohama, Tohru; Sonobe, Takashi; Shirai, Mikiyasu; Komuro, Issei; Yamashita, Shizuya

    2013-01-01

    Objectives Atherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques. Recently, a new murine model, HypoE mouse was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis and myocardial infarction; however, the HypoE mice died too early to make possible investigation of cardiac remodeling. Therefore, we aimed to modify the HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused by atherosclerotic lesions, which the ligation model does not exhibit. Methods and Results In our study, the sustained Paigen diet for the HypoE mice was shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen diet intervention starting when the mice were 8 weeks old was adequate to permit the mice to survive myocardial infarction. Our murine model, called the “modified HypoE mouse”, was maintained until 8 weeks, with a median survival period of 36 days, after the dietary intervention (male, n = 222). Echocardiography demonstrated that the fractional shortening 2 weeks after the Paigen diet (n = 14) significantly decreased compared with that just before the Paigen diet (n = 6) (31.4±11.9% vs. 54.4±2.6%, respectively, P<0.01). Coronary angiography revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were identified by serial analyses of cardiac morphological features and mRNA expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and TGF-β. Conclusion Modified HypoE mice are a suitable model for ischemic cardiomyopathy with multiple diffuse lesions and may be considered as a novel and convenient model for investigations of cardiac remodeling on a highly atherogenic background. PMID

  3. Accumulation of murine amyloid-β mimics early Alzheimer's disease.

    PubMed

    Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

    2015-08-01

    Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for <1% of all patients with Alzheimer's disease. The inherited form is even regarded a 'rare' disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer's disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows

  4. Early Molecular Events in Murine Gastric Epithelial Cells Mediated by Helicobacter pylori CagA.

    PubMed

    Banerjee, Aditi; Basu, Malini; Blanchard, Thomas G; Chintalacharuvu, Subba R; Guang, Wei; Lillehoj, Erik P; Czinn, Steven J

    2016-10-01

    Murine models of Helicobacter pylori infection are used to study host-pathogen interactions, but lack of severe gastritis in this model has limited its usefulness in studying pathogenesis. We compared the murine gastric epithelial cell line GSM06 to the human gastric epithelial AGS cell line to determine whether similar events occur when cultured with H. pylori. The lysates of cells infected with H. pylori isolates or an isogenic cagA-deficient mutant were assessed for translocation and phosphorylation of CagA and for activation of stress pathway kinases by immunoblot. Phosphorylated CagA was detected in both cell lines within 60 minutes. Phospho-ERK 1/2 was present within several minutes and distinctly present in GSM06 cells at 60 minutes. Similar results were obtained for phospho-JNK, although the 54 kDa phosphoprotein signal was dominant in AGS, whereas the lower molecular weight band was dominant in GSM06 cells. These results demonstrate that early events in H. pylori pathogenesis occur within mouse epithelial cells similar to human cells and therefore support the use of the mouse model for the study of acute CagA-associated host cell responses. These results also indicate that reduced disease in H. pylori-infected mice may be due to lack of the Cag PAI, or by differences in the mouse response downstream of the initial activation events. © 2016 John Wiley & Sons Ltd.

  5. Detection of early seizures by diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Zhang, Tao; Hajihashemi, M. Reza; Zhou, Junli; Carney, Paul R.; Jiang, Huabei

    2015-03-01

    In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Besides, preclinical seizure experiments need to be conducted in awake animals with images reconstructed and displayed in real-time. We demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking brain activities with high spatiotemporal resolution. We developed methods to conduct seizure experiments in fully awake rats using a subject-specific helmet and a restraining mechanism. For the first time, we detected early hemodynamic responses with heterogeneous patterns several minutes preceding the electroencephalographic seizure onset, supporting the presence of a "pre-seizure" state both in anesthetized and awake rats. Using a novel time-series analysis of scattering images, we show that the analysis of scattered diffuse light is a sensitive and reliable modality for detecting changes in neural activity associated with generalized seizure. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.

  6. Pre-Clinical Study of Panobinostat in Xenograft and Genetically Engineered Murine Diffuse Intrinsic Pontine Glioma Models.

    PubMed

    Hennika, Tammy; Hu, Guo; Olaciregui, Nagore G; Barton, Kelly L; Ehteda, Anahid; Chitranjan, Arjanna; Chang, Cecilia; Gifford, Andrew J; Tsoli, Maria; Ziegler, David S; Carcaboso, Angel M; Becher, Oren J

    2017-01-01

    Diffuse intrinsic pontine glioma (DIPG), or high-grade brainstem glioma (BSG), is one of the major causes of brain tumor-related deaths in children. Its prognosis has remained poor despite numerous efforts to improve survival. Panobinostat, a histone deacetylase inhibitor, is a targeted agent that has recently shown pre-clinical efficacy and entered a phase I clinical trial for the treatment of children with recurrent or progressive DIPG. A collaborative pre-clinical study was conducted using both a genetic BSG mouse model driven by PDGF-B signaling, p53 loss, and ectopic H3.3-K27M or H3.3-WT expression and an H3.3-K27M orthotopic DIPG xenograft model to confirm and extend previously published findings regarding the efficacy of panobinostat in vitro and in vivo. In vitro, panobinostat potently inhibited cell proliferation, viability, and clonogenicity and induced apoptosis of human and murine DIPG cells. In vivo analyses of tissue after short-term systemic administration of panobinostat to genetically engineered tumor-bearing mice indicated that the drug reached brainstem tumor tissue to a greater extent than normal brain tissue, reduced proliferation of tumor cells and increased levels of H3 acetylation, demonstrating target inhibition. Extended consecutive daily treatment of both genetic and orthotopic xenograft models with 10 or 20 mg/kg panobinostat consistently led to significant toxicity. Reduced, well-tolerated doses of panobinostat, however, did not prolong overall survival compared to vehicle-treated mice. Our collaborative pre-clinical study confirms that panobinostat is an effective targeted agent against DIPG human and murine tumor cells in vitro and in short-term in vivo efficacy studies in mice but does not significantly impact survival of mice bearing H3.3-K27M-mutant tumors. We suggest this may be due to toxicity associated with systemic administration of panobinostat that necessitated dose de-escalation.

  7. Early Acidification of Phagosomes Containing Brucella suis Is Essential for Intracellular Survival in Murine Macrophages

    PubMed Central

    Porte, Françoise; Liautard, Jean-Pierre; Köhler, Stephan

    1999-01-01

    Brucella suis is a facultative intracellular pathogen of mammals, residing in macrophage vacuoles. In this work, we studied the phagosomal environment of these bacteria in order to better understand the mechanisms allowing survival and multiplication of B. suis. Intraphagosomal pH in murine J774 cells was determined by measuring the fluorescence intensity of opsonized, carboxyfluorescein-rhodamine- and Oregon Green 488-rhodamine-labeled bacteria. Compartments containing live B. suis acidified to a pH of about 4.0 to 4.5 within 60 min. Acidification of B. suis-containing phagosomes in the early phase of infection was abolished by treatment of host cells with 100 nM bafilomycin A1, a specific inhibitor of vacuolar proton-ATPases. This neutralization at 1 h postinfection resulted in a 2- to 34-fold reduction of opsonized and nonopsonized viable intracellular bacteria at 4 and 6 h postinfection, respectively. Ammonium chloride and monensin, other pH-neutralizing reagents, led to comparable loss of intracellular viability. Addition of ammonium chloride at 7 h after the beginning of infection, however, did not affect intracellular multiplication of B. suis, in contrast to treatment at 1 h postinfection, where bacteria were completely eradicated within 48 h. Thus, we conclude that phagosomes with B. suis acidify rapidly after infection, and that this early acidification is essential for replication of the bacteria within the macrophage. PMID:10417172

  8. Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease

    PubMed Central

    Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm

    2011-01-01

    Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877

  9. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.

    PubMed Central

    Goulding, M D; Chalepakis, G; Deutsch, U; Erselius, J R; Gruss, P

    1991-01-01

    We describe the isolation and characterization of Pax-3, a novel murine paired box gene expressed exclusively during embryogenesis. Pax-3 encodes a 479 amino acid protein with an Mr of 56 kd containing both a paired domain and a paired-type homeodomain. The Pax-3 protein is a DNA binding protein that specifically recognizes the e5 sequence present upstream of the Drosophila even-skipped gene. Pax-3 transcripts are first detected in 8.5 day mouse embryos where they are restricted to the dorsal part of the neuroepithelium and to the adjacent segmented dermomyotome. During early neurogenesis, Pax-3 expression is limited to mitotic cells in the ventricular zone of the developing spinal cord and to distinct regions in the hindbrain, midbrain and diencephalon. In 10-12 day embryos, expression of Pax-3 is also seen in neural crest cells of the developing spinal ganglia, the craniofacial mesectoderm and in limb mesenchyme of 10 and 11 day embryos. Images PMID:2022185

  10. Structure and Early Soot Oxidation Properties of Laminar Diffusion Flames

    NASA Technical Reports Server (NTRS)

    El-Leathy, A. M.; Xu, F.; Faeth, G. M.

    2001-01-01

    Soot is an important unsolved problem of combustion science because it is present in most hydrocarbon-fueled flames and current understanding of the reactive and physical properties of soot in flame environments is limited. This lack of understanding affects progress toward developing reliable predictions of flame radiation properties, reliable predictions of flame pollutant emission properties and reliable methods of computational combustion, among others. Motivated by these observations, the present investigation extended past studies of soot formation in this laboratory, to consider soot oxidation in laminar diffusion flames using similar methods. Early work showed that O2 was responsible for soot oxidation in high temperature O2-rich environments. Subsequent work in high temperature flame environments having small O2 concentrations, however, showed that soot oxidation rates substantially exceeded estimates based on the classical O2 oxidation rates of Nagle and Strickland-Constable and suggests that radicals such as O and OH might be strong contributors to soot oxidation for such conditions. Neoh et al. subsequently made observations in premixed flames, supported by later work, that showed that OH was responsible for soot oxidation at these conditions with a very reasonable collision efficiency of 0.13. Subsequent studies in diffusion flames, however, were not in agreement with the premixed flame studies: they agreed that OH played a dominant role in soot oxidation in flames, but found collision efficiencies that varied with flame conditions and were not in good agreement with each other or with Neoh et al. One explanation for these discrepancies is that optical scattering and extinction properties were used to infer soot structure properties for the studies that have not been very successful for representing the optical properties of soot. Whatever the source of the problem, however, these differences among observations of soot oxidation in premixed and

  11. Diffusion MRI in early cancer therapeutic response assessment

    PubMed Central

    Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

    2016-01-01

    Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

  12. ISG15 Functions as an Interferon-Mediated Antiviral Effector Early in the Murine Norovirus Life Cycle

    PubMed Central

    Rodriguez, Marisela R.; Monte, Kristen; Thackray, Larissa B.

    2014-01-01

    ABSTRACT Human noroviruses (HuNoV) are the leading cause of nonbacterial gastroenteritis worldwide. Similar to HuNoV, murine noroviruses (MNV) are enteric pathogens spread via the fecal-oral route and have been isolated from numerous mouse facilities worldwide. Type I and type II interferons (IFN) restrict MNV-1 replication; however, the antiviral effectors impacting MNV-1 downstream of IFN signaling are largely unknown. Studies using dendritic cells, macrophages, and mice deficient in free and conjugated forms of interferon-stimulated gene 15 (ISG15) revealed that ISG15 conjugation contributes to protection against MNV-1 both in vitro and in vivo. ISG15 inhibited a step early in the viral life cycle upstream of viral genome transcription. Directly transfecting MNV-1 RNA into IFN-stimulated mouse embryonic fibroblasts (MEFs) and bone marrow-derived dendritic cells (BMDC) lacking ISG15 conjugates bypassed the antiviral activity of ISG15, further suggesting that ISG15 conjugates restrict the MNV-1 life cycle at the viral entry/uncoating step. These results identify ISG15 as the first type I IFN effector regulating MNV-1 infection both in vitro and in vivo and for the first time implicate the ISG15 pathway in the regulation of early stages of MNV-1 replication. IMPORTANCE Type I IFNs are important in controlling murine norovirus 1 (MNV-1) infections; however, the proteins induced by IFNs that restrict viral growth are largely unknown. This report reveals that interferon-stimulated gene 15 (ISG15) mitigates MNV-1 replication both in vitro and in vivo. In addition, it shows that ISG15 inhibits MNV-1 replication by targeting an early step in the viral life cycle, MNV-1 entry and/or uncoating. These results identify ISG15 as the first type I IFN effector regulating MNV-1 infection both in vitro and in vivo and for the first time implicate the ISG15 pathway in the regulation of viral entry/uncoating. PMID:24899198

  13. Spontaneous Transformation of Murine Epithelial Cells Requires the Early Acquisition of Specific Chromosomal Aneuploidies and Genomic Imbalances

    PubMed Central

    Padilla-Nash, Hesed M.; Hathcock, Karen; McNeil, Nicole E.; Mack, David; Hoeppner, Daniel; Ravin, Rea; Knutsen, Turid; Yonescu, Raluca; Wangsa, Danny; Dorritie, Kathleen; Barenboim, Linda; Hu, Yue; Ried, Thomas

    2011-01-01

    Human carcinomas are defined by recurrent chromosomal aneuploidies, which result in tissue-specific distribution of genomic imbalances. In order to develop models for these genome mutations and determine their role in tumorigenesis, we generated 45 spontaneously transformed murine cell lines from normal epithelial cells derived from bladder, cervix, colon, kidney, lung, and mammary gland. Phenotypic changes, chromosomal aberrations, centrosome number, and telomerase activity were assayed in control uncultured cells and in three subsequent stages of transformation. Supernumerary centrosomes, bi-nucleate cells, and tetraploidy were observed as early as 48 hr after explantation. In addition, telomerase activity increased throughout progression. Live-cell imaging revealed that failure of cytokinesis, not cell fusion, promoted genome duplication. Spectral karyotyping demonstrated that aneuploidy preceded immortalization, consisting predominantly of whole chromosome losses (4, 9, 12, 13, 16, and Y) and gains (1, 10, 15, and 19). After transformation, focal amplifications of the oncogenes Myc and Mdm2 were frequently detected. Fifty percent of the transformed lines resulted in tumors upon injection into immuno-compromised mice. The phenotypic and genomic alterations observed in spontaneously transformed murine epithelial cells recapitulated the aberration pattern observed during human carcinogenesis. The dominant aberration of these cell lines was the presence of specific chromosomal aneuploidies. We propose that our newly derived cancer models will be useful tools to dissect the sequential steps of genome mutations during malignant transformation, and also to identify cancer-specific genes, signaling pathways, and the role of chromosomal instability in this process. PMID:22161874

  14. Experimental murine fascioliasis derives early immune suppression with increased levels of TGF-β and IL-4.

    PubMed

    Chung, Joon-Yong; Bae, Young-An; Yun, Doo-Hee; Yang, Hyun-Jong; Kong, Yoon

    2012-12-01

    In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of CD19(+) B cells was observed as early as week 1 post-infection while CD4(+)/CD8(+) T cells were down-regulated. Accumulation of Mac1(+) cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-α mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-1β expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-β were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-β and IL-4 during the early stages of infection.

  15. Slowdown of surface diffusion during early stages of bacterial colonization

    NASA Astrophysics Data System (ADS)

    Vourc'h, T.; Peerhossaini, H.; Léopoldès, J.; Méjean, A.; Chauvat, F.; Cassier-Chauvat, C.

    2018-03-01

    We study the surface diffusion of the model cyanobacterium Synechocystis sp. PCC6803 during the incipient stages of cell contact with a glass surface in the dilute regime. We observe a twitching motility with alternating immobile tumble and mobile run periods, resulting in a normal diffusion described by a continuous-time random walk with a coefficient of diffusion D . Surprisingly, D is found to decrease with time down to a plateau. This is observed only when the cyanobacterial cells are able to produce released extracellular polysaccharides, as shown by a comparative study between the wild-type strain and various polysaccharides-depleted mutants. The analysis of the trajectories taken by the bacterial cells shows that the temporal characteristics of their intermittent motion depend on the instantaneous fraction of visited sites during diffusion. This describes quantitatively the time dependence of D , related to the progressive surface coverage by the polysaccharides. The observed slowdown of the surface diffusion may constitute a basic precursor mechanism for microcolony formation and provides clues for controlling biofilm formation.

  16. Diffusion and scaling during early embryonic pattern formation.

    PubMed

    Gregor, Thomas; Bialek, William; de Ruyter van Steveninck, Rob R; Tank, David W; Wieschaus, Eric F

    2005-12-20

    Development of spatial patterns in multicellular organisms depends on gradients in the concentration of signaling molecules that control gene expression. In the Drosophila embryo, Bicoid (Bcd) morphogen controls cell fate along 70% of the anteroposterior axis but is translated from mRNA localized at the anterior pole. Gradients of Bcd and other morphogens are thought to arise through diffusion, but this basic assumption has never been rigorously tested in living embryos. Furthermore, because diffusion sets a relationship between length and time scales, it is hard to see how patterns of gene expression established by diffusion would scale proportionately as egg size changes during evolution. Here, we show that the motion of inert molecules through the embryo is well described by the diffusion equation on the relevant length and time scales, and that effective diffusion constants are essentially the same in closely related dipteran species with embryos of very different size. Nonetheless, patterns of gene expression in these different species scale with egg length. We show that this scaling can be traced back to scaling of the Bcd gradient itself. Our results, together with constraints imposed by the time scales of development, suggest that the mechanism for scaling is a species-specific adaptation of the Bcd lifetime.

  17. Diffusion and scaling during early embryonic pattern formation

    PubMed Central

    Gregor, Thomas; Bialek, William; van Steveninck, Rob R. de Ruyter; Tank, David W.; Wieschaus, Eric F.

    2005-01-01

    Development of spatial patterns in multicellular organisms depends on gradients in the concentration of signaling molecules that control gene expression. In the Drosophila embryo, Bicoid (Bcd) morphogen controls cell fate along 70% of the anteroposterior axis but is translated from mRNA localized at the anterior pole. Gradients of Bcd and other morphogens are thought to arise through diffusion, but this basic assumption has never been rigorously tested in living embryos. Furthermore, because diffusion sets a relationship between length and time scales, it is hard to see how patterns of gene expression established by diffusion would scale proportionately as egg size changes during evolution. Here, we show that the motion of inert molecules through the embryo is well described by the diffusion equation on the relevant length and time scales, and that effective diffusion constants are essentially the same in closely related dipteran species with embryos of very different size. Nonetheless, patterns of gene expression in these different species scale with egg length. We show that this scaling can be traced back to scaling of the Bcd gradient itself. Our results, together with constraints imposed by the time scales of development, suggest that the mechanism for scaling is a species-specific adaptation of the Bcd lifetime. PMID:16352710

  18. Validation of diffuse correlation spectroscopy sensitivity to nicotinamide-induced blood flow elevation in the murine hindlimb using the fluorescent microsphere technique

    NASA Astrophysics Data System (ADS)

    Proctor, Ashley R.; Ramirez, Gabriel A.; Han, Songfeng; Liu, Ziping; Bubel, Tracy M.; Choe, Regine

    2018-03-01

    Nicotinamide has been shown to affect blood flow in both tumor and normal tissues, including skeletal muscle. Intraperitoneal injection of nicotinamide was used as a simple intervention to test the sensitivity of noninvasive diffuse correlation spectroscopy (DCS) to changes in blood flow in the murine left quadriceps femoris skeletal muscle. DCS was then compared with the gold-standard fluorescent microsphere (FM) technique for validation. The nicotinamide dose-response experiment showed that relative blood flow measured by DCS increased following treatment with 500- and 1000-mg / kg nicotinamide. The DCS and FM technique comparison showed that blood flow index measured by DCS was correlated with FM counts quantified by image analysis. The results of this study show that DCS is sensitive to nicotinamide-induced blood flow elevation in the murine left quadriceps femoris. Additionally, the results of the comparison were consistent with similar studies in higher-order animal models, suggesting that mouse models can be effectively employed to investigate the utility of DCS for various blood flow measurement applications.

  19. Decrease of murine cytomegalovirus-induced retinitis by intravenous delivery of immediate early protein-3-specific siRNA.

    PubMed

    Marshall, Brendan; Mo, Juan; Covar, Jason; Atherton, Sally S; Zhang, Ming

    2014-06-06

    Retinitis induced by both human and murine cytomegaloviruses following immunosuppression is characterized by progressive loss of retinal architecture, due to necrosis of virus-infected cells as well as widespread apoptosis of uninfected bystander cells. Because small inhibitory RNA molecules (siRNA) can reduce murine cytomegalovirus (MCMV) gene expression and thereby inhibit virus replication in vitro, we tested siRNAs directed against MCMV immediate early protein-3 (IE-3) to determine if MCMV-induced retinitis could be alleviated in vivo. Immunosuppressed Balb/c mice (2.0 mg methylprednisolone acetate every 3 days beginning on day -2) were infected with 5 × 10(3) pfu of the K181 strain of MCMV via the supraciliary route. At day 2 post infection, mice were treated with various doses of IE-3-specific siRNA ranging from 0.1 nmol to 10 nmol, in a volume of 20 μL PBS via tail vein injection. Injected eyes were collected at various times post inoculation and subjected to plaque assay for virus titer, MCMV antigen staining, H&E staining, TUNEL assay, and Western blot for MCMV IE-3 protein. Small but significant amounts of fluorescently labeled IE-3-specific siRNA localized to the RPE layer 48 hours after intravenous injection. IE-3-specific siRNA significantly reduced virus titers at all concentrations tested (ranging from 0.1 nmol to 10 nmol), but the most potent effect of siRNA was observed at a dose of 1 nmol. We also observed that IE-3-specific siRNA produced a substantial decrease in MCMV titers and a substantial reduction in bystander cell apoptosis over the time course of virus infection. Systemic administration of IE-3-specific siRNA could alleviate MCMV retinitis by inhibiting virus replication and subsequent death of uninfected retinal cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  20. The Ornithine Decarboxylase Gene Is Essential for Cell Survival during Early Murine Development

    PubMed Central

    Pendeville, Hélène; Carpino, Nick; Marine, Jean-Christophe; Takahashi, Yutaka; Muller, Marc; Martial, Joseph A.; Cleveland, John L.

    2001-01-01

    Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODC-deficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation. PMID:11533243

  1. Principles of diffusion kurtosis imaging and its role in early diagnosis of neurodegenerative disorders.

    PubMed

    Arab, Anas; Wojna-Pelczar, Anna; Khairnar, Amit; Szabó, Nikoletta; Ruda-Kucerova, Jana

    2018-05-01

    Pathology of neurodegenerative diseases can be correlated with intra-neuronal as well as extracellular changes which lead to neuronal degeneration. The central nervous system (CNS) is a complex structure comprising of many biological barriers. These microstructural barriers might be affected by a variety of pathological processes. Specifically, changes in the brain tissue's microstructure affect the diffusion of water which can be assessed non-invasively by diffusion weighted (DW) magnetic resonance imaging (MRI) techniques. Diffusion tensor imaging (DTI) is a diffusion MRI technique that considers diffusivity as a Gaussian process, i.e. does not account for any diffusion hindrance. However, environment of the brain tissues is characterized by a non-Gaussian diffusion. Therefore, diffusion kurtosis imaging (DKI) was developed as an extension of DTI method in order to quantify the non-Gaussian distribution of water diffusion. This technique represents a promising approach for early diagnosis of neurodegenerative diseases when the neurodegenerative process starts. Hence, the purpose of this article is to summarize the ongoing clinical and preclinical research on Parkinson's, Alzheimer's and Huntington diseases, using DKI and to discuss the role of this technique as an early stage biomarker of neurodegenerative conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    SciT

    Liu, Yu-Ching; Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan; Ho, Heng-Chien

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2more » h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.« less

  3. Noncanonical expression of a murine cytomegalovirus early protein CD8 T-cell epitope as an immediate early epitope based on transcription from an upstream gene.

    PubMed

    Fink, Annette; Büttner, Julia K; Thomas, Doris; Holtappels, Rafaela; Reddehase, Matthias J; Lemmermann, Niels A W

    2014-02-14

    Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by "reverse immunology", a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs) based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 Dd and that is immunodominant in BALB/c (H-2d haplotype) mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E) phase protein, the m164 epitope is presented already during the Immediate Early (IE) phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164.

  4. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

    PubMed Central

    Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  5. γδ T Cells Regulate the Early Inflammatory Response to Bordetella pertussis Infection in the Murine Respiratory Tract

    PubMed Central

    Zachariadis, O.; Cassidy, J. P.; Brady, J.; Mahon, B. P.

    2006-01-01

    The role of γδ T cells in the regulation of pulmonary inflammation following Bordetella pertussis infection was investigated. Using a well-characterized murine aerosol challenge model, inflammatory events in mice with targeted disruption of the T-cell receptor δ-chain gene (γδ TCR−/− mice) were compared with those in wild-type animals. Early following challenge with B. pertussis, γδ TCR−/− mice exhibited greater pulmonary inflammation, as measured by intra-alveolar albumin leakage and lesion histomorphometry, yet had lower contemporaneous bacterial lung loads. The larger numbers of neutrophils and macrophages and the greater concentration of the neutrophil marker myeloperoxidase in bronchoalveolar lavage fluid from γδ TCR−/− mice at this time suggested that differences in lung injury were mediated through increased leukocyte trafficking into infected alveoli. Furthermore, flow cytometric analysis found the pattern of recruitment of natural killer (NK) and NK receptor+ T cells into airspaces differed between the two mouse types over the same time period. Taken together, these findings suggest a regulatory influence for γδ T cells over the early pulmonary inflammatory response to bacterial infection. The absence of γδ T cells also influenced the subsequent adaptive immune response to specific bacterial components, as evidenced by a shift from a Th1 to a Th2 type response against the B. pertussis virulence factor filamentous hemagglutinin in γδ TCR−/− mice. The findings are relevant to the study of conditions such as neonatal B. pertussis infection and acute respiratory distress syndrome where γδ T cell dysfunction has been implicated in the inflammatory process. PMID:16495558

  6. The Early Diffusion of Smart Meters in the US Electric Power Industry

    NASA Astrophysics Data System (ADS)

    Strong, Derek Ryan

    The impact of new technologies within and across industries is only felt through their widespread diffusion, yet studies of technology diffusion are scarce compared to other aspects of the innovation process. The electric power industry is one industry that is currently undergoing substantial change as a result of both technological and institutional innovations. In this dissertation I examine the economic rationale for the adoption of smart meters by electric power utilities and the relationship between smart meters and the evolving electric power industry. I contribute to empirical research on technology diffusion by studying the early diffusion of smart meters in the US electric power industry. Using a panel dataset and econometric models, I analyze the determinants of both the interfirm and intrafirm diffusion of smart meters in the United States. The empirical findings suggest multiple drivers of smart meter diffusion. Policy and regulatory support have had a significant, positive impact on adoption but have not been the only relevant determinants. The findings also suggest that utility characteristics and some combination of learning, cost reductions, and technology standards have been important determinants affecting smart meter diffusion. I also explore the policy implications resulting from this analysis for enhancing the diffusion of smart meters. The costs and benefits of adopting smart meters have been more uncertain than initially thought, suggesting that some policy support for adoption was premature. The coordination of policies is also necessary to achieve the full benefits of using smart meters.

  7. Early effects of 16O radiation on neuronal morphology and cognition in a murine model

    NASA Astrophysics Data System (ADS)

    Carr, Hannah; Alexander, Tyler C.; Groves, Thomas; Kiffer, Frederico; Wang, Jing; Price, Elvin; Boerma, Marjan; Allen, Antiño R.

    2018-05-01

    Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

  8. Identification of factors for physicians to facilitate early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever in Taiwan.

    PubMed

    Chang, Ko; Lee, Nan-Yao; Ko, Wen-Chien; Tsai, Jih-Jin; Lin, Wei-Ru; Chen, Tun-Chieh; Lu, Po-Liang; Chen, Yen-Hsu

    2017-02-01

    Dengue fever, rickettsial diseases, and Q fever are acute febrile illnesses with similar manifestations in tropical areas. Early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever may be made by understanding the distinguishing clinical characteristics and the significance of demographic and weather factors. We conducted a retrospective study to identify clinical, demographic, and meteorological characteristics of 454 dengue fever, 178 scrub typhus, 143 Q fever, and 81 murine typhus cases in three Taiwan hospitals. Case numbers of murine typhus and Q fever correlated significantly with temperature and rainfall; the scrub typhus case number was only significantly related with temperature. Neither temperature nor rainfall correlated with the case number of dengue fever. The rarity of dengue fever cases from January to June in Taiwan may be a helpful clue for diagnosis in the area. A male predominance was observed, as the male-to-female rate was 2.1 for murine typhus and 7.4 for Q fever. Multivariate analysis revealed the following six important factors for differentiating the rickettsial diseases and Q fever group from the dengue fever group: fever ≥8 days, alanine aminotransferase > aspartate aminotransferase, platelets >63,000/mL, C-reactive protein >31.9 mg/L, absence of bone pain, and absence of a bleeding syndrome. Understanding the rarity of dengue in the first half of a year in Taiwan and the six differentiating factors may help facilitate the early differential diagnosis of rickettsial diseases and Q fever from dengue fever, permitting early antibiotic treatment. Copyright © 2015. Published by Elsevier B.V.

  9. Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis

    PubMed Central

    Casas, Caty; Herrando-Grabulosa, Mireia; Manzano, Raquel; Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

    2013-01-01

    Sporadic and familiar amyotrophic lateral sclerosis (ALS) cases presented lower cholinergic activity than in healthy individuals in their still preserved spinal motoneurons (MNs) suggesting that cholinergic reduction might occur before MN death. To unravel how and when cholinergic function is compromised, we have analyzed the spatiotemporal expression of choline acetyltransferase (ChAT) from early presymptomatic stages of the SOD1G93A ALS mouse model by confocal immunohistochemistry. The analysis showed an early reduction in ChAT content in soma and presynaptic boutons apposed onto MNs (to 76%) as well as in cholinergic interneurons in the lumbar spinal cord of the 30-day-old SOD1G93A mice. Cholinergic synaptic stripping occurred simultaneously to the presence of abundant surrounding major histocompatibility complex II (MHC-II)-positive microglia and the accumulation of nuclear Tdp-43 and the appearance of mild oxidative stress within MNs. Besides, there was a loss of neuronal MHC-I expression, which is necessary for balanced synaptic stripping after axotomy. These events occurred before the selective raise of markers of denervation such as ATF3. By the same time, alterations in postsynaptic cholinergic-related structures were also revealed with a loss of the presence of sigma-1 receptor, a Ca2+ buffering chaperone in the postsynaptic cisternae. By 2 months of age, ChAT seemed to accumulate in the soma of MNs, and thus efferences toward Renshaw interneurons were drastically diminished. In conclusion, cholinergic dysfunction in the local circuitry of the spinal cord may be one of the earliest events in ALS etiopathogenesis. PMID:23531559

  10. Effect of disease progression on liver apparent diffusion coefficient values in a murine model of NASH at 11.7 Tesla MRI.

    PubMed

    Anderson, Stephan W; Soto, Jorge A; Milch, Holly N; Ozonoff, Al; O'Brien, Michael; Hamilton, James A; Jara, Hernan J

    2011-04-01

    To evaluate the apparent diffusion coefficient (ADC) values of liver in a murine model of non-alcoholic steatohepatitis using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male C57BL/6 mice were divided into control (n = 3) and experimental groups (n = 14) fed a methionine-deficient choline-deficient (MCD) diet to induce steatohepatitis. Livers underwent ex vivo diffusion-weighted MR imaging and ADC maps were calculated. A pathologist determined subjective scores of steatosis, classified from 0 to 3. Digital image analysis was used to determine percentage areas of steatosis. Graphs comparing ADC to subjective and digital image analysis (DIA) determinations of steatosis were plotted. Subjective assessments of steatosis ranged up to values of 3 and DIA determined areas of steatosis to range up to approximately 16%. ADC values approximated 800 × 10(-6) mm(2) /s (range, 749-811 × 10(-6) mm(2) /s, mean 786 × 10(-6) mm(2) /s) in controls and 500 × 10(-6) mm(2) /s (range, 478-733 × 10(-6) mm(2) /s, mean 625 × 10(-6) mm(2) /s) in experimental mice. Moderate correlation between ADC and subjective scores of steatosis (R = -0.56) was observed. Strong correlation between ADC values and percentage areas of steatosis was between ADC values and percentage areas of steatosis was observed greater (R = -0.81) and very strong correlation was observed with the exclusion of a single outlying data point (R = -0.91). Based on the comparison of ADC values and steatosis determinations by DIA, increasing degrees of steatosis are seen to result in decreased hepatic ADC values. Copyright © 2011 Wiley-Liss, Inc.

  11. Hypermagnetic helicity evolution in early universe: leptogenesis and hypermagnetic diffusion

    SciT

    Semikoz, V.B.; Smirnov, A.Yu.; Sokoloff, D.D., E-mail: semikoz@yandex.ru, E-mail: smirnoff.alexandr@gmail.com, E-mail: sokoloff.dd@gmail.com

    2013-10-01

    We study hypermagnetic helicity and lepton asymmetry evolution in plasma of the early Universe before the electroweak phase transition (EWPT) accounting for chirality flip processes via inverse Higgs decays and sphaleron transitions which violate the left lepton number and wash out the baryon asymmetry of the Universe (BAU). In the scenario where the right electron asymmetry supports the BAU alone through the conservation law B/3−L{sub eR} = const at temperatures T > T{sub RL} ≅ 10 TeV the following universe cooling leads to the production of a non-zero left lepton (electrons and neutrinos) asymmetry. This is due to the Higgsmore » decays becoming more faster when entering the equilibrium at T = T{sub RL} with the universe expansion, Γ{sub RL} ∼ T > H ∼ T{sup 2}, resulting in the parallel evolution of both the right and the left electron asymmetries at T < T{sub RL} through the corresponding Abelian anomalies in SM in the presence of a seed hypermagnetic field. The hypermagnetic helicity evolution proceeds in a self-consistent way with the lepton asymmetry growth. The role of sphaleron transitions decreasing the left lepton number turns out to be negligible in given scenario. The hypermagnetic helicity can be a supply for the magnetic one in Higgs phase assuming a strong seed hypermagnetic field in symmetric phase.« less

  12. Diffusion radiomics analysis of intratumoral heterogeneity in a murine prostate cancer model following radiotherapy: Pixelwise correlation with histology.

    PubMed

    Lin, Yu-Chun; Lin, Gigin; Hong, Ji-Hong; Lin, Yi-Ping; Chen, Fang-Hsin; Ng, Shu-Hang; Wang, Chun-Chieh

    2017-08-01

    To investigate the biological meaning of apparent diffusion coefficient (ADC) values in tumors following radiotherapy. Five mice bearing TRAMP-C1 tumor were half-irradiated with a dose of 15 Gy. Diffusion-weighted images, using multiple b-values from 0 to 3000 s/mm 2 , were acquired at 7T on day 6. ADC values calculated by a two-point estimate and monoexponential fitting of signal decay were compared between the irradiated and nonirradiated regions of the tumor. Pixelwise ADC maps were correlated with histological metrics including nuclear counts, nuclear sizes, nuclear spaces, cytoplasmic spaces, and extracellular spaces. As compared with the nonirradiated region, the irradiated region exhibited significant increases in ADC, extracellular space, and nuclear size, and a significant decrease in nuclear counts (P < 0.001 for all). Optimal ADC to differentiate the irradiated from nonirradiated regions was achieved at a b-value of 800 s/mm 2 by the two-point method and monoexponential curve fitting. ADC positively correlated with extracellular spaces (r = 0.74) and nuclear sizes (r = 0.72), and negatively correlated with nuclear counts (r = -0.82, P < 0.001 for all). As a radiomic biomarker, ADC maps correlating with histological metrics pixelwise could be a means of evaluating tumor heterogeneity and responses to radiotherapy. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:483-489. © 2017 International Society for Magnetic Resonance in Medicine.

  13. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    SciT

    Roesler, J.; Baccarini, M.; Vogt, B.

    1989-08-01

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereasmore » the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens.« less

  14. KDR (VEGFR2) identifies a conserved human and murine hepatic progenitor and instructs early liver development

    PubMed Central

    Goldman, Orit; Han, Songyan; Sourrisseau, Marion; Dziedzic, Noelle; Hamou, Wissam; Corneo, Barbara; D’Souza, Sunita; Sato, Thomas; Kotton, Darrell N.; Bissig, Karl-Dimiter; Kalir, Tamara; Jacobs, Adam; Evans, Todd; Evans, Matthew J.; Gouon-Evans, Valerie

    2013-01-01

    SUMMARY Understanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like (hepatic) cells from human embryonic stem cells (hESCs). Here, we show that KDR (VEGFR2), previously assumed to be mostly restricted to mesodermal lineages, marks a hESC-derived hepatic progenitor. hESC-derived endoderm cells do not express KDR, but when cultured in media supporting hepatic differentiation, generate KDR+ hepatic progenitors and KDR- hepatic cells. KDR+ progenitors require active KDR signaling both to instruct their own differentiation into hepatic cells, and to support non-cell-autonomously the functional maturation of co-cultured KDR- hepatic cells. Analysis of human fetal livers suggests that similar progenitors are present in human livers. Lineage tracing in mice provides in vivo evidence of a KDR+ hepatic progenitor for fetal hepatoblasts and subsequently adult hepatocytes and cholangiocytes. Altogether, our findings reveal that KDR is a conserved marker for endoderm-derived hepatic progenitors, and a functional receptor instructing early liver development. PMID:23746980

  15. The effect of penicillin administration in early life on murine gut microbiota and blood lymphocyte subsets.

    PubMed

    Daniluk, Jaroslaw; Daniluk, Urszula; Rusak, Malgorzata; Dabrowska, Milena; Reszec, Joanna; Garbowicz, Magdalena; Huminska, Kinga; Dabrowski, Andrzej

    2017-10-01

    Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice. 21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected. We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4 + cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells. Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Early detection and staging of spontaneous embryo resorption by ultrasound biomicroscopy in murine pregnancy.

    PubMed

    Flores, Luis E; Hildebrandt, Thomas B; Kühl, Anja A; Drews, Barbara

    2014-05-10

    Embryo resorption is a major problem in human medicine, agricultural animal production and in conservation breeding programs. Underlying mechanisms have been investigated in the well characterised mouse model. However, post mortem studies are limited by the rapid disintegration of embryonic structures. A method to reliably identify embryo resorption in alive animals has not been established yet. In our study we aim to detect embryos undergoing resorption in vivo at the earliest possible stage by ultra-high frequency ultrasound. In a longitudinal study, we monitored 30 pregnancies of wild type C57BI/6 mice using ultra-high frequency ultrasound (30-70 MHz), so called ultrasound biomicroscopy (UBM). We compared the sonoembryology of mouse conceptuses under spontaneous resorption and neighbouring healthy conceptuses and correlated the live ultrasound data with the respective histology. The process of embryo resorption comprised of four stages: first, the conceptus exhibited growth retardation, second, bradycardia and pericardial edema were observed, third, further development ceased and the embryo died, and finally embryo remnants were resorbed by maternal immune cells. In early gestation (day 7 and 8), growth retardation was characterized by a small embryonic cavity. The embryo and its membranes were ill defined or did not develop at all. The echodensity of the embryonic fluid increased and within one to two days, the embryo and its cavity disappeared and was transformed into echodense tissue surrounded by fluid filled caverns. In corresponding histologic preparations, fibrinoid material interspersed with maternal granulocytes and lacunae filled with maternal blood were observed. In later stages (day 9-11) resorption prone embryos were one day behind in their development compared to their normal siblings. The space between Reichert's membrane and inner yolk sac membrane was enlarged The growth retarded embryos exhibited bradycardia and ultimately cessation of heart

  17. Early detection and staging of spontaneous embryo resorption by ultrasound biomicroscopy in murine pregnancy

    PubMed Central

    2014-01-01

    Background Embryo resorption is a major problem in human medicine, agricultural animal production and in conservation breeding programs. Underlying mechanisms have been investigated in the well characterised mouse model. However, post mortem studies are limited by the rapid disintegration of embryonic structures. A method to reliably identify embryo resorption in alive animals has not been established yet. In our study we aim to detect embryos undergoing resorption in vivo at the earliest possible stage by ultra-high frequency ultrasound. Methods In a longitudinal study, we monitored 30 pregnancies of wild type C57BI/6 mice using ultra-high frequency ultrasound (30-70 MHz), so called ultrasound biomicroscopy (UBM). We compared the sonoembryology of mouse conceptuses under spontaneous resorption and neighbouring healthy conceptuses and correlated the live ultrasound data with the respective histology. Results The process of embryo resorption comprised of four stages: first, the conceptus exhibited growth retardation, second, bradycardia and pericardial edema were observed, third, further development ceased and the embryo died, and finally embryo remnants were resorbed by maternal immune cells. In early gestation (day 7 and 8), growth retardation was characterized by a small embryonic cavity. The embryo and its membranes were ill defined or did not develop at all. The echodensity of the embryonic fluid increased and within one to two days, the embryo and its cavity disappeared and was transformed into echodense tissue surrounded by fluid filled caverns. In corresponding histologic preparations, fibrinoid material interspersed with maternal granulocytes and lacunae filled with maternal blood were observed. In later stages (day 9–11) resorption prone embryos were one day behind in their development compared to their normal siblings. The space between Reichert’s membrane and inner yolk sac membrane was enlarged The growth retarded embryos exhibited bradycardia and

  18. PreImplantation Factor (PIF) correlates with early mammalian embryo development-bovine and murine models

    PubMed Central

    2011-01-01

    Background PreImplantation Factor (PIF), a novel peptide secreted by viable embryos is essential for pregnancy: PIF modulates local immunity, promotes decidual pro-adhesion molecules and enhances trophoblast invasion. To determine the role of PIF in post-fertilization embryo development, we measured the peptide's concentration in the culture medium and tested endogenous PIF's potential trophic effects and direct interaction with the embryo. Methods Determine PIF levels in culture medium of multiple mouse and single bovine embryos cultured up to the blastocyst stage using PIF-ELISA. Examine the inhibitory effects of anti-PIF-monoclonal antibody (mAb) added to medium on cultured mouse embryos development. Test FITC-PIF uptake by cultured bovine blastocysts using fluorescent microscopy. Results PIF levels in mouse embryo culture medium significantly increased from the morula to the blastocyst stage (ANOVA, P = 0.01). In contrast, atretic embryos medium was similar to the medium only control. Detectable - though low - PIF levels were secreted already by 2-cell stage mouse embryos. In single bovine IVF-derived embryos, PIF levels in medium at day 3 of culture were higher than non-cleaving embryos (control) (P = 0.01) and at day 7 were higher than day 3 (P = 0.03). In non-cleaving embryos culture medium was similar to medium alone (control). Anti-PIF-mAb added to mouse embryo cultures lowered blastocyst formation rate 3-fold in a dose-dependent manner (2-way contingency table, multiple groups, X2; P = 0.01) as compared with non-specific mouse mAb, and medium alone, control. FITC-PIF was taken-up by cultured bovine blastocysts, but not by scrambled FITC-PIF (control). Conclusions PIF is an early embryo viability marker that has a direct supportive role on embryo development in culture. PIF-ELISA use to assess IVF embryo quality prior to transfer is warranted. Overall, our data supports PIF's endogenous self sustaining role in embryo development and the utility of PIF

  19. Putaminal volume and diffusion in early familial Creutzfeldt-Jakob disease.

    PubMed

    Seror, Ilana; Lee, Hedok; Cohen, Oren S; Hoffmann, Chen; Prohovnik, Isak

    2010-01-15

    The putamen is centrally implicated in the pathophysiology of Creutzfeldt-Jakob Disease (CJD). To our knowledge, its volume has never been measured in this disease. We investigated whether gross putaminal atrophy can be detected by MRI in early stages, when the diffusion is already reduced. Twelve familial CJD patients with the E200K mutation and 22 healthy controls underwent structural and diffusion MRI scans. The putamen was identified in anatomical scans by two methods: manual tracing by a blinded investigator, and automatic parcellation by a computerized segmentation procedure (FSL FIRST). For each method, volume and mean Apparent Diffusion Coefficient (ADC) were calculated. ADC was significantly lower in CJD patients (697+/-64 microm(2)/s vs. 750+/-31 microm(2)/s, p<0.005), as expected, but the volume was not reduced. The computerized FIRST delineation yielded comparable ADC values to the manual method, but computerized volumes were smaller than manual tracing values. We conclude that significant diffusion reduction in the putamen can be detected by delineating the structure manually or with a computerized algorithm. Our findings confirm and extend previous voxel-based and observational studies. Putaminal volume was not reduced in our early-stage patients, thus confirming that diffusion abnormalities precede detectible atrophy in this structure.

  20. Heparan sulfates and the decrease of N-glycans promote early adipogenic differentiation rather than myogenesis of murine myogenic progenitor cells.

    PubMed

    Grassot, Vincent; Bouchatal, Amel; Da Silva, Anne; Chantepie, Sandrine; Papy-Garcia, Dulce; Maftah, Abderrahman; Gallet, Paul-François; Petit, Jean-Michel

    In vitro, extracted muscle satellite cells, called myogenic progenitor cells, can differentiate either in myotubes or preadipocytes, depending on environmental factors and the medium. Transcriptomic analyses on glycosylation genes during satellite cells differentiation into myotubes showed that 31 genes present a significant variation of expression at the early stages of murine myogenic progenitor cells (MPC) differentiation. In the present study, we analyzed the expression of 383 glycosylation related genes during murine MPC differentiation into preadipocytes and compared the data to those previously obtained during their differentiation into myotubes. Fifty-six glycosylation related genes are specifically modified in their expression during early adipogenesis. The variations correspond mainly to: a decrease of N-glycans, and of alpha (2,3) and (2,6) linked sialic acids, and to a high level of heparan sulfates. A high amount of TGF-β1 in extracellular media during early adipogenesis was also observed. It seems that the increases of heparan sulfates and TGF-β1 favor pre-adipogenic differentition of MPC and possibly prevent their myogenic differentiation. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  1. Diffusion-weighted MR imaging findings of kidneys in patients with early phase of obstruction.

    PubMed

    Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet

    2009-04-01

    Diffusion-weighted (DW) magnetic resonance (MR) imaging is an MR technique used to show molecular diffusion. The apparent diffusion coefficient (ADC), as a quantitative parameter calculated from the DW MR images. The purpose of this study is to evaluate the ability of DW MR imaging in early phase of obstruction due to urolithiasis. Twenty-six patients with acute dilatation of the pelvicalyceal system detected by intravenous urography were included in this study. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. DW imaging can be performed using single-shot spin-echo, echo-planar imaging (EPI) sequences with the following diffusion gradient b values: 100, 600, 1000 s/mm(2). Circular region of interest (ROI) was placed in the renal parenchyma for the measurement of ADC values in the normal and obstructed kidney. For statistical analyses, Paired t test were used. In spite of obstructed kidneys had the lower ADC values compared to normal kidneys, these alterations were statistically insignificant. We did not observe significantly different ADC values of early phase of obstructed kidneys compared to normal kidneys.

  2. Significance of palpable tendon friction rubs in early diffuse cutaneous systemic sclerosis.

    PubMed

    Doré, Adam; Lucas, Mary; Ivanco, Dana; Medsger, Thomas A; Domsic, Robyn T

    2013-08-01

    Palpable tendon friction rubs (TFRs) in systemic sclerosis (SSc; scleroderma) have been associated with diffuse skin thickening, increased disability, and poor survival. Our objective was to quantify the prognostic implications of palpable TFRs on the development of disease complications and longer-term mortality in an incident cohort of early diffuse cutaneous SSc (dcSSc) patients. We identified early dcSSc patients (disease duration <2 years from the first SSc symptom) first evaluated at the University of Pittsburgh Scleroderma Center between 1980 and 2006 and found to have palpable TFRs. These patients were matched 1:1 with the next consecutive early dcSSc patient without TFRs as a control. All had ≥2 clinic visits and 5 years of followup from the first visit. A total of 287 early dcSSc patients with TFR were identified and matched to 287 controls. The median disease duration was 0.83 years in TFR patients and 1.04 years in controls. The median followup was 10.1 years in TFR patients and 7.9 years in controls. Over the course of their illness, patients with TFRs had a >2-fold risk of developing renal crisis and cardiac and gastrointestinal disease complications, even after adjustment for other known risk factors. Patients with TFRs had poorer 5- and 10-year survival rates. Patients with early dcSSc having ≥1 TFRs are at an increased risk of developing renal, cardiac, and gastrointestinal involvement before and after their first Scleroderma Center visit and have reduced survival. Patients presenting with TFRs should be carefully monitored for serious internal organ involvement. Copyright © 2013 by the American College of Rheumatology.

  3. Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns.

    PubMed

    Righini, Andrea; Doneda, Chiara; Parazzini, Cecilia; Arrigoni, Filippo; Matta, Ursula; Triulzi, Fabio

    2010-11-01

    The main purpose was to investigate any early diffusion tensor imaging (DTI) changes in corpus callosum (CC) associated with acute cerebral hemisphere lesions in term newborns. We retrospectively analysed 19 cases of term newborns acutely affected by focal or multi-focal lesions: hypoxic-ischemic encephalopathy, hypoglycaemic encephalopathy, focal ischemic stroke and deep medullary vein associated lesions. DTI was acquired at 1.5 Tesla with dedicated neonatal coil. DTI metrics (apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial λ(∐) and radial λ(⟂) diffusivity) were measured in the hemisphere lesions and in the CC. The control group included seven normal newborns. The following significant differences were found between patients and normal controls in the CC: mean ADC was lower in patients (0.88 SD 0.23 versus 1.18 SD 0.07 μm(2)/s) and so was mean FA (0.50 SD 0.1 versus 0.67 SD 0.05) and mean λ(∐) value (1.61 SD 0.52 versus 2.36 SD 0.14 μm(2)/s). In CC the percentage of ADC always diminished independently of lesion age (with one exception), whereas in hemisphere lesions, it was negative in earlier lesions, but exceeded normal values in the older lesions. CC may undergo early DTI changes in newborns with acute focal or multi-focal hemisphere lesions of different aetiology. Although a direct insult to CC cannot be totally ruled out, DTI changes in CC (in particular λ(∐)) may also be compatible with very early Wallerian degeneration or pre-Wallerian degeneration.

  4. Factors influencing early referral, early diagnosis and management in patients with diffuse cutaneous systemic sclerosis.

    PubMed

    Distler, Oliver; Allanore, Yannick; Denton, Christopher P; Matucci-Cerinic, Marco; Pope, Janet E; Hinzmann, Barbara; Davies, Siobhan; de Oliveira Pena, Janethe; Khanna, Dinesh

    2018-05-01

    To gain insight into clinical practice regarding referral, early diagnosis and other aspects of the management of patients with dcSSc in Europe and the USA. Semi-structured interviews were conducted with 84 rheumatologists (or internal medicine physicians) and 40 dermatologists in different countries (the UK, France, Germany, Italy, Spain and the USA). Physicians were asked to identify key steps in the patient pathway relating to patient presentation, diagnosis and referral, in addition to other treatment and follow-up processes. The interviewed physicians reported that late presentation with dcSSc was common, with some patients presenting to primary care physicians after symptoms had persisted for up to 1 year. Awareness of dcSSc is reported to vary widely among primary care physicians. Final diagnosis, generally following guideline-based recommendations, was by rheumatologists in most cases (or internal medicine physicians in France) and they remained responsible for global patient management, with lesser involvement in diagnosis and management by dermatologists. Specialist centres were not well defined and did not exist in all countries. Patients and primary healthcare providers can be unaware of the symptoms of dcSSc, therefore presentation and referral to specialist care are often late. Thus, improved awareness among patients and primary care physicians is necessary to facilitate earlier referral and diagnosis. Once referred, more consistent use of the modified Rodnan skin score at diagnosis and follow-up may help to monitor disease progression. Furthermore, establishing specialist centres may help to promote such changes and improve patient care.

  5. Longitudinal regression analysis of spatial-temporal growth patterns of geometrical diffusion measures in early postnatal brain development with diffusion tensor imaging

    PubMed Central

    Chen, Yasheng; An, Hongyu; Zhu, Hongtu; Jewells, Valerie; Armao, Diane; Shen, Dinggang; Gilmore, John H.; Lin, Weili

    2011-01-01

    Although diffusion tensor imaging (DTI) has provided substantial insights into early brain development, most DTI studies based on fractional anisotropy (FA) and mean diffusivity (MD) may not capitalize on the information derived from the three principal diffusivities (e.g. eigenvalues). In this study, we explored the spatial and temporal evolution of white matter structures during early brain development using two geometrical diffusion measures, namely, linear (Cl) and planar (Cp) diffusion anisotropies, from 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects. The growth trajectories were estimated with generalized estimating equations (GEE) using linear fitting with logarithm of age (days). The presence of the white matter structures in Cl and Cp was observed in neonates, suggesting that both the cylindrical and fanning or crossing structures in various white matter regions may already have been formed at birth. Moreover, we found that both Cl and Cp evolved in a temporally nonlinear and spatially inhomogeneous manner. The growth velocities of Cl in central white matter were significantly higher when compared to peripheral, or more laterally located, white matter: central growth velocity Cl = 0.0465±0.0273/log(days), versus peripheral growth velocity Cl=0.0198±0.0127/log(days), p<10−6. In contrast, the growth velocities of Cp in central white matter were significantly lower than that in peripheral white matter: central growth velocity Cp= 0.0014±0.0058/log(days), versus peripheral growth velocity Cp = 0.0289±0.0101/log(days), p<10−6. Depending on the underlying white matter site which is analyzed, our findings suggest that ongoing physiologic and microstructural changes in the developing brain may exert different effects on the temporal evolution of these two geometrical diffusion measures. Thus, future studies utilizing DTI with correlative histological analysis in the study of early brain development are warranted. PMID

  6. Early detection of a two-long-terminal-repeat junction molecule in the cytoplasm of recombinant murine leukemia virus-infected cells.

    PubMed

    Serhan, Fatima; Penaud, Magalie; Petit, Caroline; Leste-Lasserre, Thierry; Trajcevski, Stéphane; Klatzmann, David; Duisit, Ghislaine; Sonigo, Pierre; Moullier, Philippe

    2004-06-01

    We showed that a U5-U3 junction was reproducibly detected by a PCR assay as early as 1 to 2 h postinfection with a DNase-treated murine leukemia virus (MLV)-containing supernatant in aphidicolin-arrested NIH 3T3 cells, as well as in nonarrested cells. Such detection is azidothymidine sensitive and corresponded to neosynthesized products of the reverse transcriptase. This observation was confirmed in two additional human cell lines, TE671 and ARPE-19. Using cell fractionation combined with careful controls, we found that a two-long-terminal-repeat (two-LTR) junction molecule was detectable in the cytoplasm as early as 2 h post virus entry. Altogether, our data indicated that the neosynthesized retroviral DNA led to the early formation of structures including true two-LTR junctions in the cytoplasm of MLV-infected cells. Thus, the classical assumption that two-LTR circles are a mitosis-dependent dead-end product accumulating in the nucleus must be reconsidered. MLV-derived products containing a two-LTR junction can no longer be used as an exclusive surrogate for the preintegration complex nuclear translocation event.

  7. Decrease of Murine Cytomegalovirus–Induced Retinitis by Intravenous Delivery of Immediate Early Protein-3–Specific siRNA

    PubMed Central

    Marshall, Brendan; Mo, Juan; Covar, Jason; Atherton, Sally S.; Zhang, Ming

    2014-01-01

    Purpose. Retinitis induced by both human and murine cytomegaloviruses following immunosuppression is characterized by progressive loss of retinal architecture, due to necrosis of virus-infected cells as well as widespread apoptosis of uninfected bystander cells. Because small inhibitory RNA molecules (siRNA) can reduce murine cytomegalovirus (MCMV) gene expression and thereby inhibit virus replication in vitro, we tested siRNAs directed against MCMV immediate early protein-3 (IE-3) to determine if MCMV-induced retinitis could be alleviated in vivo. Methods. Immunosuppressed Balb/c mice (2.0 mg methylprednisolone acetate every 3 days beginning on day −2) were infected with 5 × 103 pfu of the K181 strain of MCMV via the supraciliary route. At day 2 post infection, mice were treated with various doses of IE-3–specific siRNA ranging from 0.1 nmol to 10 nmol, in a volume of 20 μL PBS via tail vein injection. Injected eyes were collected at various times post inoculation and subjected to plaque assay for virus titer, MCMV antigen staining, H&E staining, TUNEL assay, and Western blot for MCMV IE-3 protein. Results. Small but significant amounts of fluorescently labeled IE-3–specific siRNA localized to the RPE layer 48 hours after intravenous injection. IE-3–specific siRNA significantly reduced virus titers at all concentrations tested (ranging from 0.1 nmol to 10 nmol), but the most potent effect of siRNA was observed at a dose of 1 nmol. We also observed that IE-3–specific siRNA produced a substantial decrease in MCMV titers and a substantial reduction in bystander cell apoptosis over the time course of virus infection. Conclusions. Systemic administration of IE-3–specific siRNA could alleviate MCMV retinitis by inhibiting virus replication and subsequent death of uninfected retinal cells. PMID:24906861

  8. Detection of early changes in renal function using 99mTc-MAG3 imaging in a murine model of ischemia-reperfusion injury

    PubMed Central

    Roberts, John; Chen, Bo; Curtis, Lisa M.; Agarwal, Anupam; Sanders, Paul W.; Zinn, Kurt R.

    2012-01-01

    Accurate determination of renal function in mice is a major impediment to the use of murine models in acute kidney injury. The purpose of this study was to determine whether early changes in renal function could be detected using dynamic gamma camera imaging in a mouse model of ischemia-reperfusion (I/R) injury. C57BL/6 mice (n = 5/group) underwent a right nephrectomy, followed by either 30 min of I/R injury or sham surgery of the remaining kidney. Dynamic renal studies (21 min, 10 s/frame) were conducted before surgery (baseline) and at 5, 24, and 48 h by injection of 99mTc-mercaptoacetyltriglycine (MAG3; ~1.0 mCi/mouse) via the tail vein. The percentage of injected dose (%ID) in the kidney was calculated for each 10-s interval after MAG3 injection, using standard region of interest analyses. A defect in renal function in I/R-treated mice was detected as early as 5 h after surgery compared with sham-treated mice, identified by the increased %ID (at peak) in the I/R-treated kidneys at 100 s (P < 0.01) that remained significantly higher than sham-treated mice for the duration of the scan until 600 s (P < 0.05). At 48 h, the renal scan demonstrated functional renal recovery of the I/R mice and was comparable to sham-treated mice. Our study shows that using dynamic imaging, renal dysfunction can be detected and quantified reliably as early as 5 h after I/R insult, allowing for evaluation of early treatment interventions. PMID:17634403

  9. An adjoint-based method for a linear mechanically-coupled tumor model: application to estimate the spatial variation of murine glioma growth based on diffusion weighted magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Feng, Xinzeng; Hormuth, David A.; Yankeelov, Thomas E.

    2018-06-01

    We present an efficient numerical method to quantify the spatial variation of glioma growth based on subject-specific medical images using a mechanically-coupled tumor model. The method is illustrated in a murine model of glioma in which we consider the tumor as a growing elastic mass that continuously deforms the surrounding healthy-appearing brain tissue. As an inverse parameter identification problem, we quantify the volumetric growth of glioma and the growth component of deformation by fitting the model predicted cell density to the cell density estimated using the diffusion-weighted magnetic resonance imaging data. Numerically, we developed an adjoint-based approach to solve the optimization problem. Results on a set of experimentally measured, in vivo rat glioma data indicate good agreement between the fitted and measured tumor area and suggest a wide variation of in-plane glioma growth with the growth-induced Jacobian ranging from 1.0 to 6.0.

  10. Murine Typhus

    PubMed Central

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

  11. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

    NASA Astrophysics Data System (ADS)

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-08-01

    This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs‧) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96.

  12. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

    PubMed Central

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-01-01

    Abstract. This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs′) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96. PMID:27564315

  13. Delineation of early brain development from fetuses to infants with diffusion MRI and beyond.

    PubMed

    Ouyang, Minhui; Dubois, Jessica; Yu, Qinlin; Mukherjee, Pratik; Huang, Hao

    2018-04-12

    Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Numerical insights into the early stages of nanoscale electrodeposition: nanocluster surface diffusion and aggregative growth.

    PubMed

    Mamme, Mesfin Haile; Köhn, Christoph; Deconinck, Johan; Ustarroz, Jon

    2018-04-19

    Fundamental understanding of the early stages of electrodeposition at the nanoscale is key to address the challenges in a wide range of applications. Despite having been studied for decades, a comprehensive understanding of the whole process is still out of reach. In this work, we introduce a novel modelling approach that couples a finite element method (FEM) with a random walk algorithm, to study the early stages of nanocluster formation, aggregation and growth, during electrochemical deposition. This approach takes into account not only electrochemical kinetics and transport of active species, but also the surface diffusion and aggregation of adatoms and small nanoclusters. The simulation results reveal that the relative surface mobility of the nanoclusters compared to that of the adatoms plays a crucial role in the early growth stages. The number of clusters, their size and their size dispersion are influenced more significantly by nanocluster mobility than by the applied overpotential itself. Increasing the overpotential results in shorter induction times and leads to aggregation prevalence at shorter times. A higher mobility results in longer induction times, a delayed transition from nucleation to aggregation prevalence, and as a consequence, a larger surface coverage of smaller clusters with a smaller size dispersion. As a consequence, it is shown that a classical first-order nucleation kinetics equation cannot describe the evolution of the number of clusters with time, N(t), in potentiostatic electrodeposition. Instead, a more accurate representation of N(t) is provided. We show that an evaluation of N(t), which neglects the effect of nanocluster mobility and aggregation, can induce errors of several orders of magnitude in the determination of nucleation rate constants. These findings are extremely important towards evaluating the elementary electrodeposition processes, considering not only adatoms, but also nanoclusters as building blocks.

  15. Optimization of illumination for a diffuse-spectroscopy-based early melanoma diagnostic imager

    NASA Astrophysics Data System (ADS)

    Rawicz, Andrew H.; Melnyk, Ivan; Oldham, Bradley

    2004-10-01

    An optical system injecting light directly to the skin and collecting the backscattered portion of the light that has been spectrally modified within the skin has been designed and fabricated. This method reduces the noise generated by the specular component practically to zero. The initial device involved a single channel, optical-fibre-based illuminator and collector connected with a spectroscope. The single channel probing head scanned the skin using a mechanical shifting device. Seven clinical tests performed on patients with suspect skin lesions have been tested with our device, and later biopsy was taken as a "gold standard" procedure. Three cases proved to be melanoma and our spectra indicated differences from those collected from non-melanoma lesions. The process of collecting spectral data was time consuming (about 30 min) and thus not acceptable for a medical procedure. To accelerate the process of data collection from the skin, using the same principle of diffuse spectroscopy, an imaging device was conceived which is able to collect the skin spectral response at once from a relatively sizeable skin area. The requirement of negligible specular component was considered of paramount importance. Two possible approaches are feasible to satisfy this requirement: 1. Collection of backscattered light directly from the skin 2. Injection of illuminating light directly to the skin without creating reflections directly from skin. We decided to use the second approach and construct a circular, circumferential illuminator with angled light injection. Before fabricating this illuminator, a thorough analysis was performed to optimize its radius and angle of injection in order to receive the highest uniformity of diffuse light in the skin. Monte-Carlo simulation was applied to a three layer skin approximation. Only three layers were considered due to the assumption that the device must be able to diagnose early melanoma before reaching metastasis. The results of the

  16. Diffusion tensor imaging can detect the early stages of cartilage damage: a comparison study.

    PubMed

    Ukai, Taku; Sato, Masato; Yamashita, Tomohiro; Imai, Yutaka; Mitani, Genya; Takagaki, Tomonori; Serigano, Kenji; Mochida, Joji

    2015-02-21

    In the present study, we measured damaged areas of cartilage with diffusion tensor (DT) imaging and T2 mapping, and investigated the extent to which cartilage damage could be determined using these techniques. Forty-one patients underwent arthroscopic knee surgery for osteoarthritis of the knee, a meniscus injury, or an anterior cruciate ligament injury. Preoperative magnetic resonance imaging of the knee was performed, including T2 mapping and diffusion tensor imaging. The presence of cartilage injury involving the medial and lateral femoral condyles and tibia plateau was assessed during surgery using the Outerbridge scale. The ADC, T2 values and fractional anisotropy of areas of cartilage injury were then retrospectively analysed. The ADC results identified significant differences between Outerbridge grades 0 and 2 (P = 0.041); 0 and 3 (P < 0.001); 1 and 2 (P = 0.045); 1 and 3 (P < 0.001); and 2 and 3 (P = 0.028). The FA results identified significant differences between grades 0 and 1 (P < 0.001); 0 and 2 (P < 0.001); and 0 and 3 (P < 0.001). T2 mapping identified significant differences between Outerbridge grades 0 and 2 (P = 0.032); 0 and 3 (P < 0.001); 1 and 3 (P < 0.001); and 2 and 3 (P < 0.001). Both the T2 mapping (R(2) = 0.7883) and the ADC (R(2) = 0.9184) correlated significantly with the Outerbridge grade. The FA (R(2) = 0.6616) correlated slightly with the Outerbridge grade. T2 mapping can be useful for detecting moderate or severe cartilage damage, and the ADC can be used to detect early stage cartilage damage. The FA can also distinguish normal from damaged cartilage.

  17. Use of intravoxel incoherent motion diffusion-weighted imaging to detect early changes in diabetic kidneys.

    PubMed

    Deng, Yi; Yang, Biran; Peng, Yan; Liu, Zhiqiang; Luo, Jinwen; Du, Guoxin

    2018-03-14

    The purpose of the study was to examine differences in kidney intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in early-stage diabetic patients versus healthy controls. Nineteen type 2 diabetic patients (group A) with a urinary albumin-to-creatinine ratio (ACR) < 30 mg/g and an estimated glomerular filtration rate (eGFR) of 80-120 mL/(min 1.73 m 2 ) and twelve healthy volunteers (group B) were recruited. Kidneys were scanned with 1.5-Tesla IVIM-DWI. Nine b values (0, 50, 100, 150, 200, 300, 400, 600, and 800 s/mm 2 ) were used. The parameters derived from IVIM-DWI were calculated for each kidney by two radiologists and included the perfusion fraction (f), diffusion coefficient (D), and pseudo-diffusion coefficient (D*). The mean values of f, D, and D* were calculated by selecting multiple regions of interest in the kidney. The diagnostic performance of the f, D, and D* values for the diagnosis of early diabetic kidney changes was determined by receiver operating characteristic analysis. Three radiologists independently measured the parameters derived from IVIM-DWI in the two groups by free-hand placing regions of interest, and the interclass coefficients (ICCs) were analyzed by SPSS.16.0 software. The f values of the kidneys were significantly higher in diabetic patients than in healthy volunteers. The D value of the kidneys was significantly lower in diabetic patients than in healthy volunteers. No significant differences in the D* values of the kidneys were observed between diabetic patients and healthy volunteers. The D values of the right kidneys were significantly higher than those of the left kidneys in both groups. The results of the receiver operating characteristic analysis were as follows: left kidney-f value AUC = 0.650 (cutoff point ≥ 27.49%) and D value AUC = 0.752 (cutoff point ≤ 1.68 × 10 -3  mm 2 /s); and right kidney-f value AUC = 0.650 (cutoff point ≥ 28.24%) and D value AUC = 0

  18. Diffusion-reaction modelling of early diagenesis of sediments affected by acid mine drainage.

    NASA Astrophysics Data System (ADS)

    Torres, E.; Ayora, C.; Arias, J. L.; Garcia Robledo, E.; Papaspyrou, S.; Corzo, A.

    2012-04-01

    The Sancho Reservoir (SW Spain) is a monomictic water reservoir affected by acid mine drainage. It has a pH of ~4, with high sulfate (200 ppm) and heavy metal concentrations in the water column. The reservoir develops reducing conditions at the bottom during the stratification period. A laboratory experiment was carried out to study the effect of this oxygen variation on the early diagenesis processes and the cycling of metals. Sediment cores and bottom water were collected during the stratification period and brought to the laboratory. The cores were maintained in an aquarium bubbled with nitrogen gas to maintain hypoxic conditions (~10 µmol O2 L-1) for 1 day. Then, oxic conditions were induced by bubbling with air and maintained for 50 days. Finally, hypoxia was re-established for 10 days. Triplicate cores were sliced in a anaerobic glove box at each stage. Pore water was extracted by centrifugation and: Eh, pH, DO, DOC, sulfate, Fe and trace metals were analyzed. The sediment was freeze-dried and a sequential extraction protocol was applied to determine the exchangeable, AVS, Fe-(oxy)hydroxides, Fe-oxides, organic matter, pyrite sulfur and residual phase iron fractions. Organic carbon and total C, N, H and S were also analyzed in the sediment. A reactive diffusion model has been used to obtain the rates of biogeochemical reactions by fitting to the experimental data. During hypoxic conditions sulfate and Fe-(oxy)hydroxides are reduced, due to the anaerobic oxidation of organic matter, at the very first few cm, releasing sulfide and Fe(II) which precipitate as iron sulfide. When oxygen diffuses in the sediment, sulfate-reduction and the sulfide peaks are displaced deeper into the sediment. Oxygen penetration depth and its consumption rates in the sediment increase quickly, resulting in the reoxidation of the iron sulfides that had precipitated during hypoxic conditions. Sulfide and Fe(II) are released and are again oxidized to Fe(III) and sulfate respectively

  19. Diffusion tensor imaging and T2 mapping in early denervated skeletal muscle in rats.

    PubMed

    Ha, Dong-Ho; Choi, Sunseob; Kang, Eun-Ju; Park, Hwan Tae

    2015-09-01

    To evaluate the temporal changes of diffusion tensor imaging (DTI) indices, T2 values, and visual signal intensity on various fat suppression techniques in the early state of denervated skeletal muscle in a rat model. Institutional Animal Care and Use Committee approval was obtained. Sciatic nerves of eight rats were transected for irreversible neurotmesis model. We examined normal lower leg and denervated muscles at 3 days, 1 week, and 2 weeks on a 3 Tesla MR. fractional anisotropy (FA), mean apparent diffusion coefficient (mADC), and T2 values were measured by using DTI and T2 mapping scan. We subjectively classified the signal intensity change on various fat suppression images into the following three grades: negative, suspicious, and definite change. Wilcoxon-sign rank test and Kruskal-Wallis test were used for the comparison of FA, mADC, T2 values. McNemar's test was used for comparing signal intensity change among fat suppression techniques. FA values of denervated muscles at 3 days (0.35 ± 0.06), 1 week (0.29 ± 0.04), and 2 weeks (0.34 ± 0.05) were significantly (P < 0.05) lower than that in the control group (0.54 ± 0.17). mADC of denervated muscles decreased without statistically significant (P > 0.05) change. T2 values were significantly increased at 1 week (38.11 ± 6.42 ms, P = 0.017) and markedly increased at 2 weeks (46.53 ± 5.17 ms, P = 0.012). The grade of visual signal intensity change on chemical shift selective fat saturation, STIR and IDEAL images were identical in all cases (P = 1.000). FA and T2 values can demonstrate the early temporal changes in denervated rat skeletal muscle. © 2014 Wiley Periodicals, Inc.

  20. Early detection of chemotherapy-refractory patients by monitoring textural alterations in diffuse optical spectroscopic images.

    PubMed

    Sadeghi-Naini, Ali; Vorauer, Eric; Chin, Lee; Falou, Omar; Tran, William T; Wright, Frances C; Gandhi, Sonal; Yaffe, Martin J; Czarnota, Gregory J

    2015-11-01

    Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean values of these functional metabolic maps. Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001

  1. Wedelolactone mitigates UVB induced oxidative stress, inflammation and early tumor promotion events in murine skin: plausible role of NFkB pathway.

    PubMed

    Ali, Farrah; Khan, Bilal Azhar; Sultana, Sarwat

    2016-09-05

    UVB (Ultra-violet B) radiation is one of the major etiological factors in various dermal pathology viz. dermatitis, actinic folliculitis, solar urticaria, psoriasis and cancer among many others. UVB causes toxic manifestation in tissues by inciting inflammatory and tumor promoting events. We have designed this study to assess the anti-inflammatory and anti-tumor promotion effect of Wedelolactone (WDL) a specific IKK inhibitor. Results indicate significant restoration of anti-oxidative enzymes due to WDL treatments. We also found that WDL was effective in mitigating inflammatory markers consisting of MPO (myeloperoxidase), Mast cells trafficking, Langerhans cells suppression and COX 2 expression up regulation due to UVB exposure. We also deduce that WDL presented a promising intervention in attenuating early tumor promotion events caused by UVB exposure as indicated by the results of ODC (Ornithine Decarboxylase), Thymidine assay, Vimentin and VEGF (Vascular-endothelial growth factor) expression. This study was able to provide substantial cues for the therapeutic ability of Wedelolactone against inflammatory and tumor promoting events in murine skin depicting plausible role of NFkB pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung

    PubMed Central

    Cooper, Andrea M.; Pearl, John E.; Brooks, Jason V.; Ehlers, Stefan; Orme, Ian M.

    2000-01-01

    The interleukin-12 and gamma interferon (IFN-γ) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-γ-activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controlling Mycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-γ or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-γ is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene. PMID:11083808

  3. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

    PubMed Central

    Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

    2017-01-01

    There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

  4. Magnetic single-walled carbon nanotubes as efficient drug delivery nanocarriers in breast cancer murine model: noninvasive monitoring using diffusion-weighted magnetic resonance imaging as sensitive imaging biomarker.

    PubMed

    Al Faraj, Achraf; Shaik, Abjal Pasha; Shaik, Asma Sultana

    2015-01-01

    Targeting doxorubicin (DOX) by means of single-walled carbon nanotube (SWCNT) nanocarriers may help improve the clinical utility of this highly active therapeutic agent. Active targeting of SWCNTs using tumor-specific antibody and magnetic attraction by tagging the nanotubes with iron oxide nanoparticles can potentially reduce the unnecessary side effects and provide enhanced theranostics. In the current study, the in vitro and in vivo efficacy of DOX-loaded SWCNTs as theranostic nanoprobes was evaluated in a murine breast cancer model. Iron-tagged SWCNTs conjugated with Endoglin/CD105 antibody with or without DOX were synthetized and extensively characterized. Their biocompatibility was assessed in vitro in luciferase (Luc2)-expressing 4T1 (4T1-Luc2) murine breast cancer cells using TiterTACS™ Colorimetric Apoptosis Detection Kit (apoptosis induction), poly (ADP-ribose) polymerase (marker for DNA damage), and thiobarbituric acid-reactive substances (oxidative stress generation) assays, and the efficacy of DOX-loaded SWCNTs was evaluated by measuring the radiance efficiency using bioluminescence imaging (BLI). Tumor progression and growth were monitored after 4T1-Luc2 cells inoculation using noninvasive BLI and magnetic resonance imaging (MRI) before and after subsequent injection of SWCNT complexes actively and magnetically targeted to tumor sites. Significant increases in apoptosis, DNA damage, and oxidative stress were induced by DOX-loaded SWCNTs. In addition, a tremendous decrease in bioluminescence was observed in a dose- and time-dependent manner. Noninvasive BLI and MRI revealed successful tumor growth and subsequent attenuation along with metastasis inhibition following DOX-loaded SWCNTs injection. Magnetic tagging of SWCNTs was found to produce significant discrepancies in apparent diffusion coefficient values providing a higher contrast to detect treatment-induced variations as noninvasive imaging biomarker. In addition, it allowed their sensitive

  5. Monitoring early tumor response to drug therapy with diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  6. In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL.

    PubMed

    De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

    2014-01-01

    Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

  7. Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

    PubMed

    Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki

    2017-04-01

    Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. © 2017 John Wiley & Sons Australia, Ltd.

  8. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

    PubMed Central

    Herrick, Ariane L; Pan, Xiaoyan; Peytrignet, Sébastien; Lunt, Mark; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jordan, Alison C; Jobanputra, Paresh; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susannah; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

    2017-01-01

    Objectives The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or ‘no immunosuppressant’. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: −4.0 (−5.2 to −2.7) units for methotrexate, −4.1 (−5.3 to −2.9) for MMF, −3.3 (−4.9 to −1.7) for cyclophosphamide and −2.2 (−4.0 to −0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. Trial registration number NCT02339441. PMID:28188239

  9. Real-time PCR for the early detection and quantification of Coxiella burnetii as an alternative to the murine bioassay.

    PubMed

    Howe, Gerald B; Loveless, Bonnie M; Norwood, David; Craw, Philip; Waag, David; England, Marilyn; Lowe, John R; Courtney, Bernard C; Pitt, M Louise; Kulesh, David A

    2009-01-01

    Real-time PCR was used to analyze archived blood from non-human primates (NHP) and fluid samples originating from a well-controlled Q fever vaccine efficacy trial. The PCR targets were the IS1111 element and the com1 gene of Coxiella burnetii. Data from that previous study were used to evaluate real-time PCR as an alternative to the use of sero-conversion by mouse bioassay for both quantification and early detection of C. burnetii bacteria. Real-time PCR and the mouse bioassay exhibited no statistical difference in quantifying the number of microorganisms delivered in the aerosol challenge dose. The presence of C. burnetii in peripheral blood of non-human primates was detected by real-time PCR as early after exposure as the mouse bioassay with results available within hours instead of weeks. This study demonstrates that real-time PCR has the ability to replace the mouse bioassay to measure dosage and monitor infection of C. burnetii in a non-human primate model.

  10. Enhanced caspase activity contributes to aortic wall remodeling and early aneurysm development in a murine model of Marfan syndrome.

    PubMed

    Emrich, Fabian C; Okamura, Homare; Dalal, Alex R; Penov, Kiril; Merk, Denis R; Raaz, Uwe; Hennigs, Jan K; Chin, Jocelyn T; Miller, Miquell O; Pedroza, Albert J; Craig, Juliana K; Koyano, Tiffany K; Blankenberg, Francis G; Connolly, Andrew J; Mohr, Friedrich W; Alvira, Cristina M; Rabinovitch, Marlene; Fischbein, Michael P

    2015-01-01

    Rupture and dissection of aortic root aneurysms remain the leading causes of death in patients with the Marfan syndrome, a hereditary connective tissue disorder that affects 1 in 5000 individuals worldwide. In the present study, we use a Marfan mouse model (Fbn1(C1039G/+)) to investigate the biological importance of apoptosis during aneurysm development in Marfan syndrome. Using in vivo single-photon emission computed tomographic-imaging and ex vivo autoradiography for Tc99m-annexin, we discovered increased apoptosis in the Fbn1(C1039G/+) ascending aorta during early aneurysm development peaking at 4 weeks. Immunofluorescence colocalization studies identified smooth muscle cells (SMCs) as the apoptotic cell population. As biological proof of concept that early aortic wall apoptosis plays a role in aneurysm development in Marfan syndrome, Fbn1(C1039G/+) mice were treated daily from 2 to 6 weeks with either (1) a pan-caspase inhibitor, Q-VD-OPh (20 mg/kg), or (2) vehicle control intraperitoneally. Q-VD-OPh treatment led to a significant reduction in aneurysm size and decreased extracellular matrix degradation in the aortic wall compared with control mice. In vitro studies using Fbn1(C1039G/+) ascending SMCs showed that apoptotic SMCs have increased elastolytic potential compared with viable cells, mostly because of caspase activity. Moreover, in vitro (1) cell membrane isolation, (2) immunofluorescence staining, and (3) scanning electron microscopy studies illustrate that caspases are expressed on the exterior cell surface of apoptotic SMCs. Caspase inhibition attenuates aneurysm development in an Fbn1(C1039G/+) Marfan mouse model. Mechanistically, during apoptosis, caspases are expressed on the cell surface of SMCs and likely contribute to elastin degradation and aneurysm development in Marfan syndrome. © 2014 American Heart Association, Inc.

  11. Effect of disease progression on liver apparent diffusion coefficient and T2 values in a murine model of hepatic fibrosis at 11.7 Tesla MRI.

    PubMed

    Anderson, Stephan W; Jara, Hernan; Ozonoff, Al; O'Brien, Michael; Hamilton, James A; Soto, Jorge A

    2012-01-01

    To evaluate the effects of hepatic fibrosis on ADC and T(2) values of ex vivo murine liver specimens imaged using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male, C57BL/6 mice were divided into control (n = 2) and experimental groups (n = 15), the latter fed a 3, 5-dicarbethoxy-1, 4-dihydrocollidine (DDC) supplemented diet, inducing hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7T MRI scanner. Spin-echo pulsed field gradient and multi-echo spin-echo acquisitions were used to generate parametric ADC and T(2) maps, respectively. Degrees of fibrosis were determined by the evaluation of a pathologist as well as digital image analysis. Scatterplot graphs comparing ADC and T(2) to degrees of fibrosis were generated and correlation coefficients were calculated. Strong correlation was found between degrees of hepatic fibrosis and ADC with higher degrees of fibrosis associated with lower hepatic ADC values. Moderate correlation between hepatic fibrosis and T(2) values was seen with higher degrees of fibrosis associated with lower T(2) values. Inverse relationships between degrees of fibrosis and both ADC and T(2) are seen, highlighting the utility of these parameters in the ongoing development of an MRI methodology to quantify hepatic fibrosis. Copyright © 2011 Wiley Periodicals, Inc.

  12. In Vivo High-Resolution 7 Tesla MRI Shows Early and Diffuse Cortical Alterations in CADASIL

    PubMed Central

    De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

    2014-01-01

    Background and Purpose Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin’s scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Methods Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. Results MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Conclusions Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined. PMID:25165824

  13. Early detection of chemotherapy-refractory patients by monitoring textural alterations in diffuse optical spectroscopic images

    SciT

    Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J., E-mail: Gregory.Czarnota@sunnybrook.ca

    2015-11-15

    Purpose: Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean valuesmore » of these functional metabolic maps. Methods: Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. Results: Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001 < p < 0.049), and mean value of

  14. Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model

    PubMed Central

    Lozovaya, N.; Gataullina, S.; Tsintsadze, T.; Tsintsadze, V.; Pallesi-Pocachard, E.; Minlebaev, M.; Goriounova, N. A.; Buhler, E.; Watrin, F.; Shityakov, S.; Becker, A. J.; Bordey, A.; Milh, M.; Scavarda, D.; Bulteau, C.; Dorfmuller, G.; Delalande, O.; Represa, A.; Cardoso, C.; Dulac, O.; Ben-Ari, Y.; Burnashev, N.

    2014-01-01

    Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1+/− mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (

  15. Evaluation of a fast single-photon avalanche photodiode for measurement of early transmitted photons through diffusive media.

    PubMed

    Mu, Ying; Valim, Niksa; Niedre, Mark

    2013-06-15

    We tested the performance of a fast single-photon avalanche photodiode (SPAD) in measurement of early transmitted photons through diffusive media. In combination with a femtosecond titanium:sapphire laser, the overall instrument temporal response time was 59 ps. Using two experimental models, we showed that the SPAD allowed measurement of photon-density sensitivity functions that were approximately 65% narrower than the ungated continuous wave case at very early times. This exceeds the performance that we have previously achieved with photomultiplier-tube-based systems and approaches the theoretical maximum predicted by time-resolved Monte Carlo simulations.

  16. Infarct Volume Prediction by Early Magnetic Resonance Imaging in a Murine Stroke Model Depends on Ischemia Duration and Time of Imaging.

    PubMed

    Leithner, Christoph; Füchtemeier, Martina; Jorks, Devi; Mueller, Susanne; Dirnagl, Ulrich; Royl, Georg

    2015-11-01

    Despite standardization of experimental stroke models, final infarct sizes after middle cerebral artery occlusion (MCAO) vary considerably. This introduces uncertainties in the evaluation of drug effects on stroke. Magnetic resonance imaging may detect variability of surgically induced ischemia before treatment and thus improve treatment effect evaluation. MCAO of 45 and 90 minutes induced brain infarcts in 83 mice. During, and 3 and 6 hours after MCAO, we performed multiparametric magnetic resonance imaging. We evaluated time courses of cerebral blood flow, apparent diffusion coefficient (ADC), T1, T2, accuracy of infarct prediction strategies, and impact on statistical evaluation of experimental stroke studies. ADC decreased during MCAO but recovered completely on reperfusion after 45 and partially after 90-minute MCAO, followed by a secondary decline. ADC lesion volumes during MCAO or at 6 hours after MCAO largely determined final infarct volumes for 90 but not for 45 minutes MCAO. The majority of chance findings of final infarct volume differences in random group allocations of animals were associated with significant differences in early ADC lesion volumes for 90, but not for 45-minute MCAO. The prediction accuracy of early magnetic resonance imaging for infarct volumes depends on timing of magnetic resonance imaging and MCAO duration. Variability of the posterior communicating artery in C57Bl6 mice contributes to differences in prediction accuracy between short and long MCAO. Early ADC imaging may be used to reduce errors in the interpretation of post MCAO treatment effects on stroke volumes. © 2015 American Heart Association, Inc.

  17. Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection.

    PubMed

    Bucy, Daniel S; Brown, Mark S; Bielefeldt-Ohmann, Helle; Thompson, Jesse; Bachand, Annette M; Morges, Michelle; Elder, John H; Vandewoude, Sue; Kraft, Susan L

    2011-08-01

    HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

  18. Normal development of human brain white matter from infancy to early adulthood: a diffusion tensor imaging study.

    PubMed

    Uda, Satoshi; Matsui, Mie; Tanaka, Chiaki; Uematsu, Akiko; Miura, Kayoko; Kawana, Izumi; Noguchi, Kyo

    2015-01-01

    Diffusion tensor imaging (DTI), which measures the magnitude of anisotropy of water diffusion in white matter, has recently been used to visualize and quantify parameters of neural tracts connecting brain regions. In order to investigate the developmental changes and sex and hemispheric differences of neural fibers in normal white matter, we used DTI to examine 52 healthy humans ranging in age from 2 months to 25 years. We extracted the following tracts of interest (TOIs) using the region of interest method: the corpus callosum (CC), cingulum hippocampus (CGH), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Approximate values and changes in growth rates of all DTI parameters at each age were calculated and analyzed using LOESS (locally weighted scatterplot smoothing). We found that for all TOIs, FA increased with age, whereas ADC, AD and RD values decreased with age. The turning point of growth rates was at approximately 6 years. FA in the CC was greater than that in the SLF, ILF and CGH. Moreover, FA, ADC and AD of the splenium of the CC (sCC) were greater than in the genu of the CC (gCC), whereas the RD of the sCC was lower than the RD of the gCC. The FA of right-hemisphere TOIs was significantly greater than that of left-hemisphere TOIs. In infants, growth rates of both FA and RD were larger than those of AD. Our data show that developmental patterns differ by TOIs and myelination along with the development of white matter, which can be mainly expressed as an increase in FA together with a decrease in RD. These findings clarify the long-term normal developmental characteristics of white matter microstructure from infancy to early adulthood. © 2015 S. Karger AG, Basel.

  19. Experimental investigation of early-time diffusion in the quantum kicked rotor using a Bose-Einstein condensate.

    PubMed

    Duffy, G J; Parkins, S; Müller, T; Sadgrove, M; Leonhardt, R; Wilson, A C

    2004-11-01

    We report measurements of the early-time momentum diffusion for the atom-optical delta-kicked rotor. In this experiment a Bose-Einstein condensate provides a source of ultracold atoms with an ultranarrow initial momentum distribution, which is then subjected to periodic pulses (or "kicks") using an intense far-detuned optical standing wave. We characterize the effect of varying the effective Planck's constant for the system, while keeping all other parameters fixed. The observed behavior includes both quantum resonances (ballistic energy growth) and antiresonances (re-establishment of the initial state). Our experimental results are compared with theoretical predictions.

  20. The diffuse gamma-ray background, light element abundances, and signatures of early massive star formation

    NASA Technical Reports Server (NTRS)

    Silk, Joseph; Schramm, David N.

    1992-01-01

    Attention is drawn to a potentially observable flux of diffuse extragalactic gamma rays produced by inelastic cosmic-ray interactions that is inevitably a by-product of spallation-synthesized Be. The epoch of cosmic ray-induced Population II light element nucleosynthesis is constrained to be at redshift greater than 0.5. A spectral feature in the diffuse extragalactic gamma-ray background with amplitude 0.1 above 10 MeV is predicted if the Be is synthesized at z less than 10. The possibility is discussed that the cosmic-ray flux responsible for Population II Be and B synthesis may be associated with a precursor hypothesized Population III.

  1. Three-dimensional microCT imaging of murine embryonic development from immediate post-implantation to organogenesis: application for phenotyping analysis of early embryonic lethality in mutant animals.

    PubMed

    Ermakova, Olga; Orsini, Tiziana; Gambadoro, Alessia; Chiani, Francesco; Tocchini-Valentini, Glauco P

    2018-04-01

    In this work, we applied three-dimensional microCT imaging to study murine embryogenesis in the range from immediate post-implantation period (embryonic day 5.5) to mid-gestation (embryonic day 12.5) with the resolution up to 1.4 µm/voxel. Also, we introduce an imaging procedure for non-invasive volumetric estimation of an entire litter of embryos within the maternal uterine structures. This method allows for an accurate, detailed and systematic morphometric analysis of both embryonic and extra-embryonic components during embryogenesis. Three-dimensional imaging of unperturbed embryos was performed to visualize the egg cylinder, primitive streak, gastrulation and early organogenesis stages of murine development in the C57Bl6/N mouse reference strain. Further, we applied our microCT imaging protocol to determine the earliest point when embryonic development is arrested in a mouse line with knockout for tRNA splicing endonuclease subunit Tsen54 gene. Our analysis determined that the embryonic development in Tsen54 null embryos does not proceed beyond implantation. We demonstrated that application of microCT imaging to entire litter of non-perturbed embryos greatly facilitate studies to unravel gene function during early embryogenesis and to determine the precise point at which embryonic development is arrested in mutant animals. The described method is inexpensive, does not require lengthy embryos dissection and can be applicable for detailed analysis of mutant mice at laboratory scale as well as for high-throughput projects.

  2. Early diffusion of gene expression profiling in breast cancer patients associated with areas of high income inequality.

    PubMed

    Ponce, Ninez A; Ko, Michelle; Liang, Su-Ying; Armstrong, Joanne; Toscano, Michele; Chanfreau-Coffinier, Catherine; Haas, Jennifer S

    2015-04-01

    With the Affordable Care Act reducing coverage disparities, social factors could prominently determine where and for whom innovations first diffuse in health care markets. Gene expression profiling is a potentially cost-effective innovation that guides chemotherapy decisions in early-stage breast cancer, but adoption has been uneven across the United States. Using a sample of commercially insured women, we evaluated whether income inequality in metropolitan areas was associated with receipt of gene expression profiling during its initial diffusion in 2006-07. In areas with high income inequality, gene expression profiling receipt was higher than elsewhere, but it was associated with a 10.6-percentage-point gap between high- and low-income women. In areas with low rates of income inequality, gene expression profiling receipt was lower, with no significant differences by income. Even among insured women, income inequality may indirectly shape diffusion of gene expression profiling, with benefits accruing to the highest-income patients in the most unequal places. Policies reducing gene expression profiling disparities should address low-inequality areas and, in unequal places, practice settings serving low-income patients. Project HOPE—The People-to-People Health Foundation, Inc.

  3. Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters

    PubMed Central

    2013-01-01

    Background Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. Methods 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers’ model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Results Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Conclusions Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition

  4. Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters.

    PubMed

    Larson, Peter S; Yadav, Prashant; Alphs, Sarah; Arkedis, Jean; Massaga, Julius; Sabot, Oliver; Cohen, Jessica L

    2013-12-18

    Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers' model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly

  5. Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline.

    PubMed

    Loh, K B; Ramli, N; Tan, L K; Roziah, M; Rahmat, K; Ariffin, H

    2012-07-01

    The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas. Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction. DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued. DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data. Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

  6. State policy influence on the early diffusion of buprenorphine in community treatment programs.

    PubMed

    Ducharme, Lori J; Abraham, Amanda J

    2008-06-20

    Buprenorphine was approved for use in the treatment of opioid dependence in 2002, but its diffusion into everyday clinical practice in community-based treatment programs has been slow. This study examines the net impact of efforts by state agencies, including provision of Medicaid coverage, on program-level adoption of buprenorphine as of 2006. Interviews were conducted with key informants in 49 of the 50 state agencies with oversight responsibility for addiction treatment services. Information from these interviews was integrated with organizational data from the 2006 National Survey of Substance Abuse Treatment Services. A multivariate logistic regression model was estimated to identify the effects of state efforts to promote the use of this medication, net of a host of organizational characteristics. The availability of Medicaid coverage for buprenorphine was a significant predictor of its adoption by treatment organizations. Inclusion of buprenorphine on state Medicaid formularies appears to be a key element in ensuring that patients have access to this state-of-the-art treatment option. Other potential barriers to the diffusion of buprenorphine require identification, and the value of additional state-level policies to promote its use should be evaluated.

  7. White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

    PubMed

    Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

    2014-07-01

    The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Alteration of diffusion-tensor MRI measures in brain regions involved in early stages of Parkinson's disease.

    PubMed

    Chen, Nan-Kuei; Chou, Ying-Hui; Sundman, Mark; Hickey, Patrick; Kasoff, Willard S; Bernstein, Adam; Trouard, Theodore P; Lin, Tanya; Rapcsak, Steven Z; Sherman, Scott J; Weingarten, Carol

    2018-06-07

    Many non-motor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion tensor imaging (DTI) is suitable for detecting changes of brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved ROI based analysis methods. Results showed that 1) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; 2) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

  9. Diffusion tensor imaging detects early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus

    PubMed Central

    Zhao, Cailei; Li, Yongxin; Cao, Weiguo; Xiang, Kui; Zhang, Heye; Yang, Jian; Gan, Yungen

    2016-01-01

    Abstract To explore the use of diffusion tensor imaging (DTI) parameters in the quantitative assessment of early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus. Ten patients with communicating hydrocephalus (age: 2–36 months) and 14 age-/gender-matched controls (age: 2–36 months) were enrolled in this study. All patients underwent the ventriculoperitoneal shunt procedure. The imaging data were collected before and 3 months after the operation. Regions of interests (ROIs) included the white matter near the frontal horn of the lateral ventricles (FHLV), the occipital horn of the lateral ventricles (OHLV), occipital subcortical (OS) area, frontal subcortical (FS) area, and thalamus. Fractional anisotropies (FA) and apparent diffusion coefficients (ADC) of the ROIs before and after ventriculoperitoneal shunt were compared between the patients and the controls. Three months after surgery, the patients recovered from the surgery with ameliorated intracranial pressure and slight improvement of clinical intelligence scale and motor scale. Before ventriculoperitoneal shunt, the FA values (except the right FHLV) were significantly decreased and the ADC values were significantly increased in the patients with hydrocephalus, compared with the controls. After the ventriculoperitoneal shunt, the FA values in the FHLV and OHLV of the patients were similar to the controls, but the FA values in other ROIs were still significantly lower than controls. The ADC values in the FS and OS white matter areas of the patients were similar to the controls; however, the ADC values in other ROIs were still significantly higher in patients. The increase of FA and the reduction in ADC in the ROIs preceded the clinical function improvement in patients with high intracranial pressure hydrocephalus and reflected the early changes in brain tissue microstructure, such as the compression of the white matter areas in

  10. Will the 'principles of effectiveness' improve prevention practice? Early findings from a diffusion study.

    PubMed

    Hallfors, D; Godette, D

    2002-08-01

    This study examines adoption and implementation of the US Department of Education's new policy, the 'Principles of Effectiveness', from a diffusion of innovations theoretical framework. In this report, we evaluate adoption in relation to Principle 3: the requirement to select research-based programs. Results from a sample of 104 school districts in 12 states indicate that many districts appear to be selecting research-based curricula, but that the quality of implementation is low. Only 19% of the responding district coordinators indicated that schools were implementing a research-based curriculum with fidelity. Common problems included lack of teacher training, lack of requisite materials, use of some but not all of the required lessons and teaching strategies, and failure to deliver lessons to age-appropriate student groups. This study represents the first attempt to assess the quality of implementation of research-based programs as required by the Principles of Effectiveness. We conclude that low levels of funding, inadequate infrastructure, decentralized decision making and lack of program guidance have contributed to the slow progress in improving school-based prevention.

  11. Planck early results. XXIV. Dust in the diffuse interstellar medium and the Galactic halo

    NASA Astrophysics Data System (ADS)

    Planck Collaboration; Abergel, A.; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Balbi, A.; Banday, A. J.; Barreiro, R. B.; Bartlett, J. G.; Battaner, E.; Benabed, K.; Benoît, A.; Bernard, J.-P.; Bersanelli, M.; Bhatia, R.; Blagrave, K.; Bock, J. J.; Bonaldi, A.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bucher, M.; Burigana, C.; Cabella, P.; Cantalupo, C. M.; Cardoso, J.-F.; Catalano, A.; Cayón, L.; Challinor, A.; Chamballu, A.; Chiang, L.-Y.; Chiang, C.; Christensen, P. R.; Clements, D. L.; Colombi, S.; Couchot, F.; Coulais, A.; Crill, B. P.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Gasperis, G.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Dickinson, C.; Donzelli, S.; Doré, O.; Dörl, U.; Douspis, M.; Dupac, X.; Efstathiou, G.; Enßlin, T. A.; Eriksen, H. K.; Finelli, F.; Forni, O.; Frailis, M.; Franceschi, E.; Galeotta, S.; Ganga, K.; Giard, M.; Giardino, G.; Giraud-Héraud, Y.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Hansen, F. K.; Harrison, D.; Helou, G.; Henrot-Versillé, S.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hovest, W.; Hoyland, R. J.; Huffenberger, K. M.; Jaffe, A. H.; Joncas, G.; Jones, A.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knox, L.; Kurki-Suonio, H.; Lagache, G.; Lamarre, J.-M.; Lasenby, A.; Laureijs, R. J.; Lawrence, C. R.; Leach, S.; Leonardi, R.; Leroy, C.; Linden-Vørnle, M.; Lockman, F. J.; López-Caniego, M.; Lubin, P. M.; Macías-Pérez, J. F.; MacTavish, C. J.; Maffei, B.; Maino, D.; Mandolesi, N.; Mann, R.; Maris, M.; Marshall, D. J.; Martin, P.; Martínez-González, E.; Masi, S.; Matarrese, S.; Matthai, F.; Mazzotta, P.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Mendes, L.; Mennella, A.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Munshi, D.; Murphy, A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; O'Dwyer, I. J.; Osborne, S.; Pajot, F.; Paladini, R.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Piacentini, F.; Piat, M.; Pinheiro Gonçalves, D.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Ponthieu, N.; Poutanen, T.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Reach, W. T.; Reinecke, M.; Renault, C.; Ricciardi, S.; Riller, T.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rowan-Robinson, M.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Santos, D.; Savini, G.; Scott, D.; Seiffert, M. D.; Shellard, P.; Smoot, G. F.; Starck, J.-L.; Stivoli, F.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Torre, J.-P.; Tristram, M.; Tuovinen, J.; Umana, G.; Valenziano, L.; Vielva, P.; Villa, F.; Vittorio, N.; Wade, L. A.; Wandelt, B. D.; Wilkinson, A.; Yvon, D.; Zacchei, A.; Zonca, A.

    2011-12-01

    This paper presents the first results from a comparison of Planck dust maps at 353, 545 and 857GHz, along with IRAS data at 3000 (100 μm) and 5000GHz (60 μm), with Green Bank Telescope 21-cm observations of Hi in 14 fields covering more than 800 deg2 at high Galactic latitude. The main goal of this study is to estimate the far-infrared to sub-millimeter (submm) emissivity of dust in the diffuse local interstellar medium (ISM) and in the intermediate-velocity (IVC) and high-velocity clouds (HVC) of the Galactic halo. Galactic dust emission for fields with average Hi column density lower than 2 × 1020 cm-2 is well correlated with 21-cm emission because in such diffuse areas the hydrogen is predominantly in the neutral atomic phase. The residual emission in these fields, once the Hi-correlated emission is removed, is consistent with the expected statistical properties of the cosmic infrared background fluctuations. The brighter fields in our sample, with an average Hi column density greater than 2 × 1020 cm-2, show significant excess dust emission compared to the Hi column density. Regions of excess lie in organized structures that suggest the presence of hydrogen in molecular form, though they are not always correlated with CO emission. In the higher Hi column density fields the excess emission at 857 GHz is about 40% of that coming from the Hi, but over all the high latitude fields surveyed the molecular mass faction is about 10%. Dust emission from IVCs is detected with high significance by this correlation analysis. Its spectral properties are consistent with, compared to the local ISM values, significantly hotter dust (T ~ 20K), lower submm dust opacity normalized per H-atom, and a relative abundance of very small grains to large grains about four times higher. These results are compatible with expectations for clouds that are part of the Galactic fountain in which there is dust shattering and fragmentation. Correlated dust emission in HVCs is not detected

  12. A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

    PubMed

    Balachandar, R; John, J P; Saini, J; Kumar, K J; Joshi, H; Sadanand, S; Aiyappan, S; Sivakumar, P T; Loganathan, S; Varghese, M; Bharath, S

    2015-05-01

    Alzheimer's disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD. Fifteen mild AD subjects and 15 cognitively healthy controls (CHc) matched for age and gender, underwent detailed neurocognitive assessment and magnetic resonance imaging (MRI) of resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Rest fMRI was analyzed using dual regression approach and DTI by voxel wise statistics. Patients with mild AD had significantly lower functional connectivity (FC) within the default mode network and increased FC within the executive network. The mild AD group scored significantly lower in all domains of cognition compared with CHc. But fractional anisotropy did not significantly (p < 0.05) differ between the groups. Resting state functional connectivity alterations are noted during initial stages of cognitive decline in AD, even when there are no significant white matter microstructural changes. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Role of Early Postradiation Magnetic Resonance Imaging Scans in Children With Diffuse Intrinsic Pontine Glioma

    SciT

    Ko, Christine; Kaushal, Aradhana, E-mail: kaushala@mail.nih.gov; Hammoud, Dima A.

    2012-07-15

    Purpose: To determine optimal timing of assessing postradiation radiographic response on magnetic resonance imaging (MRI) scans in pediatric patients with diffuse intrinsic pontine glioma (DIPG). Methods and Materials: Patients were treated on a prospective study at the National Cancer Institute (Protocol no. 06-C-0219) evaluating the effects of radiotherapy (RT). Standard RT was administered in standard fractionation over 6 weeks. Postradiation MRI scans were performed at 2 and 6-8 weeks. Results: Eleven patients with DIPG were evaluated. Median age was 6 years (range, 4-13 years). Patients were treated with external-beam RT to 55.8 Gy (n = 10) or 54 Gy (nmore » = 1), with a gross tumor volume to planning target volume expansion of 1.8-2.0 cm. All patients received prescribed dose and underwent posttreatment MRI scans at 2 and 6-8 weeks. Pretreatment imaging revealed compression of fourth ventricle (n = 11); basilar artery encasement (n = 9); tumor extension outside the pons (n = 11); and tumor hemorrhage (n = 2). At the 2-week scan, basilar artery encasement improved in 7 of 9 patients, and extent of tumor was reduced in 5 of 11 patients. Fourth ventricle compression improved in 6 of 11 patients but worsened in 3 of 11 patients. Presumed necrosis was observed in 5 of 11 patients at 2 weeks and in 1 additional patient at 6-8 weeks. There was no significant difference in mean anteroposterior and transverse diameters of tumor between the 2- and 6-8-week time points. Six of 11 patients had increasing ventricular size, with no evidence of obstruction. Conclusions: There is no significant difference in tumor size of DIPG patients who have received standard RT when measured at 2 weeks vs. 6-8 weeks after RT. The majority of patients had the largest change in tumor size at the 2-week post-RT scan, with evolving changes documented on the 6-8-week scan. Six of 11 patients had progressive ventriculomegaly without obstruction, suggestive of communicating hydrocephalus. To

  14. Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

    PubMed

    Mardor, Yael; Pfeffer, Raphael; Spiegelmann, Roberto; Roth, Yiftach; Maier, Stephan E; Nissim, Ouzi; Berger, Raanan; Glicksman, Ami; Baram, Jacob; Orenstein, Arie; Cohen, Jack S; Tichler, Thomas

    2003-03-15

    To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

  15. Early Upper Paleolithic colonization across Europe: Time and mode of the Gravettian diffusion

    PubMed Central

    Cascalheira, João; Gonçalves, Célia

    2017-01-01

    This study presents new models on the origin, speed and mode of the wave-of-advance leading to the definitive occupation of Europe’s outskirts by Anatomically Modern Humans, during the Gravettian, between c. 37 and 30 ka ago. These models provide the estimation for possible demic dispersal routes for AMH at a stable spread rate of c. 0.7 km/year, with the likely origin in Central Europe at the site of Geissenklosterle in Germany and reaching all areas of the European landscape. The results imply that: 1. The arrival of the Gravettian populations into the far eastern European plains and to southern Iberia found regions with very low human occupation or even devoid of hominins; 2. Human demography was likely lower than previous estimates for the Upper Paleolithic; 3. The likely early AMH paths across Europe followed the European central plains and the Mediterranean coast to reach to the ends of the Italian and Iberian peninsulas. PMID:28542642

  16. Cingulum correlates of cognitive functions in patients with mild cognitive impairment and early Alzheimer's disease: a diffusion spectrum imaging study.

    PubMed

    Lin, Yi-Cheng; Shih, Yao-Chia; Tseng, Wen-Yih I; Chu, Yu-Hsiu; Wu, Meng-Tien; Chen, Ta-Fu; Tang, Pei-Fang; Chiu, Ming-Jang

    2014-05-01

    Diffusion spectrum imaging (DSI) of MRI can detect neural fiber tract changes. We investigated integrity of cingulum bundle (CB) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (EAD) using DSI tractography and explored its relationship with cognitive functions. We recruited 8 patients with MCI, 9 with EAD and 15 healthy controls (HC). All subjects received a battery of neuropsychological tests to access their executive, memory and language functions. We used a 3.0-tesla MRI scanner to obtain T1- and T2-weighted images for anatomy and used a pulsed gradient twice-refocused spin-echo diffusion echo-planar imaging sequence to acquire DSI. Patients with EAD performed significantly poorer than the HC on most tests in executive and memory functions. Significantly smaller general fractional anisotropy (GFA) values were found in the posterior and inferior segments of left CB and of the anterior segment of right CB of the EAD compared with those of the HC. Spearman's correlation on the patient groups showed that GFA values of the posterior segment of the left CB were significantly negatively associated with the time used to complete Color Trails Test Part II and positively correlated with performance of the logical memory and visual reproduction. GFA values of inferior segment of bilateral CB were positively associated with the performance of visual recognition. DSI tractography demonstrates significant preferential degeneration of the CB on the left side in patients with EAD. The location-specific degeneration is associated with corresponding declines in both executive and memory functions.

  17. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of radiation therapy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Shang, Yu; Li, Xingzhe; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-03-01

    Radiation therapy is a principal modality for head and neck cancers and its efficacy depends on tumor hemodynamics. Our laboratory developed a hybrid diffuse optical instrument allowing for simultaneous measurements of tumor blood flow and oxygenation. In this study, the clinically involved cervical lymph node was monitored by the hybrid instrument once a week over the treatment period of seven weeks. Based on treatment outcomes within one year, patients were classified into a complete response group (CR) and an incomplete response group (IR) with remote metastasis and/or local recurrence. A linear mixed models was used to compare tumor hemodynamic responses to the treatment between the two groups. Interestingly, we found that human papilloma virus (HPV-16) status largely affected tumor hemodynamic responses. For HPV-16 negative tumors, significant differences in blood flow index (BFI, p = 0.007) and reduced scattering coefficient (μs', p = 0.0005) were observed between the two groups; IR tumors exhibited higher μs' values and a continuous increase in BFI over the treatment period. For HPV-16 positive tumors, oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) were significant different (p = 0.003 and 0.01, respectively); IR group showed lower [HbO2] and StO2. Our results imply HPV-16 negative tumors with higher density of vasculature (μs') and higher blood flow show poor responses to radiotherapy and HPV-16 positive tumors with lower tissue oxygenation level (lower StO2 and [HbO2]) exhibit poor treatment outcomes. Our diffuse optical measurements show the great potential for early prediction of radiotherapy in head and neck cancers.

  18. High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

    PubMed

    Roth, Yiftach; Tichler, Thomas; Kostenich, Genady; Ruiz-Cabello, Jesus; Maier, Stephan E; Cohen, Jack S; Orenstein, Arie; Mardor, Yael

    2004-09-01

    To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy. Copyright RSNA, 2004

  19. Prediction of early neurological deterioration using diffusion- and perfusion-weighted imaging in hyperacute middle cerebral artery ischemic stroke.

    PubMed

    Arenillas, Juan F; Rovira, Alex; Molina, Carlos A; Grivé, Elisenda; Montaner, Joan; Alvarez-Sabín, José

    2002-09-01

    Early neurological deterioration (END) occurs in approximately one third of all ischemic stroke patients and is associated with a poor outcome. Our study sought to assess the value of ultra-early MRI in the prediction of END in stroke patients. Between August 1999 and November 2001, 38 stroke patients with a proven middle cerebral artery (MCA) or intracranial internal carotid artery (ICA) occlusion on MR angiography underwent perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) within 6 hours after onset, and 30 fulfilled all inclusion criteria. Control DWI and MR angiography were performed between days 3 and 5. Cranial CT was performed to rule out hemorrhagic transformation. Vascular risk factors, temperature, blood pressure, glycemia, and blood count were assessed on admission. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 6, 12, 24, and 48 hours. At the same time points, transcranial Doppler (TCD) examinations were conducted to assess arterial recanalization. END was defined as an increase in the NIHSS score >4. A logistic regression model was applied to detect independent predictors of END. The Kruskal-Wallis test was used to evaluate the relationship between infarct growth and duration of vessel occlusion. Initial MR angiography showed an occlusion of intracranial ICA in 7 patients (23.3%), of proximal MCA in 14 (46.6%), and of distal MCA in the remaining 9 (30%). A PWI-DWI mismatch >20% was observed in 28 patients (93.3%). END occurred in 7 patients (23.3%). Baseline NIHSS score (P=0.05), proximal site of occlusion (P=0.002), initial DWI (P=0.002) and PWI (P=0.003) volumes, and reduced PWI-DWI mismatch (P=0.038) were associated with END in the univariate analysis. Only hyperacute DWI volume remained as a predictor of END when a logistic regression model was applied (odds ratio, 11.5; 95% CI, 2.31 to 57.10; P=0.0028). A receiver operator characteristic curve identified a cutoff point of DWI >89 cm(3

  20. Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection

    PubMed Central

    Valle-Tenney, Roger; Opazo, Tatiana; Cancino, Jorge; Goff, Stephen P.

    2016-01-01

    ABSTRACT During the early steps of infection, retroviruses must direct the movement of the viral genome into the nucleus to complete their replication cycle. This process is mediated by cellular proteins that interact first with the reverse transcription complex and later with the preintegration complex (PIC), allowing it to reach and enter the nucleus. For simple retroviruses, such as murine leukemia virus (MLV), the identities of the cellular proteins involved in trafficking of the PIC in infection are unknown. To identify cellular proteins that interact with the MLV PIC, we developed a replication-competent MLV in which the integrase protein was tagged with a FLAG epitope. Using a combination of immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the incoming viral particles and the dynein complex regulators. Further experiments showed that RNA interference (RNAi)-mediated silencing of either DCTN2/p50/dynamitin or another dynein regulator, NudEL, profoundly reduced the efficiency of infection by ecotropic, but not amphotropic, MLV reporters. We propose that the cytoplasmic dynein regulators are a critical component of the host machinery needed for infection by the retroviruses entering the cell via the ecotropic envelope pathway. IMPORTANCE Retroviruses must access the chromatin of host cells to integrate the viral DNA, but before this crucial event, they must reach the nucleus. The movement through the cytoplasm—a crowded environment where diffusion is slow—is thought to utilize retrograde transport along the microtubule network by the dynein complex. Different viruses use different components of this multisubunit complex. We found that the preintegration complex of murine leukemia virus (MLV) interacts with the dynein complex and that regulators of this complex are essential for

  1. Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection.

    PubMed

    Xu, Jinxian; Mo, Juan; Liu, Xinglou; Marshall, Brendan; Atherton, Sally S; Dong, Zheng; Smith, Sylvia; Zhang, Ming

    2018-05-01

    The purpose of this study was to determine if the receptor-interacting protein kinase 3 (RIP3) plays a significant role in innate immune responses and death of bystander retinal neurons during murine cytomegalovirus (MCMV) retinal infection, by comparing the innate immune response and cell death in RIP3-depleted mice (Rip3-/-) and Rip3+/+ control mice. Rip3-/- and Rip3+/+ mice were immunosuppressed (IS) and inoculated with MCMV via the supraciliary route. Virus-injected and mock-injected control eyes were removed at days 4, 7, and 10 post infection (p.i.) and markers of innate immunity and cell death were analyzed. Compared to Rip3+/+ mice, significantly more MCMV was recovered and more MCMV-infected RPE cells were observed in injected eyes of Rip3-/- mice at days 4 and 7 p.i. In contrast, fewer TUNEL-stained photoreceptors were observed in Rip3-/- eyes than in Rip3+/+ eyes at these times. Electron microscopy showed that significantly more apoptotic photoreceptor cells were present in Rip3+/+ mice than in Rip3-/- mice. Immunohistochemistry showed that the majority of TUNEL-stained photoreceptors died via mitochondrial flavoprotein apoptosis-inducing factor (AIF)-mediated, caspase 3-independent apoptosis. The majority of RIP3-expressing cells in infected eyes were RPE cells, microglia/macrophages, and glia, whereas retinal neurons contained much lower amounts of RIP3. Western blots showed significantly higher levels of activated nuclear factor-κB and caspase 1 were present in Rip3+/+ eyes compared to Rip3-/- eyes. Our results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor-κB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.

  2. Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection

    PubMed Central

    Xu, Jinxian; Mo, Juan; Liu, Xinglou; Marshall, Brendan; Atherton, Sally S.; Dong, Zheng; Smith, Sylvia

    2018-01-01

    Purpose The purpose of this study was to determine if the receptor-interacting protein kinase 3 (RIP3) plays a significant role in innate immune responses and death of bystander retinal neurons during murine cytomegalovirus (MCMV) retinal infection, by comparing the innate immune response and cell death in RIP3-depleted mice (Rip3−/−) and Rip3+/+ control mice. Methods Rip3−/− and Rip3+/+ mice were immunosuppressed (IS) and inoculated with MCMV via the supraciliary route. Virus-injected and mock-injected control eyes were removed at days 4, 7, and 10 post infection (p.i.) and markers of innate immunity and cell death were analyzed. Results Compared to Rip3+/+ mice, significantly more MCMV was recovered and more MCMV-infected RPE cells were observed in injected eyes of Rip3−/− mice at days 4 and 7 p.i. In contrast, fewer TUNEL-stained photoreceptors were observed in Rip3−/− eyes than in Rip3+/+ eyes at these times. Electron microscopy showed that significantly more apoptotic photoreceptor cells were present in Rip3+/+ mice than in Rip3−/− mice. Immunohistochemistry showed that the majority of TUNEL-stained photoreceptors died via mitochondrial flavoprotein apoptosis-inducing factor (AIF)-mediated, caspase 3–independent apoptosis. The majority of RIP3-expressing cells in infected eyes were RPE cells, microglia/macrophages, and glia, whereas retinal neurons contained much lower amounts of RIP3. Western blots showed significantly higher levels of activated nuclear factor–κB and caspase 1 were present in Rip3+/+ eyes compared to Rip3−/− eyes. Conclusions Our results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor–κB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.

  3. CCL2 and CCR2 regulate pain-related behaviour and early gene expression in post-traumatic murine osteoarthritis but contribute little to chondropathy.

    PubMed

    Miotla Zarebska, J; Chanalaris, A; Driscoll, C; Burleigh, A; Miller, R E; Malfait, A M; Stott, B; Vincent, T L

    2017-03-01

    The role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator of inflammation is the chemokine CCL2, primarily responsible for attracting monocytes to sites of injury. We investigated the role of CCL2 and its receptor CCR2 in experimental OA. OA was induced in 10 weeks old male wild type (WT), Ccl2 -/- and Ccr2 -/- mice, by destabilisation of the medial meniscus (DMM). RNA was extracted from whole joints at 6 h and 7 days post-surgery and examined by reverse transcription polymerase chain reaction (RT-PCR). Gene expression changes between naïve and DMM-operated mice were compared. Chondropathy scores, from mice at 8, 12, 16 and 20 weeks post DMM were calculated using modified Osteoarthritis Research Society International (OARSI) grading systems. Changes in hind paw weight distribution, as a measure of pain, were assessed by Linton incapacitance. Absence of CCL2 strongly suppressed (>90%) selective inflammatory response genes in the joint 6 h post DMM, including arginase 1, prostaglandin synthase 2, nitric oxide synthase 2 and inhibin A. IL6, MMP3 and tissue inhibitor of metalloproteinase 1 were also significantly suppressed. Similar trends were also observed in the absence of CCR2. A lower average chondropathy score was observed in both Ccl2 -/- and Ccr2 -/- mice at 12, 16 and 20 weeks post DMM compared with WT mice, but this was only statistically significant at 20 weeks in Ccr2 -/- mice. Pain-related behaviour in Ccl2 -/- and Ccr2 -/- mice post DMM was delayed in onset. The CCL2/CCR2 axis plays an important role in the development of pain in murine OA, but contributes little to cartilage damage. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

    PubMed

    Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

    2018-04-01

    Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

    PubMed Central

    Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

    2018-01-01

    Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. ‘Progressors’ were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. PMID:29306872

  6. Correlates and responsiveness to change of measures of skin and musculoskeletal disease in early diffuse systemic sclerosis.

    PubMed

    Wiese, Alexandra B; Berrocal, Veronica J; Furst, Daniel E; Seibold, James R; Merkel, Peter A; Mayes, Maureen D; Khanna, Dinesh

    2014-11-01

    Skin and musculoskeletal involvement are frequently present early in diffuse cutaneous systemic sclerosis (dcSSc). The current study examined the correlates for skin and musculoskeletal measures in a 1-year longitudinal observational study. Patients with dcSSc were recruited at 4 US centers and enrolled in a 1-year study. Prespecified and standardized measures included physician and patient assessments of skin involvement, modified Rodnan skin score (MRSS), durometer score, Health Assessment Questionnaire disability index, serum creatine phosphokinase, tender joint counts, and presence/absence of tendon friction rubs, small joint contractures, and large joint contractures. Additionally, physician and patient global health assessments and health-related quality of life assessments were recorded. Correlations were computed among the baseline global assessments, skin variables, and musculoskeletal variables. Using the followup physician and patient anchors, effect sizes were calculated. A total of 200 patients were studied: 75% were women, mean ± SD age was 50.0 ± 11.9 years, and mean ± SD disease duration from first non-Raynaud's phenomenon symptom was 1.6 ± 1.4 years. Physician global health assessment had large correlations with MRSS (r = 0.60) and physician-reported skin involvement visual analog scale in the last month (r = 0.74), whereas patient global assessment had large correlations with MRSS, the Short Form 36 health survey physical component scale, skin interference, and skin involvement in the last month (r = 0.37-0.72). Four of 9 skin variables had moderate to large effect sizes (0.51-1.09). Physician and patient global assessments have larger correlations with skin measures compared to musculoskeletal measures. From a clinical trial perspective, skin variables were more responsive to change than musculoskeletal variables over a 1-year period, although both provide complementary information. Copyright © 2014 by the American College of Rheumatology.

  7. [Early diffuse hypertrophic osteitis recurrence. Unexpected and consternating development after a large évidement cavity. Apropos of 15 cases].

    PubMed

    Fleury, P; Basset, J M; Candau, P; Bré, M; Despreaux, G; Fabre, A; Saliba, N

    1985-01-01

    The authors report 15 cases collected over a period of 13 years (1972 - 1984) of a particularly serious eventuality affecting certain evacuation cavities: Early recurrence of diffuse hypertrophic osteitis (E.R.D.H.O.). This is a rare complication, occurring in 1.5% of cases of chronic otitis. However, the fact of having operated upon 7 cases in 1984 alone, whilst during the previous 12 years, only 8 had been seen, raised the alarm. The classical pattern of this complication occurs in 3 stages, each involving surgical operation: at the outset, chronic otitis with cholesteatoma or osteitis, most often mixed, for which an "inadequate" surgical procedure is performed. then, after a variable period which may exceed 10 years, a very large evacuation cavity was created by the authors. finally, 3rd and final stage: within 6 months, this cavity filled progressively and, at operation, the authors discovered a cavity virtually completely filled with a "fantastic" "moist sugar" osteitis, requiring a new evacuation cavity, even larger than that created before. In all cases, a successful result was obtained within a varying period, sometimes accompanied by spectacular improvement in general condition. The most plausible etiopathogenic hypothesis advanced to attempt to explain this phenomenon is that of secondary infection by a varied microbial flora, including, on the one hand, aerobic organisms usually discovered in such cases (pseudomonas pyocyaneus, proteus mirabilis) and, secondly, this being of essential importance, "anaerobic" bacteria, the bacteriological diagnosis of which requires application of a strict protocol. The authors have taken three decisions following their bibliographic investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Diffusion of surgical techniques in early stage breast cancer: variables related to adoption and implementation of sentinel lymph node biopsy.

    PubMed

    Vanderveen, Kimberly A; Paterniti, Debora A; Kravitz, Richard L; Bold, Richard J

    2007-05-01

    Understanding how physicians acquire and adopt new technologies for cancer diagnosis and treatment is poorly understood, yet is critical to the dissemination of evidence-based practices. Sentinel lymph node biopsy (SLNB) has recently become a standard technique for axillary staging in early breast cancer and is an ideal platform for studying medical technology diffusion. We sought to describe the timing of SLNB adoption and patterns of surgeon interactions with the following educational sources: local university training program, surgical literature, national meetings/courses, national specialty centers, and other local surgeons. A cross-sectional survey that used semistructured interviews was used to assess timing of adoption, practice patterns, and learning sources for SLNB among surgical oncologists and general surgeons in a single metropolitan area. A total of 44 eligible surgeons were identified; 38 (86%) participated. All surgical oncologists (11 of 11) and most general surgeons (26 of 27) had implemented SLNB. Surgical oncologists were older (mean 51 vs. 48 years, P = .02) and had used SLNB longer (6.1 vs. 3.3 years, P = .01) than general surgeons. By use of social network diagrams, surgical oncologists and the university training program were shown to be key intermediaries between general surgeons and national specialty centers. Surgeons in group practice tended to use more learning sources than solo practitioners. Surgical oncologists and university-based surgeons play key educational roles in disseminating new cancer treatments and therefore have a professional responsibility to educate other community physicians to increase the use of the most current, evidence-based practices.

  9. Correlates and Responsiveness to Change of Measures of Skin and Musculoskeletal Disease in Early Diffuse Systemic Sclerosis

    PubMed Central

    Wiese, Alexandra B.; Berrocal, Veronica J.; Furst, Daniel E.; Seibold, James R.; Merkel, Peter A.; Mayes, Maureen D.; Khanna, Dinesh

    2015-01-01

    Objective Skin and musculoskeletal involvement are frequently present early in diffuse cutaneous systemic sclerosis (dcSSc). The current study examined the correlates for skin and musculoskeletal measures in a 1-year longitudinal observational study. Methods Patients with dcSSc were recruited at 4 US centers and enrolled in a 1-year study. Prespecified and standardized measures included physician and patient assessments of skin involvement, modified Rodnan skin score (MRSS), durometer score, Health Assessment Questionnaire disability index, serum creatine phosphokinase, tender joint counts, and presence/absence of tendon friction rubs, small joint contractures, and large joint contractures. Additionally, physician and patient global health assessments and health-related quality of life assessments were recorded. Correlations were computed among the baseline global assessments, skin variables, and musculoskeletal variables. Using the followup physician and patient anchors, effect sizes were calculated. Results A total of 200 patients were studied: 75% were women, mean ± SD age was 50.0 ± 11.9 years, and mean ± SD disease duration from first non–Raynaud’s phenomenon symptom was 1.6 ± 1.4 years. Physician global health assessment had large correlations with MRSS (r = 0.60) and physician-reported skin involvement visual analog scale in the last month (r = 0.74), whereas patient global assessment had large correlations with MRSS, the Short Form 36 health survey physical component scale, skin interference, and skin involvement in the last month (r = 0.37–0.72). Four of 9 skin variables had moderate to large effect sizes (0.51–1.09). Conclusion Physician and patient global assessments have larger correlations with skin measures compared to musculoskeletal measures. From a clinical trial perspective, skin variables were more responsive to change than musculoskeletal variables over a 1-year period, although both provide complementary information. PMID:24692361

  10. Comparison of CT perfusion summary maps to early diffusion-weighted images in suspected acute middle cerebral artery stroke.

    PubMed

    Benson, John; Payabvash, Seyedmehdi; Salazar, Pascal; Jagadeesan, Bharathi; Palmer, Christopher S; Truwit, Charles L; McKinney, Alexander M

    2015-04-01

    To assess the accuracy and reliability of one vendor's (Vital Images, Toshiba Medical, Minnetonka, MN) automated CT perfusion (CTP) summary maps in identification and volume estimation of infarcted tissue in patients with acute middle cerebral artery (MCA) distribution infarcts. From 1085 CTP examinations over 5.5 years, 43 diffusion-weighted imaging (DWI)-positive patients were included who underwent both CTP and DWI <12 h after symptom onset, with another 43 age-matched patients as controls (DWI-negative). Automated delay-corrected postprocessing software (DC-SVD) generated both infarct "core only" and "core+penumbra" CTP summary maps. Three reviewers independently tabulated Alberta Stroke Program Early CT scores (ASPECTS) of both CTP summary maps and coregistered DWI. Of 86 included patients, 36 had DWI infarct volumes ≤70 ml, 7 had volumes >70 ml, and 43 were negative; the automated CTP "core only" map correctly classified each as >70 ml or ≤70 ml, while the "core+penumbra" map misclassified 4 as >70 ml. There were strong correlations between DWI volume with both summary map-based volumes: "core only" (r=0.93), and "core+penumbra" (r=0.77) (both p<0.0001). Agreement between ASPECTS scores of infarct core on DWI with summary maps was 0.65-0.74 for "core only" map, and 0.61-0.65 for "core+penumbra" (both p<0.0001). Using DWI-based ASPECTS scores as the standard, the accuracy of the CTP-based maps were 79.1-86.0% for the "core only" map, and 83.7-88.4% for "core+penumbra." Automated CTP summary maps appear to be relatively accurate in both the detection of acute MCA distribution infarcts, and the discrimination of volumes using a 70 ml threshold. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Murine respiratory mycoplasmosis (MRM) in C57BL/6N and C3H/HeN mice: strain differences in early host responses and exacerbation by nitrogen dioxide

    SciT

    Parker, R.F.

    1987-01-01

    The studies reported here used genetic differences in susceptibility of C57BL/6N and C3H/HeN mice and exacerbation of the disease by nitrogen dioxide (NO/sub 2/) as tools in assessing the role of early host responses in the pathogenesis of MRM. The two strains did not differ in susceptibility to infection, but C3H/HeN mice were more susceptible to and had increased severity of lung lesions 14 days after intranasal inoculation as determined by 50% biological endpoints and morphometric analysis of tissues. Exposure to NO/sub 2/ for 4 hours prior to exposure to infectious aerosols exacerbated murine respiratory mycoplasmosis (MRM) by 7 daysmore » after exposure in both mouse strains. NO/sub 2/ appeared to affect host lung defense mechanisms responsible for limiting mycoplasmal growth in the lungs. The NO/sub 2/ exposure concentration required for this effect varied with the genetic background of the host, the dose of mycoplasmas administered, and the endpoint measured. Pulmonary clearance of radiolabeled M. pulmonis was determined in both mouse strains, and in C57BL/6N mice exposed to NO/sub 2/.« less

  12. Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy

    PubMed Central

    Rodríguez-Peña, Ana B.; Fuentes-Calvo, Isabel; Docherty, Neil G.; Arévalo, Miguel; Grande, María T.; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M.

    2014-01-01

    Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis. PMID:25101263

  13. Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy.

    PubMed

    Rodríguez-Peña, Ana B; Fuentes-Calvo, Isabel; Docherty, Neil G; Arévalo, Miguel; Grande, María T; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M

    2014-01-01

    Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.

  14. Effectiveness of diffusion tensor imaging in differentiating early-stage subcortical ischemic vascular disease, Alzheimer's disease and normal ageing.

    PubMed

    Tu, Min-Chien; Lo, Chung-Ping; Huang, Ching-Feng; Hsu, Yen-Hsuan; Huang, Wen-Hui; Deng, Jie Fu; Lee, Yung-Chuan

    2017-01-01

    To describe and compare diffusion tensor imaging (DTI) parameters between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance. Thirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC) subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations. Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA) and mean diffusivity (MD) values were performed. Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters. With regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB) compared to those with AD (p < 0.05) in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores. With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD. Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05), while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05). Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001) with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value of 73

  15. Commonly dysregulated genes in murine APL cells

    PubMed Central

    Yuan, Wenlin; Payton, Jacqueline E.; Holt, Matthew S.; Link, Daniel C.; Watson, Mark A.; DiPersio, John F.; Ley, Timothy J.

    2007-01-01

    To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial gene expression profiling studies were performed with primary murine hematopoietic progenitors that were induced to undergo myeloid maturation in vitro with G-CSF. Many genes were reproducibly expressed in restricted developmental “windows,” suggesting a structured hierarchy of expression that is relevant for the induction of developmental fates and/or differentiated cell functions. We compared the normal myeloid developmental transcriptome with that of APL cells derived from mice expressing PML-RARα under control of the murine cathepsin G locus. While many promyelocyte-specific genes were highly expressed in all APL samples, 116 genes were reproducibly dysregulated in many independent APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was expressed normally in preleukemic, early myeloid cells from the same mouse model, suggesting that dysregulation occurs as a “downstream” event during disease progression. These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis. PMID:17008535

  16. More insights into early brain development through statistical analyses of eigen-structural elements of diffusion tensor imaging using multivariate adaptive regression splines

    PubMed Central

    Chen, Yasheng; Zhu, Hongtu; An, Hongyu; Armao, Diane; Shen, Dinggang; Gilmore, John H.; Lin, Weili

    2013-01-01

    The aim of this study was to characterize the maturational changes of the three eigenvalues (λ1 ≥ λ2 ≥ λ3) of diffusion tensor imaging (DTI) during early postnatal life for more insights into early brain development. In order to overcome the limitations of using presumed growth trajectories for regression analysis, we employed Multivariate Adaptive Regression Splines (MARS) to derive data-driven growth trajectories for the three eigenvalues. We further employed Generalized Estimating Equations (GEE) to carry out statistical inferences on the growth trajectories obtained with MARS. With a total of 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects, we found that the growth velocities of the three eigenvalues were highly correlated, but significantly different from each other. This paradox suggested the existence of mechanisms coordinating the maturations of the three eigenvalues even though different physiological origins may be responsible for their temporal evolutions. Furthermore, our results revealed the limitations of using the average of λ2 and λ3 as the radial diffusivity in interpreting DTI findings during early brain development because these two eigenvalues had significantly different growth velocities even in central white matter. In addition, based upon the three eigenvalues, we have documented the growth trajectory differences between central and peripheral white matter, between anterior and posterior limbs of internal capsule, and between inferior and superior longitudinal fasciculus. Taken together, we have demonstrated that more insights into early brain maturation can be gained through analyzing eigen-structural elements of DTI. PMID:23455648

  17. Histogram analysis of apparent diffusion coefficient for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

    PubMed

    Meng, Jie; Zhu, Lijing; Zhu, Li; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

    2017-11-01

    Background Apparent diffusion coefficient (ADC) histogram analysis has been widely used in determining tumor prognosis. Purpose To investigate the dynamic changes of ADC histogram parameters during concurrent chemo-radiotherapy (CCRT) in patients with advanced cervical cancers. Material and Methods This prospective study enrolled 32 patients with advanced cervical cancers undergoing CCRT who received diffusion-weighted (DW) magnetic resonance imaging (MRI) before CCRT, at the end of the second and fourth week during CCRT and one month after CCRT completion. The ADC histogram for the entire tumor volume was generated, and a series of histogram parameters was obtained. Dynamic changes of those parameters in cervical cancers were investigated as early biomarkers for treatment response. Results All histogram parameters except AUC low showed significant changes during CCRT (all P < 0.05). There were three variable trends involving different parameters. The mode, 5th, 10th, and 25th percentiles showed similar early increase rates (33.33%, 33.99%, 34.12%, and 30.49%, respectively) at the end of the second week of CCRT. The pre-CCRT 5th and 25th percentiles of the complete response (CR) group were significantly lower than those of the partial response (PR) group. Conclusion A series of ADC histogram parameters of cervical cancers changed significantly at the early stage of CCRT, indicating their potential in monitoring early tumor response to therapy.

  18. Early low-grade gastric MALToma rarely transforms into diffuse large cell lymphoma or progresses beyond the stomach and regional lymph nodes.

    PubMed

    Liu, Ting-Yun; Dei, Pei-Han; Kuo, Sung-Hsin; Lin, Chung-Wu

    2010-06-01

    Gastric mucosa-associated lymphoid tissue lymphoma (MALToma) usually presents at an early stage involving only the stomach and/or regional lymph nodes. Although a sequential transformation from low-grade gastric MALToma (GM) to high-grade GM to secondary diffuse large B-cell lymphoma (DLBCL) is commonly assumed, documented cases of transformation are rare. We aim to determine the frequency of transformation. We identified 55 early low-grade GMs, 18 early high-grade GMs, and 13 advanced GMs at the National Taiwan University Hospital from 1995 to 2005. The median follow-up time was 59 months. We found that only one early low-grade GM and two early high-grade GMs transformed into secondary DLBCLs and progressed outside the stomach and regional lymph nodes. Significantly, we identified 13 low-grade GMs that were refractory to Helicobacter eradication therapy or relapsed after initial response. All 13 cases had been followed-up for at least 3 years without development of secondary DLBCLs. The frequency of transformation for early low-grade GM was less than 2% (1/55). Although two lymphoma-unrelated mortalities were identified, none of the 55 patients with early-low grade GMs died of the disease. Compared with chronic lymphocytic leukemia, which has a 16% transformation rate and a median transformation time of 24 months, we conclude that early low-grade GM rarely transforms into secondary DLBCL or progresses beyond the stomach. Without transformation or progression, patients with early low-grade GM rarely die of the disease and should be treated conservatively. Copyright (c) 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

  19. Apparent diffusion coefficient histogram shape analysis for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

    PubMed

    Meng, Jie; Zhu, Lijing; Zhu, Li; Wang, Huanhuan; Liu, Song; Yan, Jing; Liu, Baorui; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

    2016-10-22

    To explore the role of apparent diffusion coefficient (ADC) histogram shape related parameters in early assessment of treatment response during the concurrent chemo-radiotherapy (CCRT) course of advanced cervical cancers. This prospective study was approved by the local ethics committee and informed consent was obtained from all patients. Thirty-two patients with advanced cervical squamous cell carcinomas underwent diffusion weighted magnetic resonance imaging (b values, 0 and 800 s/mm 2 ) before CCRT, at the end of 2nd and 4th week during CCRT and immediately after CCRT completion. Whole lesion ADC histogram analysis generated several histogram shape related parameters including skewness, kurtosis, s-sD av , width, standard deviation, as well as first-order entropy and second-order entropies. The averaged ADC histograms of 32 patients were generated to visually observe dynamic changes of the histogram shape following CCRT. All parameters except width and standard deviation showed significant changes during CCRT (all P < 0.05), and their variation trends fell into four different patterns. Skewness and kurtosis both showed high early decline rate (43.10 %, 48.29 %) at the end of 2nd week of CCRT. All entropies kept decreasing significantly since 2 weeks after CCRT initiated. The shape of averaged ADC histogram also changed obviously following CCRT. ADC histogram shape analysis held the potential in monitoring early tumor response in patients with advanced cervical cancers undergoing CCRT.

  20. Pathological analysis of the Candida albicans-infected tongue tissues of a murine oral candidiasis model in the early infection stage.

    PubMed

    Okada, Masashi; Hisajima, Tatsuya; Ishibashi, Hiroko; Miyasaka, Takahiro; Abe, Shigeru; Satoh, Tazuko

    2013-04-01

    The early pathological process of Candida infection and immunological responses in tongues of the mice with experimental oral candidiasis was analysed. CD-1 mice, pretreated by prednisolone were orally inoculated with Candida albicans. Symptoms were monitored by measuring the area of white tongue coating and number of viable Candida cells in oral cavity. The histopathological analysis was carried by PAS-stain and immunofluorescent staining. IL-4, IL-12p70, IFN-γ, TNF-α in recovered from the homogenates of the tongues were measured by ELISA. The fungus invaded the tongue surface of the mice and white patches developed within 24h after inoculation. Histopathological examination indicated the presence of local acute inflammation in superficial tissues of tongues covered by mycelium of C. albicans. Pathological exacerbation was observed from 24 to 48 h after the inoculation and from then the symptoms of oral candidiasis appeared to move into the recovery phase. Inflammatory cells mainly consisting of neutrophils was accumulated and located under the lesions covered by Candida-hyphae. An increase in IL-12p70 and IFN-γ in tongue homogenates was observed at 48 h after inoculation. The worst condition in the pathological process in experimental oral candidiasis was found 48 h after C. albicans inoculation. When the surface of the Candida-inoculated tongues was covered with Candida-hyphae, a dense accumulation of neutrophils was observed under the lesions and homogenates of the tongues contained increased levels of IL-12p70 and IFN-γ. These suggested that local pathological condition of Candida-infected tongues may be affected by neutrophils accumulation and increased levels of some cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

    SciT

    Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian

    Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating verymore » good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.« less

  2. Achieving Quality Early Childhood Education for All: Insights from the Policy Innovation Diffusion Research. Working Paper Series.

    ERIC Educational Resources Information Center

    Mintrom, Michael

    Based on the view that major changes in the social and economic context in the United States require major policy changes related to early childhood education, this paper examines the factors supporting public policy changes and how advocates for change in early childhood education might incorporate effective strategies. The paper is presented in…

  3. Simulation of the early startup period of high-temperature heat pipes from the frozen state by a rarefied vapor self-diffusion model

    NASA Technical Reports Server (NTRS)

    Cao, Y.; Faghri, A.

    1993-01-01

    The heat pipe startup process is described physically and is divided into five periods for convenience of analysis. The literature survey revealed that none of the previous attempts to simulate the heat pipe startup process numerically were successful, since the rarefied vapor flow in the heat pipe was not considered. Therefore, a rarefied vapor self-diffusion model is proposed, and the early startup periods, in which the rarefied vapor flow is dominant within the heat pipe, are first simulated numerically. The numerical results show that large vapor density gradients existed along the heat pipe length, and the vapor flow reaches supersonic velocities when the density is extremely low. The numerical results are compared with the experimental data of the early startup period with good agreement.

  4. Utility of intravoxel incoherent motion diffusion-weighted imaging in predicting early response to concurrent chemoradiotherapy in oesophageal squamous cell carcinoma.

    PubMed

    Li, F P; Wang, H; Hou, J; Tang, J; Lu, Q; Wang, L L; Yu, X P

    2018-05-03

    To investigate the utility of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in predicting the early response to concurrent chemoradiotherapy (CRT) in oesophageal squamous cell carcinoma (OSCC). Thirty-three patients with OSCC who received CRT underwent IVIM-DWI at three time points (before CRT, at the end of radiotherapy 20 Gy, and immediately after CRT). After CRT, the patients were divided into the responders (complete response or partial response) and the non-responders (stable disease) based on RECIST 1.1. The IVIM-DWI parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], the pseudo-diffusion coefficient [D*], and the perfusion fraction [f]) values and their percentage changes (Δvalue) at different time points were compared between the responders and the non-responders. Receiver-operating characteristic (ROC) curve analysis was used to determine the efficacy of IVIM-DWI parameters in identifying the response to CRT. The tumour regression ratio showed negative correlations with ADC pre (r=-0.610, p=0.000), ADC 20 Gy (r=-0.518, p=0.002), D pre (r=-0.584, p=0.000), and D 20 Gy (r=-0.454, p=0.008), and positive correlation with ΔD 20 Gy (r=0.361, p=0.039) and ΔD post (r=0.626, p=0.000). Compared to the non-responders, the responders exhibited lower ADC pre , D pre , ADC 20 Gy , and D 20 Gy , as well as higher ΔADC 20 Gy , ΔD 20 Gy , and ΔD post (all p<0.05). D pre had the highest sensitivity (92.9%) and value of area under the ROC curve (0.865) in differentiating the responders from the non-responders. Diffusion-related IVIM-DWI parameters (ADC and D) are potentially helpful in predicting the early treatment effect of CRT in OSCC. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  5. Contrast-enhanced dynamic and diffusion-weighted magnetic resonance imaging at 3.0 T to assess early-stage nasopharyngeal carcinoma.

    PubMed

    Ni, Liangping; Liu, Ying

    2018-04-01

    The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant ( K trans ), flux rate constant between extravascular extracellular space and plasma ( K ep ), the volume of extravascular extracellular space per unit volume of tissue ( V e ) and the apparent diffusion coefficient (ADC) of tumours were investigated. Furthermore, the correlation between clinical stages and ADC value and K trans were analysed. The diagnostic accuracy of K trans and ADC were estimated using receiver operating characteristic curves. NPC stage correlated positively with K trans and negatively with ADC values. Additionally, tumour K trans negatively correlated with ADC value. The sensitivity and accuracy of combined K trans and ADC in distinguishing between stage II and stage III and stage III and IV were higher than the values of either measurement used separately. The present study suggested that K trans and ADC derived from DCE-MRI and DWI may be useful to detect stage early NPC accurately. K trans and ADC in combination were superior than either alone.

  6. Early Results of Coronary Endarterectomy Combined with Coronary Artery Bypass Grafting in Patients with Diffused Coronary Artery Disease

    PubMed Central

    Chi, Li-Qun; Zhang, Jian-Qun; Kong, Qing-Yu; Xiao, Wei; Liang, Lin; Chen, Xin-Liang

    2015-01-01

    Background: It is still a challenge for the cardiac surgeons to achieve adequate revascularization for diffused coronary artery disease (CAD). Coronary endarterectomy (CE) offers an alternative choice of coronary artery reconstruction and revascularization. In this study, short-term result of CE combined with coronary artery bypass graft (CABG) was discussed in the treatment for the diffused CAD. Methods: From January 2012 to April 2014, 221 cases of CABG were performed by the same surgeon in our unit. Among these cases, 38 cases of CE + CABG were performed, which was about 17.2% (38/221) of the cohort. All these patients were divided into two groups: CE + CABG group (Group A) and CABG alone group (Group B). All clinical data were compared between the two groups, and postoperative complications and in-hospital mortality were analyzed. The categorical and continuous variables were analyzed by Chi-square test and Student's t-test respectively. Results: Diabetes mellitus, hypertension, hyperlipidemia, and peripheral vascular disease were more common in group A. In this cohort, a total of 50 vessels were endarterectomized. Among them, CE was performed on left anterior descending artery in 11 cases, on right coronary artery in 29 cases, on diagonal artery in 3 cases, on intermediate artery in 2 cases, on obtuse marginal artery in 5 cases. There was no hospital mortality in both groups. The intro-aortic balloon pump was required in 3 cases in Group A (3/38), which was more often than that in Group B (3/183). At the time of follow-up, coronary computed tomography angiogram showed all the grafts with CE were patent (50/50). There is no cardio-related mortality in both groups. All these patients were free from coronary re-intervention. Conclusions: Coronary endarterectomy + CABG can offer satisfactory result for patients with diffused CAD in a short-term after the operation. PMID:26021501

  7. Diffusion Tensor Imaging Parameters in Mild Traumatic Brain Injury and Its Correlation with Early Neuropsychological Impairment: A Longitudinal Study.

    PubMed

    Veeramuthu, Vigneswaran; Narayanan, Vairavan; Kuo, Tan Li; Delano-Wood, Lisa; Chinna, Karuthan; Bondi, Mark William; Waran, Vicknes; Ganesan, Dharmendra; Ramli, Norlisah

    2015-10-01

    We explored the prognostic value of diffusion tensor imaging (DTI) parameters of selected white matter (WM) tracts in predicting neuropsychological outcome, both at baseline and 6 months later, among well-characterized patients diagnosed with mild traumatic brain injury (mTBI). Sixty-one patients with mTBI (mean age=27.08; standard deviation [SD], 8.55) underwent scanning at an average of 10 h (SD, 4.26) post-trauma along with assessment of their neuropsychological performance at an average of 4.35 h (SD, 7.08) upon full Glasgow Coma Scale recovery. Results were then compared to 19 healthy control participants (mean age=29.05; SD, 5.84), both in the acute stage and 6 months post-trauma. DTI and neuropsychological measures between acute and chronic phases were compared, and significant differences emerged. Specifically, chronic-phase fractional anisotropy and radial diffusivity values showed significant group differences in the corona radiata, anterior limb of internal capsule, cingulum, superior longitudinal fasciculus, optic radiation, and genu of corpus callosum. Findings also demonstrated associations between DTI indices and neuropsychological outcome across two time points. Our results provide new evidence for the use of DTI as an imaging biomarker and indicator of WM damage occurring in the context of mTBI, and they underscore the dynamic nature of brain injury and possible biological basis of chronic neurocognitive alterations.

  8. Utility of the PET-CT in the evaluation of early response to treatment in the diffuse large B-cell lymphoma. Preliminary results.

    PubMed

    Cortés Romera, M; Gámez Cenzano, C; Caresia Aróztegui, A P; Martín-Comín, J; González-Barca, E; Ricart Brulles, Y; Palacios Abufón, A; Robles Barba, J; Rodríguez-Bel, L; Rossi Seoane, S; Fernández de Sevilla, A

    2012-01-01

    To assess the role of FDG-PET/CT performed after the first cycles of chemotherapy in the prediction of response to treatment in patients with diffuse large B-cell lymphoma. Twenty patients (mean age: 48 years) were included, 16 initial staging and 4 relapse. All patients underwent PET/CT at 3 times: 1) Baseline, 2) After 1-3 cycles of chemotherapy (early response assessment), and 3) End of treatment (evaluation of final response). Early PET/CT findings were correlated to the end-treatment PET/CT and follow-up. The evaluation of the response was established according to the decrease in uptake of the lesions (SUVmax). In the early assessment, a good response indicator (GRI) was obtained when the lesion disappeared or had more than 50% reduction in SUVmax. At the end of the treatment, a complete metabolic response (CMR) was determined in negative PET scans. Follow-up was superior to 19 months and final outcome was established as progression/relapse or no evidence of disease (NED). At the early treatment evaluation, 16/16 patients of initial staging (100%) and 2/4 of relapse (50%) achieved GRI. At the end of treatment evaluation, 14/16 patients of initial staging with GRI achieved CMR and 1/16 PMR: 14 were alive with NED in the follow-up while 1 relapsed. In the second group, 2/2 patients with GRI achieved CMR (100%): 1 continued with NED in the follow-up and another relapsed. FDG-PET/CT after the first cycles of chemotherapy is useful to monitor treatment due to its high negative predictive value (87.5%), using it to modify treatment early in the non-responders. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

  9. Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method

    SciT

    Rundle-Thiele, Dayle; Day, Bryan; Stringer, Brett

    Accurate knowledge of O{sup 6}-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC. We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC withinmore » contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods. A strong trend between a measure of ‘minimum ADC’ and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the ‘low ADC’ component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246). This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.« less

  10. Disparities in the early adoption of chemo-immunotherapy for diffuse large B-cell lymphoma in the United States

    PubMed Central

    Flowers, Christopher R.; Fedewa, Stacey A.; Chen, Amy Y.; Nastoupil, Loretta J; Lipscomb, Joseph; Brawley, Otis W.; Ward, Elizabeth M.

    2014-01-01

    Background Since the 1970s, CHOP chemotherapy has been the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). In 2002, randomized trials changed this standard by demonstrating that adding rituximab immunotherapy to CHOP improved survival. However, how these results influenced chemo-immunotherapy adoption in clinical practice remains unclear. Methods Using the National Cancer Database to compare chemo-immunotherapy use with chemotherapy alone, we collected data on demographics, stage, health insurance, area-level socio-economic status (SES), facility characteristics, and type of treatment for DLBCL patients diagnosed in the United States 2001-2004. Multivariable log binomial models examined associations between race, insurance, and treatment allocation, adjusting for covariates. Results Among 38,002 patients with DLBCL, 27% received chemo-immunotherapy and 50% chemotherapy alone. Patients who had localized disease, were diagnosed in 2001, black, uninsured/Medicaid insured, or lower SES were less likely to receive any form of chemotherapy (all p<0.0001). Patients who were diagnosed 2001, black [relative risk (RR) 0.83, 95% Confidence Interval (CI) 0.78-0.89], >60 years (RR 0.94, 95% CI 0.90-0.98), or had localized disease (RR 0.89, 95% CI 0.86-0.92) were less likely to receive chemo-immunotherapy. Receiving treatment at high DLBCL volume teaching/research facilities was associated with the greatest likelihood of chemo-immunotherapy (RR 1.69, 95% CI 1.52-1.89). Conclusions Black DLBCL patients were less likely to receive chemotherapy or chemo-immunotherapy during this period. Impact This large national cohort study demonstrates disparities in the diffusion of chemo-immunotherapy for DLBCL. Improving DLBCL outcomes will require efforts to extend access to proven advances in therapy to all segments of the population. PMID:22771484

  11. DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery) Mismatch in Thrombectomy Candidates: An Intrarater and Interrater Agreement Study.

    PubMed

    Fahed, Robert; Lecler, Augustin; Sabben, Candice; Khoury, Naim; Ducroux, Célina; Chalumeau, Vanessa; Botta, Daniele; Kalsoum, Erwah; Boisseau, William; Duron, Loïc; Cabral, Dominique; Koskas, Patricia; Benaïssa, Azzedine; Koulakian, Hasmik; Obadia, Michael; Maïer, Benjamin; Weisenburger-Lile, David; Lapergue, Bertrand; Wang, Adrien; Redjem, Hocine; Ciccio, Gabriele; Smajda, Stanislas; Desilles, Jean-Philippe; Mazighi, Mikaël; Ben Maacha, Malek; Akkari, Inès; Zuber, Kevin; Blanc, Raphaël; Raymond, Jean; Piotin, Michel

    2018-01-01

    We aimed to study the intrarater and interrater agreement of clinicians attributing DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery) mismatch in patients with acute ischemic stroke referred for mechanical thrombectomy. Eighteen raters independently scored anonymized magnetic resonance imaging scans of 30 participants from a multicentre thrombectomy trial, in 2 different reading sessions. Agreement was measured using Fleiss κ and Cohen κ statistics. Interrater agreement for DWI-ASPECTS was slight (κ=0.17 [0.14-0.21]). Four raters (22.2%) had a substantial (or higher) intrarater agreement. Dichotomization of the DWI-ASPECTS (0-5 versus 6-10 or 0-6 versus 7-10) increased the interrater agreement to a substantial level (κ=0.62 [0.48-0.75] and 0.68 [0.55-0.79], respectively) and more raters reached a substantial (or higher) intrarater agreement (17/18 raters [94.4%]). Interrater agreement for DWI-FLAIR mismatch was moderate (κ=0.43 [0.33-0.57]); 11 raters (61.1%) reached a substantial (or higher) intrarater agreement. Agreement between clinicians assessing DWI-ASPECTS and DWI-FLAIR mismatch may not be sufficient to make repeatable clinical decisions in mechanical thrombectomy. The dichotomization of the DWI-ASPECTS (0-5 versus 0-6 or 0-6 versus 7-10) improved interrater and intrarater agreement, however, its relevance for patients selection for mechanical thrombectomy needs to be validated in a randomized trial. © 2017 American Heart Association, Inc.

  12. Early Therapy Evaluation of Combined Anti-DR5 Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts by Diffusion Weighted Magnetic Resonance Imaging

    PubMed Central

    Kim, Hyunki; Morgan, Desiree E.; Buchsbaum, Donald J.; Zeng, Huadong; Grizzle, William E.; Warram, Jason M.; Stockard, Cecil R.; McNally, Lacey R.; Long, Joshua W.; Sellers, Jeffrey C.; Forero, Andres; Zinn, Kurt R.

    2008-01-01

    Early therapeutic efficacy of anti-DR5 antibody (TRA-8) combined with gemcitabine was measured using diffusion-weighted magnetic resonance imaging (DWI) in an orthotopic pancreatic tumor model. Groups 1–4 of SCID mice (n=5–7/group) bearing orthotopically implanted, luciferase-positive human pancreatic tumors (MIA PaCa-2) were subsequently (4–5 weeks thereafter) injected with saline (control), gemcitabine (120mg/kg), TRA-8 (200μg), or TRA-8 combined with gemcitabine, respectively, on day 0. DWI, anatomical MRI, and bioluminescence imaging were performed on days 0, 1, 2, and 3 after treatment. Three tumors from each group were collected randomly on day 3 after imaging, and TUNEL staining was performed to quantify apoptotic cellularity. At just 1 day after starting therapy, the changes of apparent diffusion coefficient (ADC) in tumor regions for groups 3 (TRA-8) and 4 (TRA-8/Gem) were 21±9% (mean±SE) and 27±3%, respectively, significantly higher (p <0.05) than those of groups 1 (−1±5%) and 2 (−2±4%). There was no statistical difference in tumor volumes for the groups at this time. The mean ADC values of groups 2–4 gradually increased over 3 days, which were concurrent with tumor-volume regressions and bioluminescence-signal decreases. Apoptotic-cell densities of tumors in groups 1–4 were 0.7±0.4%, 0.6±0.2%, 3.1±0.9%, and 4.7±1.0%, respectively, linearly proportional to the ADC changes on day 1. Further, the ADC changes were highly correlated with the previously reported mean survival times of animals treated with the same agents and doses. This study supports the clinical use of DWI for pancreatic tumor patients for early assessment of drug efficacy. PMID:18922909

  13. Early detection of secondary damage in ipsilateral thalamus after acute infarction at unilateral corona radiata by diffusion tensor imaging and magnetic resonance spectroscopy

    PubMed Central

    2011-01-01

    Background Traditional magnetic resonance (MR) imaging can identify abnormal changes in ipsilateral thalamus in patients with unilateral middle cerebral artery (MCA) infarcts. However, it is difficult to demonstrate these early changes quantitatively. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (MRS) are potentially sensitive and quantitative methods of detection in examining changes of tissue microstructure and metabolism. In this study, We used both DTI and MRS to examine possible secondary damage of thalamus in patients with corona radiata infarction. Methods Twelve patients with unilateral corona radiata infarction underwent MR imaging including DTI and MRS at one week (W1), four weeks (W4), and twelve weeks (W12) after onset of stroke. Twelve age-matched controls were imaged. Mean diffusivity (MD), fractional anisotropy (FA), N-acetylaspartate (NAA), choline(Cho), and creatine(Cr) were measured in thalami. Results T1-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted, and T2-FLAIR imaging showed an infarct at unilateral corona radiate but no other lesion in each patient brain. In patients, MD was significantly increased at W12, compared to W1 and W4 (all P< 0.05). NAA was significantly decreased at W4 compared to W1, and at W12 compared to W4 (all P< 0.05) in the ipsilateral thalamus. There was no significant change in FA, Cho, or Cr in the ipsilateral thalamus from W1 to W12. Spearman's rank correlation analysis revealed a significant negative correlation between MD and the peak area of NAA, Cho, and Cr at W1, W4, and W12 and a significant positive correlation of FA with NAA at W1. Conclusions These findings indicate that DTI and MRS can detect the early changes indicating secondary damage in the ipsilateral thalamus after unilateral corona radiata infarction. MRS may reveal the progressive course of damage in the ipsilateral thalamus over time. PMID:21542942

  14. Early changes in the apparent diffusion coefficient and MMP-9 expression of a cervical carcinoma U14 allograft model following irradiation.

    PubMed

    Huang, Yecai; Huang, Jianming; Feng, Mei; Ren, Jing; Mi, Kun; Cheng, Jia; Song, Bing; Lang, Jinyi

    2017-12-01

    A cervical carcinoma allograft model was designed to assess the correlation between early changes in the apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance imaging (DW-MRI) and the expression of matrix metalloproteinase-9 (MMP-9) in tumors. BALB/c mice with U14 tumor allografts on the right rear flank were irradiated with a single 20 Gy dose. All tumor-bearing mice were subjected to DW-MRI, followed by calculation of the ADC values and characterization of the T1 and T2 relaxation time constants. Pre- and post-irradiation ADC values were compared with the tumor volume, and the immunohistochemical staining of MMP-9 and hematoxylin-eosin (HE) staining of tumor allografts. However, no correlations between the pre-treatment ADC values and changes in tumor volumes following irradiation were observed. Notably, the mean ADC value was significantly higher in the irradiated tumors (0.756±0.102×10 -3 mm 2 /sec) as compared with those in the untreated tumors (0.501±0.052×10 -3 mm 2 /sec; P=0.002; r=0.682). Additionally, immunohistochemical staining demonstrated that MMP-9 expression in the irradiated tumors was significantly increased. The mean ADC value was significantly higher in the irradiated tumors with high MMP-9 expression levels (0.815±0.112×10 -3 mm 2 /sec), as compared with in the untreated tumors with low MMP-9 expression levels (0.631±0.068×10 -3 mm 2 /sec). Quantitative analysis determined that the ADC values were correlated with MMP-9 expression (r=0.752; P=0.003). Combined, these results suggest that radiation-induced increases in MMP-9 expression levels may be responsible for early changes in the mean ADC value and the response to irradiation in cervical carcinoma.

  15. Early Detection of Ventilation-Induced Brain Injury Using Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: An In Vivo Study in Preterm Lambs

    PubMed Central

    Skiöld, Béatrice; Wu, Qizhu; Hooper, Stuart B.; Davis, Peter G.; McIntyre, Richard; Tolcos, Mary; Pearson, James; Vreys, Ruth; Egan, Gary F.; Barton, Samantha K.; Cheong, Jeanie L. Y.; Polglase, Graeme R.

    2014-01-01

    Background and Aim High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs. Methods Newborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations. Results No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups. Conclusion Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is

  16. Prevalence and impact of diffuse axonal injury in patients with moderate and severe head injury: a cohort study of early magnetic resonance imaging findings and 1-year outcome.

    PubMed

    Skandsen, Toril; Kvistad, Kjell Arne; Solheim, Ole; Strand, Ingrid Haavde; Folvik, Mari; Vik, Anne

    2010-09-01

    In this prospective cohort study the authors examined patients with moderate to severe head injuries using MR imaging in the early phase. The objective was to explore the occurrence of diffuse axonal injury (DAI) and determine whether DAI was related to level of consciousness and patient outcome. One hundred and fifty-nine patients (age range 5-65 years) with traumatic brain injury, who survived the acute phase, and who had a Glasgow Coma Scale (GCS) score of 3-13 were admitted between October 2004 and August 2008. Of these 159 patients, 106 were examined using MR imaging within 4 weeks postinjury. Patients were classified into 1 of 3 stages of DAI: Stage 1, in which lesions were confined to the lobar white matter; Stage 2, in which there were callosal lesions; and Stage 3, in which lesions occurred in the dorsolateral brainstem. The outcome measure used 12 months postinjury was the Glasgow Outcome Scale-Extended (GOSE). Diffuse axonal injury was detected in 72% of the patients and a combination of DAI and contusions or hematomas was found in 50%. The GCS score was significantly lower in patients with "pure DAI" (median GCS Score 9) than in patients without DAI (median GCS Score 12; p < 0.001). The GCS score was related to outcome only in those patients with DAI (r = 0.47; p = 0.001). Patients with DAI had a median GOSE score of 7, and patients without DAI had a median GOSE score of 8 (p = 0.10). Outcome was better in patients with DAI Stage 1 (median GOSE Score 8) and DAI Stage 2 (median GOSE Score 7.5) than in patients with DAI Stage 3 (median GOSE Score 4; p < 0.001). Thus, in patients without any brainstem injury, there was no difference in good recovery between patients with DAI (67%) and patients without DAI (66%). Diffuse axonal injury was found in almost three-quarters of the patients with moderate and severe head injury who survived the acute phase. Diffuse axonal injury influenced the level of consciousness, and only in patients with DAI was GCS score

  17. A comparative study of the sensitivity of diffusion-related parameters obtained from diffusion tensor imaging, diffusional kurtosis imaging, q-space analysis and bi-exponential modelling in the early disease course (24 h) of hyperacute (6 h) ischemic stroke patients.

    PubMed

    Duchêne, Gaëtan; Peeters, Frank; Peeters, André; Duprez, Thierry

    2017-08-01

    To compare the sensitivity and early temporal changes of diffusion parameters obtained from diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), q-space analysis (QSA) and bi-exponential modelling in hyperacute stroke patients. A single investigational acquisition allowing the four diffusion analyses was performed on seven hyperacute stroke patients with a 3T system. The percentage change between ipsi- and contralateral regions were compared at admission and 24 h later. Two out of the seven patients were imaged every 6 h during this period. Kurtoses from both DKI and QSA were the most sensitive of the tested diffusion parameters in the few hours following ischemia. An early increase-maximum-decrease pattern of evolution was highlighted during the 24-h period for all parameters proportional to diffusion coefficients. A similar pattern was observed for both kurtoses in only one of two patients. Our comparison was performed using identical diffusion encoding timings and on patients in the same stage of their condition. Although preliminary, our findings confirm those of previous studies that showed enhanced sensitivity of kurtosis. A fine time mapping of diffusion metrics in hyperacute stroke patients was presented which advocates for further investigations on larger animal or human cohorts.

  18. The usefulness of diffusion-weighted magnetic resonance imaging performed in the acute phase as an early predictor of delayed neuropsychiatric sequelae in acute carbon monoxide poisoning.

    PubMed

    Kim, Y S; Cha, Y S; Kim, M S; Kim, H J; Lee, Y S; Youk, H; Kim, H I; Kim, O H; Cha, K-C; Kim, H; Lee, K H; Hwang, S O

    2018-06-01

    Delayed onset of neuropsychiatric symptoms after apparent recovery from acute carbon monoxide (CO) poisoning has been described as delayed neuropsychiatric sequelae (DNS). No previous study has determined whether early use of diffusion-weighted magnetic resonance imaging (DWI) can predict which patients will develop DNS in the acute CO poisoning. This retrospective observational study was performed on adult patients with acute CO poisoning consecutively treated over a 17-month period. All included patients with acute CO poisoning underwent DWI to evaluate brain injury within 72 h after CO exposure. DWI was evaluated as follows: (1) presence of pathology, (2) number of pathologies, (3) asymmetry, and (4) location of pathology. Patients were divided into two groups. The DNS group was composed of patients with delayed sequelae, while the non-DNS group included patients with no sequelae. A total of 102 patients with acute CO poisoning were finally enrolled in this study. DNS developed in 10 patients (9.8%). Between the DNS group and the non-DNS group, presence of pathology on DWI and initial Glasgow Coma Scale (GCS) showed significant difference. There was also a statistical difference between the non-DNS group and DNS group in terms of CO exposure time, troponin I, rhabdomyolysis, acute kidney injury, and pneumonia. The presence of pathology in DWI and initial GCS (cutoff: <12) at the emergency department served as an early predictors of DNS.

  19. Diffusion tractography and graph theory analysis reveal the disrupted rich-club organization of white matter structural networks in early Tourette Syndrome children

    NASA Astrophysics Data System (ADS)

    Wen, Hongwei; Liu, Yue; Wang, Shengpei; Zhang, Jishui; Peng, Yun; He, Huiguang

    2017-03-01

    Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. At present, the topological disruptions of the whole brain white matter (WM) structural networks remain poorly understood in TS children. Considering the unique position of the topologically central role of densely interconnected brain hubs, namely the rich club regions, therefore, we aimed to investigate whether the rich club regions and their related connections would be particularly vulnerable in early TS children. In our study, we used diffusion tractography and graph theoretical analyses to explore the rich club structures in 44 TS children and 48 healthy children. The structural networks of TS children exhibited significantly increased normalized rich club coefficient, suggesting that TS is characterized by increased structural integrity of this centrally embedded rich club backbone, potentially resulting in increased global communication capacity. In addition, TS children showed a reorganization of rich club regions, as well as significantly increased density and decreased number in feeder connections. Furthermore, the increased rich club coefficients and feeder connections density of TS children were significantly positively correlated to tic severity, indicating that TS may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher bridging with non-rich club regions, which may increase the integration among tic-related brain circuits with more excitability but less inhibition for information exchanges between highly centered brain regions and peripheral areas. In all, our results suggest the disrupted rich club organization in early TS children and provide structural insights into the brain networks.

  20. Functional characterization of cell hybrids generated by induced fusion of primary porcine mesenchymal stem cells with an immortal murine cell line.

    PubMed

    Islam, M Q; Ringe, J; Reichmann, E; Migotti, R; Sittinger, M; da S Meirelles, L; Nardi, N B; Magnusson, P; Islam, K

    2006-10-01

    Bone marrow mesenchymal stem cells (MSC) integrate into various organs and contribute to the regeneration of diverse tissues. However, the mechanistic basis of the plasticity of MSC is not fully understood. The change of cell fate has been suggested to occur through cell fusion. We have generated hybrid cell lines by polyethylene-glycol-mediated cell fusion of primary porcine MSC with the immortal murine fibroblast cell line F7, a derivative of the GM05267 cell line. The hybrid cell lines display fibroblastic morphology and proliferate like immortal cells. They contain tetraploid to hexaploid porcine chromosomes accompanied by hypo-diploid murine chromosomes. Interestingly, many hybrid cell lines also express high levels of tissue-nonspecific alkaline phosphatase, which is considered to be a marker of undifferentiated embryonic stem cells. All tested hybrid cell lines retain osteogenic differentiation, a few of them also retain adipogenic potential, but none retain chondrogenic differentiation. Conditioned media from hybrid cells enhance the proliferation of both early-passage and late-passage porcine MSC, indicating that the hybrid cells secrete diffusible growth stimulatory factors. Murine F7 cells thus have the unique property of generating immortal cell hybrids containing unusually high numbers of chromosomes derived from normal cells. These hybrid cells can be employed in various studies to improve our understanding of regenerative biology. This is the first report, to our knowledge, describing the generation of experimentally induced cell hybrids by using normal primary MSC.

  1. Analysis of cardiomyocyte movement in the developing murine heart

    SciT

    Hashimoto, Hisayuki; Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp; Tabata, Hidenori

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cellmore » cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.« less

  2. Invasion of the Placenta during Murine Listeriosis

    PubMed Central

    Le Monnier, Alban; Join-Lambert, Olivier F.; Jaubert, Francis; Berche, Patrick; Kayal, Samer

    2006-01-01

    Feto-placental infections due to Listeria monocytogenes represent a major threat during pregnancy, and the underlying mechanisms of placental invasion remain poorly understood. Here we used a murine model of listeriosis (pregnant mice, infected at day 14 of gestation) to investigate how this pathogen invades and grows within the placenta to ultimately infect the fetus. When L. monocytogenes is injected intravenously, the invasion of the placenta occurs early after the initial bacteremia, allowing the placental growth of the bacteria, which is an absolute requirement for vertical transmission to the fetus. Kinetically, bacteria first target the cells lining the central arterial canal of the placenta, which stain positively with cytokeratin, demonstrating their fetal trophoblast origin. Bacteria then disseminate rapidly to the other trophoblastic structures, like syncytiotrophoblast cells lining the villous core in the labyrinthine zone of placenta. Additionally, we found that an inflammatory reaction predominantly constituted of polymorphonuclear cells occurs in the villous placenta and participates in the control of infection. Altogether, our results suggest that the infection of murine placenta is dependent, at the early phase, on circulating bacteria and their interaction with endovascular trophoblastic cells. Subsequently, the bacteria spread to the other trophoblastic cells before crossing the placental barrier. PMID:16369023

  3. Provider-based research networks and diffusion of surgical technologies among patients with early-stage kidney cancer.

    PubMed

    Tan, Hung-Jui; Meyer, Anne-Marie; Kuo, Tzy-Mey; Smith, Angela B; Wheeler, Stephanie B; Carpenter, William R; Nielsen, Matthew E

    2015-03-15

    Provider-based research networks such as the National Cancer Institute's Community Clinical Oncology Program (CCOP) have been shown to facilitate the translation of evidence-based cancer care into clinical practice. This study compared the utilization of laparoscopy and partial nephrectomy among patients with early-stage kidney cancer according to their exposure to CCOP-affiliated providers. With linked Surveillance, Epidemiology, and End Results-Medicare data, patients with T1aN0M0 kidney cancer who had been treated with nephrectomy from 2000 to 2007 were identified. For each patient, the receipt of care from a CCOP physician or hospital and treatment with laparoscopy or partial nephrectomy were determined. Adjusted for patient characteristics (eg, age, sex, and marital status) and other organizational features (eg, community hospital and National Cancer Institute-designated cancer center), multivariate logistic regression was used to estimate the association between each surgical innovation and CCOP affiliation. During the study interval, 1578 patients (26.8%) were treated by a provider with a CCOP affiliation. Trends in the utilization of laparoscopy and partial nephrectomy remained similar between affiliated and nonaffiliated providers (P ≥ .05). With adjustments for patient characteristics, organizational features, and clustering, no association was noted between CCOP affiliation and the use of laparoscopy (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.81-1.53) or partial nephrectomy (OR, 1.04; 95% CI, 0.82-1.32) despite the more frequent receipt of these treatments in academic settings (P < .05). At a population level, patients treated by providers affiliated with CCOP were no more likely to receive at least 1 of 2 surgical innovations for treatment of their kidney cancer, indicating perhaps a more limited scope to provider-based research networks as they pertain to translational efforts in cancer care. © 2014 American Cancer Society.

  4. Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map

    PubMed Central

    2013-01-01

    Background Radiologic response of brain tumors is traditionally assessed according to the Macdonald criteria 10 weeks from the start of therapy. Because glioblastoma (GB) responds in days rather than weeks after boron neutron capture therapy (BNCT) that is a form of tumor-selective particle radiation, it is inconvenient to use the Macdonald criteria to assess the therapeutic efficacy of BNCT by gadolinium-magnetic resonance imaging (Gd-MRI). Our study assessed the utility of functional diffusion map (fDM) for evaluating response patterns in GB treated by BNCT. Methods The fDM is an image assessment using time-dependent changes of apparent diffusion coefficient (ADC) in tumors on a voxel-by-voxel approach. Other than time-dependent changes of ADC, fDM can automatically assess minimum/maximum ADC, Response Evaluation Criteria In Solid Tumors (RECIST), and the volume of enhanced lesions on Gd-MRI over time. We assessed 17 GB patients treated by BNCT using fDM. Additionally, in order to verify our results, we performed a histopathological examination using F98 rat glioma models. Results Only the volume of tumor with decreased ADC by fDM at 2 days after BNCT was a good predictor for GB patients treated by BNCT (P value = 0.022 by log-rank test and 0.033 by wilcoxon test). In a histopathological examination, brain sections of F98 rat glioma models treated by BNCT showed cell swelling of both the nuclei and the cytoplasm compared with untreated rat glioma models. Conclusions The fDM could identify response patterns in BNCT-treated GB earlier than a standard radiographic assessment. Early detection of treatment failure can allow a change or supplementation before tumor progression and might lead to an improvement of GB patients’ prognosis. PMID:23915330

  5. The Value of Diffusion-Weighted Imaging in Combination With Conventional Magnetic Resonance Imaging for Improving Tumor Detection for Early Cervical Carcinoma Treated With Fertility-Sparing Surgery.

    PubMed

    Li, Xiulei; Wang, Ling; Li, Yong; Song, Peiji

    2017-10-01

    This study aimed to investigate the value of diffusion-weighted imaging (DWI) in combination with conventional magnetic resonance imaging (MRI) for improving tumor detection in young patients treated with fertility-sparing surgery because of early cervical carcinoma. Fifty-four patients with stage Ia or Ib1 cervical carcinoma were enrolled into this study. Magnetic resonance examinations were performed for these patients using conventional MRI (including T1-weighted imaging, T2-weighted imaging, and dynamic contrast-enhanced MRI) and DWI. The apparent diffusion coefficient (ADC) values of cervical carcinoma were analyzed quantitatively and compared with that of adjacent epithelium. Sensitivity, positive predictive value, and accuracy of 2 sets of MRI sequences were calculated on the basis of histologic results, and the diagnostic ability of conventional MRI/DWI combinations was compared with that of conventional MRI. The mean ADC value from cervical carcinoma (mean, 786 × 10 mm/s ± 100) was significantly lower than that from adjacent epithelium (mean, 1352 × 10 mm/s ± 147) (P = 0.01). When the threshold ADC value set as 1010 × 10 mm/s, the sensitivity and specificity for differentiating cervical carcinoma from nontumor epithelium were 78.2% and 67.2%, respectively. The sensitivity and accuracy of conventional MRI for tumor detection were 76.0% and 70.4%, whereas the sensitivity and accuracy of conventional MRI/DWI combinations were 91.7% and 90.7%, respectively. Conventional MRI/DWI combinations revealed a positive predictive value of 97.8% and only 4 false-negative findings. The addition of DWI to conventional MRI considerably improves the sensitivity and accuracy of tumor detection in young patients treated with fertility-sparing surgery, which supports the inclusion quantitative analysis of ADC value in routine MRI protocol before fertility-sparing surgery.

  6. Diffusion-Weighted Magnetic Resonance Imaging Early After Chemoradiotherapy to Monitor Treatment Response in Head-and-Neck Squamous Cell Carcinoma

    SciT

    Vandecaveye, Vincent, E-mail: Vincent.Vandecaveye@uzleuven.be; Dirix, Piet; De Keyzer, Frederik

    2012-03-01

    Purpose: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in head and neck squamous cell carcinoma (HNSCC) three weeks after the end of chemoradiotherapy (CRT). Methods and Materials: Twenty-nine patients with HNSCC underwent magnetic resonance imaging (MRI) prior to and 3 weeks after CRT, including T{sub 2}-weighted and pre- and postcontrast T{sub 1}-weighted sequences and an echo-planar DWI sequence with six b values (0 to 1,000 s/mm{sup 2}), from which the apparent diffusion coefficient (ADC) was calculated. ADC changes 3 weeks posttreatment compared to baseline ( Increment ADC) between responding and nonresponding primary lesions and adenopathies were correlatedmore » with 2 years locoregional control and compared with a Mann-Whitney test. In a blinded manner, the Increment ADC was compared to conventional MRI 3 weeks post-CRT and the routinely implemented CT, on average 3 months post-CRT, which used size-related and morphological criteria. Positive and negative predictive values (PPV and NPV, respectively) were compared between the Increment ADC and anatomical imaging. Results: The Increment ADC of lesions with later tumor recurrence was significantly lower than lesions with complete remission for both primary lesions (-2.3% {+-} 0.3% vs. 80% {+-} 41%; p < 0.0001) and adenopathies (19.9% {+-} 32% vs. 63% {+-} 36%; p = 0.003). The Increment ADC showed a PPV of 89% and an NPV of 100% for primary lesions and a PPV of 70% and an NPV of 96% for adenopathies per neck side. DWI improved PPV and NPV compared to anatomical imaging. Conclusion: DWI with the Increment ADC 3 weeks after concluding CRT for HNSCC allows for early assessment of treatment response.« less

  7. Imaging Biomarker Dynamics in an Intracranial Murine Glioma Study of Radiation and Antiangiogenic Therapy

    SciT

    Chung, Caroline, E-mail: caroline.chung@rmp.uhn.on.ca; Jalali, Shahrzad; Foltz, Warren

    2013-03-01

    Purpose: There is a growing need for noninvasive biomarkers to guide individualized spatiotemporal delivery of radiation therapy (RT) and antiangiogenic (AA) therapy for brain tumors. This study explored early biomarkers of response to RT and the AA agent sunitinib (SU), in a murine intracranial glioma model, using serial magnetic resonance imaging (MRI). Methods and Materials: Mice with MRI-visible tumors were stratified by tumor size into 4 therapy arms: control, RT, SU, and SU plus RT (SURT). Single-fraction conformal RT was delivered using MRI and on-line cone beam computed tomography (CT) guidance. Serial MR images (T2-weighted, diffusion, dynamic contrast-enhanced and gadolinium-enhancedmore » T1-weighted scans) were acquired biweekly to evaluate tumor volume, apparent diffusion coefficient (ADC), and tumor perfusion and permeability responses (K{sub trans}, K{sub ep}). Results: Mice in all treatment arms survived longer than those in control, with a median survival of 35 days for SURT (P<.0001) and 30 days for RT (P=.009) and SU (P=.01) mice vs 26 days for control mice. At Day 3, ADC rise was greater with RT than without (P=.002). Sunitinib treatment reduced tumor perfusion/permeability values with mean K{sub trans} reduction of 27.6% for SU (P=.04) and 26.3% for SURT (P=.04) mice and mean K{sub ep} reduction of 38.1% for SU (P=.01) and 27.3% for SURT (P=.02) mice. The magnitude of individual mouse ADC responses at Days 3 and 7 correlated with subsequent tumor growth rate R values of −0.878 (P=.002) and −0.80 (P=.01), respectively. Conclusions: Early quantitative changes in diffusion and perfusion MRI measures reflect treatment responses soon after starting therapy and thereby raise the potential for these imaging biomarkers to guide adaptive and potentially individualized therapy approaches in the future.« less

  8. Value of Diffusion-Weighted Magnetic Resonance Imaging for Prediction and Early Assessment of Response to Neoadjuvant Radiochemotherapy in Rectal Cancer: Preliminary Results

    SciT

    Lambrecht, Maarten, E-mail: maarten.lambrecht@uzleuven.be; Vandecaveye, Vincent; De Keyzer, Frederik

    2012-02-01

    Purpose: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). Methods and Materials: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm{sup 2}) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change ( Increment ADC), and volume change ( Increment V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectalmore » excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, Increment ADC, and Increment V for the detection of pCR was compared with receiver operating characteristics analysis. Results: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm{sup 2}/s: 0.94 {+-} 0.12 Multiplication-Sign 10{sup -3} vs. 1.19 {+-} 0.22 Multiplication-Sign 10{sup -3}, p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: {Delta}V{sub during}: -62 {+-} 16 vs. -33 {+-} 16, respectively, p = 0.015; and {Delta}V{sub post}: -86 {+-} 12 vs. -60 {+-} 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the {Delta}V{sub during} and, respectively, 83% and 86% for the {Delta}V{sub post}. The Increment ADC during ({Delta}ADC{sub during}) and after RCT ({Delta}ADC{sub post}) showed a significantly higher value in patients with pCR compared with patients without (in %: {Delta}ADC{sub during}: 72 {+-} 14 vs. 16 {+-} 12, p = 0.0006; and {Delta

  9. Murine fetal echocardiography.

    PubMed

    Kim, Gene H

    2013-02-15

    Transgenic mice displaying abnormalities in cardiac development and function represent a powerful tool for the understanding the molecular mechanisms underlying both normal cardiovascular function and the pathophysiological basis of human cardiovascular disease. Fetal and perinatal death is a common feature when studying genetic alterations affecting cardiac development. In order to study the role of genetic or pharmacologic alterations in the early development of cardiac function, ultrasound imaging of the live fetus has become an important tool for early recognition of abnormalities and longitudinal follow-up. Noninvasive ultrasound imaging is an ideal method for detecting and studying congenital malformations and the impact on cardiac function prior to death. It allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Until recently, imaging of fetal mouse hearts frequently involved invasive methods. The fetus had to be sacrificed to perform magnetic resonance microscopy and electron microscopy or surgically delivered for transillumination microscopy. An application of high-frequency probes with conventional 2-D and pulsed-wave Doppler imaging has been shown to provide measurements of cardiac contraction and heart rates during embryonic development with databases of normal developmental changes now available. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. High-frequency ultrasound imaging of the fetus has improved 2-D resolution and can provide excellent information on the early development of cardiac structures.

  10. MRI and MRS alterations in the preclinical phase of murine prion disease: association with neuropathological and behavioural changes.

    PubMed

    Broom, Kerry A; Anthony, Daniel C; Lowe, John P; Griffin, Julian L; Scott, Helen; Blamire, Andrew M; Styles, Peter; Perry, V Hugh; Sibson, Nicola R

    2007-06-01

    Prion diseases are fatal chronic neurodegenerative diseases. Previous qualitative magnetic resonance imaging (MRI) and spectroscopy (MRS) studies report conflicting results in the symptomatic stages of the disease, but little work has been carried out during the earlier stages of the disease. Here we have used the murine ME7 model of prion disease to quantitatively investigate MRI and MRS changes during the period prior to the onset of overt clinical signs (20+ weeks) and have correlated these with pathological and behavioural abnormalities. Using in vivo MRI, at the later stages of the preclinical period (18 weeks) the diffusion of tissue water was significantly reduced, coinciding with significant microglial activation and behavioural hyperactivity. Using in vivo MRS, we found early (12 weeks) decreases in the ratio of N-acetyl aspartate to both choline (NAA/Cho) and creatine (NAA/Cr) in the thalamus and hippocampus, which were associated with early behavioural deficits. Ex vivo MRS of brain extracts confirmed and extended these findings, showing early (8-12 weeks) decreases in both the neuronal metabolites NAA and glutamate, and the metabolic metabolites lactate and glucose. Increases in the glial metabolite myo-inositol were observed at later stages when microglial and astrocyte activation is substantial. These changes in MRI and MRS signals, which precede overt clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.

  11. Bone marrow-derived mesenchymal stem cells from early diffuse systemic sclerosis exhibit a paracrine machinery and stimulate angiogenesis in vitro.

    PubMed

    Guiducci, Serena; Manetti, Mirko; Romano, Eloisa; Mazzanti, Benedetta; Ceccarelli, Claudia; Dal Pozzo, Simone; Milia, Anna Franca; Bellando-Randone, Silvia; Fiori, Ginevra; Conforti, Maria Letizia; Saccardi, Riccardo; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco

    2011-11-01

    To characterise bone marrow-derived mesenchymal stem cells (MSCs) from patients with systemic sclerosis (SSc) for the expression of factors implicated in MSC recruitment at sites of injury, angiogenesis and fibrosis. The study also analysed whether the production/release of bioactive mediators by MSCs were affected by stimulation with cytokines found upregulated in SSc serum and tissues, and whether MSCs could modulate dermal microvascular endothelial cell (MVEC) angiogenesis. MSCs obtained from five patients with early severe diffuse SSc (SSc-MSCs) and five healthy donors (H-MSCs) were stimulated with vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ) or stromal cell-derived factor-1 (SDF-1). Transcript and protein levels of SDF-1 and its receptor CXCR4, VEGF, TGFβ(1) and receptors TβRI and TβRII were evaluated by quantitative real-time PCR, western blotting and confocal microscopy. VEGF, SDF-1 and TGFβ(1) secretion in culture supernatant was measured by ELISA. MVEC capillary morphogenesis was performed on Matrigel with the addition of MSC-conditioned medium. In SSc-MSCs the basal expression of proangiogenic SDF-1/CXCR4 and VEGF was significantly increased compared with H-MSCs. SSc-MSCs constitutively released higher levels of SDF-1 and VEGF. SDF-1/CXCR4 were upregulated after VEGF stimulation and CXCR4 redistributed from the cytoplasm to the cell surface. VEGF was increased by SDF-1 challenge. VEGF, TGFβ and SDF-1 stimulation upregulated TGFβ(1), TβRI and TβRII in SSc-MSCs. TβRII redistributed from the cytoplasm to focal adhesion contacts. SSc-MSC-conditioned medium showed a greater proangiogenic effect on MVECs than H-MSCs. Experiments with blocking antibodies showed that MSC-derived cytokines were responsible for this potent proangiogenic effect. SSc-MSCs constitutively overexpress and release bioactive mediators/proangiogenic factors and potentiate dermal MVEC angiogenesis.

  12. Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI.

    PubMed

    Wang, Xue; Zhao, Yu; Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen; Wang, Jinhong; Yan, Zhihan

    2017-07-11

    Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10-3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers.

  13. Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI

    PubMed Central

    Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen

    2017-01-01

    Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10−3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers. PMID:28634318

  14. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging.

    PubMed

    Kattah, Jorge C; Talkad, Arun V; Wang, David Z; Hsieh, Yu-Hsiang; Newman-Toker, David E

    2009-11-01

    Acute vestibular syndrome (AVS) is often due to vestibular neuritis but can result from vertebrobasilar strokes. Misdiagnosis of posterior fossa infarcts in emergency care settings is frequent. Bedside oculomotor findings may reliably identify stroke in AVS, but prospective studies have been lacking. The authors conducted a prospective, cross-sectional study at an academic hospital. Consecutive patients with AVS (vertigo, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with >or=1 stroke risk factor underwent structured examination, including horizontal head impulse test of vestibulo-ocular reflex function, observation of nystagmus in different gaze positions, and prism cross-cover test of ocular alignment. All underwent neuroimaging and admission (generally <72 hours after symptom onset). Strokes were diagnosed by MRI or CT. Peripheral lesions were diagnosed by normal MRI and clinical follow-up. One hundred one high-risk patients with AVS included 25 peripheral and 76 central lesions (69 ischemic strokes, 4 hemorrhages, 3 other). The presence of normal horizontal head impulse test, direction-changing nystagmus in eccentric gaze, or skew deviation (vertical ocular misalignment) was 100% sensitive and 96% specific for stroke. Skew was present in 17% and associated with brainstem lesions (4% peripheral, 4% pure cerebellar, 30% brainstem involvement; chi(2), P=0.003). Skew correctly predicted lateral pontine stroke in 2 of 3 cases in which an abnormal horizontal head impulse test erroneously suggested peripheral localization. Initial MRI diffusion-weighted imaging was falsely negative in 12% (all <48 hours after symptom onset). Skew predicts brainstem involvement in AVS and can identify stroke when an abnormal horizontal head impulse test falsely suggests a peripheral lesion. A 3-step bedside oculomotor examination (HINTS: Head-Impulse-Nystagmus-Test-of-Skew) appears more sensitive for stroke than early MRI in AVS.

  15. Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

    SciT

    Liu, Xin; Fang, Hui; Tian, Yuan

    Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: Themore » median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early

  16. Short Diffusion Time Diffusion-Weighted Imaging With Oscillating Gradient Preparation as an Early Magnetic Resonance Imaging Biomarker for Radiation Therapy Response Monitoring in Glioblastoma: A Preclinical Feasibility Study.

    PubMed

    Bongers, Andre; Hau, Eric; Shen, Han

    2018-01-04

    To investigate a novel alternative diffusion-weighted imaging (DWI) approach using oscillating gradients preparation (OGSE) to obtain much shorter effective diffusion times (Δ eff ) for tumor response monitoring by apparent diffusion coefficient (ADC) mapping in a glioblastoma mouse model. Twenty-four BALB/c nude mice inoculated with U87 glioblastoma cells were randomized into a control group and an irradiation group, which underwent a 15-day fractioned radiation therapy (RT) course with 2 Gy/d. Therapy response was assessed by mapping of ADCs at 6 time points using an in-house implementation of a cos-OGSE DWI sequence with Δ eff  = 1.25 ms and compared with a standard pulsed gradient DWI protocol (PGSE) with typical clinical diffusion time Δ eff  = 18 ms. Longitudinal ADC changes in tumor and contralateral white matter (WM) were statistically assessed using repeated-measures analysis of variance and post hoc (Sidak) testing. On short Δ eff OGSE maps tumor ADC was generally 30%-50% higher than in surrounding WM. Areas correlated well with histology. Tumor identification was generally more difficult on PGSE maps owing to nonsignificant WM/tumor contrast. During RT, OGSE maps also showed significant tumor ADC increase (approximately 15%) in response to radiation, consistently seen after 14-Gy RT dose. The clinical reference (PGSE) showed lower sensitivity to radiation changes, and no significant response across the radiation group and time course could be detected. Our short Δ eff DWI method using OGSE better reflected histologically defined tumor areas and enabled more consistent and earlier detection of microstructural radiation changes than conventional methods. Oscillating gradients preparation offers significant potential as a robust microstructural RT response biomarker, potentially helping to shift important therapy decisions to earlier stages in the RT time course. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis▿

    PubMed Central

    Grayo, Solène; Lott-Desroches, Marie-Catherine; Dussurget, Olivier; Respaud, Renaud; Fontanet, Arnaud; Join-Lambert, Olivier; Singlas, Eric; Le Monnier, Alban

    2008-01-01

    Listeriosis is a rare but life-threatening infection. A favorable outcome is greatly aided by early administration of antibiotics with rapid bactericidal activity against Listeria monocytogenes. Moxifloxacin, a new-generation fluoroquinolone with extended activity against gram-positive bacteria, has proved its effectiveness in vitro against intracellular reservoirs of bacteria. The efficacies of moxifloxacin and amoxicillin were compared in vivo by survival curve assays and by studying the kinetics of bacterial growth in blood and organs in a murine model of central nervous system (CNS) listeriosis. We combined pharmacokinetic and pharmacodynamic approaches to correlate the observed efficacy in vivo with plasma and tissue moxifloxacin concentrations. Death was significantly delayed for animals treated with a single dose of moxifloxacin compared to a single dose of amoxicillin. We observed rapid bacterial clearance from blood and organs of animals treated with moxifloxacin. The decrease in the bacterial counts in blood and brain correlated with plasma and cerebral concentrations of antibiotic. Moxifloxacin peaked in the brain at 1.92 ± 0.32 μg/g 1 hour after intraperitoneal injection. This suggests that moxifloxacin rapidly crosses the blood-brain barrier and diffuses into the cerebral parenchyma. Moreover, no resistant strains were selected during in vivo experiments. Our results indicate that moxifloxacin combines useful pharmacokinetic properties and rapid bactericidal activity and that it may be a valuable alternative for the treatment of CNS listeriosis. PMID:18573932

  18. Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe.

    PubMed

    Huang, J; Friedland, R P; Auchus, A P

    2007-01-01

    Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. We used DTI to characterize microstructural white matter changes and their associations with cognitive dysfunction in Alzheimer disease (AD) and mild cognitive impairment (MCI). We studied elderly subjects with mild AD (n = 6), MCI (n = 11), or normal cognition (n = 8). A standardized clinical and neuropsychological evaluation was conducted on each subject. DTI images were acquired, and fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) of normal-appearing white matter (NAWM) in frontal, temporal, parietal, and occipital lobes were determined. These diffusion measurements were compared across the 3 groups, and significant differences were further examined for correlations with tests of cognitive function. Compared with normal controls, AD subjects demonstrated decreased FA and increased DR in the temporal, parietal, and frontal NAWM and decreased DA in temporal NAWM. MCI subjects also showed decreased FA and decreased DA in temporal NAWM, with decreased FA and increased DR in parietal NAWM. Diffusion measurements showed no differences in occipital NAWM. Across all subjects, temporal lobe FA and DR correlated with episodic memory, frontal FA and DR correlated with executive function, and parietal DR significantly correlated with visuospatial ability. We found evidence for functionally relevant microstructural changes in the NAWM of patients with AD and MCI. These changes were present in brain regions serving higher cortical functions, but not in regions serving primary functions, and are consistent with a hypothesized loss of axonal processes in the temporal lobe.

  19. Diffuse Large B-Cell Lymphoma: Prospective Multicenter Comparison of Early Interim FLT PET/CT versus FDG PET/CT with IHP, EORTC, Deauville, and PERCIST Criteria for Early Therapeutic Monitoring

    PubMed Central

    Minamimoto, Ryogo; Fayad, Luis; Advani, Ranjana; Vose, Julie; Macapinlac, Homer; Meza, Jane; Hankins, Jordan; Mottaghy, Felix; Juweid, Malik

    2016-01-01

    Purpose To compare the performance characteristics of interim fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (after two cycles of chemotherapy) by using the most prominent standardized interpretive criteria (including International Harmonization Project [IHP] criteria, European Organization for Research and Treatment of Cancer [EORTC] criteria, and PET Response Criteria in Solid Tumors (PERCIST) versus those of interim 18F fluorothymidine (FLT) PET/CT and simple visual interpretation. Materials and Methods This HIPAA-compliant prospective study was approved by the institutional review boards, and written informed consent was obtained. Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) underwent both FLT and FDG PET/CT 18–24 days after two cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. For FDG PET/CT interpretation, IHP criteria, EORTC criteria, PERCIST, Deauville criteria, standardized uptake value, total lesion glycolysis, and metabolic tumor volume were used. FLT PET/CT images were interpreted with visual assessment by two reviewers in consensus. The interim (after cycle 2) FDG and FLT PET/CT studies were then compared with the end-of-treatment FDG PET/CT studies to determine which interim examination and/or criteria best predicted the result after six cycles of chemotherapy. Results From November 2011 to May 2014, there were 60 potential patients for inclusion, of whom 46 patients (24 men [mean age, 60.9 years ± 13.7; range, 28–78 years] and 22 women [mean age, 57.2 years ± 13.4; range, 25–76 years]) fulfilled the criteria. Thirty-four patients had complete response, and 12 had residual disease at the end of treatment. FLT PET/CT had a significantly higher positive predictive value (PPV) (91%) in predicting residual disease than did any FDG PET/CT interpretation

  20. Integrin Based Isolation Enables Purification of Murine Lineage Committed Cardiomyocytes

    PubMed Central

    Tarnawski, Laura; Xian, Xiaojie; Monnerat, Gustavo; Macaulay, Iain C.; Malan, Daniela; Borgman, Andrew; Wu, Sean M.; Fleischmann, Bernd K.; Jovinge, Stefan

    2015-01-01

    In contrast to mature cardiomyocytes which have limited regenerative capacity, pluripotent stem cells represent a promising source for the generation of new cardiomyocytes. The tendency of pluripotent stem cells to form teratomas and the heterogeneity from various differentiation stages and cardiomyocyte cell sub-types, however, are major obstacles to overcome before this type of therapy could be applied in a clinical setting. Thus, the identification of extracellular markers for specific cardiomyocyte progenitors and mature subpopulations is of particular importance. The delineation of cardiomyocyte surface marker patterns not only serves as a means to derive homogeneous cell populations by FACS, but is also an essential tool to understand cardiac development. By using single-cell expression profiling in early mouse embryonic hearts, we found that a combination of integrin alpha-1, alpha-5, alpha-6 and N-cadherin enables isolation of lineage committed murine cardiomyocytes. Additionally, we were able to separate trabecular cardiomyocytes from solid ventricular myocardium and atrial murine cells. These cells exhibit expected subtype specific phenotype confirmed by electrophysiological analysis. We show that integrin expression can be used for the isolation of living, functional and lineage-specific murine cardiomyocytes. PMID:26323090

  1. Essential roles for Cdx in murine primitive hematopoiesis.

    PubMed

    Brooke-Bisschop, Travis; Savory, Joanne G A; Foley, Tanya; Ringuette, Randy; Lohnes, David

    2017-02-15

    The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis. We found that Cdx1/Cdx2 double mutants exhibited defects in primitive hematopoiesis and yolk sac vasculature concomitant with reduced expression of several genes encoding hematopoietic transcription factors including Scl/Tal1. Chromatin immunoprecipitation analysis revealed that Scl was occupied by Cdx2 in vivo, and Cdx mutant hematopoietic yolk sac differentiation defects could be rescued by expression of exogenous Scl. These findings demonstrate critical roles for Cdx members in murine primitive hematopoiesis upstream of Scl. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Orientation diffusions.

    PubMed

    Perona, P

    1998-01-01

    Diffusions are useful for image processing and computer vision because they provide a convenient way of smoothing noisy data, analyzing images at multiple scales, and enhancing discontinuities. A number of diffusions of image brightness have been defined and studied so far; they may be applied to scalar and vector-valued quantities that are naturally associated with intervals of either the real line, or other flat manifolds. Some quantities of interest in computer vision, and other areas of engineering that deal with images, are defined on curved manifolds;typical examples are orientation and hue that are defined on the circle. Generalizing brightness diffusions to orientation is not straightforward, especially in the case where a discrete implementation is sought. An example of what may go wrong is presented.A method is proposed to define diffusions of orientation-like quantities. First a definition in the continuum is discussed, then a discrete orientation diffusion is proposed. The behavior of such diffusions is explored both analytically and experimentally. It is shown how such orientation diffusions contain a nonlinearity that is reminiscent of edge-process and anisotropic diffusion. A number of open questions are proposed at the end.

  3. Murine Typhus, Reunion, France, 2011–2013

    PubMed Central

    Camuset, Guillaume; Socolovschi, Cristina; Moiton, Marie-Pierre; Kuli, Barbara; Foucher, Aurélie; Poubeau, Patrice; Borgherini, Gianandrea; Wartel, Guillaume; Audin, Héla; Raoult, Didier; Filleul, Laurent; Parola, Philippe; Pagès, Fréderic

    2015-01-01

    Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011–January 2013 in Reunion. Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin. PMID:25625653

  4. [Functional electrical stimulation based on a working pattern influences function of lower extremity in subjects with early stroke and effects on diffusion tensor imaging: a randomized controlled trial].

    PubMed

    Chen, Danfeng; Yan, Tiebin; Li, Guandong; Li, Fangming; Liang, Qitang

    2014-10-14

    To explore the possible mechanisms for improving lower extremity motor function in patients with early stroke through combining magnetic resonance diffusion tensor imaging (DTI) technology and functional electrical stimulation (FES) based on human walking patterns. From August 2012 to September 2013, a total of 48 eligible patients were stratified according to age, gender, disease course, Brunnstrom staging and types of stroke. And the Minimize software was used to divided them randomly into four-channel FES group (n = 18), dual-channel FES group (n = 15) and comfort stimulation group (n = 15). For all three groups, general medication and standard rehabilitation were provided. Based on normal walking pattern design of FES treatment, four-channel FES groups received the stimulations of quadriceps, hamstring, anterior tibialis and medial gastrocnemius. For the dual-channel FES group, the stimulations of tibialis anterior, peroneus longus and peroneus brevis muscles were applied. In comfort electrical stimulation group, the electrode positions were identical to the stimulation group, but there was no current output during stimulation. Before and after 3-week treatment, three groups received weekly rehabilitation evaluations of Fugl-Meyer assessment (FMA), posture assessment of stroke scale (PASS), Brunel balance assessment (BBA), Berg balance scale (BBS) and modified Barthel index (MBI). Before and after treatment, DTI examination was performed for some patients. Among three groups, general patient profiles and pre-treatment evaluations showed no significant difference. For intra-group comparisons versus pre-treatment, at week 1, 2 and 3, the scores of PASS, BBA, BBS, FMA and MBI had statistically significant differences (P < 0.05); At week 3 post-treatment, when four-channel and double-channel FES groups were compared versus pre-treatment, the scores of ipsilateral FA had statistically significant differences (P < 0.05). At week 1 post-treatment, MBI had

  5. Inhibition of Granulopoiesis in Diffusion Chambers by a Granulocyte Chalone

    DTIC Science & Technology

    1974-07-01

    culture has o 5_g a been well documented. ’ Breivik et al. , using chamber to chamber transfers in nonpretreated hosts, have illustrated the...1972. 7. Breivik , H. and Benestad, H. B. Regulation of granulocyte and macrophage formation in diffusion chamber cultures of mouse...haematopoietic cells. Exptl. Cell Res. 70:340-348, 1972. 8. Breivik , H., Benestad, H. B. and B^yum, A. Diffusion chamber and spleen colony assay of murine

  6. Gd-EOB-DTPA-enhanced T1ρ imaging vs diffusion metrics for assessment liver inflammation and early stage fibrosis of nonalcoholic steatohepatitis in rabbits.

    PubMed

    Xie, Yuanliang; Zhang, Hongfeng; Jin, Chaoling; Wang, Xiang; Wang, Xiaoqi; Chen, Jingting; Xu, Yikai

    2018-05-01

    To assess the value of T1ρ,T1ρ on hepatobiliary phase (HBP) and diffusion metrics in staging of Non-alcoholic fatty liver disease (NAFLD) activity scores, inflammation, fibrosis in NASH rabbits model. Non-alcoholic steatohepatitis (NASH) rabbits model was induced by feeding a varied duration of high-fat, high-cholesterol diet. T1ρ,T1ρ (HBP) 20min after administration of Gd-EOB-DTPA, and Intravoxel incoherent motion imaging (IVIM) diffusion-weighted imaging were performed on a 3.0T magnetic resonance (MR) imaging unit. The diagnostic value of each parameter for NAS, inflammation and fibrosis severity were determined. T1ρ (r=0.658) and T1ρ (HBP) (r=0.750) have strong association with NASH overall activity, T1ρ (HBP) is strongly relevant to inflammation stage (r=0.812). There was negative association between f and inflammation (r=-0.480), whilst no significant relation between other three parameters (apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*) and true diffusion coefficient (D)) and inflammation or overall activity. The areas under the receiver operating characteristic curves (AUCs) of f, ADC, T1ρ and T1ρ-HBP were 0.871, 0.728, 0.849 and 0.949 for differentiating NASH; 0.731, 0.552, 0.925 and 0.922 for G2-3 inflammation; and 0.767, 0.625, 0.816, and 0.882 for S1-2 fibrosis. Comparison of ROC curve showed T1ρ (HBP) had an optimal diagnostic performance for NASH [T1ρ (HBP) vs ADC, AUC:0.949 vs 0.728, P=0.043], inflammation [T1ρ (HBP) vs ADC, AUC:0.922 vs 0.552, P=0.003], fibrosis [T1ρ (HBP) vs ADC, AUC:0.882 vs 0.625, P=0.046]. The combination of T1ρ (HBP)+perfusion fraction (f) showed highest diagnostic value for NASH (AUC:0.971), inflammation (AUC:0.935). Among T1ρ imaging and IVIM diffusion metrics, combination of T1rho (HBP)+f was found to be superior noninvasive imaging biomarker for NASH activity assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Fetal wound healing using a genetically modified murine model: the contribution of P-selectin

    During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wo...

  8. NASA/DOD Aerospace Knowledge Diffusion Research Project. Report 34: How early career-stage US aerospace engineers and scientists produce and use information

    NASA Technical Reports Server (NTRS)

    Pinelli, Thomas E.; Barclay, Rebecca O.; Kennedy, John M.

    1995-01-01

    The U.S. government technical report is a primary means by which the results of federally funded research and development (R&D) are transferred to the U.S. aerospace industry. However, little is known about this information product in terms of its actual use, importance, and value in the transfer of federally funded R&D. To help establish a body of knowledge, the U.S. government technical report is being investigated as part of the NASA/DOD Aerospace Knowledge Diffusion Research Project. In this report, we summarize the literature on technical reports and provide a model that depicts the transfer of federally funded aerospace R&D via the U.S. government technical report. We present results from our investigation of aerospace knowledge diffusion vis-a-vis the U.S. government technical report, and present the results of research that investigated aerospace knowledge diffusion vis-a-vis the production and use of information by U.S. aerospace engineers and scientists who had changed their American Institute of Aeronautics and Astronautics (AIAA) membership from student to professional in the past five years.

  9. Apoplastic Diffusion Barriers in Arabidopsis

    PubMed Central

    Schreiber, Lukas; Franke, Rochus Benni; Geldner, Niko; Reina-Pinto, José J.; Kunst, Ljerka

    2013-01-01

    During the development of Arabidopsis and other land plants, diffusion barriers are formed in the apoplast of specialized tissues within a variety of plant organs. While the cuticle of the epidermis is the primary diffusion barrier in the shoot, the Casparian strips and suberin lamellae of the endodermis and the periderm represent the diffusion barriers in the root. Different classes of molecules contribute to the formation of extracellular diffusion barriers in an organ- and tissue-specific manner. Cutin and wax are the major components of the cuticle, lignin forms the early Casparian strip, and suberin is deposited in the stage II endodermis and the periderm. The current status of our understanding of the relationships between the chemical structure, ultrastructure and physiological functions of plant diffusion barriers is discussed. Specific aspects of the synthesis of diffusion barrier components and protocols that can be used for the assessment of barrier function and important barrier properties are also presented. PMID:24465172

  10. Diffusion barriers

    NASA Technical Reports Server (NTRS)

    Nicolet, M. A.

    1983-01-01

    The choice of the metallic film for the contact to a semiconductor device is discussed. One way to try to stabilize a contact is by interposing a thin film of a material that has low diffusivity for the atoms in question. This thin film application is known as a diffusion barrier. Three types of barriers can be distinguished. The stuffed barrier derives its low atomic diffusivity to impurities that concentrate along the extended defects of a polycrystalline layer. Sacrificial barriers exploit the fact that some (elemental) thin films react in a laterally uniform and reproducible fashion. Sacrificial barriers have the advantage that the point of their failure is predictable. Passive barriers are those most closely approximating an ideal barrier. The most-studied case is that of sputtered TiN films. Stuffed barriers may be viewed as passive barriers whose low diffusivity material extends along the defects of the polycrystalline host.

  11. Diffuse radiation

    NASA Technical Reports Server (NTRS)

    1981-01-01

    A diffuse celestial radiation which is isotropic at least on a course scale were measured from the soft X-ray region to about 150 MeV, at which energy the intensity falls below that of the galactic emission for most galactic latitudes. The spectral shape, the intensity, and the established degree of isotropy of this diffuse radiation already place severe constraints on the possible explanations for this radiation. Among the extragalactic theories, the more promising explanations of the isotropic diffuse emission appear to be radiation from exceptional galaxies from matter antimatter annihilation at the boundaries of superclusters of galaxies of matter and antimatter in baryon symmetric big bang models. Other possible sources for extragalactic diffuse gamma radiation are discussed and include normal galaxies, clusters of galaxies, primordial cosmic rays interacting with intergalactic matter, primordial black holes, and cosmic ray leakage from galaxies.

  12. Murine epithelial cells: isolation and culture.

    PubMed

    Davidson, Donald J; Gray, Michael A; Kilanowski, Fiona M; Tarran, Robert; Randell, Scott H; Sheppard, David N; Argent, Barry E; Dorin, Julia R

    2004-08-01

    We describe an air-liquid interface primary culture method for murine tracheal epithelial cells on semi-permeable membranes, forming polarized epithelia with a high transepithelial resistance, differentiation to ciliated and secretory cells, and physiologically appropriate expression of key genes and ion channels. We also describe the isolation of primary murine nasal epithelial cells for patch-clamp analysis, generating polarised cells with physiologically appropriate distribution and ion channel expression. These methods enable more physiologically relevant analysis of murine airway epithelial cells in vitro and ex vivo, better utilisation of transgenic mouse models of human pulmonary diseases, and have been approved by the European Working Group on CFTR expression.

  13. Dietary Fructo-Oligosaccharides Attenuate Early Activation of CD4+ T Cells Which Produce both Th1 and Th2 Cytokines in the Intestinal Lymphoid Tissues of a Murine Food Allergy Model.

    PubMed

    Tsuda, Masato; Arakawa, Haruka; Ishii, Narumi; Ubukata, Chihiro; Michimori, Mana; Noda, Masanari; Takahashi, Kyoko; Kaminogawa, Shuichi; Hosono, Akira

    2017-01-01

    Fructo-oligosaccharides (FOS) are prebiotic agents with immunomodulatory effects involving improvement of the intestinal microbiota and metabolome. In this study, we investigated the cellular mechanisms through which FOS modulate intestinal antigen-specific CD4+ T cell responses in food allergy, using OVA23-3 mice. OVA23-3 mice were fed an experimental diet containing either ovalbumin (OVA) or OVA and FOS for 1 week. Body weight and mucosal mast cell protease 1 in the serum were measured as the indicator of intestinal inflammation. Single-cell suspensions were prepared from intestinal and systemic lymphoid tissues for cellular analysis. Cytokine production was measured by ELISA. Activation markers and intracellular cytokines in CD4+ T cells were analyzed by flow cytometry. Activated CD4+ T cells were purified to examine cytokine production. Dietary intake of FOS provided moderate protection from the intestinal inflammation induced by the OVA-containing diet. FOS significantly reduced food allergy-induced Th2 cytokine responses in intestinal tissues but not in systemic tissues. FOS decreased OVA diet-induced IFN-γ+IL-4+ double-positive CD4+ T cells and early-activated CD45RBhighCD69+CD4+ T cells in the mesenteric lymph nodes. Furthermore, we confirmed that these CD45RBhighCD69+CD4+ T cells are able to produce high levels of IFN-γ and moderate level of IL-4, IL-10, and IL-13. Dietary intake of FOS during the development of food allergy attenuates the induction of intestinal Th2 cytokine responses by regulating early activation of naïve CD4+ T cells, which produce both Th1 and Th2 cytokines. Our results suggest FOS might be a potential food agent for the prevention of food allergy by modulating oral sensitization to food antigens. © 2017 S. Karger AG, Basel.

  14. A preclinical murine model for the early detection of radiation-induced brain injury using magnetic resonance imaging and behavioral tests for learning and memory: with applications for the evaluation of possible stem cell imaging agents and therapies.

    PubMed

    Ngen, Ethel J; Wang, Lee; Gandhi, Nishant; Kato, Yoshinori; Armour, Michael; Zhu, Wenlian; Wong, John; Gabrielson, Kathleen L; Artemov, Dmitri

    2016-06-01

    Stem cell therapies are being developed for radiotherapy-induced brain injuries (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging transplanted stem cells. However, most MRI cell-tracking techniques employ superparamagnetic iron oxide particles (SPIOs), which are difficult to distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage occurs concurrently with other injury markers. This makes the evaluation of the recruitment of transplanted SPIO-labeled stem cells to injury sites difficult. Here, we developed a RIBI model, with early injury markers reflective of hippocampal dysfunction, which can be detected noninvasively with MRI and behavioral tests. Lesions were generated by sub-hemispheric irradiation of mouse hippocampi with single X-ray beams of 80 Gy. Lesion formation was monitored with anatomical and contrast-enhanced MRI and changes in memory and learning were assessed with fear-conditioning tests. Early injury markers were detected 2 weeks after irradiation. These included an increase in the permeability of the blood-brain barrier, demonstrated by a 92 ± 20 % contrast enhancement of the irradiated versus the non-irradiated brain hemispheres, within 15 min of the administration of an MRI contrast agent. A change in short-term memory was also detected, as demonstrated by a 40.88 ± 5.03 % decrease in the freezing time measured during the short-term memory context test at this time point, compared to that before irradiation. SPIO-labeled stem cells transplanted contralateral to the lesion migrated toward the lesion at this time point. No hemorrhage was detected up to 10 weeks after irradiation. This model can be used to evaluate SPIO-based stem cell-tracking agents, short-term.

  15. Diffusion in random networks

    DOE PAGES

    Zhang, Duan Z.; Padrino, Juan C.

    2017-06-01

    The ensemble averaging technique is applied to model mass transport by diffusion in random networks. The system consists of an ensemble of random networks, where each network is made of pockets connected by tortuous channels. Inside a channel, fluid transport is assumed to be governed by the one-dimensional diffusion equation. Mass balance leads to an integro-differential equation for the pocket mass density. The so-called dual-porosity model is found to be equivalent to the leading order approximation of the integration kernel when the diffusion time scale inside the channels is small compared to the macroscopic time scale. As a test problem,more » we consider the one-dimensional mass diffusion in a semi-infinite domain. Because of the required time to establish the linear concentration profile inside a channel, for early times the similarity variable is xt $-$1/4 rather than xt $-$1/2 as in the traditional theory. We found this early time similarity can be explained by random walk theory through the network.« less

  16. Optimal Network Modularity for Information Diffusion

    NASA Astrophysics Data System (ADS)

    Nematzadeh, Azadeh; Ferrara, Emilio; Flammini, Alessandro; Ahn, Yong-Yeol

    2014-08-01

    We investigate the impact of community structure on information diffusion with the linear threshold model. Our results demonstrate that modular structure may have counterintuitive effects on information diffusion when social reinforcement is present. We show that strong communities can facilitate global diffusion by enhancing local, intracommunity spreading. Using both analytic approaches and numerical simulations, we demonstrate the existence of an optimal network modularity, where global diffusion requires the minimal number of early adopters.

  17. Convection enhanced delivery of carmustine to the murine brainstem: a feasibility study.

    PubMed

    Sewing, A Charlotte P; Caretti, Viola; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H A; van Vuurden, Dannis G; Idema, Sander; Molthoff, Carla F M; Vandertop, W Peter; Kaspers, Gertjan J L; Noske, David P; Hulleman, Esther

    2014-12-30

    Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients. The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol. Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors. Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals. CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Ten-year outcome of early childhood traumatic brain injury: Diffusion tensor imaging of the ventral striatum in relation to executive functioning.

    PubMed

    Faber, J; Wilde, E A; Hanten, G; Ewing-Cobbs, L; Aitken, M E; Yallampalli, R; MacLeod, M C; Mullins, S H; Chu, Z D; Li, X; Hunter, J V; Noble-Haeusslein, L; Levin, H S

    2016-01-01

    The long-term effects of TBI on verbal fluency and related structures, as well as the relation between cognition and structural integrity, were evaluated. It was hypothesized that the group with TBI would evidence poorer performance on cognitive measures and a decrease in structural integrity. Between a paediatric group with TBI and a group of typically-developing children, the long-term effects of traumatic brain injury were investigated in relation to both structural integrity and cognition. Common metrics for diffusion tensor imaging (DTI) were used as indicators of white matter integrity. Using DTI, this study examined ventral striatum (VS) integrity in 21 patients aged 10-18 years sustaining moderate-to-severe traumatic brain injury (TBI) 5-15 years earlier and 16 demographically comparable subjects. All participants completed Delis-Kaplan Executive Functioning System (D-KEFS) sub-tests. The group with TBI exhibited lower fractional anisotropy (FA) and executive functioning performance and higher apparent diffusion coefficient (ADC). DTI metrics correlated with D-KEFS performance (right VS FA with Inhibition errors, right VS ADC with Letter Fluency, left VS FA and ADC with Category Switching). TBI affects VS integrity, even in a chronic phase, and may contribute to executive functioning deficits.

  19. Fractional Diffusion Equations and Anomalous Diffusion

    NASA Astrophysics Data System (ADS)

    Evangelista, Luiz Roberto; Kaminski Lenzi, Ervin

    2018-01-01

    Preface; 1. Mathematical preliminaries; 2. A survey of the fractional calculus; 3. From normal to anomalous diffusion; 4. Fractional diffusion equations: elementary applications; 5. Fractional diffusion equations: surface effects; 6. Fractional nonlinear diffusion equation; 7. Anomalous diffusion: anisotropic case; 8. Fractional Schrödinger equations; 9. Anomalous diffusion and impedance spectroscopy; 10. The Poisson–Nernst–Planck anomalous (PNPA) models; References; Index.

  20. Diffuser Test

    2007-09-13

    Tests begun at Stennis Space Center's E Complex Sept. 13 evaluated a liquid oxygen lead for engine start performance, part of the A-3 Test Facility Subscale Diffuser Risk Mitigation Project at SSC's E-3 Test Facility. Phase 1 of the subscale diffuser project, completed Sept. 24, was a series of 18 hot-fire tests using a 1,000-pound liquid oxygen and gaseous hydrogen thruster to verify maximum duration and repeatability for steam generation supporting the A-3 Test Stand project. The thruster is a stand-in for NASA's developing J-2X engine, to validate a 6 percent scale version of A-3's exhaust diffuser. Testing the J-2X at altitude conditions requires an enormous diffuser. Engineers will generate nearly 4,600 pounds per second of steam to reduce pressure inside A-3's test cell to simulate altitude conditions. A-3's exhaust diffuser has to be able to withstand regulated pressure, temperatures and the safe discharge of the steam produced during those tests. Before the real thing is built, engineers hope to work out any issues on the miniature version. Phase 2 testing is scheduled to begin this month.

  1. Demonstrating Diffusion

    ERIC Educational Resources Information Center

    Foy, Barry G.

    1977-01-01

    Two demonstrations are described. Materials and instructions for demonstrating movement of molecules into cytoplasm using agar blocks, phenolphthalein, and sodium hydroxide are given. A simple method for demonstrating that the rate of diffusion of a gas is inversely proportional to its molecular weight is also presented. (AJ)

  2. Defusing Diffusion

    ERIC Educational Resources Information Center

    Dou, Remy; Hogan, DaNel; Kossover, Mark; Spuck, Timothy; Young, Sarah

    2013-01-01

    Diffusion has often been taught in science courses as one of the primary ways by which molecules travel, particularly within organisms. For years, classroom teachers have used the same common demonstrations to illustrate this concept (e.g., placing drops of food coloring in a beaker of water). Most of the time, the main contributor to the motion…

  3. The mechanical fingerprint of murine excisional wounds.

    PubMed

    Pensalfini, Marco; Haertel, Eric; Hopf, Raoul; Wietecha, Mateusz; Werner, Sabine; Mazza, Edoardo

    2018-01-01

    A multiscale mechanics approach to the characterization of murine excisional wounds subjected to uniaxial tensile loading is presented. Local strain analysis at a physiological level of tension uncovers the presence of two distinct regions within the wound: i) a very compliant peripheral cushion and ii) a core area undergoing modest deformation. Microstructural visualizations of stretched wound specimens show negligible engagement of the collagen located in the center of a 7-day old wound; fibers remain coiled despite the applied tension, confirming the existence of a mechanically isolated wound core. The compliant cushion located at the wound periphery appears to protect the newly-formed tissue from excessive deformation during the phase of new tissue formation. The early remodeling phase (day 14) is characterized by a restored mechanical connection between far field and wound center. The latter remains less deformable, a characteristic possibly required for cell activities during tissue remodeling. The distribution of fibrillary collagens at these two time points corresponds well to the identified heterogeneity of mechanical properties of the wound region. This novel approach provides new insight into the mechanical properties of wounded skin and will be applicable to the analysis of compound-treated wounds or wounds in genetically modified tissue. Biophysical characterization of healing wounds is crucial to assess the recovery of the skin barrier function and the associated mechanobiological processes. For the first time, we performed highly resolved local deformation analysis to identify mechanical characteristics of the wound and its periphery. Our results reveal the presence of a compliant cushion surrounding a stiffer wound core; we refer to this heterogeneous mechanical behavior as "mechanical fingerprint" of the wound. The mechanical response is shown to progress towards that of the intact skin as healing takes place. Histology and multiphoton microscopy

  4. Diffusion bonding

    DOEpatents

    Anderson, Robert C.

    1976-06-22

    1. A method for joining beryllium to beryllium by diffusion bonding, comprising the steps of coating at least one surface portion of at least two beryllium pieces with nickel, positioning a coated surface portion in a contiguous relationship with an other surface portion, subjecting the contiguously disposed surface portions to an environment having an atmosphere at a pressure lower than ambient pressure, applying a force upon the beryllium pieces for causing the contiguous surface portions to abut against each other, heating the contiguous surface portions to a maximum temperature less than the melting temperature of the beryllium, substantially uniformly decreasing the applied force while increasing the temperature after attaining a temperature substantially above room temperature, and maintaining a portion of the applied force at a temperature corresponding to about maximum temperature for a duration sufficient to effect the diffusion bond between the contiguous surface portions.

  5. 3He Diffusion MRI of the Lung

    PubMed Central

    Conradi, Mark S.; Yablonskiy, Dmitriy A.; Woods, Jason C.; Gierada, David S.; Jacob, Richard E.; Chang, Yulin V.; Choong, Cliff K.; Sukstanskii, Alex L.; Tanoli, Tariq; Lefrak, Stephen S.; Cooper, Joel D.

    2007-01-01

    Rationale and Objectives MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. Results We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. Methods Techniques for purging and imaging excised lungs are discussed. PMID:16253852

  6. Improved Murine Blastocyst Quality and Development in a Single Culture Medium Compared to Sequential Culture Media

    PubMed Central

    Hennings, Justin M.; Zimmer, Randall L.; Nabli, Henda; Davis, J. Wade; Sutovsky, Peter; Sutovsky, Miriam; Sharpe-Timms, Kathy L.

    2015-01-01

    Objective: Validate single versus sequential culture media for murine embryo development. Design: Prospective laboratory experiment. Setting: Assisted Reproduction Laboratory. Animals: Murine embryos. Interventions: Thawed murine zygotes cultured for 3 or 5 days (d3 or d5) in single or sequential embryo culture media developed for human in vitro fertilization. Main Outcome Measures: On d3, zygotes developing to the 8 cell (8C) stage or greater were quantified using 4’,6-diamidino-2-phenylindole (DAPI), and quality was assessed by morphological analysis. On d5, the number of embryos reaching the blastocyst stage was counted. DAPI was used to quantify total nuclei and inner cell mass nuclei. Localization of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase L3 (UCHL3) was reference points for evaluating cell quality. Results: Comparing outcomes in single versus to sequential media, the odds of embryos developing to the 8C stage on d3 were 2.34 time greater (P = .06). On d5, more embryos reached the blastocyst stage (P = <.0001), hatched, and had significantly more trophoblast cells (P = .005) contributing to the increased total cell number. Also at d5, localization of distinct cytoplasmic UCHL1 and nuclear UCHL3 was found in high-quality hatching blastocysts. Localization of UCHL1 and UCHL3 was diffuse and inappropriately dispersed throughout the cytoplasm in low-quality nonhatching blastocysts. Conclusions: Single medium yields greater cell numbers, an increased growth rate, and more hatching of murine embryos. Cytoplasmic UCHL1 and nuclear UHCL3 localization patterns were indicative of embryo quality. Our conclusions are limited to murine embryos but one might speculate that single medium may also be more beneficial for human embryo culture. Human embryo studies are needed. PMID:26668049

  7. Improved Murine Blastocyst Quality and Development in a Single Culture Medium Compared to Sequential Culture Media.

    PubMed

    Hennings, Justin M; Zimmer, Randall L; Nabli, Henda; Davis, J Wade; Sutovsky, Peter; Sutovsky, Miriam; Sharpe-Timms, Kathy L

    2016-03-01

    Validate single versus sequential culture media for murine embryo development. Prospective laboratory experiment. Assisted Reproduction Laboratory. Murine embryos. Thawed murine zygotes cultured for 3 or 5 days (d3 or d5) in single or sequential embryo culture media developed for human in vitro fertilization. On d3, zygotes developing to the 8 cell (8C) stage or greater were quantified using 4',6-diamidino-2-phenylindole (DAPI), and quality was assessed by morphological analysis. On d5, the number of embryos reaching the blastocyst stage was counted. DAPI was used to quantify total nuclei and inner cell mass nuclei. Localization of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase L3 (UCHL3) was reference points for evaluating cell quality. Comparing outcomes in single versus to sequential media, the odds of embryos developing to the 8C stage on d3 were 2.34 time greater (P = .06). On d5, more embryos reached the blastocyst stage (P = <.0001), hatched, and had significantly more trophoblast cells (P = .005) contributing to the increased total cell number. Also at d5, localization of distinct cytoplasmic UCHL1 and nuclear UCHL3 was found in high-quality hatching blastocysts. Localization of UCHL1 and UCHL3 was diffuse and inappropriately dispersed throughout the cytoplasm in low-quality nonhatching blastocysts. Single medium yields greater cell numbers, an increased growth rate, and more hatching of murine embryos. Cytoplasmic UCHL1 and nuclear UHCL3 localization patterns were indicative of embryo quality. Our conclusions are limited to murine embryos but one might speculate that single medium may also be more beneficial for human embryo culture. Human embryo studies are needed. © The Author(s) 2015.

  8. Isolation and Differentiation of Murine Macrophages.

    PubMed

    Rios, Francisco J; Touyz, Rhian M; Montezano, Augusto C

    2017-01-01

    Macrophages play a major role in inflammation, wound healing, and tissue repair. Infiltrated monocytes differentiate into different macrophage subtypes with protective or pathogenic activities in vascular lesions. In the heart and vascular tissues, pathological activation promotes cardiovascular inflammation and remodeling and there is increasing evidence that macrophages play important mechanisms in this environment. Primary murine macrophages can be obtained from: bone marrow by different treatments (granulocyte-macrophage colony-stimulating factor-GM-CSF, macrophage colony-stimulating factor-M-CSF or supernatant of murine fibroblast L929), peritoneal cavity (resident or thioglycolate elicit macrophages), from the lung (alveolar macrophages) or from adipose tissue. In this chapter we describe some protocols to obtain primary murine macrophages and how to identify a pure macrophage population or activation phenotypes using different markers.

  9. DIFFUSION PUMP

    DOEpatents

    Levenson, L.

    1963-09-01

    A high-vacuum diffusion pump is described, featuring a novel housing geometry for enhancing pumping speed. An upright, cylindrical lower housing portion is surmounted by a concentric, upright, cylindrical upper housing portion of substantially larger diameter; an uppermost nozzle, disposed concentrically within the upper portion, is adapted to eject downwardly a conical sheet of liquid outwardly to impinge upon the uppermost extremity of the interior wall of the lower portion. Preferably this nozzle is mounted upon a pedestal rising coaxially from within the lower portion and projecting up into said upper portion. (AEC)

  10. Hereditary Diffuse Gastric Cancer

    MedlinePlus

    ... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

  11. TU-F-CAMPUS-J-02: Evaluation of Textural Feature Extraction for Radiotherapy Response Assessment of Early Stage Breast Cancer Patients Using Diffusion Weighted MRI and Dynamic Contrast Enhanced MRI

    SciT

    Xie, Y; Wang, C; Horton, J

    Purpose: To investigate the feasibility of using classic textural feature extraction in radiotherapy response assessment, we studied a unique cohort of early stage breast cancer patients with paired pre - and post-radiation Diffusion Weighted MRI (DWI-MRI) and Dynamic Contrast Enhanced MRI (DCE-MRI). Methods: 15 female patients from our prospective phase I trial evaluating preoperative radiotherapy were included in this retrospective study. Each patient received a single-fraction radiation treatment, and DWI and DCE scans were conducted before and after the radiotherapy. DWI scans were acquired using a spin-echo EPI sequence with diffusion weighting factors of b = 0 and b =more » 500 mm{sup 2} /s, and the apparent diffusion coefficient (ADC) maps were calculated. DCE-MRI scans were acquired using a T{sub 1}-weighted 3D SPGR sequence with a temporal resolution of about 1 minute. The contrast agent (CA) was intravenously injected with a 0.1 mmol/kg bodyweight dose at 2 ml/s. Two parameters, volume transfer constant (K{sup trans} ) and k{sub ep} were analyzed using the two-compartment Tofts kinetic model. For DCE parametric maps and ADC maps, 33 textural features were generated from the clinical target volume (CTV) in a 3D fashion using the classic gray level co-occurrence matrix (GLCOM) and gray level run length matrix (GLRLM). Wilcoxon signed-rank test was used to determine the significance of each texture feature’s change after the radiotherapy. The significance was set to 0.05 with Bonferroni correction. Results: For ADC maps calculated from DWI-MRI, 24 out of 33 CTV features changed significantly after the radiotherapy. For DCE-MRI pharmacokinetic parameters, all 33 CTV features of K{sup trans} and 33 features of k{sub ep} changed significantly. Conclusion: Initial results indicate that those significantly changed classic texture features are sensitive to radiation-induced changes and can be used for assessment of radiotherapy response in breast cancer.« less

  12. A Novel Murine Model for Localized Radiation Necrosis and its Characterization Using Advanced Magnetic Resonance Imaging

    SciT

    Jost, Sarah C.; Hope, Andrew; Kiehl, Erich

    Purpose: To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques. Methods and Materials: Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis. Results: Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressivemore » radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 {mu}m{sup 2}/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 {mu}m{sup 2}/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis. Conclusions: This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.« less

  13. Diffuse reflectance spectroscopy of liver tissue

    NASA Astrophysics Data System (ADS)

    Reistad, Nina; Nilsson, Jan; Vilhelmsson Timmermand, Oskar; Sturesson, Christian; Andersson-Engels, Stefan

    2015-06-01

    Diffuse reflectance spectroscopy (DRS) with a fiber-optic contact probe is a cost-effective, rapid, and non-invasive optical method used to extract diagnosis information of tissue. By combining commercially available VIS- and NIR-spectrometers with various fiber-optic contact-probes, we have access to the full wavelength range from around 400 to 1600 nm. Using this flexible and portable spectroscopy system, we have acquired ex-vivo DRS-spectra from murine, porcine, and human liver tissue. For extracting the tissue optical properties from the measured spectra, we have employed and compared predictions from two models for light propagation in tissue, diffusion theory model (DT) and Monte Carlo simulations (MC). The focus in this work is on the capacity of this DRS-technique in discriminating metastatic tumor tissue from normal liver tissue as well as in assessing and characterizing damage to non-malignant liver tissue induced by preoperative chemotherapy for colorectal liver metastases.

  14. Effect of cooling rate on human and murine hemopoietic precursor cell recovery

    SciT

    Niskanen, E.; Pirsch, G.

    1983-08-01

    The effect of cooling rate on recovery of human and murine hemopoietic precursor cells was studied. In the presence of 10% Me2SO, a cooling rate of 7 degrees C/min from -4 to -30 degrees C was optimal for recovery of both human and murine precursor cells which give rise to colonies in diffusion chambers implanted in mice (CFU-DG). Cooling of human marrow at a rate between 3 and 7 degrees C/min resulted in the best CFU-C recovery, although no good correlation between the cooling rate and murine CFU-C recovery was demonstrated. These data suggest that recovery of the primitive hemopoieticmore » precursor cells can be improved by changing the standard cryopreservation programs used presently. However, improved recovery of CFU-DG does not necessarily translate into faster reconstitution of hemopoiesis. No significant difference was observed in overall recovery of bone marrow cellularity in lethally irradiated mice following injection of untreated marrow and marrow cooled at a rate of 1 and 7 degrees C/min.« less

  15. Diffusion archeology for diffusion progression history reconstruction.

    PubMed

    Sefer, Emre; Kingsford, Carl

    2016-11-01

    Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring - perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial diffusion data. Here, we tackle the problem of reconstructing a diffusion history from one or more snapshots of the diffusion state. This ability can be invaluable to learn when certain computer nodes are infected or which people are the initial disease spreaders to control future diffusions. We formulate this problem over discrete-time SEIRS-type diffusion models in terms of maximum likelihood. We design methods that are based on submodularity and a novel prize-collecting dominating-set vertex cover (PCDSVC) relaxation that can identify likely diffusion steps with some provable performance guarantees. Our methods are the first to be able to reconstruct complete diffusion histories accurately in real and simulated situations. As a special case, they can also identify the initial spreaders better than the existing methods for that problem. Our results for both meme and contaminant diffusion show that the partial diffusion data problem can be overcome with proper modeling and methods, and that hidden temporal characteristics of diffusion can be predicted from limited data.

  16. Diffusion archeology for diffusion progression history reconstruction

    PubMed Central

    Sefer, Emre; Kingsford, Carl

    2015-01-01

    Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring — perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial diffusion data. Here, we tackle the problem of reconstructing a diffusion history from one or more snapshots of the diffusion state. This ability can be invaluable to learn when certain computer nodes are infected or which people are the initial disease spreaders to control future diffusions. We formulate this problem over discrete-time SEIRS-type diffusion models in terms of maximum likelihood. We design methods that are based on submodularity and a novel prize-collecting dominating-set vertex cover (PCDSVC) relaxation that can identify likely diffusion steps with some provable performance guarantees. Our methods are the first to be able to reconstruct complete diffusion histories accurately in real and simulated situations. As a special case, they can also identify the initial spreaders better than the existing methods for that problem. Our results for both meme and contaminant diffusion show that the partial diffusion data problem can be overcome with proper modeling and methods, and that hidden temporal characteristics of diffusion can be predicted from limited data. PMID:27821901

  17. NIST Diffusion Data Center

    National Institute of Standards and Technology Data Gateway

    NIST Diffusion Data Center (Web, free access)   The NIST Diffusion Data Center is a collection of over 14,100 international papers, theses, and government reports on diffusion published before 1980.

  18. Parallel flow diffusion battery

    DOEpatents

    Yeh, H.C.; Cheng, Y.S.

    1984-01-01

    A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

  19. Parallel flow diffusion battery

    DOEpatents

    Yeh, Hsu-Chi; Cheng, Yung-Sung

    1984-08-07

    A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

  20. Enhanced Cultivation Of Stimulated Murine B Cells

    NASA Technical Reports Server (NTRS)

    Sammons, David W.

    1994-01-01

    Method of in vitro cultivation of large numbers of stimulated murine B lymphocytes. Cells electrofused with other cells to produce hybridomas and monoclonal antibodies. Offers several advantages: polyclonally stimulated B-cell blasts cultivated for as long as 14 days, hybridomas created throughout culture period, yield of hybridomas increases during cultivation, and possible to expand polyclonally in vitro number of B cells specific for antigenic determinants first recognized in vivo.

  1. FRACTIONAL PEARSON DIFFUSIONS.

    PubMed

    Leonenko, Nikolai N; Meerschaert, Mark M; Sikorskii, Alla

    2013-07-15

    Pearson diffusions are governed by diffusion equations with polynomial coefficients. Fractional Pearson diffusions are governed by the corresponding time-fractional diffusion equation. They are useful for modeling sub-diffusive phenomena, caused by particle sticking and trapping. This paper provides explicit strong solutions for fractional Pearson diffusions, using spectral methods. It also presents stochastic solutions, using a non-Markovian inverse stable time change.

  2. Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model

    PubMed Central

    Nagata, Towako; Mukae, Hiroshi; Kadota, Junichi; Hayashi, Tomayoshi; Fujii, Takeshi; Kuroki, Misuzu; Shirai, Ryo; Yanagihara, Katsunori; Tomono, Kazunori; Koji, Takehiko; Kohno, Shigeru

    2004-01-01

    Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stage Pseudomonas aeruginosa infection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratory P. aeruginosa infection. ERY or saline was administered from day 80 after intubation with a P. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viable P. aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P. aeruginosa on the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction in P. aeruginosa biofilm formation. PMID:15155229

  3. Tissue distribution, regulation and intracellular localization of murine CD1 molecules.

    PubMed

    Mandal, M; Chen, X R; Alegre, M L; Chiu, N M; Chen, Y H; Castaño, A R; Wang, C R

    1998-06-01

    CD1 molecules are MHC-unlinked class Ib molecules consisting of classical (human CD 1a-c) and non-classical subsets (human CD1d and murine CD1). The characterization of non-classical subsets of CD1 is limited due to the lack of reagents. In this study, we have generated two new anti-mouse CD1 monoclonal antibodies, 3H3 and 5C6, by immunization of hamsters with purified CD1 protein. These antibodies recognize CD1-transfected cells and have no reactivity to cells isolated from CD1-/- mice. Both antibodies precipitate the 52 kDa heavy chain and 12 kDa beta2m from thymocytes and splenocytes by radio-immunoprecipitation. Deglycosylation of CD1 reduces molecular mass of the heavy chain by 7.5 kDa, which can be detected by 3H3 but not 5C6. 3H3 and 5C6 detect surface CD1 expression on cells from the thymus, spleen, lymph node and bone marrow, but not on intestinal epithelial cells. Developmentally, CD1 is expressed on thymocytes prior to TCR rearrangement and remains constant throughout thymic development. CD1 is expressed early in the fetal liver (day 14) and remains expressed in hepatocytes postnatally. These data support evidence of a role for CD1 in the selection and/or expansion of NK1- T cells of both thymic origin and extrathymic origin. Unlike classical class I molecules, murine CD1 levels are not affected by IFN-gamma, but like human CD1b can be up-regulated by IL-4 and GM-CSF although only moderately. Similar to human CD1b, murine CD1 is found by immunofluorescence microscopy on the cell surface, and in various intracellular vesicles, including early and late endosomes. Localization in endocytic compartments indicates that murine CD1 may be capable of binding endocytosed antigens.

  4. Successful Reperfusion With Mechanical Thrombectomy Is Associated With Reduced Disability and Mortality in Patients With Pretreatment Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score ≤6.

    PubMed

    Desilles, Jean-Philippe; Consoli, Arthuro; Redjem, Hocine; Coskun, Oguzhan; Ciccio, Gabriele; Smajda, Stanislas; Labreuche, Julien; Preda, Cristian; Ruiz Guerrero, Clara; Decroix, Jean-Pierre; Rodesch, Georges; Mazighi, Mikael; Blanc, Raphaël; Piotin, Michel; Lapergue, Bertrand

    2017-04-01

    In acute ischemic stroke patients, diffusion-weighted imaging (DWI)-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is correlated with infarct volume and is an independent factor of functional outcome. Patients with pretreatment DWI-ASPECTS ≤6 were excluded or under-represented in the recent randomized mechanical thrombectomy trials. Our aim was to assess the impact of reperfusion in pretreatment DWI-ASPECTS ≤6 patients treated with mechanical thrombectomy. We analyzed data collected between January 2012 and August 2015 in a bicentric prospective clinical registry of consecutive acute ischemic stroke patients treated with mechanical thrombectomy. Every patient with a documented internal carotid artery or middle cerebral artery occlusion with pretreatment DWI-ASPECTS ≤6 was eligible for this study. The primary end point was a favorable outcome defined by a modified Rankin Scale score ≤2 at 90 days. Two hundred and eighteen patients with a DWI-ASPECTS ≤6 were included. Among them, 145 (66%) patients had successful reperfusion at the end of mechanical thrombectomy. Reperfused patients had an increased rate of favorable outcome (38.7% versus 17.4%; P =0.002) and a decreased rate of mortality at 3 months (22.5% versus 39.1%; P =0.013) compared with nonreperfused patients. The symptomatic intracranial hemorrhage rate was not different between the 2 groups (13.0% versus 14.1%; P =0.83). However, in patients with DWI-ASPECTS <5, favorable outcome was low (13.0% versus 9.5%; P =0.68) with a high mortality rate (45.7% versus 57.1%; P =0.38) with or without successful reperfusion. Successful reperfusion is associated with reduced mortality and disability in patients with a pretreatment DWI-ASPECTS ≤6. Further data from randomized studies are needed, particularly in patients with DWI-ASPECTS <5. © 2017 American Heart Association, Inc.

  5. Diffusing diffusivity: Rotational diffusion in two and three dimensions

    NASA Astrophysics Data System (ADS)

    Jain, Rohit; Sebastian, K. L.

    2017-06-01

    We consider the problem of calculating the probability distribution function (pdf) of angular displacement for rotational diffusion in a crowded, rearranging medium. We use the diffusing diffusivity model and following our previous work on translational diffusion [R. Jain and K. L. Sebastian, J. Phys. Chem. B 120, 3988 (2016)], we show that the problem can be reduced to that of calculating the survival probability of a particle undergoing Brownian motion, in the presence of a sink. We use the approach to calculate the pdf for the rotational motion in two and three dimensions. We also propose new dimensionless, time dependent parameters, αr o t ,2 D and αr o t ,3 D, which can be used to analyze the experimental/simulation data to find the extent of deviation from the normal behavior, i.e., constant diffusivity, and obtain explicit analytical expressions for them, within our model.

  6. Murine Toxicity of Cochliobolus carbonum1

    PubMed Central

    Hamilton, Pat B.; Nelson, R. R.; Harris, B. S. H.

    1968-01-01

    Seventeen wild-type strains of the phytopathogenic fungus Cochliobolus carbonum, tested by intraperitoneal injection into mice, were lethal within 48 hr. The lethal effect appeared to be a toxic rather than an infectious process, because death occurred within 3 hr after injection of two of the isolates and heat-killed cultures were lethal. Assays of ascospore progeny from two crosses involving three isolates indicated that the toxic metabolites were under genetic control and quantitative regulation. Studies of the toxicological, cultural, and chemical characteristics of these three strains indicated that more than one murine toxin was present. PMID:16349821

  7. Irradiation Design for an Experimental Murine Model

    SciT

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.

    2010-12-07

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  8. Efficacy of Posaconazole in Murine Experimental Sporotrichosis

    PubMed Central

    Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio

    2012-01-01

    We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology. PMID:22330929

  9. Efficacy of posaconazole in murine experimental sporotrichosis.

    PubMed

    Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

    2012-05-01

    We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

  10. Thrombopoietin inhibits murine mast cell differentiation

    PubMed Central

    Martelli, Fabrizio; Ghinassi, Barbara; Lorenzini, Rodolfo; Vannucchi, Alessandro M; Rana, Rosa Alba; Nishikawa, Mitsuo; Partamian, Sandra; Migliaccio, Giovanni; Migliaccio, Anna Rita

    2009-01-01

    We have recently shown that Mpl, the thrombopoietin receptor, is expressed on murine mast cells and on their precursors and that targeted deletion of the Mpl gene increases mast cell differentiation in mice. Here we report that treatment of mice with thrombopoietin, or addition of this growth factor to bone marrow-derived mast cell cultures, severely hampers the generation of mature cells from their precursors by inducing apoptosis. Analysis of the expression profiling of mast cells obtained in the presence of thrombopoietin suggests that thrombopoietin induces apoptosis of mast cells by reducing expression of the transcription factor Mitf and its target anti-apoptotic gene Bcl2. PMID:18276801

  11. Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis.

    PubMed

    Laudes, Matthias; Christodoulides, Constantinos; Sewter, Ciaran; Rochford, Justin J; Considine, Robert V; Sethi, Jaswinder K; Vidal-Puig, Antonio; O'Rahilly, Stephen

    2004-03-19

    Poxvirus zinc finger (POZ) zinc finger domain transcription factors have been shown to play a role in the control of growth arrest and differentiation in several types of mesenchymal cells but not, as yet, adipocytes. We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2-4. FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for accelerated adipogenesis with earlier induction of markers of differentiation and enhanced lipid accumulation, suggesting that FBI-1 may be an active participant in the differentiation process. Consistent with the properties of this family of proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase 2, and p107, proteins known to be involved in the regulation of mitotic clonal expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced during the early phases of human and murine preadipocyte differentiation where it may contribute to adipogenesis through influencing the switch from cellular proliferation to terminal differentiation.

  12. Role of the POZ Zinc Finger Transcription Factor FBI-1 in Human and Murine Adipogenesis

    PubMed Central

    Laudes, Matthias; Christodoulides, Constantinos; Sewter, Ciaran; Rochford, Justin J.; Considine, Robert V.; Sethi, Jaswinder K.; Vidal-Puig, Antonio; O’Rahilly, Stephen

    2015-01-01

    Poxvirus zinc finger (POZ) zinc finger domain transcription factors have been shown to play a role in the control of growth arrest and differentiation in several types of mesenchymal cells but not, as yet, adipocytes. We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2–4. FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for accelerated adipogenesis with earlier induction of markers of differentiation and enhanced lipid accumulation, suggesting that FBI-1 may be an active participant in the differentiation process. Consistent with the properties of this family of proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase 2, and p107, proteins known to be involved in the regulation of mitotic clonal expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced during the early phases of human and murine preadipocyte differentiation where it may contribute to adipogenesis through influencing the switch from cellular proliferation to terminal differentiation. PMID:14701838

  13. Properties of murine embryonic stem cells maintained on human foreskin fibroblasts without LIF.

    PubMed

    Meng, G L; Zur Nieden, N I; Liu, S Y; Cormier, J T; Kallos, M S; Rancourt, D E

    2008-04-01

    In embryonic stem (ES) cells, leukemia inhibitory factor (LIF)/STAT3, wnt and nodal/activin signaling are mainly active to control pluripotency during expansion. To maintain pluripotency, ES cells are typically cultured on feeder cells of varying origins. Murine ES cells are commonly cultured on murine embryonic fibroblasts (MEFs), which senesce early and must be frequently prepared. This process is laborious and leads to batch variation presenting a challenge for high-throughput ES cell expansion. Although some cell lines can be sustained by exogenous LIF, this method is costly. We present here a novel and inexpensive culture method for expanding murine ES cells on human foreskin fibroblast (HFF) feeders. After 20 passages on HFFs without LIF, ES cell lines showed normal expression levels of pluripotency markers, maintained a normal karyotype and retained the ability to contribute to the germline. As HFFs do not senesce for at least 62 passages, they present a vast supply of feeders. Copyright 2007 Wiley-Liss, Inc.

  14. Diffusion in Brain Extracellular Space

    PubMed Central

    Syková, Eva; Nicholson, Charles

    2009-01-01

    Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecules in the brain. Deviations from the equation reveal loss of molecules across the blood-brain barrier, through cellular uptake, binding or other mechanisms. Early diffusion measurements used radiolabeled sucrose and other tracers. Presently, the real-time iontophoresis (RTI) method is employed for small ions and the integrative optical imaging (IOI) method for fluorescent macromolecules, including dextrans or proteins. Theoretical models and simulations of the ECS have explored the influence of ECS geometry, effects of dead-space microdomains, extracellular matrix and interaction of macromolecules with ECS channels. Extensive experimental studies with the RTI method employing the cation tetramethylammonium (TMA) in normal brain tissue show that the volume fraction of the ECS typically is about 20% and the tortuosity about 1.6 (i.e. free diffusion coefficient of TMA is reduced by 2.6), although there are regional variations. These parameters change during development and aging. Diffusion properties have been characterized in several interventions, including brain stimulation, osmotic challenge and knockout of extracellular matrix components. Measurements have also been made during ischemia, in models of Alzheimer's and Parkinson's diseases and in human gliomas. Overall, these studies improve our conception of ECS structure and the roles of glia and extracellular matrix in modulating the ECS microenvironment. Knowledge of ECS diffusion properties are valuable in contexts ranging from understanding extrasynaptic volume transmission to the development of paradigms for drug delivery to the brain. PMID:18923183

  15. Spin-diffusions and diffusive molecular dynamics

    NASA Astrophysics Data System (ADS)

    Farmer, Brittan; Luskin, Mitchell; Plecháč, Petr; Simpson, Gideon

    2017-12-01

    Metastable configurations in condensed matter typically fluctuate about local energy minima at the femtosecond time scale before transitioning between local minima after nanoseconds or microseconds. This vast scale separation limits the applicability of classical molecular dynamics (MD) methods and has spurned the development of a host of approximate algorithms. One recently proposed method is diffusive MD which aims at integrating a system of ordinary differential equations describing the likelihood of occupancy by one of two species, in the case of a binary alloy, while quasistatically evolving the locations of the atoms. While diffusive MD has shown itself to be efficient and provide agreement with observations, it is fundamentally a model, with unclear connections to classical MD. In this work, we formulate a spin-diffusion stochastic process and show how it can be connected to diffusive MD. The spin-diffusion model couples a classical overdamped Langevin equation to a kinetic Monte Carlo model for exchange amongst the species of a binary alloy. Under suitable assumptions and approximations, spin-diffusion can be shown to lead to diffusive MD type models. The key assumptions and approximations include a well-defined time scale separation, a choice of spin-exchange rates, a low temperature approximation, and a mean field type approximation. We derive several models from different assumptions and show their relationship to diffusive MD. Differences and similarities amongst the models are explored in a simple test problem.

  16. Murine Electrophysiological Models of Cardiac Arrhythmogenesis

    PubMed Central

    2016-01-01

    Cardiac arrhythmias can follow disruption of the normal cellular electrophysiological processes underlying excitable activity and their tissue propagation as coherent wavefronts from the primary sinoatrial node pacemaker, through the atria, conducting structures and ventricular myocardium. These physiological events are driven by interacting, voltage-dependent, processes of activation, inactivation, and recovery in the ion channels present in cardiomyocyte membranes. Generation and conduction of these events are further modulated by intracellular Ca2+ homeostasis, and metabolic and structural change. This review describes experimental studies on murine models for known clinical arrhythmic conditions in which these mechanisms were modified by genetic, physiological, or pharmacological manipulation. These exemplars yielded molecular, physiological, and structural phenotypes often directly translatable to their corresponding clinical conditions, which could be investigated at the molecular, cellular, tissue, organ, and whole animal levels. Arrhythmogenesis could be explored during normal pacing activity, regular stimulation, following imposed extra-stimuli, or during progressively incremented steady pacing frequencies. Arrhythmic substrate was identified with temporal and spatial functional heterogeneities predisposing to reentrant excitation phenomena. These could arise from abnormalities in cardiac pacing function, tissue electrical connectivity, and cellular excitation and recovery. Triggering events during or following recovery from action potential excitation could thereby lead to sustained arrhythmia. These surface membrane processes were modified by alterations in cellular Ca2+ homeostasis and energetics, as well as cellular and tissue structural change. Study of murine systems thus offers major insights into both our understanding of normal cardiac activity and its propagation, and their relationship to mechanisms generating clinical arrhythmias. PMID:27974512

  17. [Virulence of Sporothrix globosa in murine models].

    PubMed

    Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

    The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Murine models of breast cancer bone metastasis

    PubMed Central

    Wright, Laura E; Ottewell, Penelope D; Rucci, Nadia; Peyruchaud, Olivier; Pagnotti, Gabriel M; Chiechi, Antonella; Buijs, Jeroen T; Sterling, Julie A

    2016-01-01

    Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis. We then provide protocols for four of the most common xenograft and syngeneic inoculation routes for modeling breast cancer metastasis to the skeleton in mice, including the intra-cardiac, intra-arterial, orthotopic and intra-tibial methods of tumor cell injection. Recommendations for in vivo and ex vivo assessment of tumor progression and bone destruction are provided, followed by discussion of the strengths and limitations of the available tools and translational models that aid investigators in the study of breast cancer metastasis to bone. PMID:27867497

  19. Microfabricated diffusion source

    DOEpatents

    Oborny, Michael C [Albuquerque, NM; Frye-Mason, Gregory C [Cedar Crest, NM; Manginell, Ronald P [Albuquerque, NM

    2008-07-15

    A microfabricated diffusion source to provide for a controlled diffusion rate of a vapor comprises a porous reservoir formed in a substrate that can be filled with a liquid, a headspace cavity for evaporation of the vapor therein, a diffusion channel to provide a controlled diffusion of the vapor, and an outlet to release the vapor into a gas stream. The microfabricated diffusion source can provide a calibration standard for a microanalytical system. The microanalytical system with an integral diffusion source can be fabricated with microelectromechanical systems technologies.

  20. Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma

    PubMed Central

    Monje, Michelle; Mitra, Siddhartha S.; Freret, Morgan E.; Raveh, Tal B.; Kim, James; Masek, Marilyn; Attema, Joanne L.; Haddix, Terri; Edwards, Michael S. B.; Fisher, Paul G.; Weissman, Irving L.; Rowitch, David H.; Vogel, Hannes; Wong, Albert J.; Beachy, Philip A.

    2011-01-01

    Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor. PMID:21368213

  1. In vivo imaging of malaria parasites in the murine liver.

    PubMed

    Thiberge, Sabine; Blazquez, Samantha; Baldacci, Patricia; Renaud, Olivier; Shorte, Spencer; Ménard, Robert; Amino, Rogerio

    2007-01-01

    The form of the malaria parasite inoculated by the mosquito, called the sporozoite, transforms inside the host liver into thousands of a new form of the parasite, called the merozoite, which infects erythrocytes. We present here a protocol to visualize in vivo the behavior of Plasmodium berghei parasites in the hepatic tissue of the murine host. The use of GFP-expressing parasites and a high-speed spinning disk confocal microscope allows for the acquisition of four-dimensional images, which provide a time lapse view of parasite displacement and development in tissue volumes. These data can be analyzed to give information on the early events of sporozoite penetration of the hepatic tissue, that is, sporozoite gliding in the liver sinusoids, crossing the sinusoidal barrier, gliding in the parenchyma and traversal of hepatocytes, and invasion of a final hepatocyte, as well as the terminal events of merosome and merozoite release from infected hepatocytes. Combined with the use of mice expressing fluorescent cell types or cell markers, the system will provide useful information not only on the primary infection process, but also on parasite interactions with the host immune cells in the liver.

  2. Effect of oral zinc supplementation upon Taenia crassiceps murine cysticercosis.

    PubMed

    Fragoso, G; Lastra, M D; Aguilar, A E; Pastelin, R; Rosas, G; Meneses, G; Sciutto, E; Lamoyi, E

    2001-10-01

    The effect of zinc supplementation on Taenia crassiceps murine cysticercosis was studied in susceptible BALB/cAnN mice. Female offspring of mice supplemented with high zinc throughout gestation and lactation were intraperitoneally infected with T. crassiceps cysticerci. Offspring from nonsupplemented mothers were used as controls. Significantly fewer parasites were recovered from zinc-supplemented mice (Zsm) 30 days after infection. Increased resistance was not related to the IgG antibody response. At early stages of infection, T cells from Zsm proliferated to T. crassiceps antigens, whereas cells from control mice did not respond. Infection caused in both groups a decrease in CD3+ cell percentages, which was more pronounced in the controls, and paralleled by a decrease in CD8+ cells; CD3+ and CD8+ percentages returned to normal levels at later stages of infection. In contrast, the CD4+ subpopulation only decreased in control mice. Intracellular cytokine determinations indicate that zinc supplementation favored a stronger and persistent type-1 T cell response in cysticerci-infected mice, which probably participates in the observed increased resistance.

  3. Lung diffusion testing

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003854.htm Lung diffusion testing To use the sharing features on this page, please enable JavaScript. Lung diffusion testing measures how well the lungs exchange gases. ...

  4. Diffusion bonding aeroengine components

    NASA Astrophysics Data System (ADS)

    Fitzpatrick, G. A.; Broughton, T.

    1988-10-01

    The use of diffusion bonding processes at Rolls-Royce for the manufacture of titanium-alloy aircraft engine components and structures is described. A liquid-phase diffusion bonding process called activated diffusion bonding has been developed for the manufacture of the hollow titanium wide chord fan blade. In addition, solid-state diffusion bonding is being used in the manufacture of hollow vane/blade airfoil constructions mainly in conjunction with superplastic forming and hot forming techniques.

  5. Bone marrow mononuclears from murine tibia after spaceflight on biosatellite

    NASA Astrophysics Data System (ADS)

    Andreeva, Elena; Roe, Maria; Buravkova, Ludmila; Andrianova, Irina; Goncharova, Elena; Gornostaeva, Alexandra

    Elucidation of the space flight effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this is provided by project "BION -M1". The purpose of this study was to evaluate the effects of a 30-day flight on biosatellite "BION - M1" and the subsequent 7-day recovery on the quantity, viability, immunophenotype of mononuclears from murine tibia bone marrow. Also the in vitro characterization of functional capacity of multipotent mesenchymal stromal cells (MSCs) was scheduled. Under the project, the S57black/6 mice were divided into groups: spaceflight/vivarium control, recovery after spaceflight/ vivarium control to recovery. Bone marrow mononuclears were isolated from the tibia and immunophenotyped using antibodies against CD45, CD34, CD90 on a flow cytometer Epics XL (Beckman Coulter). A part of the each pool was frozen for subsequent estimation of hematopoietic colony-forming units (CFU), the rest was used for the evaluation of fibroblast CFU (CFUf) number, MSC proliferative activity and osteogenic potency. The cell number in the flight group was significantly lower than in the vivarium control group. There were no differences in this parameter between flight and control groups after 7 days of recovery. The mononuclears viability was more than 95 percent in all examined groups. Flow cytometric analysis showed no differences in the bone marrow cell immunophenotype (CD45, CD34, CD90.1 (Thy1)), but the flight animals had more large-sized CD45+mononuclears, than the control groups of mice. There was no difference in the CFUf number between groups. After 7 days in vitro the MSC number in flight group was twice higher than in vivarium group, after 10 days - 4 times higher. These data may indicate a higher proliferative activity of MSCs after spaceflight. MSCs showed the same and high alkaline phosphatase activity, both in flight and in the control groups, suggesting no effect of spaceflight factors on early

  6. Handling stress may confound murine gut microbiota studies.

    PubMed

    Allen-Blevins, Cary R; You, Xiaomeng; Hinde, Katie; Sela, David A

    2017-01-01

    Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis) , a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantis during critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis , we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium , Bacteroides , Bacteroidetes, and Firmicutes. Our results

  7. A Student Diffusion Activity

    ERIC Educational Resources Information Center

    Kutzner, Mickey; Pearson, Bryan

    2017-01-01

    Diffusion is a truly interdisciplinary topic bridging all areas of STEM education. When biomolecules are not being moved through the body by fluid flow through the circulatory system or by molecular motors, diffusion is the primary mode of transport over short distances. The direction of the diffusive flow of particles is from high concentration…

  8. Reduce Confusion about Diffusion.

    ERIC Educational Resources Information Center

    Hebrank, Mary R.

    1997-01-01

    Presents activities that allow students to explore the fundamental but poorly understood concept of diffusion by appealing to their kinesthetic senses first, then challenging their analytical skills as they try to deduce the mathematical principle involved. Presents a computer simulation of diffusion and discusses diffusion's limitations and…

  9. Diffusion Strategy Guide.

    ERIC Educational Resources Information Center

    McCutcheon, James R.; Sanders, John R.

    A methodology is presented for planning and managing the spread of educational innovations. The first portion of the guide develops a theoretical framework for diffusion which summarizes and capitalizes on the latest marketing and on the latest marketing and diffusion research findings. Major stages in the diffusion paradigm discussed include…

  10. Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection

    PubMed Central

    Ferreira, Karen S.; Silva, Simoneide S.; Macedo, Cláudia; Bocca, Anamélia L.; Passos, Geraldo A.; Almeida, Sandro R.; Silva-Pereira, Ildinete

    2012-01-01

    Limited information is available regarding the modulation of genes involved in the innate host response to Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis. Therefore, we sought to characterize, for the first time, the transcriptional profile of murine bone marrow-derived dendritic cells (DCs) at an early stage following their initial interaction with P. brasiliensis. DCs connect innate and adaptive immunity by recognizing invading pathogens and determining the type of effector T-cell that mediates an immune response. Gene expression profiles were analyzed using microarray and validated using real-time RT-PCR and protein secretion studies. A total of 299 genes were differentially expressed, many of which are involved in immunity, signal transduction, transcription and apoptosis. Genes encoding the cytokines IL-12 and TNF-α, along with the chemokines CCL22, CCL27 and CXCL10, were up-regulated, suggesting that P. brasiliensis induces a potent proinflammatory response in DCs. In contrast, pattern recognition receptor (PRR)-encoding genes, particularly those related to Toll-like receptors, were down-regulated or unchanged. This result prompted us to evaluate the expression profiles of dectin-1 and mannose receptor, two other important fungal PRRs that were not included in the microarray target cDNA sequences. Unlike the mannose receptor, the dectin-1 receptor gene was significantly induced, suggesting that this β-glucan receptor participates in the recognition of P. brasiliensis. We also used a receptor inhibition assay to evaluate the roles of these receptors in coordinating the expression of several immune-related genes in DCs upon fungal exposure. Altogether, our results provide an initial characterization of early host responses to P. brasiliensis and a basis for better understanding the infectious process of this important neglected pathogen. PMID:22235359

  11. Anatomy and Histology of the Human and Murine Prostate.

    PubMed

    Ittmann, Michael

    2018-05-01

    The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  12. Role of cytosolic calcium diffusion in cardiac purkinje cells.

    PubMed

    Limbu, Bijay; Shah, Kushal; Deo, Makarand

    2016-08-01

    The Cardiac Purkinje cells (PCs) exhibit distinct calcium (Ca2+) homeostasis than that in ventricular myocytes (VMs). Due to lack of t-tubules in PCs, the Ca2+ ions entering the cell have to diffuse through the cytoplasm to reach the sarcoplasmic reticulum (SR) before triggering Ca2+-induced-Ca2+-release (CICR). In recent experimental studies PCs have been shown to be more susceptible to action potential (AP) abnormalities than the VMs, however the exact mechanisms are poorly understood. In this study, we utilize morphologically realistic detailed biophysical mathematical model of a murine PC to systematically examine the role intracellular Ca2+ diffusion in the APs of PCs. A biphasic spatiotemporal Ca2+ diffusion process, as observed experimentally, was implemented in the model which includes radial Ca2+ wavelets and cell wide longitudinal Ca2+ diffusion wave (CWW). The AP morphology, specifically plateau, is affected due to changes in intracellular Ca2+ dynamics. When Ca2+ concentration in sarcolemmal region is elevated, it activated inward sodium Ca2+ exchanger (NCX) current resulting into prolongation of the plateau at faster diffusion rates. Our results demonstrate that the cytosolic Ca2+ diffusion waves play a significant role in shaping APs of PCs and could provide mechanistic insights into the increased arrhythmogeneity of PCs.

  13. Murine Leukemia Viruses: Objects and Organisms

    PubMed Central

    Rein, Alan

    2011-01-01

    Murine leukemia viruses (MLVs) are among the simplest retroviruses. Prototypical gammaretroviruses encode only the three polyproteins that will be used in the assembly of progeny virus particles. These are the Gag polyprotein, which is the structural protein of a retrovirus particle, the Pol protein, comprising the three retroviral enzymes—protease, which catalyzes the maturation of the particle, reverse transcriptase, which copies the viral RNA into DNA upon infection of a new host cell, and integrase, which inserts the DNA into the chromosomal DNA of the host cell, and the Env polyprotein, which induces the fusion of the viral membrane with that of the new host cell, initiating infection. In general, a productive MLV infection has no obvious effect upon host cells. Although gammaretroviral structure and replication follow the same broad outlines as those of other retroviruses, we point out a number of significant differences between different retroviral genera. PMID:22312342

  14. Murine leukemia viruses: objects and organisms.

    PubMed

    Rein, Alan

    2011-01-01

    Murine leukemia viruses (MLVs) are among the simplest retroviruses. Prototypical gammaretroviruses encode only the three polyproteins that will be used in the assembly of progeny virus particles. These are the Gag polyprotein, which is the structural protein of a retrovirus particle, the Pol protein, comprising the three retroviral enzymes-protease, which catalyzes the maturation of the particle, reverse transcriptase, which copies the viral RNA into DNA upon infection of a new host cell, and integrase, which inserts the DNA into the chromosomal DNA of the host cell, and the Env polyprotein, which induces the fusion of the viral membrane with that of the new host cell, initiating infection. In general, a productive MLV infection has no obvious effect upon host cells. Although gammaretroviral structure and replication follow the same broad outlines as those of other retroviruses, we point out a number of significant differences between different retroviral genera.

  15. Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm

    PubMed Central

    Daniels, Brian R.; Rikhy, Richa; Renz, Malte; Dobrowsky, Terrence M.; Lippincott-Schwartz, Jennifer

    2012-01-01

    Despite the fundamental importance of diffusion for embryonic morphogen gradient formation in the early Drosophila melanogaster embryo, there remains controversy regarding both the extent and the rate of diffusion of well-characterized morphogens. Furthermore, the recent observation of diffusional “compartmentalization” has suggested that diffusion may in fact be nonideal and mediated by an as-yet-unidentified mechanism. Here, we characterize the effects of the geometry of the early syncytial Drosophila embryo on the effective diffusivity of cytoplasmic proteins. Our results demonstrate that the presence of transient mitotic membrane furrows results in a multiscale diffusion effect that has a significant impact on effective diffusion rates across the embryo. Using a combination of live-cell experiments and computational modeling, we characterize these effects and relate effective bulk diffusion rates to instantaneous diffusion coefficients throughout the syncytial blastoderm nuclear cycle phase of the early embryo. This multiscale effect may be related to the effect of interphase nuclei on effective diffusion, and thus we propose that an as-yet-unidentified role of syncytial membrane furrows is to temporally regulate bulk embryonic diffusion rates to balance the multiscale effect of interphase nuclei, which ultimately stabilizes the shapes of various morphogen gradients. PMID:22592793

  16. Murine model of long term obstructive jaundice

    PubMed Central

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A.; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-01-01

    Background With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of 3 murine models of obstructive jaundice. Methods C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Results 70% (7/10) of tCL mice died by Day 7, whereas majority 67% (10/15) of pCL mice survived with loss of jaundice. 19% (3/16) of LMHL mice died; however, jaundice continued beyond Day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 days after ligation but jaundice rapidly decreased by Day 7. The LHML group developed portal hypertension as well as severe fibrosis by Day 14 in addition to prolonged jaundice. Conclusion The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice but long term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. PMID:27916350

  17. Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition

    PubMed Central

    Taylor, A.M.; Preston, A.J.; Paulk, N.K.; Sutherland, H.; Keenan, C.M.; Wilson, P.J.M.; Wlodarski, B.; Grompe, M.; Ranganath, L.R.; Gallagher, J.A.; Jarvis, J.C.

    2012-01-01

    Objective Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU. Design The homogentisate 1,2-dioxygenase Hgd+/−Fah−/− mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl’s reagent. Results Early time point observations at 8 months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13 months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes. Conclusions Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy. PMID:22542924

  18. Anatomy of particle diffusion

    NASA Astrophysics Data System (ADS)

    Bringuier, E.

    2009-11-01

    The paper analyses particle diffusion from a thermodynamic standpoint. The main goal of the paper is to highlight the conceptual connection between particle diffusion, which belongs to non-equilibrium statistical physics, and mechanics, which deals with particle motion, at the level of third-year university courses. We start out from the fact that, near equilibrium, particle transport should occur down the gradient of the chemical potential. This yields Fick's law with two additional advantages. First, splitting the chemical potential into 'mechanical' and 'chemical' contributions shows how transport and mechanics are linked through the diffusivity-mobility relationship. Second, splitting the chemical potential into entropic and energetic contributions discloses the respective roles of entropy maximization and energy minimization in driving diffusion. The paper addresses first unary diffusion, where there is only one mobile species in an immobile medium, and next turns to binary diffusion, where two species are mobile with respect to each other in a fluid medium. The interrelationship between unary and binary diffusivities is brought out and it is shown how binary diffusion reduces to unary diffusion in the limit of high dilution of one species amidst the other one. Self- and mutual diffusion are considered and contrasted within the thermodynamic framework; self-diffusion is a time-dependent manifestation of the Gibbs paradox of mixing.

  19. Tiny Molybdenites Tell Diffusion Tales

    NASA Astrophysics Data System (ADS)

    Stein, H. J.; Hannah, J. L.

    2014-12-01

    Diffusion invokes micron-scale exchange during crystal growth and dissolution in magma chambers on short time-scales. Fundamental to interpreting such data are assumptions on magma-fluid dynamics at all scales. Nevertheless, elemental diffusion profiles are used to estimate time scales for magma storage, eruption, and recharge. An underutilized timepiece to evaluate diffusion and 3D mobility of magmatic fluids is high-precision Re-Os dating of molybdenite. With spatially unique molybdenite samples from a young ore system (e.g., 1 Ma) and a double Os spike, analytical errors of 1-3 ka unambiguously separate events in time. Re-Os ages show that hydrous shallow magma chambers locally recharge and expel Cu-Mo-Au-silica as superimposed stockwork vein networks at time scales less than a few thousand years [1]. Re-Os ages provide diffusion rates controlled by a dynamic crystal mush, accumulation and expulsion of metalliferous fluid, and magma reorganization after explosive crystallization events. Importantly, this approach has broad application far from ore deposits. Here, we use Re-Os dating of molybdenite to assess time scales for generating and diffusing metals through the deep crust. To maximize opportunity for chemical diffusion, we use a continental-scale Sveconorwegian mylonite zone for the study area. A geologically constrained suite of molybdenite samples was acquired from quarry exposures. Molybdenite, previously unreported, is extremely scarce. Tiny but telling molybdenites include samples from like occurrences to assure geologic accuracy in Re-Os ages. Ages range from mid-Mesoproterozoic to mid-Neoproterozoic, and correspond to early metamorphic dehydration of a regionally widespread biotite-rich gneiss, localized melting of gneiss to form cm-m-scale K-feldspar ± quartz pods, development of vapor-rich, vuggy mm stringers that serve as volatile collection surfaces in felsic leucosomes, and low-angle (relative to foliation) cross-cutting cm-scale quartz veins

  20. Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

    PubMed Central

    Kim, Joong H.; Loy, David N.; Wang, Qing; Budde, Matthew D.; Schmidt, Robert E.; Trinkaus, Kathryn

    2010-01-01

    Abstract Accurate diagnosis of spinal cord injury (SCI) severity must be achieved before highly aggressive experimental therapies can be tested responsibly in the early phases after trauma. These studies demonstrate for the first time that axial diffusivity (λ||), derived from diffusion tensor imaging (DTI) within 3 h after SCI, accurately predicts long-term locomotor behavioral recovery in mice. Female C57BL/6 mice underwent sham laminectomy or graded contusive spinal cord injuries at the T9 vertebral level (5 groups, n = 8 for each group). In-vivo DTI examinations were performed immediately after SCI. Longitudinal measurements of hindlimb locomotor recovery were obtained using the Basso mouse scale (BMS). Injured and spared regions of ventrolateral white matter (VLWM) were reliably separated in the hyperacute phase by threshold segmentation. Measurements of λ|| were compared with histology in the hyperacute phase and 14 days after injury. The spared normal VLWM determined by hyperacute λ|| and 14-day histology correlated well (r = 0.95). A strong correlation between hindlimb locomotor function recovery and λ||-determined spared normal VLWM was also observed. The odds of significant locomotor recovery increased by 18% with each 1% increase in normal VLWM measured in the hyperacute phase (odds ratio = 1.18, p = 0.037). The capability of measuring subclinical changes in spinal cord physiology and murine genetic advantages offer an early window into the basic mechanisms of SCI that was not previously possible. Although significant obstacles must still be overcome to derive similar data in human patients, the path to clinical translation is foreseeable and achievable. PMID:20001686

  1. δ-Aminolevulinic acid transport in murine mammary adenocarcinoma cells is mediated by beta transporters

    PubMed Central

    Bermúdez Moretti, M; Correa García, S; Perotti, C; Batlle, A; Casas, A

    2002-01-01

    δ-aminolevulinic acid, the precursor of porphyrin biosynthesis has been used to induce the endogenous synthesis of the photosensitiser protoporphyrin IX for photodynamic therapy in the treatment of various tumours. The aim of this work was to characterise the δ-aminolevulinic acid transport system in the murine mammary adenocarcinoma cell line LM3 using 14C-δ-aminolevulinic acid, to finally improve δ-aminolevulinic acid incorporation in mammalian cells. Our results showed that δ-aminolevulinic acid is incorporated into these cells by two different mechanisms, passive diffusion which is important at the beginning of the incubation, and active transport. Specificity assays suggested that the transporter involved in δ-aminolevulinic acid incorporation is a BETA transporter, probably GAT-2. British Journal of Cancer (2002) 87, 471–474. doi:10.1038/sj.bjc.6600481 www.bjcancer.com © 2002 Cancer Research UK PMID:12177786

  2. FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation

    PubMed Central

    Babaei-Jadidi, Roya; Li, Ningning; Saadeddin, Anas; Spencer-Dene, Bradley; Jandke, Anett; Muhammad, Belal; Ibrahim, ElSayed E.; Muraleedharan, Ranjithmenon; Abuzinadah, Mohammed; Davis, Hayley; Lewis, Annabelle; Watson, Susan; Behrens, Axel; Tomlinson, Ian

    2011-01-01

    The Fbxw7 (F-box/WD repeat–containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues and targets multiple transcriptional activators and protooncogenes for ubiquitin-mediated degradation. To understand Fbxw7 function in the murine intestine, in this study, we specifically deleted Fbxw7 in the murine gut using Villin-Cre (Fbxw7ΔG). In wild-type mice, loss of Fbxw7 in the gut altered homeostasis of the intestinal epithelium, resulted in elevated Notch and c-Jun expression, and induced development of adenomas at 9–10 mo of age. In the context of APC (adenomatous polyposis coli) deficiency (ApcMin/+ mice), loss of Fbxw7 accelerated intestinal tumorigenesis and death and promoted accumulation of β-catenin in adenomas at late but not early time points. At early time points, Fbxw7 mutant tumors showed accumulation of the DEK protooncogene. DEK expression promoted cell division and altered splicing of tropomyosin (TPM) RNA, which may also influence cell proliferation. DEK accumulation and altered TPM RNA splicing were also detected in FBXW7 mutant human colorectal tumor tissues. Given their reduced lifespan and increased incidence of intestinal tumors, ApcMin/+Fbxw7ΔG mice may be used for testing carcinogenicity and drug screening. PMID:21282377

  3. Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model

    PubMed Central

    Silva-Santos, Sara; van Woerden, Geeske M.; Bruinsma, Caroline F.; Mientjes, Edwin; Jolfaei, Mehrnoush Aghadavoud; Distel, Ben; Kushner, Steven A.; Elgersma, Ype

    2015-01-01

    Angelman syndrome (AS) is a severe neurodevelopmental disorder that results from loss of function of the maternal ubiquitin protein ligase E3A (UBE3A) allele. Due to neuron-specific imprinting, the paternal UBE3A copy is silenced. Previous studies in murine models have demonstrated that strategies to activate the paternal Ube3a allele are feasible; however, a recent study showed that pharmacological Ube3a gene reactivation in adulthood failed to rescue the majority of neurocognitive phenotypes in a murine AS model. Here, we performed a systematic study to investigate the possibility that neurocognitive rescue can be achieved by reinstating Ube3a during earlier neurodevelopmental windows. We developed an AS model that allows for temporally controlled Cre-dependent induction of the maternal Ube3a allele and determined that there are distinct neurodevelopmental windows during which Ube3a restoration can rescue AS-relevant phenotypes. Motor deficits were rescued by Ube3a reinstatement in adolescent mice, whereas anxiety, repetitive behavior, and epilepsy were only rescued when Ube3a was reinstated during early development. In contrast, hippocampal synaptic plasticity could be restored at any age. Together, these findings suggest that Ube3a reinstatement early in development may be necessary to prevent or rescue most AS-associated phenotypes and should be considered in future clinical trial design. PMID:25866966

  4. FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation.

    PubMed

    Babaei-Jadidi, Roya; Li, Ningning; Saadeddin, Anas; Spencer-Dene, Bradley; Jandke, Anett; Muhammad, Belal; Ibrahim, ElSayed E; Muraleedharan, Ranjithmenon; Abuzinadah, Mohammed; Davis, Hayley; Lewis, Annabelle; Watson, Susan; Behrens, Axel; Tomlinson, Ian; Nateri, Abdolrahman Shams

    2011-02-14

    The Fbxw7 (F-box/WD repeat-containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues and targets multiple transcriptional activators and protooncogenes for ubiquitin-mediated degradation. To understand Fbxw7 function in the murine intestine, in this study, we specifically deleted Fbxw7 in the murine gut using Villin-Cre (Fbxw7(ΔG)). In wild-type mice, loss of Fbxw7 in the gut altered homeostasis of the intestinal epithelium, resulted in elevated Notch and c-Jun expression, and induced development of adenomas at 9-10 mo of age. In the context of APC (adenomatous polyposis coli) deficiency (Apc(Min/+) mice), loss of Fbxw7 accelerated intestinal tumorigenesis and death and promoted accumulation of β-catenin in adenomas at late but not early time points. At early time points, Fbxw7 mutant tumors showed accumulation of the DEK protooncogene. DEK expression promoted cell division and altered splicing of tropomyosin (TPM) RNA, which may also influence cell proliferation. DEK accumulation and altered TPM RNA splicing were also detected in FBXW7 mutant human colorectal tumor tissues. Given their reduced lifespan and increased incidence of intestinal tumors, Apc(Min/+)Fbxw7(ΔG) mice may be used for testing carcinogenicity and drug screening.

  5. The effects of diffuse and distinct affect.

    PubMed

    Stapel, Diederik A; Koomen, Willem; Ruys, Kirsten I

    2002-07-01

    In a series of suboptimal priming studies, it was shown that both affective and nonaffective reactions to a stimulus may occur without awareness. Moreover, it was demonstrated that affective information is detected earlier than nonaffective information. Therefore, early reactions to an affect-laden stimulus (e.g., a smiling man) are cognitively unappraised and thus diffuse (e.g., "positive"), whereas later affective reactions can be more specific and distinct (e.g., "a smiling man"). Through variations of prime exposure (extremely short, moderately short) the impact of early diffuse and late distinct affect on judgment was investigated. Findings show that distinctness (and prime-target similarity) is an essential determinant of whether the effect of affect is null, assimilation, or contrast. Furthermore, whether affect priming activates diffuse or distinct reactions is a matter of a fraction of seconds.

  6. Suppression of Murine Retrovirus Polypeptide Termination: Effect of Amber Suppressor tRNA on the Cell-Free Translation of Rauscher Murine Leukemia Virus, Moloney Murine Leukemia Virus, and Moloney Murine Sarcoma Virus 124 RNA

    PubMed Central

    Murphy, Edwin C.; Wills, Norma; Arlinghaus, Ralph B.

    1980-01-01

    The effect of suppressor tRNA's on the cell-free translation of several leukemia and sarcoma virus RNAs was examined. Yeast amber suppressor tRNA (amber tRNA) enhanced the synthesis of the Rauscher murine leukemia virus and clone 1 Moloney murine leukemia virus Pr200gag-pol polypeptides by 10- to 45-fold, but at the same time depressed the synthesis of Rauscher murine leukemia virus Pr65gag and Moloney murine leukemia virus Pr63gag. Under suppressor-minus conditions, Moloney murine leukemia virus Pr70gag was present as a closely spaced doublet. Amber tRNA stimulated the synthesis of the “upper” Moloney murine leukemia virus Pr70gag polypeptide. Yeast ochre suppressor tRNA appeared to be ineffective. Quantitative analyses of the kinetics of viral precursor polypeptide accumulation in the presence of amber tRNA showed that during linear protein synthesis, the increase in accumulated Moloney murine leukemia virus Pr200gag-pol coincided closely with the molar loss of Pr63gag. Enhancement of Pr200gag-pol and Pr70gag by amber tRNA persisted in the presence of pactamycin, a drug which blocks the initiation of protein synthesis, thus arguing for the addition of amino acids to the C terminus of Pr63gag as the mechanism behind the amber tRNA effect. Moloney murine sarcoma virus 124 30S RNA was translated into four major polypeptides, Pr63gag, P42, P38, and P23. In the presence of amber tRNA, a new polypeptide, Pr67gag, appeared, whereas Pr63gag synthesis was decreased. Quantitative estimates indicated that for every 1 mol of Pr67gag which appeared, 1 mol of Pr63gag was lost. Images PMID:7373716

  7. Local expression of vaginal Th1 and Th2 cytokines in murine vaginal candidiasis under different immunity conditions.

    PubMed

    Chen, Shanjuan; Li, Shaohua; Wu, Yan; Liu, Zhixiang; Li, Jiawen

    2008-08-01

    To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1 (IL-2)/Th2 (IL-4, IL-10, TGF-beta1) cytokines in murine vaginal tissues was determined by RT-PCR. The cykotine in local tissues was increased to different extent under normal immune condition. IL-2 mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-beta1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10, and TGF-beta1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans (C. albicans), and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.

  8. For Export Only: Diffusion Professionals and Population Policy

    ERIC Educational Resources Information Center

    Barrett, Deborah; Kurzman, Charles; Shanahan, Suzanne

    2010-01-01

    Export-only diffusion occurs when innovators do not adopt an innovation themselves, but rather promote it to others for adoption. Potential adopters do not take their cues from early adopters, but rather from diffusion professionals who make it their job to spread a practice or institution. The global spread of national-level, population control…

  9. Gaseous diffusion system

    DOEpatents

    Garrett, George A.; Shacter, John

    1978-01-01

    1. A gaseous diffusion system comprising a plurality of diffusers connected in cascade to form a series of stages, each of said diffusers having a porous partition dividing it into a high pressure chamber and a low pressure chamber, and means for combining a portion of the enriched gas from a succeeding stage with a portion of the enriched gas from the low pressure chamber of each stage and feeding it into one extremity of the high pressure chamber thereof.

  10. Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma

    PubMed Central

    Louten, Jennifer; Mattson, Jeanine D.; Malinao, Maria-Christina; Li, Ying; Emson, Claire; Vega, Felix; Wardle, Robert L.; Van Scott, Michael R.; Fick, Robert B.; McClanahan, Terrill K.; de Waal Malefyt, Rene; Beaumont, Maribel

    2012-01-01

    Background Biomarkers facilitate early detection of disease and measurement of therapeutic efficacy, both at clinical and experimental levels. Recent advances in analytics and disease models allow comprehensive screening for biomarkers in complex diseases, such as asthma, that was previously not feasible. Objective Using murine and nonhuman primate (NHP) models of asthma, identify biomarkers associated with early and chronic stages of asthma and responses to steroid treatment. Methods The total protein content from thymic stromal lymphopoietin transgenic (TSLP Tg) mouse BAL fluid was ascertained by shotgun proteomics analysis. A subset of these potential markers was further analyzed in BAL fluid, BAL cell mRNA, and lung tissue mRNA during the stages of asthma and following corticosteroid treatment. Validation was conducted in murine and NHP models of allergic asthma. Results Over 40 proteins were increased in the BAL fluid of TSLP Tg mice that were also detected by qRT-PCR in lung tissue and BAL cells, as well as in OVA-sensitive mice and house dust mite-sensitive NHP. Previously undescribed as asthma biomarkers, KLK1, Reg3γ, ITLN2, and LTF were modulated in asthmatic mice, and Clca3, Chi3l4 (YM2), and Ear11 were the first lung biomarkers to increase during disease and the last biomarkers to decline in response to therapy. In contrast, GP-39, LCN2, sICAM-1, YM1, Epx, Mmp12, and Klk1 were good indicators of early therapeutic intervention. In NHP, AMCase, sICAM-1, CLCA1, and GP-39 were reduced upon treatment with corticosteroids. Conclusions and clinical relevance These results significantly advance our understanding of the biomarkers present in various tissue compartments in animal models of asthma, including those induced early during asthma and modulated with therapeutic intervention, and show that BAL cells (or their surrogate, induced sputum cells) are a viable choice for biomarker examination. PMID:22837640

  11. Murine norovirus infection in Brazilian animal facilities

    PubMed Central

    Rodrigues, Daniele Masselli; Moreira, Josélia Cristina de Oliveira; Lancellotti, Marcelo; Gilioli, Rovilson; Corat, Marcus Alexandre Finzi

    2016-01-01

    Murine norovirus (MNV) is a single-stranded positive-sense RNA virus of the Caliciviridae family. MNV has been reported to infect laboratory mice with the ability to cause lethal infections in strains lacking components of the innate immune response. Currently, MNV is considered the most prevalent infectious agent detected in laboratory mouse facilities. In this study, mice in 22 laboratory animal facilities within Brazil were analyzed for MNV infection. Using primers targeting a conserved region of the viral capsid, MNV was detected by RT-PCR in 137 of 359 mice from all 22 facilities. Nucleotide sequencing and phylogenetic analysis of the capsid region from the viral genome showed identity ranging from 87% to 99% when compared to reported MNV sequences. In addition, RAW264.7 cells inoculated with a mouse fecal suspension displayed cytopathic effect after the fifth passage. This study represents the first report of MNV in mouse colonies in Brazilian laboratory animal facilities, emphasizing the relevance of a health surveillance program in such environments. PMID:28049885

  12. Cytokines Induce Faster Membrane Diffusion of MHC Class I and the Ly49A Receptor in a Subpopulation of Natural Killer Cells

    PubMed Central

    Bagawath-Singh, Sunitha; Staaf, Elina; Stoppelenburg, Arie Jan; Spielmann, Thiemo; Kambayashi, Taku; Widengren, Jerker; Johansson, Sofia

    2016-01-01

    Cytokines have the potential to drastically augment immune cell activity. Apart from altering the expression of a multitude of proteins, cytokines also affect immune cell dynamics. However, how cytokines affect the molecular dynamics within the cell membrane of immune cells has not been addressed previously. Molecular movement is a vital component of all biological processes, and the rate of motion is, thus, an inherent determining factor for the pace of such processes. Natural killer (NK) cells are cytotoxic lymphocytes, which belong to the innate immune system. By fluorescence correlation spectroscopy, we investigated the influence of cytokine stimulation on the membrane density and molecular dynamics of the inhibitory receptor Ly49A and its ligand, the major histocompatibility complex class I allele H-2Dd, in freshly isolated murine NK cells. H-2Dd was densely expressed and diffused slowly in resting NK cells. Ly49A was expressed at a lower density and diffused faster. The diffusion rate in resting cells was not altered by disrupting the actin cytoskeleton. A short-term stimulation with interleukin-2 or interferon-α + β did not change the surface density of moving H-2Dd or Ly49A, despite a slight upregulation at the cellular level of H-2Dd by interferon-α + β, and of Ly49A by IL-2. However, the molecular diffusion rates of both H-2Dd and Ly49A increased significantly. A multivariate analysis revealed that the increased diffusion was especially marked in a subpopulation of NK cells, where the diffusion rate was increased around fourfold compared to resting NK cells. After IL-2 stimulation, this subpopulation of NK cells also displayed lower density of Ly49A and higher brightness per entity, indicating that Ly49A may homo-cluster to a larger extent in these cells. A faster diffusion of inhibitory receptors could enable a faster accumulation of these molecules at the immune synapse with a target cell, eventually leading to a more efficient NK cell

  13. Double diffusivity model under stochastic forcing

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Amit K.; Aifantis, Elias C.

    2017-05-01

    The "double diffusivity" model was proposed in the late 1970s, and reworked in the early 1980s, as a continuum counterpart to existing discrete models of diffusion corresponding to high diffusivity paths, such as grain boundaries and dislocation lines. It was later rejuvenated in the 1990s to interpret experimental results on diffusion in polycrystalline and nanocrystalline specimens where grain boundaries and triple grain boundary junctions act as high diffusivity paths. Technically, the model pans out as a system of coupled Fick-type diffusion equations to represent "regular" and "high" diffusivity paths with "source terms" accounting for the mass exchange between the two paths. The model remit was extended by analogy to describe flow in porous media with double porosity, as well as to model heat conduction in media with two nonequilibrium local temperature baths, e.g., ion and electron baths. Uncoupling of the two partial differential equations leads to a higher-ordered diffusion equation, solutions of which could be obtained in terms of classical diffusion equation solutions. Similar equations could also be derived within an "internal length" gradient (ILG) mechanics formulation applied to diffusion problems, i.e., by introducing nonlocal effects, together with inertia and viscosity, in a mechanics based formulation of diffusion theory. While being remarkably successful in studies related to various aspects of transport in inhomogeneous media with deterministic microstructures and nanostructures, its implications in the presence of stochasticity have not yet been considered. This issue becomes particularly important in the case of diffusion in nanopolycrystals whose deterministic ILG-based theoretical calculations predict a relaxation time that is only about one-tenth of the actual experimentally verified time scale. This article provides the "missing link" in this estimation by adding a vital element in the ILG structure, that of stochasticity, that takes into

  14. Potent and reversible lentiviral vector restriction in murine induced pluripotent stem cells.

    PubMed

    Geis, Franziska K; Galla, Melanie; Hoffmann, Dirk; Kuehle, Johannes; Zychlinski, Daniela; Maetzig, Tobias; Schott, Juliane W; Schwarzer, Adrian; Goffinet, Christine; Goff, Stephen P; Schambach, Axel

    2017-05-31

    Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers. Much remains to be elucidated in the field of anti-viral immunity in stem cells, especially in PSC. In this study, we report that transduction with HIV-1-based, lentiviral vectors (LV) is impaired in murine PSC. Analyses of early retroviral events in induced pluripotent stem cells (iPSC) revealed that the restriction is independent of envelope choice and does not affect reverse transcription, but perturbs nuclear entry and proviral integration. Proteasomal inhibition by MG132 could not circumvent the restriction. However, prevention of cyclophilin A (CypA) binding to the HIV-1 capsid via use of either a CypA inhibitor (cyclosporine A) or CypA-independent capsid mutants improved transduction. In addition, application of higher vector doses also increased transduction. Our data revealed a CypA mediated restriction in iPSC, which was acquired during reprogramming, associated with pluripotency and relieved upon subsequent differentiation. We showed that murine PSC and iPSC are less susceptible to LV. The block observed in iPSC was CypA-dependent and resulted in reduced nuclear entry of viral DNA and proviral integration. Our study helps to improve transduction of murine pluripotent cells with HIV-1-based vectors and contributes to our understanding of retrovirus-host interactions in PSC.

  15. Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines

    PubMed Central

    Kafi, Kamran; Betting, David J.; Yamada, Reiko E.; Bacica, Michael; Steward, Kristopher K.; Timmerman, John M.

    2009-01-01

    The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically-conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8+ T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies. PMID:19046770

  16. Quantum State Diffusion

    NASA Astrophysics Data System (ADS)

    Percival, Ian

    2005-10-01

    1. Introduction; 2. Brownian motion and Itô calculus; 3. Open quantum systems; 4. Quantum state diffusion; 5. Localisation; 6. Numerical methods and examples; 7. Quantum foundations; 8. Primary state diffusion; 9. Classical dynamics of quantum localisation; 10. Semiclassical theory and linear dynamics.

  17. Investigating Diffusion with Technology

    ERIC Educational Resources Information Center

    Miller, Jon S.; Windelborn, Augden F.

    2013-01-01

    The activities described here allow students to explore the concept of diffusion with the use of common equipment such as computers, webcams and analysis software. The procedure includes taking a series of digital pictures of a container of water with a webcam as a dye slowly diffuses. At known time points, measurements of the pixel densities…

  18. Anatomy of Particle Diffusion

    ERIC Educational Resources Information Center

    Bringuier, E.

    2009-01-01

    The paper analyses particle diffusion from a thermodynamic standpoint. The main goal of the paper is to highlight the conceptual connection between particle diffusion, which belongs to non-equilibrium statistical physics, and mechanics, which deals with particle motion, at the level of third-year university courses. We start out from the fact…

  19. Adaptation and Cultural Diffusion.

    ERIC Educational Resources Information Center

    Ormrod, Richard K.

    1992-01-01

    Explores the role of adaptation in cultural diffusion. Explains that adaptation theory recognizes the lack of independence between innovations and their environmental settings. Discusses testing and selection, modification, motivation, and cognition. Suggests that adaptation effects are pervasive in cultural diffusion but require a broader, more…

  20. Diffusion in Coulomb crystals.

    PubMed

    Hughto, J; Schneider, A S; Horowitz, C J; Berry, D K

    2011-07-01

    Diffusion in Coulomb crystals can be important for the structure of neutron star crusts. We determine diffusion constants D from molecular dynamics simulations. We find that D for Coulomb crystals with relatively soft-core 1/r interactions may be larger than D for Lennard-Jones or other solids with harder-core interactions. Diffusion, for simulations of nearly perfect body-centered-cubic lattices, involves the exchange of ions in ringlike configurations. Here ions "hop" in unison without the formation of long lived vacancies. Diffusion, for imperfect crystals, involves the motion of defects. Finally, we find that diffusion, for an amorphous system rapidly quenched from Coulomb parameter Γ=175 to Coulomb parameters up to Γ=1750, is fast enough that the system starts to crystalize during long simulation runs. These results strongly suggest that Coulomb solids in cold white dwarf stars, and the crust of neutron stars, will be crystalline and not amorphous.

  1. Oxygen diffusion in monazite

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.; Zhang, X. Y.; Nakamura, M.; Watson, E. B.

    2004-09-01

    We report measurements of oxygen diffusion in natural monazites under both dry, 1-atm conditions and hydrothermal conditions. For dry experiments, 18O-enriched CePO4 powder and monazite crystals were sealed in Ag-Pd capsules with a solid buffer (to buffer at NNO) and annealed in 1-atm furnaces. Hydrothermal runs were conducted in cold-seal pressure vessels, where monazite grains were encapsulated with 18O-enriched water. Following the diffusion anneals, oxygen concentration profiles were measured with Nuclear Reaction Analysis (NRA) using the reaction 18O(p,α)15N. Over the temperature range 850-1100 °C, the Arrhenius relation determined for dry diffusion experiments on monazite is given by: Under wet conditions at 100 MPa water pressure, over the temperature range 700-880 °C, oxygen diffusion can be described by the Arrhenius relationship: Oxygen diffusion under hydrothermal conditions has a significantly lower activation energy for diffusion than under dry conditions, as has been found the case for many other minerals, both silicate and nonsilicate. Given these differences in activation energies, the differences between dry and wet diffusion rates increase with lower temperatures; for example, at 600 °C, dry diffusion will be more than 4 orders of magnitude slower than diffusion under hydrothermal conditions. These disparate diffusivities will result in pronounced differences in the degree of retentivity of oxygen isotope signatures. For instance, under dry conditions (presumably rare in the crust) and high lower-crustal temperatures (∼800 °C), monazite cores of 70-μm radii will preserve O isotope ratios for about 500,000 years; by comparison, they would be retained at this temperature under wet conditions for about 15,000 years.

  2. Helium diffusion in carbonates

    NASA Astrophysics Data System (ADS)

    Amidon, W. H.; Cherniak, D. J.; Watson, E. B.; Hobbs, D.

    2013-12-01

    The abundance and large grain size of carbonate minerals make them a potentially attractive target for 4He thermochronology and 3He cosmogenic dating, although the diffusive properties of helium in carbonates remain poorly understood. This work characterizes helium diffusion in calcite and dolomite to better understand the crystal-chemical factors controlling He transport and retentivity. Slabs of cleaved natural calcite and dolomite, and polished sections of calcite cut parallel or normal to c, were implanted with 3He at 3 MeV with a dose of 5x1015/cm2. Implanted carbonates were heated in 1-atm furnaces, and 3He distributions following diffusion anneals were profiled with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. For 3He transport normal to cleavage surfaces in calcite, we obtain the following Arrhenius relation over the temperature range 78-300°C: Dcalcite = 9.0x10-9exp(-55 × 6 kJ mol-1/RT) m2sec-1. Diffusion in calcite exhibits marked anisotropy, with diffusion parallel to c about two orders of magnitude slower than diffusion normal to cleavage faces. He diffusivities for transport normal to the c-axis are similar in value to those normal to cleavage surfaces. Our findings are broadly consistent with helium diffusivities from step-heating measurements of calcite by Copeland et al. (2007); these bulk degassing data may reflect varying effects of diffusional anisotropy. Helium diffusion normal to cleavage surfaces in dolomite is significantly slower than diffusion in calcite, and has a much higher activation energy for diffusion. For dolomite, we obtain the following Arrhenius relation for He diffusion over the temperature range 150-400°C: Ddolomite = 9.0x10-8exp(-92 × 9 kJ mol-1/RT) m2sec-1. The role of crystallographic structure in influencing these differences among diffusivities was evaluated using the maximum aperture approach of Cherniak and Watson (2011), in which crystallographic structures are sectioned along possible diffusion

  3. Helium Diffusion in Olivine

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.; Watson, E. B.

    2011-12-01

    Diffusion of helium has been characterized in natural Fe-bearing olivine (~Fo90) and synthetic forsterite. Polished, oriented slabs of olivine were implanted with 3He, at 100 keV at a dose of 5x1015/cm2 or at 3.0 MeV at a dose of 1x1016/cm2. A set of experiments on the implanted olivine were run in 1-atm furnaces. In addition to the one-atm experiments, experiments on implanted samples were also run at higher pressures (2.6 and 2.7 GPa) to assess the potential effects of pressure on He diffusion and the applicability of the measured diffusivities in describing He transport in the mantle. The high-pressure experiments were conducted in a piston-cylinder apparatus using an "ultra-soft" pressure cell, with the diffusion sample directly surrounded by AgCl. 3He distributions following experiments were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. This direct profiling method permits us to evaluate anisotropy of diffusion, which cannot be easily assessed using bulk-release methods. For diffusion in forsterite parallel to c we obtain the following Arrhenius relation over the temperatures 250-950°C: D = 3.91x10-6exp(-159 ± 4 kJ mol-1/RT) m2/sec. The data define a single Arrhenius line spanning more than 7 orders of magnitude in D and 700°C in temperature. Diffusion parallel to a appears slightly slower, yielding an activation energy for diffusion of 135 kJ/mol and a pre-exponential factor of 3.73x10-8 m2/sec. Diffusion parallel to b is slower than diffusion parallel to a (by about two-thirds of a log unit); for this orientation an activation energy of 138 kJ/mol and a pre-exponential factor of 1.34x10-8 m2/sec are obtained. This anisotropy is broadly consistent with observations for diffusion of Ni and Fe-Mg in olivine. Diffusion in Fe-bearing olivine (transport parallel to b) agrees within uncertainty with findings for He diffusion in forsterite. The higher-pressure experiments yield diffusivities in agreement with those from the 1-atm

  4. Housekeeping while brain's storming Validation of normalizing factors for gene expression studies in a murine model of traumatic brain injury

    PubMed Central

    Rhinn, Hervé; Marchand-Leroux, Catherine; Croci, Nicole; Plotkine, Michel; Scherman, Daniel; Escriou, Virginie

    2008-01-01

    Background Traumatic brain injury models are widely studied, especially through gene expression, either to further understand implied biological mechanisms or to assess the efficiency of potential therapies. A large number of biological pathways are affected in brain trauma models, whose elucidation might greatly benefit from transcriptomic studies. However the suitability of reference genes needed for quantitative RT-PCR experiments is missing for these models. Results We have compared five potential reference genes as well as total cDNA level monitored using Oligreen reagent in order to determine the best normalizing factors for quantitative RT-PCR expression studies in the early phase (0–48 h post-trauma (PT)) of a murine model of diffuse brain injury. The levels of 18S rRNA, and of transcripts of β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH), β-microtubulin and S100β were determined in the injured brain region of traumatized mice sacrificed at 30 min, 3 h, 6 h, 12 h, 24 h and 48 h post-trauma. The stability of the reference genes candidates and of total cDNA was evaluated by three different methods, leading to the following rankings as normalization factors, from the most suitable to the less: by using geNorm VBA applet, we obtained the following sequence: cDNA(Oligreen); GAPDH > 18S rRNA > S100β > β-microtubulin > β-actin; by using NormFinder Excel Spreadsheet, we obtained the following sequence: GAPDH > cDNA(Oligreen) > S100β > 18S rRNA > β-actin > β-microtubulin; by using a Confidence-Interval calculation, we obtained the following sequence: cDNA(Oligreen) > 18S rRNA; GAPDH > S100β > β-microtubulin > β-actin. Conclusion This work suggests that Oligreen cDNA measurements, 18S rRNA and GAPDH or a combination of them may be used to efficiently normalize qRT-PCR gene expression in mouse brain trauma injury, and that β-actin and β-microtubulin should be avoided. The potential of total cDNA as measured by Oligreen as a first

  5. Neoclassical diffusion at low L-shel

    NASA Astrophysics Data System (ADS)

    Cunningham, G.; Ripoll, J. F.; Loridan, V.; Schulz, M.

    2017-12-01

    At very low L-shell, the lifetime of MeV electrons is dominated by pitch-angle scattering due to Coulomb collisions with background neutrals and ions. Walt's evaluation of this lifetime explained Van Allen's observations of the decay of the radiation belts in the early 1960's, for L<1.25 but Imhof et al showed that the apparent lifetime of >500 keV electrons for L=[1.15,1.21] was much greater than predicted by Walt's model when the decay was observed over 3 years rather than just a few months. Imhof et al argued that inward radial diffusion from larger L would be a source of electrons at low L, thus increasing the apparent lifetimes that were observed, but did not speculate on the cause of such diffusion across L. Newkirk and Walt estimated the radial diffusion coefficient that would be needed to explain the apparent lifetimes observed by Imhof et al. The radial diffusion coefficients they inferred dropped sharply as L increased, contrasting with the radial diffusion coefficients that had been recently developed by Falthammar [1965], which increase as a power law in L. Newkirk and Walt noted Falthammar's speculation that pitch-angle diffusion caused by Coulomb scattering, when coupled to drift-shell splitting associated with non-dipolar terms in the near-Earth geomagnetic field, might be the physical basis for the radial diffusion, but they did not attempt to quantify this effect. Roederer et al demonstrated that Coulomb scattering plus drift-shell splitting could explain the Newkirk and Walt results but they did not perform an exhaustive study. In the field of magnetically confined fusion, the movement of charged particles to different drift-shells caused by the combination of collisions and drift-shell splitting is labeled `neoclassical' diffusion. By contrast, `anomalous' diffusion results from pitch-angle diffusion caused by wave turbulence combined with drift-shell splitting, an effect recently studied by O'Brien in the outer radiation belt. We have

  6. Hedgehog signaling in the murine melanoma microenvironment.

    PubMed

    Geng, Ling; Cuneo, Kyle C; Cooper, Michael K; Wang, Hong; Sekhar, Konjeti; Fu, Allie; Hallahan, Dennis E

    2007-01-01

    The Hedgehog intercellular signaling pathway regulates cell proliferation and differentiation. This pathway has been implicated to play a role in the pathogenesis of cancer and in embryonic blood vessel development. In the current study, Hedgehog signaling in tumor related vasculature and microenvironment was examined using human umbilical vein endothelial cells and B16F0 (murine melanoma) tumors models. Use of exogenous Sonic hedgehog (Shh) peptide significantly increased BrdU incorporation in endothelial cells in vitro by a factor of 2 (P < 0.001). The Hedgehog pathway antagonist cyclopamine effectively reduced Shh-induced proliferation to control levels. To study Hedgehog signaling in vivo a hind limb tumor model with the B16F0 cell line was used. Treatment with 25 mg/kg cyclopamine significantly attenuated BrdU incorporation in tumor cells threefold (P < 0.001), in tumor related endothelial cells threefold (P = 0.004), and delayed tumor growth by 4 days. Immunohistochemistry revealed that the Hedgehog receptor Patched was localized to the tumor stroma and that B16F0 cells expressed Shh peptide. Furthermore, mouse embryonic fibroblasts required the presence of B16F0 cells to express Patched in a co-culture assay system. These studies indicate that Shh peptide produced by melanoma cells induces Patched expression in fibroblasts. To study tumor related angiogenesis a vascular window model was used to monitor tumor vascularity. Treatment with cyclopamine significantly attenuated vascular formation by a factor of 2.5 (P < 0.001) and altered vascular morphology. Furthermore, cyclopamine reduced tumor blood vessel permeability to FITC labeled dextran while having no effect on normal blood vessels. These studies suggest that Hedgehog signaling regulates melanoma related vascular formation and function.

  7. Lymph Node Macrophages Restrict Murine Cytomegalovirus Dissemination

    PubMed Central

    Farrell, Helen E.; Davis-Poynter, Nick; Bruce, Kimberley; Lawler, Clara; Dolken, Lars; Mach, Michael

    2015-01-01

    ABSTRACT Cytomegaloviruses (CMVs) establish chronic infections that spread from a primary entry site to secondary vascular sites, such as the spleen, and then to tertiary shedding sites, such as the salivary glands. Human CMV (HCMV) is difficult to analyze, because its spread precedes clinical presentation. Murine CMV (MCMV) offers a tractable model. It is hypothesized to spread from peripheral sites via vascular endothelial cells and associated monocytes. However, viral luciferase imaging showed footpad-inoculated MCMV first reaching the popliteal lymph nodes (PLN). PLN colonization was rapid and further spread was slow, implying that LN infection can be a significant bottleneck. Most acutely infected PLN cells were CD169+ subcapsular sinus macrophages (SSM). Replication-deficient MCMV also reached them, indicating direct infection. Many SSM expressed viral reporter genes, but few expressed lytic genes. SSM expressed CD11c, and MCMV with a cre-sensitive fluorochrome switch showed switched infected cells in PLN of CD11c-cre mice but yielded little switched virus. SSM depletion with liposomal clodronate or via a CD169-diphtheria toxin receptor transgene shifted infection to ER-TR7+ stromal cells, increased virus production, and accelerated its spread to the spleen. Therefore, MCMV disseminated via LN, and SSM slowed this spread by shielding permissive fibroblasts and poorly supporting viral lytic replication. IMPORTANCE HCMV chronically infects most people, and it can cause congenital disability and harm the immunocompromised. A major goal of vaccination is to prevent systemic infection. How this is established is unclear. Restriction to humans makes HCMV difficult to analyze. We show that peripheral MCMV infection spreads via lymph nodes. Here, MCMV infected filtering macrophages, which supported virus replication poorly. When these macrophages were depleted, MCMV infected susceptible fibroblasts and spread faster. The capacity of filtering macrophages to limit

  8. Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

    PubMed Central

    Soriano, Perry A.; Liu, Nian; Castillo, Erick; Foster, Brock; Artinyan, Avo; Kim, Joseph; Huang, Wendong; Wagman, Lawrence D.

    2011-01-01

    Introduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15 mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solution. Hepatectomy (70%) was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D) 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. T-tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, P = 0.048) with no difference on D7 (P = 0.21). Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg) showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3). Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis. PMID:22164336

  9. Novel Markers to Delineate Murine M1 and M2 Macrophages

    PubMed Central

    Jablonski, Kyle A.; Amici, Stephanie A.; Webb, Lindsay M.; Ruiz-Rosado, Juan de Dios; Popovich, Phillip G.; Partida-Sanchez, Santiago; Guerau-de-Arellano, Mireia

    2015-01-01

    Classically (M1) and alternatively activated (M2) macrophages exhibit distinct phenotypes and functions. It has been difficult to dissect macrophage phenotypes in vivo, where a spectrum of macrophage phenotypes exists, and also in vitro, where low or non-selective M2 marker protein expression is observed. To provide a foundation for the complexity of in vivo macrophage phenotypes, we performed a comprehensive analysis of the transcriptional signature of murine M0, M1 and M2 macrophages and identified genes common or exclusive to either subset. We validated by real-time PCR an M1-exclusive pattern of expression for CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2) whereas Early growth response protein 2 (Egr2) and c-Myc were M2-exclusive. We further confirmed these data by flow cytometry and show that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages (~70%) than the canonical M2 macrophage marker Arginase-1, which labels 24% of M2 macrophages. Conversely, CD38 labeled most (71%) in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. Overall, this work defines exclusive and common M1 and M2 signatures and provides novel and improved tools to distinguish M1 and M2 murine macrophages. PMID:26699615

  10. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

    PubMed

    Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

    2011-08-01

    Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Diffusion Flame Stabilization

    NASA Technical Reports Server (NTRS)

    Takahashi, Fumiaki; Katta, V. R.

    2006-01-01

    Diffusion flames are commonly used for industrial burners in furnaces and flares. Oxygen/fuel burners are usually diffusion burners, primarily for safety reasons, to prevent flashback and explosion in a potentially dangerous system. Furthermore, in most fires, condensed materials pyrolyze, vaporize, and burn in air as diffusion flames. As a result of the interaction of a diffusion flame with burner or condensed-fuel surfaces, a quenched space is formed, thus leaving a diffusion flame edge, which plays an important role in flame holding in combustion systems and fire spread through condensed fuels. Despite a long history of jet diffusion flame studies, lifting/blowoff mechanisms have not yet been fully understood, compared to those of premixed flames. In this study, the structure and stability of diffusion flames of gaseous hydrocarbon fuels in coflowing air at normal earth gravity have been investigated experimentally and computationally. Measurements of the critical mean jet velocity (U(sub jc)) of methane, ethane, or propane at lifting or blowoff were made as a function of the coflowing air velocity (U(sub a)) using a tube burner (i.d.: 2.87 mm). By using a computational fluid dynamics code with 33 species and 112 elementary reaction steps, the internal chemical-kinetic structures of the stabilizing region of methane and propane flames were investigated. A peak reactivity spot, i.e., reaction kernel, is formed in the flame stabilizing region due to back-diffusion of heat and radical species against an oxygen-rich incoming flow, thus holding the trailing diffusion flame. The simulated flame base moved downstream under flow conditions close to the measured stability limit.

  12. Diffusion Flame Stabilization

    NASA Technical Reports Server (NTRS)

    Takahashi, Fumiaki; Katta, Viswanath R.

    2007-01-01

    Diffusion flames are commonly used for industrial burners in furnaces and flares. Oxygen/fuel burners are usually diffusion burners, primarily for safety reasons, to prevent flashback and explosion in a potentially dangerous system. Furthermore, in most fires, condensed materials pyrolyze, vaporize, and burn in air as diffusion flames. As a result of the interaction of a diffusion flame with burner or condensed-fuel surfaces, a quenched space is formed, thus leaving a diffusion flame edge, which plays an important role in flame holding in combustion systems and fire spread through condensed fuels. Despite a long history of jet diffusion flame studies, lifting/blowoff mechanisms have not yet been fully understood, compared to those of premixed flames. In this study, the structure and stability of diffusion flames of gaseous hydrocarbon fuels in coflowing air at normal earth gravity have been investigated experimentally and computationally. Measurements of the critical mean jet velocity (U(sub jc)) of methane, ethane, or propane at lifting or blowoff were made as a function of the coflowing air velocity (U(sub a)) using a tube burner (i.d.: 2.87 mm) (Fig. 1, left). By using a computational fluid dynamics code with 33 species and 112 elementary reaction steps, the internal chemical-kinetic structures of the stabilizing region of methane and propane flames were investigated (Fig. 1, right). A peak reactivity spot, i.e., reaction kernel, is formed in the flame stabilizing region due to back-diffusion of heat and radical species against an oxygen-rich incoming flow, thus holding the trailing diffusion flame. The simulated flame base moved downstream under flow conditions close to the measured stability limit.

  13. Infrared diffuse interstellar bands

    NASA Astrophysics Data System (ADS)

    Galazutdinov, G. A.; Lee, Jae-Joon; Han, Inwoo; Lee, Byeong-Cheol; Valyavin, G.; Krełowski, J.

    2017-05-01

    We present high-resolution (R ˜ 45 000) profiles of 14 diffuse interstellar bands in the ˜1.45 to ˜2.45 μm range based on spectra obtained with the Immersion Grating INfrared Spectrograph at the McDonald Observatory. The revised list of diffuse bands with accurately estimated rest wavelengths includes six new features. The diffuse band at 15 268.2 Å demonstrates a very symmetric profile shape and thus can serve as a reference for finding the 'interstellar correction' to the rest wavelength frame in the H range, which suffers from a lack of known atomic/molecular lines.

  14. Telomere sister chromatid exchange in telomerase deficient murine cells

    SciT

    Wang, Yisong; Giannone, Richard J; Liu, Yie

    2005-01-01

    We have recently demonstrated that several types of genomic rearrangements (i.e., telomere sister chromatid exchange (T-SCE), genomic-SCE, or end-to-end fusions) were more often detected in long-term cultured murine telomerase deficient embryonic stem (ES) cells than in freshly prepared murine splenocytes, even through they possessed similar frequencies of critically short telomeres. The high rate of genomic rearrangements in telomerase deficient ES cells, when compared to murine splenocytes, may reflect the cultured cells' gained ability to protect chromosome ends with eroded telomeres allowing them to escape 'end crisis'. However, the possibility that ES cells were more permissive to genomic rearrangements than othermore » cell types or that differences in the microenvironment or genetic background of the animals might consequentially determine the rate of T-SCEs or other genomic rearrangements at critically short telomeres could not be ruled out.« less

  15. Telomere sister chromatid exchange in telomerase deficient murine cells.

    PubMed

    Wang, Yisong; Giannone, Richard J; Liu, Yie

    2005-10-01

    We have recently demonstrated that several types of genomic rearrangements (i.e., telomere sister chromatid exchange (T-SCE), genomic-SCE, or end-to-end fusions) were more often detected in long-term cultured murine telomerase deficient embryonic stem (ES) cells than in freshly prepared murine splenocytes, even through they possessed similar frequencies of critically short telomeres. The high rate of genomic rearrangements in telomerase deficient ES cells, when compared to murine splenocytes, may reflect the cultured cells' gained ability to protect chromosome ends with eroded telomeres allowing them to escape "end crisis". However, the possibility that ES cells were more permissive to genomic rearrangements than other cell types or that differences in the microenvironment or genetic background of the animals might consequentially determine the rate of T-SCEs or other genomic rearrangements at critically short telomeres could not be ruled out.

  16. [Clinicopathological study of diffuse carcinoma of stomach (author's transl)].

    PubMed

    Shimoda, T

    1978-11-01

    The biological behavior of ulcer type gastric carcinoma was studied on 114 cases of diffuse carcinoma (Borrmann's 4 type) and 262 cases of early like advanced carcinoma (including superficial spreading type). In both types of gastric carcinoma, the age distribution, location, ulcer with cancer focus and prognosis differed greatly. The early like carcinoma was speculated to have advanced maintaining the groos findings of early gastric carcinoma, and its location and associated ulcer were the same as the early ulcer type of carcinoma. The prognosis of this type of carcinoma was good, showing a figure of 70% in 3 year survival rate. On the other hand, diffuse carcinoma demonstrated diffuse extensive infiltration of tumor cells along the gastric wall, resulting in poor prognosis with a 3 year survival rate of almost 0%. Histologically, diffuse type of carcinoma showed lymphatic infiltration of tumor cells, and this is probably the main reason for the diffuse infiltration in this type of carcinoma. Diffuse carcinoma is, therefore, considered to be one special type of carcinoma having different biological behavior compared with the other ulcer type of carcinoma, and diffuse carcinoma is not the terminal stage of early like advanced carcinoma. There are three stages in diffuse carcinoma: 1. Infiltrative stage: wide spread infiltration of cancer cells through lymphatic channels (lymphangiosis carcinomatosa) 2. Edematous stage: soluble collagen appearing in gastric wall 3. Sclerosing stage: soluble collagen changing into insoluble collagen leading to marked thickening and stiffness of the gastric wall. This is the end stage of gastric diffuse carcinoma. It is difficult to explain that the marked fibrosis of gastric wall is a result to stromal reaction from tumor cell infiltration, since extensive fibrosis is found in areas without tumor cells and stiffness of the gastric wall occurs in a too short period of time. The production of abundunt soluble collagen is probably

  17. Spatial diffusion of raccoon rabies in Pennsylvania, USA.

    PubMed

    Moore, D A

    1999-05-14

    Identification of the geographic pattern of diffusion of a wildlife disease could lead to information regarding its control. The objective of this study was to model raccoon-rabies diffusion in Pennsylvania to identify geographic constraints on the diffusion pattern for potential use in bait-vaccination strategies. A trend-surface analysis (TSA) was used as a spatial filter for month to first report by county location. A cubic polynomial model was fitted (R2 = 0.80). Velocity vectors were calculated from the partial derivatives of the model and mapped to demonstrate the instantaneous speed of diffusion at each location. A main corridor of diffusion through the ridge and valley section of the state was evident early in the outbreak. Once the disease reached the northern counties, the disease moved west toward Ohio. I believe that TSA was useful in identifying the pattern of raccoon-rabies diffusion across the stage from the inherent noise of disease-reporting data.

  18. Multimodal Diffuse Optical Imaging

    NASA Astrophysics Data System (ADS)

    Intes, Xavier; Venugopal, Vivek; Chen, Jin; Azar, Fred S.

    Diffuse optical imaging, particularly diffuse optical tomography (DOT), is an emerging clinical modality capable of providing unique functional information, at a relatively low cost, and with nonionizing radiation. Multimodal diffuse optical imaging has enabled a synergistic combination of functional and anatomical information: the quality of DOT reconstructions has been significantly improved by incorporating the structural information derived by the combined anatomical modality. In this chapter, we will review the basic principles of diffuse optical imaging, including instrumentation and reconstruction algorithm design. We will also discuss the approaches for multimodal imaging strategies that integrate DOI with clinically established modalities. The merit of the multimodal imaging approaches is demonstrated in the context of optical mammography, but the techniques described herein can be translated to other clinical scenarios such as brain functional imaging or muscle functional imaging.

  19. Diffusion in translucent media.

    PubMed

    Shi, Zhou; Genack, Azriel Z

    2018-05-10

    Diffusion is the result of repeated random scattering. It governs a wide range of phenomena from Brownian motion, to heat flow through window panes, neutron flux in fuel rods, dispersion of light in human tissue, and electronic conduction. It is universally acknowledged that the diffusion approach to describing wave transport fails in translucent samples thinner than the distance between scattering events such as are encountered in meteorology, astronomy, biomedicine, and communications. Here we show in optical measurements and numerical simulations that the scaling of transmission and the intensity profiles of transmission eigenchannels have the same form in translucent as in opaque media. Paradoxically, the similarities in transport across translucent and opaque samples explain the puzzling observations of suppressed optical and ultrasonic delay times relative to predictions of diffusion theory well into the diffusive regime.

  20. Novel Diffusivity Measurement Technique

    NASA Technical Reports Server (NTRS)

    Rashidnia, Nasser

    2001-01-01

    A common-path interferometer (CPI) system was developed to measure the diffusivity of liquid pairs. The CPI is an optical technique that can be used to measure changes in the gradient of the refraction index of transparent materials. This system uses a shearing interferometer that shares the same optical path from a laser light source to the final imaging plane. Hence, the molecular diffusion coefficient of liquids can be determined using the physical relations between changes in the optical path length and the liquid phase properties. The data obtained with this interferometer were compared with similar results from other techniques and demonstrated that the instrument is superior in measuring the diffusivity of miscible liquids while keeping the system very compact and robust. CPI can also be used for studies in interface dynamics and other diffusion-dominated-process applications.

  1. Investigating diffusion with technology

    NASA Astrophysics Data System (ADS)

    Miller, Jon S.; Windelborn, Augden F.

    2013-07-01

    The activities described here allow students to explore the concept of diffusion with the use of common equipment such as computers, webcams and analysis software. The procedure includes taking a series of digital pictures of a container of water with a webcam as a dye slowly diffuses. At known time points, measurements of the pixel densities (darkness) of the digital pictures are recorded and then plotted on a graph. The resulting graph of darkness versus time allows students to see the results of diffusion of the dye over time. Through modification of the basic lesson plan, students are able to investigate the influence of a variety of variables on diffusion. Furthermore, students are able to expand the boundaries of their thinking by formulating hypotheses and testing their hypotheses through experimentation. As a result, students acquire a relevant science experience through taking measurements, organizing data into tables, analysing data and drawing conclusions.

  2. Gauge calibration by diffusion

    NASA Technical Reports Server (NTRS)

    Brock, F. J.; Feakes, F. (Inventor)

    1968-01-01

    Vacuum gage calibration by diffusing a known quantity of gas through a heated barrier into a gauge is examined. The gas flow raises the pressure in the gauge to known level and is then compared with the gauge's pressure reading.

  3. Magnetic resonance imaging and spectroscopy of the murine cardiovascular system.

    PubMed

    Akki, Ashwin; Gupta, Ashish; Weiss, Robert G

    2013-03-01

    Magnetic resonance imaging (MRI) has emerged as a powerful and reliable tool to noninvasively study the cardiovascular system in clinical practice. Because transgenic mouse models have assumed a critical role in cardiovascular research, technological advances in MRI have been extended to mice over the last decade. These have provided critical insights into cardiac and vascular morphology, function, and physiology/pathophysiology in many murine models of heart disease. Furthermore, magnetic resonance spectroscopy (MRS) has allowed the nondestructive study of myocardial metabolism in both isolated hearts and in intact mice. This article reviews the current techniques and important pathophysiological insights from the application of MRI/MRS technology to murine models of cardiovascular disease.

  4. Neurocomputation by Reaction Diffusion

    NASA Astrophysics Data System (ADS)

    Liang, Ping

    1995-08-01

    This Letter demonstrates the possible role nonsynaptic diffusion neurotransmission may play in neurocomputation using an artificial neural network model. A reaction-diffusion neural network model with field-based information-processing mechanisms is proposed. The advantages of nonsynaptic field neurotransmission from a computational viewpoint demonstrated in this Letter include long-range inhibition using only local interaction, nonhardwired and changeable (target specific) long-range communication pathways, and multiple simultaneous spatiotemporal organization processes in the same medium.

  5. Diffusion in Stellar Envelopes

    NASA Astrophysics Data System (ADS)

    Seaton, M. J.

    Abundances in stellar atmospheres can depend on diffusive movements in much deeper layers of stellar envelopes. Diffusion in envelopes is also of interest in that it can lead to changes in opacities and hence to the structures of stars. For envelopes the radiative accelerations grad can be expressed in terms of quantities which depend only on temperatures, densities and chemical compositions. Computations have been made for the elements C, N, O, Ne, Na, Mg, Al, Si, S, Ar, Ca, Cr, Mn, Fe and Ni and tables are being made generally available through CDS (Strasbourg). Some results from those computations will be presented. The computed values of grad are used to study diffusion of iron-group elements in envelopes of HgMn stars. It is shown that one can define a value tau_0 of the Rosseland-mean optical depth tau such that diffusive movements for tau >= tau_0 do not depend on those for tau <= tau_0. For Cr and Mn we obtain solutions with tau_0 = 1 and are able to make some meaningful comparisons of abundances, as computed and as observed in atmospheres. For Fe we find that diffusive movements are slowed down in regions of T ~= 10^5 K where the dominant ionisation stages are near argon-like. Diffusion of Fe-group elements can produce substantial changes in opacities.

  6. NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 53: From student to entry-level professional: Examining the technical communications practices of early career-stage US aerospace engineers and scientists

    NASA Technical Reports Server (NTRS)

    Pinelli, Thomas E.; Holloway, Karen; Barclay, Rebecca O.; Kennedy, John M.

    1995-01-01

    Studies indicate that communications and information-related activities take up a substantial portion of an engineer's work week; therefore, effective communications and information-use skills are one of the key engineering competencies that early career-stage aerospace engineers and scientists must possess to be successful. Feedback from industry rates communications and information-use skills high in terms of their importance to engineering practice; however, this same feedback rates the communications and information-use skills of early career-stage engineers low. To gather adequate and generalizable data about the communications and information-related activities of entry-level aerospace engineers and scientists, we surveyed 264 members of the AIAA who have no more than 1-5 years of aerospace engineering work experience. To learn more about the concomitant communications norms, we compared the results of this study with data (1,673 responses) we collected from student members of the AIAA and with data (341 responses) we collected from a study of aerospace engineering professionals. In this paper, we report selected results from these studies that focused on the communications practices and information-related activities of early career-stage U.S. aerospace engineers and scientists in the workplace.

  7. Redefining Myeloid Cell Subsets in Murine Spleen

    PubMed Central

    Hey, Ying-Ying; Tan, Jonathan K. H.; O’Neill, Helen C.

    2016-01-01

    Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed “L-DC” in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11bhiCD11cloMHCII−Ly6C−Ly6G− subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level of CD11c was shown to best differentiate L-DC by phenotype from conventional DC subsets. A complete analysis of all subsets in spleen led to the classification of CD11bhiCD11cloMHCII−Ly6CloLy6G− cells as monocytes expressing CX3CR1, CD43 and CD115. Siglec-F expression was used to identify a specific eosinophil population, distinguishable from both Ly6Clo and Ly6Chi monocytes, and other DC subsets. L-DC were characterized as a clear subset of CD11bhiCD11cloMHCII−Ly6C−Ly6G− cells, which are CD43+, Siglec-F− and CD115−. Changes in the prevalence of L-DC compared to other subsets in spleens of mutant mice confirmed the phenotypic distinction between L-DC, cDC and monocyte subsets. L-DC development in vivo was shown to occur independently of the BATF3 transcription factor that regulates cDC development, and also independently of the FLT3L and GM-CSF growth factors which drive cDC and monocyte development, so distinguishing L-DC from these commonly defined cell types. PMID:26793192

  8. Variable phenotype in murine transverse aortic constriction.

    PubMed

    Mohammed, Selma F; Storlie, Jimmy R; Oehler, Elise A; Bowen, Lorna A; Korinek, Josef; Lam, Carolyn S P; Simari, Robert D; Burnett, John C; Redfield, Margaret M

    2012-01-01

    In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload-induced hypertrophy (left ventricular [LV] hypertrophy, or LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, noninvasive method of prospectively identifying mice with HF versus compensated LVH after TAC. Eight-week-old male C57BL/6J mice underwent TAC or sham and then echocardiography at 3 weeks post-TAC. A group of sham and TAC mice were euthanized after the 3-week echocardiogram, while the remainder underwent repeat echocardiography and were euthanized at 9 weeks post-TAC. The presence of TAC was assessed with two-dimensional echocardiography, anatomic aortic m-mode and color flow, and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset of mice. HF was defined as lung/body weight>upper limit in sham-operated mice. As compared with sham, TAC mice had higher TA velocity, LVP and LV weight, and lower ejection fraction (EF) at 3 or 9 weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared with compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening, and more fibrosis. Both EF and LV mass measured by echocardiography at 3 weeks post-TAC were predictive of the presence of HF at 3 or 9 weeks post-TAC. In wild-type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echocardiography 3 weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Organization of the murine Cd22 locus

    SciT

    Law, Che-Leung; Torres, R.M.; Sundeberg, H.A.

    1993-07-01

    Murine CD22 (mCD22) is a B cell-associated adhesion protein with seven extracellular Ig-like domains that has 62% amino acid identify to its human homologue. Southern analysis on genomic DNA isolated from tissues and cell lines from several mouse strains using mCD22 cDNA demonstrated that the Cd22 locus encoding mCD22 is a single copy gene of [le]30 kb. Digestion of genomic DNA preparations with four restriction endonucleases revealed the presence of restriction fragment length polymorphisms (RFLP) in BALB/c, C57BL/6, and C3H strains vs DBA/2j, NZB, and NZC strains, suggesting the presence of two or more Cd22 alleles. Using a mCD22 cDNAmore » clone derived from the BALB/c strain, the authors isolated genomic clones from a DBA/2 genomic library that contained all the exons necessary to encode the full length mCD22 cDNA. Fifteen exons, including exon 3 that encodes the translation start codon, were identified. Each extracellular Ig-like domain of mCD22 is encoded by a single exon. A comparison between the nucleotide sequences of the BALB/c CD22 cDNA and the exons of the DBA/2j CD22 genomic clones revealed an 18-nucleotide deletion in exon 4 (encoding the most distal Ig-like domain 1 of mCD22) of the DBA/2j genomic sequence in addition to a number of substitutions, insertions, and deletions in other exons. These nucleotide differences were also present in a cDNA clone isolated from total RNA of LPS-activated DBA/2j splenocytes mosome 7, a region sytenic to human chromosome 19q, close to the previously reported loci, Lyb-8 and Mag (a homologue of Cd22). An antibody (CY34) against the Lyb-8.2 B cell marker reacted with a BHK transfectant expressing the full length mCd22 cDNA, thus demonstrating that Lyb-8 and Cd22 loci are identical. Furthermore, a rat anti-mCD22 mAb, NIM-R6, bound to slgM[sup +] DBA/2j B cells, confirming the expression of a CD22 protein by the Cd22[sup a]/lyb-8[sup a] allele. 63 refs., 7 figs., 1 tab.« less

  10. AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models

    PubMed Central

    Pohling, Christoph; Natarajan, Arutselvan; Witney, Timothy H.; Kaur, Jasdeep; Xu, Lingyun; Gowrishankar, Gayatri; D’Souza, Aloma L; Murty, Surya; Schick, Sophie; Chen, Liyin; Wu, Nicholas; Khaw, Phoo; Mischel, Paul; Abbasi, Taher; Usmani, Shahabuddin; Mallick, Parag

    2017-01-01

    Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O’Neill (J Neurooncol 107: 359–364, 2012). An extract from the winter cherry plant (Withania somnifera), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985–1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3–5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 μM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 μM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM. PMID:26650066

  11. AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models.

    PubMed

    Chang, Edwin; Pohling, Christoph; Natarajan, Arutselvan; Witney, Timothy H; Kaur, Jasdeep; Xu, Lingyun; Gowrishankar, Gayatri; D'Souza, Aloma L; Murty, Surya; Schick, Sophie; Chen, Liyin; Wu, Nicholas; Khaw, Phoo; Mischel, Paul; Abbasi, Taher; Usmani, Shahabuddin; Mallick, Parag; Gambhir, Sanjiv S

    2016-01-01

    Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O'Neill (J Neurooncol 107: 359-364, 2012). An extract from the winter cherry plant (Withania somnifera ), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985-1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3-5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 µM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 µM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM.

  12. Automated segmentation of murine lung tumors in x-ray micro-CT images

    NASA Astrophysics Data System (ADS)

    Swee, Joshua K. Y.; Sheridan, Clare; de Bruin, Elza; Downward, Julian; Lassailly, Francois; Pizarro, Luis

    2014-03-01

    Recent years have seen micro-CT emerge as a means of providing imaging analysis in pre-clinical study, with in-vivo micro-CT having been shown to be particularly applicable to the examination of murine lung tumors. Despite this, existing studies have involved substantial human intervention during the image analysis process, with the use of fully-automated aids found to be almost non-existent. We present a new approach to automate the segmentation of murine lung tumors designed specifically for in-vivo micro-CT-based pre-clinical lung cancer studies that addresses the specific requirements of such study, as well as the limitations human-centric segmentation approaches experience when applied to such micro-CT data. Our approach consists of three distinct stages, and begins by utilizing edge enhancing and vessel enhancing non-linear anisotropic diffusion filters to extract anatomy masks (lung/vessel structure) in a pre-processing stage. Initial candidate detection is then performed through ROI reduction utilizing obtained masks and a two-step automated segmentation approach that aims to extract all disconnected objects within the ROI, and consists of Otsu thresholding, mathematical morphology and marker-driven watershed. False positive reduction is finally performed on initial candidates through random-forest-driven classification using the shape, intensity, and spatial features of candidates. We provide validation of our approach using data from an associated lung cancer study, showing favorable results both in terms of detection (sensitivity=86%, specificity=89%) and structural recovery (Dice Similarity=0.88) when compared against manual specialist annotation.

  13. Surface-to-volume ratio mapping of tumor microstructure using oscillating gradient diffusion weighted imaging

    PubMed Central

    Reynaud, Olivier; Winters, Kerryanne Veronica; Hoang, Dung Minh; Wadghiri, Youssef Zaim; Novikov, Dmitry S; Kim, Sungheon Gene

    2015-01-01

    Purpose To disentangle the free diffusivity (D0) and cellular membrane restrictions, via their surface-to-volume ratio (S/V), using the frequency-dependence of the diffusion coefficient D(ω), measured in brain tumors in the short diffusion-time regime using oscillating gradients (OGSE). Methods In vivo and ex vivo OGSE experiments were performed on mice bearing the GL261 murine glioma model (n=10) to identify the relevant time/frequency (t/ω) domain where D(ω) linearly decreases with ω−1/2. Parametric maps (S/V, D0) are compared to conventional DWI metrics. The impact of frequency range and temperature (20°C vs. 37°C) on S/V and D0 is investigated ex vivo. Results The validity of the short diffusion-time regime is demonstrated in vivo and ex vivo. Ex vivo measurements confirm that the purely geometric restrictions embodied in S/V are independent from temperature and frequency range, while the temperature dependence of the free diffusivity D0 is similar to that of pure water. Conclusion Our results suggest that D(ω) in the short diffusion-time regime can be used to uncouple the purely geometric restriction effect, such as S/V, from the intrinsic medium diffusivity properties, and provides a non-empirical and objective way to interpret frequency/time-dependent diffusion changes in tumors in terms of objective biophysical tissue parameters. PMID:26207354

  14. Blockade of epithelial membrane protein 2 (EMP2) abrogates infection of Chlamydia muridarum murine genital infection model

    PubMed Central

    Shimazaki, Kaori; Chan, Ann M.; Moniz, Raymond J.; Wadehra, Madhuri; Nagy, Agnes; Coulam, C. Paige; Mareninov, Sergey; Lepin, Eric M.; Wu, Anna M.; Kelly, Kathleen A.; Braun, Jonathan; Gordon, Lynn K.

    2012-01-01

    New methods are needed to eradicate or prevent Chlamydia trachomatis infections. Blockade of epithelial membrane protein 2 (EMP2) by genetic silencing or neutralizing polyclonal antibody reduced chlamydial infectivity in vitro. This study tests the prediction that recombinant anti-EMP2 diabody could reduce early chlamydial infection of the genital tract in vivo. In a murine infection model, pretreatment with anti-EMP2 diabody, as compared to control diabody, significantly reduced bacterial load, tissue production of inflammatory cytokines, recruitment of polymorphonuclear leukocytes, and local tissue inflammation. These findings support EMP2 as a potential preventative and therapeutic target for genital chlamydial infection. PMID:19159428

  15. SALIVARY GLAND EXTRACTS OF CULICOIDES SONORENSIS INHIBIT MURINE LYMPHOCYTE PROLIFERATION AND NO PRODUCTION BY MACROPHAGES

    PubMed Central

    BISHOP, JEANETTE V.; MEJIA, J. SANTIAGO; PÉREZ DE LEÓN, ADALBERTO A.; TABACHNICK, WALTER J.; TITUS, RICHARD G.

    2006-01-01

    Culicoides biting midges serve as vectors of pathogens affecting humans and domestic animals. Culicoides sonorensis is a vector of several arboviruses in North American that cause substantial economic losses to the US livestock industry. Previous studies showed that C. sonorensis saliva, like the saliva of many hematophagous arthropods, contains numerous pharmacological agents that affect hemostasis and early events in the inflammatory response, which may enhance the infectivity of Culicoides-borne pathogens. This paper reports on the immunomodulatory properties of C. sonorensis salivary gland extracts on murine immune cells and discusses the possible immunomodulatory role of C. sonorensis saliva in vesicular stomatitis virus infection of vertebrate hosts. Splenocytes treated with C. sonorensis mitogens were significantly affected in their proliferative response, and peritoneal macrophages secreted significantly less NO. A 66-kDa glycoprotein was purified from C. sonorensis salivary gland extract, which may be in part responsible for these observations and may be considered as a vaccine candidate. PMID:16968936

  16. Salivary gland extracts of Culicoides sonorensis inhibit murine lymphocyte proliferation and no production by macrophages.

    PubMed

    Bishop, Jeanette V; Mejia, J Santiago; Pérez de León, Adalberto A; Tabachnick, Walter J; Titus, Richard G

    2006-09-01

    Culicoides biting midges serve as vectors of pathogens affecting humans and domestic animals. Culicoides sonorensis is a vector of several arboviruses in North American that cause substantial economic losses to the US livestock industry. Previous studies showed that C. sonorensis saliva, like the saliva of many hematophagous arthropods, contains numerous pharmacological agents that affect hemostasis and early events in the inflammatory response, which may enhance the infectivity of Culicoides-borne pathogens. This paper reports on the immunomodulatory properties of C. sonorensis salivary gland extracts on murine immune cells and discusses the possible immunomodulatory role of C. sonorensis saliva in vesicular stomatitis virus infection of vertebrate hosts. Splenocytes treated with C. sonorensis mitogens were significantly affected in their proliferative response, and peritoneal macrophages secreted significantly less NO. A 66-kDa glycoprotein was purified from C. sonorensis salivary gland extract, which may be in part responsible for these observations and may be considered as a vaccine candidate.

  17. Target Patterns in Reaction-Diffusion Systems,

    DTIC Science & Technology

    1981-01-01

    Riol. 37 (1974), 225-235. 8. M. H. COHEN AND S. A. ROBERTSON, Wave propagation in the early stages of aggregation of cellular slime molds . J. Theoret...the Zaikin-Zhabotinskii-Winfree reagent, Chem. Educ. 56 (1979), 574. 5. F. ALCANTARA AND M. MONK, Signal propagation during aggregation in the slime ... mold Dit’resteltu n discoideum. J. Gen. Microbiol. 85 (1974). 321-334. 6. M. S. COHEN AND P. S. HAGAN, Diffusion induced morphogenesis in the

  18. Characterization of intravitreally delivered capsid mutant AAV2-Cre vector to induce tissue-specific mutations in murine retinal ganglion cells.

    PubMed

    Langouet-Astrie, Christophe J; Yang, Zhiyong; Polisetti, Sraavya M; Welsbie, Derek S; Hauswirth, William W; Zack, Donald J; Merbs, Shannath L; Enke, Raymond A

    2016-10-01

    Targeted expression of Cre recombinase in murine retinal ganglion cells (RGCs) by viral vector is an effective strategy for creating tissue-specific gene knockouts for investigation of genetic contribution to RGC degeneration associated with optic neuropathies. Here we characterize dosage, efficacy and toxicity for sufficient intravitreal delivery of a capsid mutant Adeno-associated virus 2 (AAV2) vector encoding Cre recombinase. Wild type and Rosa26 (R26) LacZ mice were intravitreally injected with capsid mutant AAV2 viral vectors. Murine eyes were harvested at intervals ranging from 2 weeks to 15 weeks post-injection and were assayed for viral transduction, transgene expression and RGC survival. 10(9) vector genomes (vg) were sufficient for effective in vivo targeting of murine ganglion cell layer (GCL) retinal neurons. Transgene expression was observed as early as 2 weeks post-injection of viral vectors and persisted to 11 weeks. Early expression of Cre had no significant effect on RGC survival, while significant RGC loss was detected beginning 5 weeks post-injection. Early expression of viral Cre recombinase was robust, well-tolerated and predominantly found in GCL neurons suggesting this strategy can be effective in short-term RGC-specific mutation studies in experimental glaucoma models such as optic nerve crush and transection experiments. RGC degeneration with Cre expression for more than 4 weeks suggests that Cre toxicity is a limiting factor for targeted mutation strategies in RGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The NS2 polypeptide of parvovirus MVM is required for capsid assembly in murine cells.

    PubMed

    Cotmore, S F; D'Abramo, A M; Carbonell, L F; Bratton, J; Tattersall, P

    1997-05-12

    Mutants of minute virus of mice (MVM) which express truncated forms of the NS2 polypeptide are known to exhibit a host range defect, replicating productively in transformed human cells but not in cells from their normal murine host. To explore this deficiency we generated viruses with translation termination codons at various positions in the second exon of NS2. In human cells these mutants were viable, but showed a late defect in progeny virion release which put them at a selective disadvantage compared to the wildtype. In murine cells, however, duplex viral DNA amplification was reduced to 5% of wildtype levels and single-strand DNA synthesis was undetectable. These deficiencies could not be attributed to a failure to initiate infection or to a generalized defect in viral gene expression, since the viral replicator protein NS1 was expressed to normal or elevated levels early in infection. In contrast, truncated NS2 gene products failed to accumulate, so that each mutant exhibited a similar NS2-null phenotype. Expression of the capsid polypeptides VP1 and VP2 and their subsequent assembly into intact particles were examined in detail. Synchronized infected cell populations labeled under pulse-chase conditions were analyzed by differential immunoprecipitation of native or denatured extracts using antibodies which discriminated between intact particles and isolated polypeptide chains. These analyses showed that at early times in infection, capsid protein synthesis and stability were normal, but particle assembly was impaired. Unassembled VP proteins were retained in the cell for several hours, but as the unprocessed material accumulated, capsid protein synthesis progressively diminished, so that at later times relatively few VP molecules were synthesized. Thus in NS2-null infections of mouse cells there is a major primary defect in the folding or assembly processes required for effective capsid production.

  20. Diffusion Influenced Adsorption Kinetics.

    PubMed

    Miura, Toshiaki; Seki, Kazuhiko

    2015-08-27

    When the kinetics of adsorption is influenced by the diffusive flow of solutes, the solute concentration at the surface is influenced by the surface coverage of solutes, which is given by the Langmuir-Hinshelwood adsorption equation. The diffusion equation with the boundary condition given by the Langmuir-Hinshelwood adsorption equation leads to the nonlinear integro-differential equation for the surface coverage. In this paper, we solved the nonlinear integro-differential equation using the Grünwald-Letnikov formula developed to solve fractional kinetics. Guided by the numerical results, analytical expressions for the upper and lower bounds of the exact numerical results were obtained. The upper and lower bounds were close to the exact numerical results in the diffusion- and reaction-controlled limits, respectively. We examined the validity of the two simple analytical expressions obtained in the diffusion-controlled limit. The results were generalized to include the effect of dispersive diffusion. We also investigated the effect of molecular rearrangement of anisotropic molecules on surface coverage.

  1. Bicarbonate diffusion through mucus.

    PubMed

    Livingston, E H; Miller, J; Engel, E

    1995-09-01

    The mucus layer overlying duodenal epithelium maintains a pH gradient against high luminal acid concentrations. Despite these adverse conditions, epithelial surface pH remains close to neutrality. The exact nature of the gradient-forming barrier remains unknown. The barrier consists of mucus into which HCO3- is secreted. Quantification of the ability of HCO3- to establish and maintain the gradient depends on accurate measurement of this ion's diffusion coefficient through mucus. We describe new experimental and mathematical methods for diffusion measurement and report diffusion coefficients for HCO3- diffusion through saline, 5% mucin solutions, and rat duodenal mucus. The diffusion coefficients were 20.2 +/- 0.10, 3.02 +/- 0.31, and 1.81 +/- 0.12 x 10(-6) cm2/s, respectively. Modeling of the mucobicarbonate layer with this latter value suggests that for conditions of high luminal acid strength the neutralization of acid by HCO3- occurs just above the epithelial surface. Under these conditions the model predicts that fluid convection toward the lumen could be important in maintaining the pH gradient. In support of this hypothesis we were able to demonstrate a net luminal fluid flux of 5 microliters.min-1.cm-2 after perfusion of 0.15 N HCl in the rat duodenum.

  2. Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

    PubMed Central

    Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

  3. Diffusion in shear flow

    NASA Astrophysics Data System (ADS)

    Dufty, J. W.

    1984-09-01

    Diffusion of a tagged particle in a fluid with uniform shear flow is described. The continuity equation for the probability density describing the position of the tagged particle is considered. The diffusion tensor is identified by expanding the irreversible part of the probability current to first order in the gradient of the probability density, but with no restriction on the shear rate. The tensor is expressed as the time integral of a nonequilibrium autocorrelation function for the velocity of the tagged particle in its local fluid rest frame, generalizing the Green-Kubo expression to the nonequilibrium state. The tensor is evaluated from results obtained previously for the velocity autocorrelation function that are exact for Maxwell molecules in the Boltzmann limit. The effects of viscous heating are included and the dependence on frequency and shear rate is displayed explicitly. The mode-coupling contributions to the frequency and shear-rate dependent diffusion tensor are calculated.

  4. A quantum diffusion law

    NASA Astrophysics Data System (ADS)

    Satpathi, Urbashi; Sinha, Supurna; Sorkin, Rafael D.

    2017-12-01

    We analyse diffusion at low temperature by bringing the fluctuation-dissipation theorem (FDT) to bear on a physically natural, viscous response-function R(t) . The resulting diffusion-law exhibits several distinct regimes of time and temperature, each with its own characteristic rate of spreading. As with earlier analyses, we find logarithmic spreading in the quantum regime, indicating that this behavior is robust. A consistent R(t) must satisfy the key physical requirements of Wightman positivity and passivity, and we prove that ours does so. We also prove in general that these two conditions are equivalent when the FDT holds. Given current technology, our diffusion law can be tested in a laboratory with ultra cold atoms.

  5. Apparatus for diffusion separation

    DOEpatents

    Nierenberg, William A.; Pontius, Rex B.

    1976-08-10

    1. The method of testing the separation efficiency of porous permeable membranes which comprises causing a stream of a gaseous mixture to flow into contact with one face of a finely porous permeable membrane under such conditions that a major fraction of the mixture diffuses through the membrane, maintaining a rectangular cross section of the gaseous stream so flowing past said membrane, continuously recirculating the gas that diffuses through said membrane and continuously withdrawing the gas that does not diffuse through said membrane and maintaining the volume of said recirculating gas constant by continuously introducing into said continuously recirculating gas stream a mass of gas equivalent to that which is continuously withdrawn from said gas stream and comparing the concentrations of the light component in the entering gas, the withdrawn gas and the recirculated gas in order to determine the efficiency of said membrane.

  6. Zr diffusion in titanite

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.

    2006-11-01

    Chemical diffusion of Zr under anhydrous, pO2-buffered conditions has been measured in natural titanite. The source of diffusant was either zircon powder or a ZrO2-Al2O3-titanite mixture. Experiments were run in sealed silica glass capsules with solid buffers (to buffer at NNO or QFM). Rutherford Backscattering Spectrometry (RBS) was used to measure diffusion profiles. The following Arrhenius parameters were obtained for Zr diffusion parallel to c over the temperature range 753-1,100°C under NNO-buffered conditions: D Zr = 5.33 × 10-7 exp(-325 ± 30 kJ mol-1/RT) m2 s-1 Diffusivities are similar for experiments buffered at QFM. These data suggest that titanite should be moderately retentive of Zr chemical signatures, with diffusivities slower than those for O and Pb in titanite, but faster than those for Sr and the REE. When applied in evaluation of the relative robustness of the recently developed Zr-in-titanite geothermometer (Hayden and Watson, Abstract, 16th V.M. Goldschmidt Conference 2006), these findings suggest that Zr concentrations in titanite will be less likely to be affected by later thermal disturbance than the geothermometer based on Zr concentrations in rutile (Zack et al. in Contrib Mineral Petrol 148:471-488, 2004; Watson et al. in Contrib Mineral. Petrol, 2006), but much less resistant to diffusional alteration subsequent to crystallization than the Ti-in-Zircon geothermometer (Watson and Harrison in Science 308:841-844, 2005).

  7. Hydrogen diffusion in Zircon

    NASA Astrophysics Data System (ADS)

    Ingrin, Jannick; Zhang, Peipei

    2016-04-01

    Hydrogen mobility in gem quality zircon single crystals from Madagascar was investigated through H-D exchange experiments. Thin slices were annealed in a horizontal furnace flushed with a gas mixture of Ar/D2(10%) under ambient pressure between 900 ° C to 1150 ° C. FTIR analyses were performed on oriented slices before and after each annealing run. H diffusion along [100] and [010] follow the same diffusion law D = D0exp[-E /RT], with log D0 = 2.24 ± 1.57 (in m2/s) and E = 374 ± 39 kJ/mol. H diffusion along [001] follows a slightly more rapid diffusion law, with log D0 = 1.11 ± 0.22 (in m2/s) and E = 334 ± 49 kJ/mol. H diffusion in zircon has much higher activation energy and slower diffusivity than other NAMs below 1150 ° C even iron-poor garnets which are known to be among the slowest (Blanchard and Ingrin, 2004; Kurka et al. 2005). During H-D exchange zircon incorporates also deuterium. This hydration reaction involves uranium reduction as it is shown from the exchange of U5+ and U4+ characteristic bands in the near infrared region during annealing. It is the first time that a hydration reaction U5+ + OH- = U4+ + O2- + 1/2H2, is experimentally reported. The kinetics of deuterium incorporation is slightly slower than hydrogen diffusion, suggesting that the reaction is limited by hydrogen mobility. Hydrogen isotopic memory of zircon is higher than other NAMs. Zircons will be moderately retentive of H signatures at mid-crustal metamorphic temperatures. At 500 ° C, a zircon with a radius of 300 μm would retain its H isotopic signature over more than a million years. However, a zircon is unable to retain this information for geologically significant times under high-grade metamorphism unless the grain size is large enough. Refrences Blanchard, M. and Ingrin, J. (2004) Hydrogen diffusion in Dora Maira pyrope. Physics and Chemistry of Minerals, 31, 593-605. Kurka, A., Blanchard, M. and Ingrin, J. (2005) Kinetics of hydrogen extraction and deuteration in

  8. Multispecies diffusion models: A study of uranyl species diffusion

    NASA Astrophysics Data System (ADS)

    Liu, Chongxuan; Shang, Jianying; Zachara, John M.

    2011-12-01

    Rigorous numerical description of multispecies diffusion requires coupling of species, charge, and aqueous and surface complexation reactions that collectively affect diffusive fluxes. The applicability of a fully coupled diffusion model is, however, often constrained by the availability of species self-diffusion coefficients, as well as by computational complication in imposing charge conservation. In this study, several diffusion models with variable complexity in charge and species coupling were formulated and compared to describe reactive multispecies diffusion in groundwater. Diffusion of uranyl [U(VI)] species was used as an example in demonstrating the effectiveness of the models in describing multispecies diffusion. Numerical simulations found that a diffusion model with a single, common diffusion coefficient for all species was sufficient to describe multispecies U(VI) diffusion under a steady state condition of major chemical composition, but not under transient chemical conditions. Simulations revealed that for multispecies U(VI) diffusion under transient chemical conditions, a fully coupled diffusion model could be well approximated by a component-based diffusion model when the diffusion coefficient for each chemical component was properly selected. The component-based diffusion model considers the difference in diffusion coefficients between chemical components, but not between the species within each chemical component. This treatment significantly enhanced computational efficiency at the expense of minor charge conservation. The charge balance in the component-based diffusion model can be enforced, if necessary, by adding a secondary migration term resulting from model simplification. The effect of ion activity coefficient gradients on multispecies diffusion is also discussed. The diffusion models were applied to describe U(VI) diffusive mass transfer in intragranular domains in two sediments collected from U.S. Department of Energy's Hanford 300A

  9. Long-term surveillance of zinc implant in murine artery: Surprisingly steady biocorrosion rate.

    PubMed

    Drelich, Adam J; Zhao, Shan; Guillory, Roger J; Drelich, Jaroslaw W; Goldman, Jeremy

    2017-08-01

    Metallic zinc implanted into the abdominal aorta of rats out to 6months has been demonstrated to degrade while avoiding responses commonly associated with the restenosis of vascular implants. However, major questions remain regarding whether a zinc implant would ultimately passivate through the production of stable corrosion products or via a cell mediated fibrous encapsulation process that prevents the diffusion of critical reactants and products at the metal surface. Here, we have conducted clinically relevant long term in vivo studies in order to characterize late stage zinc implant biocorrosion behavior and products to address these critical questions. We found that zinc wires implanted in the murine artery exhibit steady corrosion without local toxicity for up to at least 20months post-implantation, despite a steady buildup of passivating corrosion products and intense fibrous encapsulation of the wire. Although fibrous encapsulation was not able to prevent continued implant corrosion, it may be related to the reduced chronic inflammation observed between 10 and 20months post-implantation. X-ray elemental and infrared spectroscopy analyses confirmed zinc oxide, zinc carbonate, and zinc phosphate as the main components of corrosion products surrounding the Zn implant. These products coincide with stable phases concluded from Pourbaix diagrams of a physiological solution and in vitro electrochemical impedance tests. The results support earlier predictions that zinc stents could become successfully bio-integrated into the arterial environment and safely degrade within a time frame of approximately 1-2years. Previous studies have shown zinc to be a promising candidate material for bioresorbable endovascular stenting applications. An outstanding question, however, is whether a zinc implant would ultimately passivate through the production of stable corrosion products or via a cell mediated tissue encapsulation process that prevented the diffusion of critical

  10. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.

    PubMed

    Zhu, Wanqu; Yao, Xiao; Liang, Yan; Liang, Dan; Song, Lu; Jing, Naihe; Li, Jinsong; Wang, Gang

    2015-02-01

    Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. © 2015. Published by The Company of Biologists Ltd.

  11. [Effects of interferon-gamma on cytotoxicity of murine activated macrophages against murine glioma cells].

    PubMed

    Ohyama, K; Kikuchi, H; Oda, Y; Moritake, K; Yamasaki, T

    1993-06-01

    We studied the effects of mouse IFN-gamma on the cytotoxic activity of murine activated macrophages (M phi) against mouse VM-Glioma cells (H-2b). Activated M phi were obtained from peritoneal exudate cells of mice from four strains, C57BL/6 (H-2b), C3H/He(H-2k), DBA/2 (H-2d), and BALB/c (H-2d), following intraperitoneal injection of (1) LPS 200 micrograms, (2) BCG 200 micrograms, (3) C. parvum 200 micrograms, or (4) MDP 350 micrograms 7 days prior to 20-hr 51Cr release-assay. Of the various combination of mouse strains and activating agents tested, that of activated M phi of the C3H/He mouse with induction by LPS had the most tumoricidal effect against the glioma cells, which was not MHC restricted. Although LPS-activated M phi underwent marked loss of cytotoxicity following initiation of in vitro culture, this 24 hr pretreatment with IFN-gamma inhibited this reduction in tumoricidal effects in a dose-dependent fashion. On the other hand, 24 hr pretreatment of target cells with IFN-gamma did not increase their susceptibility to lysis by activated M phi. These findings suggest that IFN-gamma augments the in vitro tumoricidal activation of M phi; This effect appears to be unrelated to any influence of IFN-gamma on target sensitivity to lysis by macrophages.

  12. DEVELOPMENT, DIFFUSION, AND EVALUATION.

    ERIC Educational Resources Information Center

    GUBA, EGON G.

    THE KNOWLEDGE GAP BETWEEN INITIAL RESEARCH AND FINAL USE IS DISCUSSED IN TERMS OF THE FOUR STATES OF THE THEORY-PRACTICE CONTINUUM (RESEARCH, DEVELOPMENT, DIFFUSION, AND ADOPTION). THE TWO MIDDLE STAGES ARE EMPHASIZED. RESEARCH AND DEVELOPMENT CENTERS, REGIONAL EDUCATIONAL LABORATORIES, AND TITLE III PROJECTS ARE SUGGESTED AS AGENCIES RESPONSIBLE…

  13. Water vapor diffusion membranes

    NASA Technical Reports Server (NTRS)

    Holland, F. F., Jr.; Smith, J. K.

    1974-01-01

    The program is reported, which was designed to define the membrane technology of the vapor diffusion water recovery process and to test this technology using commercially available or experimental membranes. One membrane was selected, on the basis of the defined technology, and was subjected to a 30-day demonstration trial.

  14. Osmosis and Diffusion

    ERIC Educational Resources Information Center

    Sack, Jeff

    2005-01-01

    OsmoBeaker is a CD-ROM designed to enhance the learning of diffusion and osmosis by presenting interactive experimentation to the student. The software provides several computer simulations that take the student through different scenarios with cells, having different concentrations of solutes in them.

  15. Diffusion in biased turbulence

    SciT

    Vlad, M.; Spineanu, F.; Misguich, J. H.

    2001-06-01

    Particle transport in two-dimensional divergence-free stochastic velocity fields with constant average is studied. Analytical expressions for the Lagrangian velocity correlation and for the time-dependent diffusion coefficients are obtained. They apply to stationary and homogeneous Gaussian velocity fields.

  16. Diffuse sorption modeling.

    PubMed

    Pivovarov, Sergey

    2009-04-01

    This work presents a simple solution for the diffuse double layer model, applicable to calculation of surface speciation as well as to simulation of ionic adsorption within the diffuse layer of solution in arbitrary salt media. Based on Poisson-Boltzmann equation, the Gaines-Thomas selectivity coefficient for uni-bivalent exchange on clay, K(GT)(Me(2+)/M(+))=(Q(Me)(0.5)/Q(M)){M(+)}/{Me(2+)}(0.5), (Q is the equivalent fraction of cation in the exchange capacity, and {M(+)} and {Me(2+)} are the ionic activities in solution) may be calculated as [surface charge, mueq/m(2)]/0.61. The obtained solution of the Poisson-Boltzmann equation was applied to calculation of ionic exchange on clays and to simulation of the surface charge of ferrihydrite in 0.01-6 M NaCl solutions. In addition, a new model of acid-base properties was developed. This model is based on assumption that the net proton charge is not located on the mathematical surface plane but diffusely distributed within the subsurface layer of the lattice. It is shown that the obtained solution of the Poisson-Boltzmann equation makes such calculations possible, and that this approach is more efficient than the original diffuse double layer model.

  17. Nonmonotonic diffusion in crowded environments

    PubMed Central

    Putzel, Gregory Garbès; Tagliazucchi, Mario; Szleifer, Igal

    2015-01-01

    We study the diffusive motion of particles among fixed spherical crowders. The diffusers interact with the crowders through a combination of a hard-core repulsion and a short-range attraction. The long-time effective diffusion coefficient of the diffusers is found to depend non-monotonically on the strength of their attraction to the crowders. That is, for a given concentration of crowders, a weak attraction to the crowders enhances diffusion. We show that this counterintuitive fact can be understood in terms of the mesoscopic excess chemical potential landscape experienced by the diffuser. The roughness of this excess chemical potential landscape quantitatively captures the nonmonotonic dependence of the diffusion rate on the strength of crowder-diffuser attraction; thus it is a purely static predictor of dynamic behavior. The mesoscopic view given here provides a unified explanation for enhanced diffusion effects that have been found in various systems of technological and biological interest. PMID:25302920

  18. Diffusion on Cu surfaces

    NASA Technical Reports Server (NTRS)

    Karimi, Majid

    1993-01-01

    Understanding surface diffusion is essential in understanding surface phenomena, such as crystal growth, thin film growth, corrosion, physisorption, and chemisorption. Because of its importance, various experimental and theoretical efforts have been directed to understand this phenomena. The Field Ion Microscope (FIM) has been the major experimental tool for studying surface diffusion. FIM have been employed by various research groups to study surface diffusion of adatoms. Because of limitations of the FIM, such studies are only limited to a few surfaces: nickel, platinum, aluminum, iridium, tungsten, and rhodium. From the theoretical standpoint, various atomistic simulations are performed to study surface diffusion. In most of these calculations the Embedded Atom Method (EAM) along with the molecular static (MS) simulation are utilized. The EAM is a semi-empirical approach for modeling the interatomic interactions. The MS simulation is a technique for minimizing the total energy of a system of particles with respect to the positions of its particles. One of the objectives of this work is to develop the EAM functions for Cu and use them in conjunction with the molecular static (MS) simulation to study diffusion of a Cu atom on a perfect as well as stepped Cu(100) surfaces. This will provide a test of the validity of the EAM functions on Cu(100) surface and near the stepped environments. In particular, we construct a terrace-ledge-kink (TLK) model and calculate the migration energies of an atom on a terrace, near a ledge site, near a kink site, and going over a descending step. We have also calculated formation energies of an atom on the bare surface, a vacancy in the surface, a stepped surface, and a stepped-kink surface. Our results are compared with the available experimental and theoretical results.

  19. Can Disorder Enhance Incoherent Exciton Diffusion?

    PubMed

    Lee, Elizabeth M Y; Tisdale, William A; Willard, Adam P

    2015-07-30

    Recent experiments aimed at probing the dynamics of excitons have revealed that semiconducting films composed of disordered molecular subunits, unlike expectations for their perfectly ordered counterparts, can exhibit a time-dependent diffusivity in which the effective early time diffusion constant is larger than that of the steady state. This observation has led to speculation about what role, if any, microscopic disorder may play in enhancing exciton transport properties. In this article, we present the results of a model study aimed at addressing this point. Specifically, we introduce a general model, based upon Förster theory, for incoherent exciton diffusion in a material composed of independent molecular subunits with static energetic disorder. Energetic disorder leads to heterogeneity in molecule-to-molecule transition rates, which we demonstrate has two important consequences related to exciton transport. First, the distribution of local site-specific hopping rates is broadened in a manner that results in a decrease in average exciton diffusivity relative to that in a perfectly ordered film. Second, since excitons prefer to make transitions that are downhill in energy, the steady state distribution of exciton energies is biased toward low-energy molecular subunits, those that exhibit reduced diffusivity relative to a perfectly ordered film. These effects combine to reduce the net diffusivity in a manner that is time dependent and grows more pronounced as disorder is increased. Notably, however, we demonstrate that the presence of energetic disorder can give rise to a population of molecular subunits with exciton transfer rates exceeding those of subunits in an energetically uniform material. Such enhancements may play an important role in processes that are sensitive to molecular-scale fluctuations in exciton density field.

  20. Instrumentation in Diffuse Optical Imaging

    PubMed Central

    Zhang, Xiaofeng

    2014-01-01

    Diffuse optical imaging is highly versatile and has a very broad range of applications in biology and medicine. It covers diffuse optical tomography, fluorescence diffuse optical tomography, bioluminescence, and a number of other new imaging methods. These methods of diffuse optical imaging have diversified instrument configurations but share the same core physical principle – light propagation in highly diffusive media, i.e., the biological tissue. In this review, the author summarizes the latest development in instrumentation and methodology available to diffuse optical imaging in terms of system architecture, light source, photo-detection, spectral separation, signal modulation, and lastly imaging contrast. PMID:24860804

  1. Oxygen diffusion in zircon

    NASA Astrophysics Data System (ADS)

    Watson, E. B.; Cherniak, D. J.

    1997-05-01

    Oxygen diffusion in natural, non-metamict zircon was characterized under both dry and water-present conditions at temperatures ranging from 765°C to 1500°C. Dry experiments were performed at atmospheric pressure by encapsulating polished zircon samples with a fine powder of 18O-enriched quartz and annealing the sealed capsules in air. Hydrothermal runs were conducted in cold-seal pressure vessels (7-70 MPa) or a piston cylinder apparatus (400-1000 MPa) on zircon samples encapsulated with both 18O-enriched quartz and 18O water. Diffusive-uptake profiles of 18O were measured in all samples with a particle accelerator, using the 18O(p, α) 15N reaction. For dry experimental conditions at 1100-1500°C, the resulting oxygen diffusivities (24 in all) are well described by: D dry (m 2/s) = 1.33 × 10 -4exp(-53920/T) There is no suggestion of diffusive anisotropy. Under wet conditions at 925°C, oxygen diffusion shows little or no dependence upon P H 2O in the range 7-1000 MPa, and is insensitive to total pressure as well. The results of 27 wet experiments at 767-1160°C and 7-1000 MPa can be described a single Arrhenius relationship: D wet (m 2/s) = 5.5 × 10 -12exp(-25280/T) The insensitivity of oxygen diffusion to P H 2O means that applications to geologic problems can be pursued knowing only whether the system of interest was 'wet' (i.e., P H 2O > 7MPa ) or 'dry'. Under dry conditions (presumably rare in the crust), zircons are extremely retentive of their oxygen isotopic signatures, to the extent that δ 18O would be perturbed at the center of a 200 μm zircon only during an extraordinarily hot and protracted event (e.g., 65 Ma at 900°C). Under wet conditions, δ 18O may or may not be retained in the central regions of individual crystals, cores or overgrowth rims, depending upon the specific thermal history of the system.

  2. Practical Murine Hematopathology: A Comparative Review and Implications for Research

    PubMed Central

    O'Connell, Karyn E; Mikkola, Amy M; Stepanek, Aaron M; Vernet, Andyna; Hall, Christopher D; Sun, Chia C; Yildirim, Eda; Staropoli, John F; Lee, Jeannie T; Brown, Diane E

    2015-01-01

    Hematologic parameters are important markers of disease in human and veterinary medicine. Biomedical research has benefited from mouse models that recapitulate such disease, thus expanding knowledge of pathogenetic mechanisms and investigative therapies that translate across species. Mice in health have many notable hematologic differences from humans and other veterinary species, including smaller erythrocytes, higher percentage of circulating reticulocytes or polychromasia, lower peripheral blood neutrophil and higher peripheral blood and bone marrow lymphocyte percentages, variable leukocyte morphologies, physiologic splenic hematopoiesis and iron storage, and more numerous and shorter-lived erythrocytes and platelets. For accurate and complete hematologic analyses of disease and response to investigative therapeutic interventions, these differences and the unique features of murine hematopathology must be understood. Here we review murine hematology and hematopathology for practical application to translational investigation. PMID:25926395

  3. Magnetic resonance imaging and spectroscopy of the murine cardiovascular system

    PubMed Central

    Akki, Ashwin; Gupta, Ashish

    2013-01-01

    Magnetic resonance imaging (MRI) has emerged as a powerful and reliable tool to noninvasively study the cardiovascular system in clinical practice. Because transgenic mouse models have assumed a critical role in cardiovascular research, technological advances in MRI have been extended to mice over the last decade. These have provided critical insights into cardiac and vascular morphology, function, and physiology/pathophysiology in many murine models of heart disease. Furthermore, magnetic resonance spectroscopy (MRS) has allowed the nondestructive study of myocardial metabolism in both isolated hearts and in intact mice. This article reviews the current techniques and important pathophysiological insights from the application of MRI/MRS technology to murine models of cardiovascular disease. PMID:23292717

  4. A Dominantly Acting Murine Allele of Mcm4 Causes Chromosomal Abnormalities and Promotes Tumorigenesis

    PubMed Central

    Bagley, Bruce N.; Keane, Thomas M.; Maklakova, Vilena I.; Marshall, Jonathon G.; Lester, Rachael A.; Cancel, Michelle M.; Paulsen, Alex R.; Bendzick, Laura E.; Been, Raha A.; Kogan, Scott C.; Cormier, Robert T.; Kendziorski, Christina; Adams, David J.; Collier, Lara S.

    2012-01-01

    Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4D573H). MCM4 is part of the heterohexameric complex of MCM2–7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4D573H to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities. PMID:23133403

  5. The Klebsiella pneumoniae O Antigen Contributes to Bacteremia and Lethality during Murine Pneumonia

    PubMed Central

    Shankar-Sinha, Sunita; Valencia, Gabriel A.; Janes, Brian K.; Rosenberg, Jessica K.; Whitfield, Chris; Bender, Robert A.; Standiford, Ted J.; Younger, John G.

    2004-01-01

    Bacterial surface carbohydrates are important pathogenic factors in gram-negative pneumonia infections. Among these factors, O antigen has been reported to protect pathogens against complement-mediated killing. To examine further the role of O antigen, we insertionally inactivated the gene encoding a galactosyltransferase necessary for serotype O1 O-antigen synthesis (wbbO) from Klebsiella pneumoniae 43816. Analysis of the mutant lipopolysaccharide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the absence of O antigen. In vitro, there were no detectable differences between wild-type K. pneumoniae and the O-antigen-deficient mutant in regard to avid binding by murine complement C3 or resistance to serum- or whole-blood-mediated killing. Nevertheless, the 72-h 50% lethal dose of the wild-type strain was 30-fold greater than that of the mutant (2 × 103 versus 6 × 104 CFU) after intratracheal injection in ICR strain mice. Despite being less lethal, the mutant organism exhibited comparable intrapulmonary proliferation at 24 h compared to the level of the wild type. Whole-lung chemokine expression (CCL3 and CXCL2) and bronchoalveolar inflammatory cell content were also similar between the two infections. However, whereas the wild-type organism produced bacteremia within 24 h of infection in every instance, bacteremia was not seen in mutant-infected mice. These results suggest that during murine pneumonia caused by K. pneumoniae, O antigen contributes to lethality by increasing the propensity for bacteremia and not by significantly changing the early course of intrapulmonary infection. PMID:14977947

  6. Long-Term Survival of Photoreceptors Transplanted into the Adult Murine Neural Retina Requires Immune Modulation

    PubMed Central

    West, Emma L.; Pearson, Rachael A.; Barker, Susie E.; Luhmann, Ulrich F. O.; Maclaren, Robert E.; Barber, Amanda C.; Duran, Yanai; Smith, Alexander J.; Sowden, Jane C.; Ali, Robin R.

    2012-01-01

    Stem cell therapy presents an opportunity to replace photoreceptors that are lost as a result of inherited and age-related degenerative disease. We have previously shown that murine postmitotic rod photoreceptor precursor cells, identified by expression of the rod-specific transcription factor Nrl, are able to migrate into and integrate within the adult murine neural retina. However, their long-term survival has yet to be determined. Here, we found that integrated Nrl.gfp+ve photoreceptors were present up to 12 months post-transplantation, albeit in significantly reduced numbers. Surviving cells had rod-like morphology, including inner/outer segments and spherule synapses. In a minority of eyes, we observed an early, marked reduction in integrated photoreceptors within 1 month post-transplantation, which correlated with increased numbers of amoeboid macrophages, indicating acute loss of transplanted cells due to an inflammatory response. In the majority of transplants, similar numbers of integrated cells were observed between 1 and 2 months post-transplantation. By 4 months, however, we observed a significant decrease in integrated cell survival. Macrophages and T cells were present around the transplantation site, indicating a chronic immune response. Immune suppression of recipients significantly increased transplanted photoreceptor survival, indicating that the loss observed in unsuppressed recipients resulted from T cell-mediated host immune responses. Thus, if immune responses are modulated, correctly integrated transplanted photoreceptors can survive for extended periods of time in hosts with partially mismatched H-2 haplotypes. These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective. PMID:20857496

  7. A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis.

    PubMed

    Bagley, Bruce N; Keane, Thomas M; Maklakova, Vilena I; Marshall, Jonathon G; Lester, Rachael A; Cancel, Michelle M; Paulsen, Alex R; Bendzick, Laura E; Been, Raha A; Kogan, Scott C; Cormier, Robert T; Kendziorski, Christina; Adams, David J; Collier, Lara S

    2012-01-01

    Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H)). MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H) to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.

  8. Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle

    PubMed Central

    Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L

    1999-01-01

    We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014

  9. A Murine Model of Robotic Training to Evaluate Skeletal Muscle Recovery after Injury.

    PubMed

    Lai, Stefano; Panarese, Alessandro; Lawrence, Ross; Boninger, Michael L; Micera, Silvestro; Ambrosio, Fabrisia

    2017-04-01

    In vivo studies have suggested that motor exercise can improve muscle regeneration after injury. Nevertheless, preclinical investigations still lack reliable tools to monitor motor performance over time and to deliver optimal training protocols to maximize force recovery. Here, we evaluated the utility of a murine robotic platform (i) to detect early impairment and longitudinal recovery after acute skeletal muscle injury and (ii) to administer varying intensity training protocols to enhance forelimb motor performance. A custom-designed robotic platform was used to train mice to perform a forelimb retraction task. After an acute injury to bilateral biceps brachii muscles, animals performed a daily training protocol in the platform at high (HL) or low (LL) loading levels over the course of 3 wk. Control animals were not trained (NT). Motor performance was assessed by quantifying force, time, submovement count, and number of movement attempts to accomplish the task. Myofiber number and cross-sectional area at the injury site were quantified histologically. Two days after injury, significant differences in the time, submovement count, number of movement attempts, and exerted force were observed in all mice, as compared with baseline values. Interestingly, the recovery time of muscle force production differed significantly between intervention groups, with HL group showing a significantly accelerated recovery. Three weeks after injury, all groups showed motor performance comparable with baseline values. Accordingly, there were no differences in the number of myofibers or average cross-sectional area among groups after 3 wk. Our findings demonstrate the utility of our custom-designed robotic device for the quantitative assessment of skeletal muscle function in preclinical murine studies. Moreover, we demonstrate that this device may be used to apply varying levels of resistance longitudinally as a means manipulate physiological muscle responses.

  10. Genotoxicity of nimesulide in murine bone marrow cells.

    PubMed

    Khan, P K; Amod, K; Haque, M; Nath, A

    2003-01-01

    The genotoxic potentiality of nimesulide was evaluated in vivo in murine bone marrow cells. The human equivalent prophylactic dose of nimesulide (5 mg/kg body wt/day) was given to animals orally, once daily for seven consecutive days. Metaphase chromosome analyses revealed the significant increase in the incidence of chromosomal aberrations with preference to structural over the numerical ones. It therefore suggested the clastogenic effect of the nimesulide. The molecular mechanism of mutagenesis is yet to be determined.

  11. Miniature Microwave Applicator for Murine Bladder Hyperthermia Studies

    PubMed Central

    Salahi, Sara; Maccarini, Paolo F.; Rodrigues, Dario B.; Etienne, Wiguins; Landon, Chelsea D.; Inman, Brant A.; Dewhirst, Mark W.; Stauffer, Paul R.

    2012-01-01

    Purpose Novel combinations of heat with chemotherapeutic agents are often studied in murine tumor models. Currently, no device exists to selectively heat small tumors at depth in mice. In this project, we modelled, built and tested a miniature microwave heat applicator, the physical dimensions of which can be scaled to adjust the volume and depth of heating to focus on the tumor volume. Of particular interest is a device that can selectively heat murine bladder. Materials and Methods Using Avizo® segmentation software, we created a numerical mouse model based on micro-MRI scan data. The model was imported into HFSS™ simulation software and parametric studies were performed to optimize the dimensions of a water-loaded circular waveguide for selective power deposition inside a 0.15ml bladder. A working prototype was constructed operating at 2.45GHz. Heating performance was characterized by mapping fiber-optic temperature sensors along catheters inserted at depths of 0-1mm (subcutaneous), 2-3mm (vaginal), and 4-5mm (rectal) below the abdominal wall, with the mid-depth catheter adjacent to the bladder. Core temperature was monitored orally. Results Thermal measurements confirm the simulations which demonstrate that this applicator can provide local heating at depth in small animals. Measured temperatures in murine pelvis show well-localized bladder heating to 42-43°C while maintaining normothermic skin and core temperatures. Conclusions Simulation techniques facilitate the design optimization of microwave antennas for use in pre-clinical applications such as localized tumor heating in small animals. Laboratory measurements demonstrate the effectiveness of a new miniature water-coupled microwave applicator for localized heating of murine bladder. PMID:22690856

  12. Miniature microwave applicator for murine bladder hyperthermia studies.

    PubMed

    Salahi, Sara; Maccarini, Paolo F; Rodrigues, Dario B; Etienne, Wiguins; Landon, Chelsea D; Inman, Brant A; Dewhirst, Mark W; Stauffer, Paul R

    2012-01-01

    Novel combinations of heat with chemotherapeutic agents are often studied in murine tumour models. Currently, no device exists to selectively heat small tumours at depth in mice. In this project we modelled, built and tested a miniature microwave heat applicator, the physical dimensions of which can be scaled to adjust the volume and depth of heating to focus on the tumour volume. Of particular interest is a device that can selectively heat murine bladder. Using Avizo(®) segmentation software, we created a numerical mouse model based on micro-MRI scan data. The model was imported into HFSS™ (Ansys) simulation software and parametric studies were performed to optimise the dimensions of a water-loaded circular waveguide for selective power deposition inside a 0.15 mL bladder. A working prototype was constructed operating at 2.45 GHz. Heating performance was characterised by mapping fibre-optic temperature sensors along catheters inserted at depths of 0-1 mm (subcutaneous), 2-3 mm (vaginal), and 4-5 mm (rectal) below the abdominal wall, with the mid depth catheter adjacent to the bladder. Core temperature was monitored orally. Thermal measurements confirm the simulations which demonstrate that this applicator can provide local heating at depth in small animals. Measured temperatures in murine pelvis show well-localised bladder heating to 42-43°C while maintaining normothermic skin and core temperatures. Simulation techniques facilitate the design optimisation of microwave antennas for use in pre-clinical applications such as localised tumour heating in small animals. Laboratory measurements demonstrate the effectiveness of a new miniature water-coupled microwave applicator for localised heating of murine bladder.

  13. The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression.

    PubMed

    Klochendler-Yeivin, A; Fiette, L; Barra, J; Muchardt, C; Babinet, C; Yaniv, M

    2000-12-01

    The assembly of eukaryotic DNA into nucleosomes and derived higher order structures constitutes a barrier for transcription, replication and repair. A number of chromatin remodeling complexes, as well as histone acetylation, were shown to facilitate gene activation. To investigate the function of two closely related mammalian SWI/SNF complexes in vivo, we inactivated the murine SNF5/INI1 gene, a common subunit of these two complexes. Mice lacking SNF5 protein stop developing at the peri-implantation stage, showing that the SWI/SNF complex is essential for early development and viability of early embryonic cells. Furthermore, heterozygous mice develop nervous system and soft tissue sarcomas. In these tumors the wild-type allele was lost, providing further evidence that SNF5 functions as a tumor suppressor gene in certain cell types.

  14. The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression

    PubMed Central

    Klochendler-Yeivin, Agnes; Fiette, Laurence; Barra, Jaqueline; Muchardt, Christian; Babinet, Charles; Yaniv, Moshe

    2000-01-01

    The assembly of eukaryotic DNA into nucleosomes and derived higher order structures constitutes a barrier for transcription, replication and repair. A number of chromatin remodeling complexes, as well as histone acetylation, were shown to facilitate gene activation. To investigate the function of two closely related mammalian SWI/SNF complexes in vivo, we inactivated the murine SNF5/INI1 gene, a common subunit of these two complexes. Mice lacking SNF5 protein stop developing at the peri-implantation stage, showing that the SWI/SNF complex is essential for early development and viability of early embryonic cells. Furthermore, heterozygous mice develop nervous system and soft tissue sarcomas. In these tumors the wild-type allele was lost, providing further evidence that SNF5 functions as a tumor suppressor gene in certain cell types. PMID:11263494

  15. General Model of Hindered Diffusion.

    PubMed

    Eloul, Shaltiel; Compton, Richard G

    2016-11-03

    The diffusion of a particle from bulk solution is slowed as it moves close to an adsorbing surface. A general model is reported that is easily applied by theoreticians and experimentalists. Specifically, it is shown here that in general and regardless of the space size, the magnitude of the effect of hindered diffusion on the flux is a property of the diffusion layer thickness. We explain and approximate the effect. Predictions of concentration profiles show that a "hindered diffusion layer" is formed near the adsorbing surface within the diffusion layer, observed even when the particle radius is just a 0.1% of the diffusion layer thickness. In particular, we focus on modern electrochemistry processes involving with impact of particles with either ultrasmall electrodes or particles in convective systems. The concept of the "hindered diffusion layer" is generally important for example in recent biophysical models of particles diffusion to small targets.

  16. Turbo fluid machinery and diffusers

    NASA Technical Reports Server (NTRS)

    Sakurai, T.

    1984-01-01

    The general theory behind turbo devices and diffusers is explained. Problems and the state of research on basic equations of flow and experimental and measuring methods are discussed. Conventional centrifugation-type compressor and fan diffusers are considered in detail.

  17. Nonlocal electrical diffusion equation

    NASA Astrophysics Data System (ADS)

    Gómez-Aguilar, J. F.; Escobar-Jiménez, R. F.; Olivares-Peregrino, V. H.; Benavides-Cruz, M.; Calderón-Ramón, C.

    2016-07-01

    In this paper, we present an analysis and modeling of the electrical diffusion equation using the fractional calculus approach. This alternative representation for the current density is expressed in terms of the Caputo derivatives, the order for the space domain is 0<β≤1 and for the time domain is 0<γ≤2. We present solutions for the full fractional equation involving space and time fractional derivatives using numerical methods based on Fourier variable separation. The case with spatial fractional derivatives leads to Levy flight type phenomena, while the time fractional equation is related to sub- or super diffusion. We show that the mathematical concept of fractional derivatives can be useful to understand the behavior of semiconductors, the design of solar panels, electrochemical phenomena and the description of anomalous complex processes.

  18. Three-dimensional alginate spheroid culture system of murine osteosarcoma.

    PubMed

    Akeda, Koji; Nishimura, Akinobu; Satonaka, Haruhiko; Shintani, Ken; Kusuzaki, Katsuyuki; Matsumine, Akihiko; Kasai, Yuichi; Masuda, Koichi; Uchida, Atsumasa

    2009-11-01

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone and often forms pulmonary metastases, which are the most important prognostic factor. For further elucidation of the mechanism underlying the progression and metastasis of human OS, a culture system mimicking the microenvironment of the tumor in vivo is needed. We report a novel three-dimensional (3D) alginate spheroid culture system of murine osteosarcoma. Two different metastatic clones, the parental Dunn and its derivative line LM8, which has a higher metastatic potential to the lungs, were encapsulated in alginate beads to develop the 3D culture system. The beads containing murine OS cells were also transplanted into mice to determine their metastatic potential in vivo. In this culture system, murine OS cells encapsulated in alginate beads were able to grow in a 3D structure with cells detaching from the alginate environment. The number of detaching cells was higher in the LM8 cell line than the Dunn cell line. In the in vivo alginate bead transplantation model, the rate of pulmonary metastasis was higher with LM8 cells compared with that of Dunn cells. The cell characteristics and kinetics in this culture system closely reflect the original malignant potential of the cells in vivo.

  19. Evaluation of a Murine Single-Blood-Injection SAH Model

    PubMed Central

    Sommer, Clemens; Steiger, Hans-Jakob; Schneider, Toni; Hänggi, Daniel

    2014-01-01

    The molecular pathways underlying the pathogenesis after subarachnoid haemorrhage (SAH) are poorly understood and continue to be a matter of debate. A valid murine SAH injection model is not yet available but would be the prerequisite for further transgenic studies assessing the mechanisms following SAH. Using the murine single injection model, we examined the effects of SAH on regional cerebral blood flow (rCBF) in the somatosensory (S1) and cerebellar cortex, neuro-behavioural and morphological integrity and changes in quantitative electrocorticographic and electrocardiographic parameters. Micro CT imaging verified successful blood delivery into the cisterna magna. An acute impairment of rCBF was observed immediately after injection in the SAH and after 6, 12 and 24 hours in the S1 and 6 and 12 hours after SAH in the cerebellum. Injection of blood into the foramen magnum reduced telemetric recorded total ECoG power by an average of 65%. Spectral analysis of ECoGs revealed significantly increased absolute delta power, i.e., slowing, cortical depolarisations and changes in ripples and fast ripple oscillations 12 hours and 24 hours after SAH. Therefore, murine single-blood-injection SAH model is suitable for pathophysiological and further molecular analysis following SAH. PMID:25545775

  20. Diagnostic imaging advances in murine models of colitis.

    PubMed

    Brückner, Markus; Lenz, Philipp; Mücke, Marcus M; Gohar, Faekah; Willeke, Peter; Domagk, Dirk; Bettenworth, Dominik

    2016-01-21

    Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.

  1. First steps to define murine amniotic fluid stem cell microenvironment.

    PubMed

    Bertin, E; Piccoli, M; Franzin, C; Spiro, G; Donà, S; Dedja, A; Schiavi, F; Taschin, E; Bonaldo, P; Braghetta, P; De Coppi, P; Pozzobon, M

    2016-11-15

    Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit + cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit + cells present both in the amniotic fluid and in the amnion. Secondly, to analyze the AFS cell microenvironment, we injected murine YFP + embryonic stem cells (ESC) into the amniotic fluid of E13.5 wild type embryos. Four days after transplantation we found that YFP + sorted cells maintained the expression of pluripotency markers and that ESC adherent to the amnion were more similar to original ESC in respect to those isolated from the amniotic fluid. Moreover, cytokines evaluation and oxygen concentration analysis revealed in this microenvironment the presence of factors that are considered key regulators in stem cell niches. This is the first indication that AFS cells reside in a microenvironment that possess specific characteristics able to maintain stemness of resident and exogenous stem cells.

  2. Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology.

    PubMed

    Hölsken, Annett; Schwarz, Marc; Gillmann, Clarissa; Pfister, Christina; Uder, Michael; Doerfler, Arnd; Buchfelder, Michael; Schlaffer, Sven; Fahlbusch, Rudolf; Buslei, Rolf; Bäuerle, Tobias

    2018-01-01

    Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3). In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content. Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non-vital grafts, when using a cut off value of 15% for vital tumor cell content. MRI enables the assessment of craniopharyngioma PDX vitality in vivo as validated histologically.

  3. Purification and Crystallization of Murine Myostatin: A Negative Regulator of Muscle Mass

    NASA Technical Reports Server (NTRS)

    Hong, Young S.; Adamek, Daniel; Bridge, Kristi; Malone, Christine C.; Young, Ronald B.; Miller, Teresa; Karr, Laurel

    2004-01-01

    Myostatin (MSTN) has been crystallized and its preliminary X-ray diffraction data were collected. MSTN is a negative regulator of muscle growt/differentiation and suppressor of fat accumulation. It is a member of TGF-b family of proteins. Like other members of this family, the regulation of MSTN is critically tied to its process of maturation. This process involves the formation of a homodimer followed by two proteolytic steps. The first proteolytic cleavage produces a species where the n-terminal portion of the dimer is covalently separated from, but remains non-covalently bound to, the c-terminal, functional, portion of the protein. The protein is activated upon removal of the n-terminal "pro-segment" by a second n-terminal proteolytic cut by BMP-1 in vivo, or by acid treatment in vitro. Understanding the structural nature and physical interactions involved in these regulatory processes is the objective of our studies. Murine MSTN was purified from culture media of genetically engineered Chinese Hamster Ovary cells by multicolumn purification process and crystallized using the vapor diffusion method.

  4. The effect of transfer factor on lymph node morphology in murine toxoplasmosis.

    PubMed Central

    Dundas, S. A.; Clark, A.

    1986-01-01

    Mice were infected intraperitoneally with a low virulence strain of Toxoplasma gondii (TO) and transfer factor (TF) was prepared from the spleens of infected (TFT) and uninfected control mice (TFC). Three experimental groups of 12 mice were given either saline, TFC or TFT, by intraperitoneal injection. After 24 h half of each group of these animals were infected by intraperitoneal injection of TO cysts. In three separate experiments animals were killed at 11, 28 and 35 days and the flank and axillary nodes removed for histological examination. There was generalized lymph node enlargement with cortical and paracortical expansion. In most animals there was diffuse infiltration of the nodes by clusters of histiocytes. Administration of TFC alone led to a mild increase in node size at 11 and 28 days. Administration of TFT alone had a moderate stimulatory effect on the mouse lymph nodes with a significant increase in size at 11 days due predominantly to expansion of the paracortex. Administration of TFT and TFC followed by inoculation of TO led to an increased and more consistent histiocyte response and an increased number of paracortical T blasts compared with animals given TO alone. TFT and TFC had no demonstrable protective effect in experimental murine toxoplasmosis as assessed by quantitation of toxoplasma brain cysts. The effect of transfer factor was not antigen specific in this system. Images Fig. 4 Fig. 5 Fig. 2 Fig. 3 Fig. 1 Fig. 6 PMID:2423107

  5. Mass transport by diffusion

    NASA Technical Reports Server (NTRS)

    Baird, James K.

    1987-01-01

    For the purpose of determining diffusion coefficients as required for electrodeposition studies and other applications, a diaphragm cell and an isothermal water bath were constructed. the calibration of the system is discussed. On the basis of three calibration runs on the diaphram cell, researchers concluded that the cell constant beta equals 0.12 cm -2 . Other calibration runs in progress should permit the cell constant to be determined with an accuracy of one percent.

  6. Peridynamic thermal diffusion

    SciT

    Oterkus, Selda; Madenci, Erdogan, E-mail: madenci@email.arizona.edu; Agwai, Abigail

    This study presents the derivation of ordinary state-based peridynamic heat conduction equation based on the Lagrangian formalism. The peridynamic heat conduction parameters are related to those of the classical theory. An explicit time stepping scheme is adopted for numerical solution of various benchmark problems with known solutions. It paves the way for applying the peridynamic theory to other physical fields such as neutronic diffusion and electrical potential distribution.

  7. Enhanced diffusion welding

    NASA Technical Reports Server (NTRS)

    Holko, K. H.; Moore, T. J. (Inventor)

    1973-01-01

    Surfaces of unrecrystallized alloys are sanded and polished. This is followed by a two-step welding process by which the strength of the parent metal is retained at the weld joint. The first step forces the surfaces into intimate contact at a temperature where the metal still has good ductility. The second step causes diffusion, recrystallization, and grain growth across the original weld interface.

  8. [The diffusion of knowledge].

    PubMed

    Ramiro-H, Manuel; Cruz-A, Enrique

    2016-01-01

    Between August 19 and 21, the Feria del Libro de las Ciencias de la Salud (Healthcare Book Fair) took place in the Palacio de Medicina in Mexico City. Archives of Medical Research, Revista Médica del IMSS, and Saber IMSS, three of the main instruments of knowledge diffusion of the Instituto Mexicano del Seguro Social, assisted to this book fair, which was organized by the Facultad de Medicina of UNAM.

  9. Diffusion orientation transform revisited.

    PubMed

    Canales-Rodríguez, Erick Jorge; Lin, Ching-Po; Iturria-Medina, Yasser; Yeh, Chun-Hung; Cho, Kuan-Hung; Melie-García, Lester

    2010-01-15

    Diffusion orientation transform (DOT) is a powerful imaging technique that allows the reconstruction of the microgeometry of fibrous tissues based on diffusion MRI data. The three main error sources involving this methodology are the finite sampling of the q-space, the practical truncation of the series of spherical harmonics and the use of a mono-exponential model for the attenuation of the measured signal. In this work, a detailed mathematical description that provides an extension to the DOT methodology is presented. In particular, the limitations implied by the use of measurements with a finite support in q-space are investigated and clarified as well as the impact of the harmonic series truncation. Near- and far-field analytical patterns for the diffusion propagator are examined. The near-field pattern makes available the direct computation of the probability of return to the origin. The far-field pattern allows probing the limitations of the mono-exponential model, which suggests the existence of a limit of validity for DOT. In the regimen from moderate to large displacement lengths the isosurfaces of the diffusion propagator reveal aberrations in form of artifactual peaks. Finally, the major contribution of this work is the derivation of analytical equations that facilitate the accurate reconstruction of some orientational distribution functions (ODFs) and skewness ODFs that are relatively immune to these artifacts. The new formalism was tested using synthetic and real data from a phantom of intersecting capillaries. The results support the hypothesis that the revisited DOT methodology could enhance the estimation of the microgeometry of fiber tissues.

  10. Solute diffusion in liquid metals

    NASA Technical Reports Server (NTRS)

    Bhat, B. N.

    1973-01-01

    A gas model of diffusion in liquid metals is presented. In this model, ions of liquid metals are assumed to behave like the molecules in a dense gas. Diffusion coefficient of solute is discussed with reference to its mass, ionic size, and pair potential. The model is applied to the case of solute diffusion in liquid silver. An attempt was made to predict diffusion coefficients of solutes with reasonable accuracy.

  11. Upper Bound on Diffusivity

    NASA Astrophysics Data System (ADS)

    Hartman, Thomas; Hartnoll, Sean A.; Mahajan, Raghu

    2017-10-01

    The linear growth of operators in local quantum systems leads to an effective light cone even if the system is nonrelativistic. We show that the consistency of diffusive transport with this light cone places an upper bound on the diffusivity: D ≲v2τeq. The operator growth velocity v defines the light cone, and τeq is the local equilibration time scale, beyond which the dynamics of conserved densities is diffusive. We verify that the bound is obeyed in various weakly and strongly interacting theories. In holographic models, this bound establishes a relation between the hydrodynamic and leading nonhydrodynamic quasinormal modes of planar black holes. Our bound relates transport data—including the electrical resistivity and the shear viscosity—to the local equilibration time, even in the absence of a quasiparticle description. In this way, the bound sheds light on the observed T -linear resistivity of many unconventional metals, the shear viscosity of the quark-gluon plasma, and the spin transport of unitary fermions.

  12. Methodology and apparatus for diffuse photon imaging

    DOEpatents

    Feng, S.C.; Zeng, F.; Zhao, H.L.

    1997-12-09

    Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue. 58 figs.

  13. Methodology and apparatus for diffuse photon mimaging

    DOEpatents

    Feng, Shechao C.; Zeng, Fanan; Zhao, Hui-Lin

    1997-12-09

    Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue.

  14. New imaging algorithm in diffusion tomography

    NASA Astrophysics Data System (ADS)

    Klibanov, Michael V.; Lucas, Thomas R.; Frank, Robert M.

    1997-08-01

    A novel imaging algorithm for diffusion/optical tomography is presented for the case of the time dependent diffusion equation. Numerical tests are conducted for ranges of parameters realistic for applications to an early breast cancer diagnosis using ultrafast laser pulses. This is a perturbation-like method which works for both homogeneous a heterogeneous background media. Its main innovation lies in a new approach for a novel linearized problem (LP). Such an LP is derived and reduced to a boundary value problem for a coupled system of elliptic partial differential equations. As is well known, the solution of such a system amounts to the factorization of well conditioned, sparse matrices with few non-zero entries clustered along the diagonal, which can be done very rapidly. Thus, the main advantages of this technique are that it is fast and accurate. The authors call this approach the elliptic systems method (ESM). The ESM can be extended for other data collection schemes.

  15. Diffusion of Zonal Variables Using Node-Centered Diffusion Solver

    SciT

    Yang, T B

    2007-08-06

    Tom Kaiser [1] has done some preliminary work to use the node-centered diffusion solver (originally developed by T. Palmer [2]) in Kull for diffusion of zonal variables such as electron temperature. To avoid numerical diffusion, Tom used a scheme developed by Shestakov et al. [3] and found their scheme could, in the vicinity of steep gradients, decouple nearest-neighbor zonal sub-meshes leading to 'alternating-zone' (red-black mode) errors. Tom extended their scheme to couple the sub-meshes with appropriate chosen artificial diffusion and thereby solved the 'alternating-zone' problem. Because the choice of the artificial diffusion coefficient could be very delicate, it is desirablemore » to use a scheme that does not require the artificial diffusion but still able to avoid both numerical diffusion and the 'alternating-zone' problem. In this document we present such a scheme.« less

  16. Diffusion models for innovation: s-curves, networks, power laws, catastrophes, and entropy.

    PubMed

    Jacobsen, Joseph J; Guastello, Stephen J

    2011-04-01

    This article considers models for the diffusion of innovation would be most relevant to the dynamics of early 21st century technologies. The article presents an overview of diffusion models and examines the adoption S-curve, network theories, difference models, influence models, geographical models, a cusp catastrophe model, and self-organizing dynamics that emanate from principles of network configuration and principles of heat diffusion. The diffusion dynamics that are relevant to information technologies and energy-efficient technologies are compared. Finally, principles of nonlinear dynamics for innovation diffusion that could be used to rehabilitate the global economic situation are discussed.

  17. An in vitro study of functional maturation of murine thymus cells.

    PubMed

    Chakravarty, A K

    1977-05-26

    Critical time of onset of thymus cell functions in ontogeny was studied in vitro. Collaborative function in an antibody response and ability to induce a graft-versus-host (GvH) response by murine thymocytes from different stages of ontogeny were investigated. Thymocytes from as early as 16-day mouse embryos were capable of collaborating in the antibody response to sheep-erythrocyte-antigen in vitro following 24 h of pretreatment with concanavalin A (con A). By contrast, maturation of thymus cell function as measured by competence to induce a graft-versus-host reaction, was first manifested by newborn thymus cells, and pretreatment with con A did not facilitate the maturation of this thymus cell function. Experiments to understand the effect of con A on the expression of cell surface antigens have also been reported. Con A-treated thymus cells of different ontogenic stages tested were less susceptible to killing by anti-theta serum than nontreated thymus cells; reverse was true with anti-H-2 serum. The significance of the differential susceptibility of con A-treated thymus cells to anti-sera treatment and the finding that mouse thymocytes can provide helper function as early as the 16th day of gestation have been discussed.

  18. Diffusion for holographic lattices

    NASA Astrophysics Data System (ADS)

    Donos, Aristomenis; Gauntlett, Jerome P.; Ziogas, Vaios

    2018-03-01

    We consider black hole spacetimes that are holographically dual to strongly coupled field theories in which spatial translations are broken explicitly. We discuss how the quasinormal modes associated with diffusion of heat and charge can be systematically constructed in a long wavelength perturbative expansion. We show that the dispersion relation for these modes is given in terms of the thermoelectric DC conductivity and static susceptibilities of the dual field theory and thus we derive a generalised Einstein relation from Einstein's equations. A corollary of our results is that thermodynamic instabilities imply specific types of dynamical instabilities of the associated black hole solutions.

  19. Apparatus for diffusion separation

    DOEpatents

    Nierenberg, William A.

    1976-08-10

    1. A diffuser separator apparatus which comprises a plurality of flow channels in a single stage, each of said channels having an inlet port and an outlet port and a constant cross sectional area between said ports, at least a portion of the defining surface of each of said channels being a diffusion separation membrane, and each of said channels having a different cross sectional area, means for connecting said channels in series so that each successive channel of said series has a smaller cross sectional area than the previous channel of said series, a source of gaseous mixture, individual means for flowing said gaseous mixture to the inlet port of each of said channels, gas receiving and analyzing means, individual means for flowing gas passing from each of said outlet ports and means for flowing gas passing through said membranes to said receiving and analyzing means, and individual means for connecting the outlet port of each channel with the inlet port of the channel having the next smaller cross sectional area.

  20. Diffusion controlled initial recombination

    NASA Astrophysics Data System (ADS)

    Christen, T.; Büttiker, M.

    1998-08-01

    This work addresses nucleation rates in systems with strong initial recombination. Initial (or ``geminate'') recombination is a process where a dissociated structure (anion, vortex, kink, etc.) recombines with its twin brother (cation, antivortex, antikink) generated in the same nucleation event. Initial recombination is important if there is an asymptotically vanishing interaction force instead of a generic saddle-type activation barrier. At low temperatures, initial recombination strongly dominates homogeneous recombination. In a first part, we discuss the effect in one-, two-, and three-dimensional diffusion controlled systems with spherical symmetry. Since there is no well-defined saddle, we introduce a threshold which is to some extent arbitrary but which is restricted by physically reasonable conditions. We show that the dependence of the nucleation rate on the specific choice of this threshold is strongest for one-dimensional systems and decreases in higher dimensions. We also discuss the influence of a weak driving force, and show that the transport current is directly determined by the imbalance of the activation rate in the direction of the field and the rate against this direction. In a second part, we apply the results to the overdamped sine-Gordon system at equilibrium. It turns out that diffusive initial recombination is the essential mechanism which governs the equilibrium kink nucleation rate. We emphasize analogies between the single particle problem with initial recombination and the multidimensional kink-antikink nucleation problem.

  1. Anisotropic Thermal Diffusion

    NASA Astrophysics Data System (ADS)

    Gardiner, Thomas

    2013-10-01

    Anisotropic thermal diffusion in magnetized plasmas is an important physical phenomena for a diverse set of physical conditions ranging from astrophysical plasmas to MFE and ICF. Yet numerically simulating this phenomenon accurately poses significant challenges when the computational mesh is misaligned with respect to the magnetic field. Particularly when the temperature gradients are unresolved, one frequently finds entropy violating solutions with heat flowing from cold to hot zones for χ∥ /χ⊥ >=102 which is substantially smaller than the range of interest which can reach 1010 or higher. In this talk we present a new implicit algorithm for solving the anisotropic thermal diffusion equations and demonstrate its characteristics on what has become a fairly standard set of test problems in the literature. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. SAND2013-5687A.

  2. Stochastic mechanics of reciprocal diffusions

    NASA Astrophysics Data System (ADS)

    Levy, Bernard C.; Krener, Arthur J.

    1996-02-01

    The dynamics and kinematics of reciprocal diffusions were examined in a previous paper [J. Math. Phys. 34, 1846 (1993)], where it was shown that reciprocal diffusions admit a chain of conservation laws, which close after the first two laws for two disjoint subclasses of reciprocal diffusions, the Markov and quantum diffusions. For the case of quantum diffusions, the conservation laws are equivalent to Schrödinger's equation. The Markov diffusions were employed by Schrödinger [Sitzungsber. Preuss. Akad. Wiss. Phys. Math Kl. 144 (1931); Ann. Inst. H. Poincaré 2, 269 (1932)], Nelson [Dynamical Theories of Brownian Motion (Princeton University, Princeton, NJ, 1967); Quantum Fluctuations (Princeton University, Princeton, NJ, 1985)], and other researchers to develop stochastic formulations of quantum mechanics, called stochastic mechanics. We propose here an alternative version of stochastic mechanics based on quantum diffusions. A procedure is presented for constructing the quantum diffusion associated to a given wave function. It is shown that quantum diffusions satisfy the uncertainty principle, and have a locality property, whereby given two dynamically uncoupled but statistically correlated particles, the marginal statistics of each particle depend only on the local fields to which the particle is subjected. However, like Wigner's joint probability distribution for the position and momentum of a particle, the finite joint probability densities of quantum diffusions may take negative values.

  3. Sucrose diffusion in aqueous solution

    PubMed Central

    Murray, Benjamin J.

    2016-01-01

    The diffusion of sugar in aqueous solution is important both in nature and in technological applications, yet measurements of diffusion coefficients at low water content are scarce. We report directly measured sucrose diffusion coefficients in aqueous solution. Our technique utilises a Raman isotope tracer method to monitor the diffusion of non-deuterated and deuterated sucrose across a boundary between the two aqueous solutions. At a water activity of 0.4 (equivalent to 90 wt% sucrose) at room temperature, the diffusion coefficient of sucrose was determined to be approximately four orders of magnitude smaller than that of water in the same material. Using literature viscosity data, we show that, although inappropriate for the prediction of water diffusion, the Stokes–Einstein equation works well for predicting sucrose diffusion under the conditions studied. As well as providing information of importance to the fundamental understanding of diffusion in binary solutions, these data have technological, pharmaceutical and medical implications, for example in cryopreservation. Moreover, in the atmosphere, slow organic diffusion may have important implications for aerosol growth, chemistry and evaporation, where processes may be limited by the inability of a molecule to diffuse between the bulk and the surface of a particle. PMID:27364512

  4. A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.

    PubMed

    Schröder, Paul C; Segura, Víctor; Riezu, José Ignacio; Sangro, Bruno; Mato, José M; Prieto, Jesús; Santamaría, Enrique; Corrales, Fernando J

    2011-09-01

    Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study, we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray-based approach. Expression of 190 genes was impaired in murine HCC from which 65 were further validated by low-density array real-time polymerase chain reaction (RT-PCR). The expression of the best 45 genes was then investigated in human samples resulting in 18 genes in which expression was significantly modified in HCC. Among them, JUN, methionine adenosyltransferase 1A and 2A, phosphoglucomutase 1, and acyl CoA dehydrogenase short/branched chain indicate defective cell proliferation as well as one carbon pathway, glucose and fatty acid metabolism, both in HCC and cirrhotic liver, a well-known preneoplastic condition. These alterations were further confirmed in public transcriptomic datasets from other authors. In addition, vasodilator-stimulated phosphoprotein, an actin-associated protein involved in cytoskeleton remodeling, was also found to be increased in the liver and serum of cirrhotic and HCC patients. In addition to revealing the impairment of central metabolic pathways for liver homeostasis, further studies may probe the potential value of the reported genes for the early detection of HCC.

  5. Murine Endogenous Retroviruses Are Detectable in Patient-Derived Xenografts but Not in Patient-Individual Cell Lines of Human Colorectal Cancer.

    PubMed

    Bock, Stephanie; Mullins, Christina S; Klar, Ernst; Pérot, Philippe; Maletzki, Claudia; Linnebacher, Michael

    2018-01-01

    murine cells, in PDX tissues and early thereof-derived cell cultures. We conclude that further analysis is needed concerning their impact on results obtained from studies performed with PDX but also with murine tumor models.

  6. Early Intervention.

    ERIC Educational Resources Information Center

    Nathanson, Jeanne H., Ed.

    1992-01-01

    This theme issue focuses on early intervention. The four articles presented on this theme are: (1) "Deaf Infants, Hearing Mothers: A Research Report" (Kathryn P. Meadow-Orlans, and others), reporting findings on effects of auditory loss on early development; (2) "Maintaining Involvement of Inner City Families in Early Intervention Programs through…

  7. Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.

    PubMed

    Milstone, Zachary J; Lawson, Grace; Trivedi, Chinmay M

    2017-12-01

    Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown. The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch. Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches by means of repression of cyclin-dependent kinase inhibitors. Developmental Dynamics 246:1015-1026, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Cited2 Gene Controls Pluripotency and Cardiomyocyte Differentiation of Murine Embryonic Stem Cells through Oct4 Gene*

    PubMed Central

    Li, Qiang; Ramírez-Bergeron, Diana L.; Dunwoodie, Sally L.; Yang, Yu-Chung

    2012-01-01

    Cited2 (CBP/p300-interacting transactivator with glutamic acid (E)/aspartic acid (D)-rich tail 2) is a transcriptional modulator critical for the development of multiple organs. Although many Cited2-mediated phenotypes and molecular events have been well characterized using in vivo genetic murine models, Cited2-directed cell fate decision in embryonic stem cells (ESCs) remains elusive. In this study, we examined the role of Cited2 in the maintenance of stemness and pluripotency of murine ESCs by a gene-targeting approach. Cited2 knock-out (Cited2Δ/−, KO) ESCs display defective differentiation. Loss of Cited2 in differentiating ESCs results in delayed silencing of the genes involved in the maintenance of pluripotency and self-renewal of stem cells (Oct4, Klf4, Sox2, and c-Myc) and the disturbance in cardiomyocyte, hematopoietic, and neuronal differentiation. In addition, Cited2 KO ESCs experience a delayed induction of cardiomyocyte differentiation-associated proteins, NFAT3 (along with the reduced expression of NFAT3 target genes, Nkx2.5 and β-MHC), N-cadherin, and smooth muscle actin. CITED2 is recruited to the Oct4 promoter to regulate its expression during early ESC differentiation. This is the first demonstration that Cited2 controls ESC pluripotency and differentiation via direct regulation of Oct4 gene expression. PMID:22761414

  9. Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

    PubMed

    Langford-Smith, Kia J; Sandiford, Zara; Langford-Smith, Alex; Wilkinson, Fiona L; Jones, Simon A; Wraith, J Ed; Wynn, Robert F; Bigger, Brian W

    2013-01-01

    Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM):blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg) and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan). We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

  10. The Harrison Diffusion Kinetics Regimes in Solute Grain Boundary Diffusion

    SciT

    Belova, Irina; Fiedler, T; Kulkarni, Nagraj S

    2012-01-01

    Knowledge of the limits of the principal Harrison kinetics regimes (Type-A, B and C) for grain boundary diffusion is very important for the correct analysis of the depth profiles in a tracer diffusion experiment. These regimes for self-diffusion have been extensively studied in the past by making use of the phenomenological Lattice Monte Carlo (LMC) method with the result that the limits are now well established. The relationship of those self-diffusion limits to the corresponding ones for solute diffusion in the presence of solute segregation to the grain boundaries remains unclear. In the present study, the influence of solute segregationmore » on the limits is investigated with the LMC method for the well-known parallel grain boundary slab model by showing the equivalence of two diffusion models. It is shown which diffusion parameters are useful for identifying the limits of the Harrison kinetics regimes for solute grain boundary diffusion. It is also shown how the measured segregation factor from the diffusion experiment in the Harrison Type-B kinetics regime may differ from the global segregation factor.« less

  11. Characterization of a Novel Murine Model to Study Zika Virus.

    PubMed

    Rossi, Shannan L; Tesh, Robert B; Azar, Sasha R; Muruato, Antonio E; Hanley, Kathryn A; Auguste, Albert J; Langsjoen, Rose M; Paessler, Slobodan; Vasilakis, Nikos; Weaver, Scott C

    2016-06-01

    The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain-Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼10(7) plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines. © The American Society of Tropical Medicine and Hygiene.

  12. Giardia Alters Commensal Microbial Diversity throughout the Murine Gut

    PubMed Central

    Barash, N. R.; Maloney, J. G.

    2017-01-01

    ABSTRACT Giardia lamblia is the most frequently identified protozoan cause of intestinal infection. Over 200 million people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in areas where Giardia is endemic. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear, as the parasite neither produces a known toxin nor induces a robust inflammatory response. Giardia colonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact of Giardia infection on the host microbiota, we used culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the gastrointestinal tract in mice infected with Giardia. We discovered that Giardia's colonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic commensal bacteria. Specifically, Giardia colonization is typified by both expansions in aerobic Proteobacteria and decreases in anaerobic Firmicutes and Melainabacteria in the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murine Giardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. Giardiasis could be an ecological disease, and the observed dysbiosis may be mediated directly via the parasite's unique anaerobic fermentative metabolism or indirectly via parasite induction of gut inflammation. This systemic alteration of murine gut commensal diversity may be the cause or the consequence of inflammatory and metabolic changes throughout the gut. Shifts in the commensal microbiota may explain observed variations in giardiasis between hosts with respect to host pathology, degree of parasite colonization

  13. Lactoferrin Expression in Human and Murine Ocular Tissue.

    PubMed

    Rageh, Abrar A; Ferrington, Deborah A; Roehrich, Heidi; Yuan, Ching; Terluk, Marcia R; Nelson, Elizabeth F; Montezuma, Sandra R

    2016-07-01

    Lactoferrin (LF) is a multifunctional protein known to provide innate defense due to its antimicrobial and anti-inflammatory properties. In the eye, LF has been identified in the tears and vitreous humor. Its presence in other ocular tissues has not been determined. Our aim is to assess the presence of LF in the cornea, iris, retina and retinal pigment epithelium (RPE) of humans and mice. To test for the endogenous production of LF, reverse transcription polymerase chain reaction was performed in cultured human cells from the cornea and RPE and in murine tissues. To confirm LF localization in specific ocular tissue, immunohistochemistry was performed on flat mounts of cornea, retina and RPE in human donor eyes. The presence of LF was assessed by western blotting in human and mouse ocular tissue and human culture cells (cornea and RPE). To verify antibody specificity, purified human LF and transferrin (TF) were used on 1D and 2D western blots. LF gene expression was confirmed in the cornea and RPE cell cultures from humans, suggesting that LF is an endogenously produced protein. PCR results from mouse ocular tissue showed LF expression in cornea, iris, RPE, but not in retina. These results were also consistent with immunohistochemical localization of LF in human donor tissue. Antibody reaction for human LF was specific and western blotting showed its presence in the cornea, iris and RPE tissues. A faint reaction for the retina was observed but was likely due to contamination from other ocular tissues. Multiple commercially available antibodies for murine LF cross-reacted with TF, so no reliable results were obtained for murine western blot. LF is expressed in multiple eye tissues of humans and mice. This widespread expression and multifunctional activity of LF suggests that it may play an important role in protecting eye tissues from inflammation-associated diseases.

  14. [Evaluation of Fusarium spp. pathogenicity in plant and murine models].

    PubMed

    Forero-Reyes, Consuelo M; Alvarado-Fernández, Angela M; Ceballos-Rojas, Ana M; González-Carmona, Lady C; Linares-Linares, Melva Y; Castañeda-Salazar, Rubiela; Pulido-Villamarín, Adriana; Góngora-Medina, Manuel E; Cortés-Vecino, Jesús A; Rodríguez-Bocanegra, María X

    The genus Fusarium is widely recognized for its phytopathogenic capacity. However, it has been reported as an opportunistic pathogen in immunocompetent and immunocompromised patients. Thus, it can be considered a microorganism of interest in pathogenicity studies on different hosts. Therefore, this work evaluated the pathogenicity of Fusarium spp. isolates from different origins in plants and animals (murine hosts). Twelve isolates of Fusarium spp. from plants, animal superficial mycoses, and human superficial and systemic mycoses were inoculated in tomato, passion fruit and carnation plants, and in immunocompetent and immunosuppressed BALB/c mice. Pathogenicity tests in plants did not show all the symptoms associated with vascular wilt in the three plant models; however, colonization and necrosis of the vascular bundles, regardless of the species and origin of the isolates, showed the infective potential of Fusarium spp. in different plant species. Moreover, the pathogenicity tests in the murine model revealed behavioral changes. It was noteworthy that only five isolates (different origin and species) caused mortality. Additionally, it was observed that all isolates infected and colonized different organs, regardless of the species and origin of the isolates or host immune status. In contrast, the superficial inoculation test showed no evidence of epidermal injury or colonization. The observed results in plant and murine models suggest the pathogenic potential of Fusarium spp. isolates in different types of hosts. However, further studies on pathogenicity are needed to confirm the multihost capacity of this genus. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Early osteoarthritis of the knee.

    PubMed

    Madry, Henning; Kon, Elizaveta; Condello, Vincenzo; Peretti, Giuseppe M; Steinwachs, Matthias; Seil, Romain; Berruto, Massimo; Engebretsen, Lars; Filardo, Giuseppe; Angele, Peter

    2016-06-01

    There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.

  16. [From Brownian motion to mind imaging: diffusion MRI].

    PubMed

    Le Bihan, Denis

    2006-11-01

    The success of diffusion MRI, which was introduced in the mid 1980s is deeply rooted in the powerful concept that during their random, diffusion-driven movements water molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. The observation of these movements thus provides valuable information on the structure and the geometric organization of tissues. The most successful application of diffusion MRI has been in brain ischemia, following the discovery that water diffusion drops at a very early stage of the ischemic event. Diffusion MRI provides some patients with the opportunity to receive suitable treatment at a very acute stage when brain tissue might still be salvageable. On the other hand, diffusion is modulated by the spatial orientation of large bundles of myelinated axons running in parallel through in brain white matter. This feature can be exploited to map out the orientation in space of the white matter tracks and to visualize the connections between different parts of the brain on an individual basis. Furthermore, recent data suggest that diffusion MRI may also be used to visualize rapid dynamic tissue changes, such as neuronal swelling, associated with cortical activation, offering a new and direct approach to brain functional imaging.

  17. Murine Gammaherpesvirus 68 LANA and SOX Homologs Counteract ATM-Driven p53 Activity during Lytic Viral Replication

    PubMed Central

    Sifford, Jeffrey M.; Stahl, James A.; Salinas, Eduardo

    2015-01-01

    ABSTRACT Tumor suppressor p53 is activated in response to numerous cellular stresses, including viral infection. However, whether murine gammaherpesvirus 68 (MHV68) provokes p53 during the lytic replication cycle has not been extensively evaluated. Here, we demonstrate that MHV68 lytic infection induces p53 phosphorylation and stabilization in a manner that is dependent on the DNA damage response (DDR) kinase ataxia telangiectasia mutated (ATM). The induction of p53 during MHV68 infection occurred in multiple cell types, including splenocytes of infected mice. ATM and p53 activation required early viral gene expression but occurred independently of viral DNA replication. At early time points during infection, p53-responsive cellular genes were induced, coinciding with p53 stabilization and phosphorylation. However, p53-related gene expression subsided as infection progressed, even though p53 remained stable and phosphorylated. Infected cells also failed to initiate p53-dependent gene expression and undergo apoptosis in response to treatment with exogenous p53 agonists. The inhibition of p53 responses during infection required the expression of the MHV68 homologs of the shutoff and exonuclease protein (muSOX) and latency-associated nuclear antigen (mLANA). Interestingly, mLANA, but not muSOX, was necessary to prevent p53-mediated death in MHV68-infected cells under the conditions tested. This suggests that muSOX and mLANA are differentially required for inhibiting p53 in specific settings. These data reveal that DDR responses triggered by MHV68 infection promote p53 activation. However, MHV68 encodes at least two proteins capable of limiting the potential consequences of p53 function. IMPORTANCE Gammaherpesviruses are oncogenic herpesviruses that establish lifelong chronic infections. Defining how gammaherpesviruses overcome host responses to infection is important for understanding how these viruses infect and cause disease. Here, we establish that murine

  18. Lessons from the Murine Models of West Nile Virus Infection.

    PubMed

    McGruder, Brenna; Saxena, Vandana; Wang, Tian

    2016-01-01

    West Nile virus (WNV), a mosquito-borne, single positive-stranded RNA virus, has been the leading cause of arboviral encephalitis in the U.S. and other parts of the world over the past decade. Up to 50 % of WNV convalescent patients were reported to have long-term neurological sequelae or chronic kidney diseases. However, there are neither antiviral drugs nor vaccines available for humans. The underlying mechanism of the long-term sequelae is not clearly understood either. Animal models have been an effective tool to investigate viral pathogenesis and host immunity in humans. Here, we will review several commonly used murine models of WNV infection.

  19. Corn silk induced cyclooxygenase-2 in murine macrophages.

    PubMed

    Kim, Kyung A; Shin, Hyun-Hee; Choi, Sang Kyu; Choi, Hye-Seon

    2005-10-01

    Stimulation of murine macrophages with corn silk induced cyclooxygenase (COX)-2 with secretion of PGE2. Expression of COX-2 was inhibited by pyrolidine dithiocarbamate (PDTC), and increased DNA binding by nuclear factor kappa B (NF-kappaB), indicating that COX-2 induction proceeds also via the NF-kappaB signaling pathway. A specific inhibitor of COX-2 decreased the expression level of inducible nitric oxide synthase (iNOS) stimulated by corn silk. PGE2 elevated the expression level of iNOS, probably via EP2 and EP4 receptors on the surface of the macrophages.

  20. Spatial distribution of endogenous retinoids in the murine embryonic mandible.

    PubMed

    Kronmiller, J E; Beeman, C S

    1994-12-01

    Retinoids play an important part in pattern formation during embryonic development. Exogenous retinoids alter the pattern of skeletal, neural and odontogenic tissues. Endogenous retinoids have been demonstrated previously in the murine embryonic mandible, reaching a concentration peak during the initiation of odontogenesis. It was now found that endogenous retinoids are present in a concentration gradient in the embryonic mouse mandible at the time of the initiation of the dental lamina. All-trans-retinoic acid was more concentrated in the incisor region and retinol in the molar region. These results, and the fact that exogenous retinoids produce supernumerary incisors and missing molars, suggest that all-trans-retinoic acid may instruct incisor morphology.

  1. Characterization of airway and vascular responses in murine lungs

    PubMed Central

    Held, Heinz-Dieter; Martin, Christian; Uhlig, Stefan

    1999-01-01

    We characterized the responses of murine airways and pulmonary vessels to a variety of endogenous mediators in the isolated perfused and ventilated mouse lung (IPL) and compared them with those in precision-cut lung slices. Airways: The EC50 (μM) for contractions of airways in IPL/slices was methacholine (Mch), 6.1/1.5>serotonin, 0.7/2.0>U46619 (TP-receptor agonist), 0.1/0.06>endothelin-1, 0.1/0.05. In the IPL, maximum increase in airway resistance (RL) was 0.6, 0.4, 0.8 and 11 cmH2O s ml−1, respectively. Adenosine (⩽1 mM), bombesin (⩽100 μM), histamine (⩽10 mM), LTC4 (⩽1 μM), PAF (0.25 μM) and substance P (⩽100 μM) had only weak effects (<5% of Mch) on RL. Vessels: The EC50 (μM) for vasoconstriction in the IPL was LTC4, 0.06>U46619, 0.05Murine precision-cut lung slices maintain important characteristics of the whole organ. The maximum reagibility of murine airways to endogenous mediators is serotoninmurine pulmonary vasculature is serotonin

  2. Murine cell glycolipids customization by modular expression of glycosyltransferases.

    PubMed

    Cid, Emili; Yamamoto, Miyako; Buschbeck, Marcus; Yamamoto, Fumiichiro

    2013-01-01

    Functional analysis of glycolipids has been hampered by their complex nature and combinatorial expression in cells and tissues. We report an efficient and easy method to generate cells with specific glycolipids. In our proof of principle experiments we have demonstrated the customized expression of two relevant glycosphingolipids on murine fibroblasts, stage-specific embryonic antigen 3 (SSEA-3), a marker for stem cells, and Forssman glycolipid, a xenoantigen. Sets of genes encoding glycosyltansferases were transduced by viral infection followed by multi-color cell sorting based on coupled expression of fluorescent proteins.

  3. Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene.

    PubMed

    Chester, N; Kuo, F; Kozak, C; O'Hara, C D; Leder, P

    1998-11-01

    Bloom's syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease include proportional dwarfism and a predisposition to develop a wide variety of malignancies. The human BLM gene has been cloned recently and encodes a DNA helicase. Mouse embryos homozygous for a targeted mutation in the murine Bloom's syndrome gene (Blm) are developmentally delayed and die by embryonic day 13.5. The fact that the interrupted gene is the homolog of the human BLM gene was confirmed by its homologous sequence, its chromosomal location, and by demonstrating high numbers of SCEs in cultured murine Blm-/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12-24 hr) seen during mid-gestation in murine Blm-/- embryos. Interestingly, the growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early post-implantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm-/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes.

  4. Severe interstitial pneumonia due to murine typhus in a patient returning from Bali.

    PubMed

    Malheiro, Luís; Ceia, Filipa; Alves, João; Carvalho, Ana Cláudia; Sobrinho-Simões, Joana; Sousa, Rita; Sarmento, António; Santos, Lurdes

    2017-01-01

    Murine typhus has been increasingly reported as a cause of fever in returning travelers from Southeast Asia. We report a case of a previously healthy traveler returning from Bali with an non-specific febrile illness which quickly progressed to a severe form of interstitial pneumonia. After a careful epidemiological evaluation and laboratory analysis, murine typhus was diagnosed.

  5. Murine Intracisternal A Type Particles Fail to Separate from the Membrane of the Endoplasmic Reticulum

    PubMed Central

    Perk, Kalman; Dahlberg, John E.

    1974-01-01

    Analysis of serial sections of murine cells containing intracisternal A particles revealed that over 99% of all A particles remain in a budding configuration. This indicates that these particles fail to detach from the membrane of the endoplasmic reticulum. This observation explains how, despite their intracellular abundance in certain murine tumors, no extracellular A-type particles can be found. Images PMID:4431082

  6. Murine typhus in two travelers returning from Bali, Indonesia: an underdiagnosed disease.

    PubMed

    Takeshita, Nozomi; Imoto, Kazuya; Ando, Shuji; Yanagisawa, Kunio; Ohji, Goh; Kato, Yasuyuki; Sakata, Akiko; Hosokawa, Naoto; Kishimoto, Toshio

    2010-01-01

    Two Japanese travelers from Bali were diagnosed with murine typhus in Japan during the same period. Although one had only mild illness, the other experienced liver and kidney dysfunction. Murine typhus may be missed not only in endemic areas around the world, but also in travelers, especially those returning from marine resorts in these areas. © 2010 International Society of Travel Medicine.

  7. Mycobacterial Nucleoside Diphosphate Kinase Blocks Phagosome Maturation in Murine Raw 264.7 Macrophages

    PubMed Central

    Sun, Jim; Wang, Xuetao; Lau, Alice; Liao, Ting-Yu Angela; Bucci, Cecilia; Hmama, Zakaria

    2010-01-01

    Background Microorganisms capable of surviving within macrophages are rare, but represent very successful pathogens. One of them is Mycobacterium tuberculosis (Mtb) whose resistance to early mechanisms of macrophage killing and failure of its phagosomes to fuse with lysosomes causes tuberculosis (TB) disease in humans. Thus, defining the mechanisms of phagosome maturation arrest and identifying mycobacterial factors responsible for it are key to rational design of novel drugs for the treatment of TB. Previous studies have shown that Mtb and the related vaccine strain, M. bovis bacille Calmette-Guérin (BCG), disrupt the normal function of host Rab5 and Rab7, two small GTPases that are instrumental in the control of phagosome fusion with early endosomes and late endosomes/lysosomes respectively. Methodology/Principal Findings Here we show that recombinant Mtb nucleoside diphosphate kinase (Ndk) exhibits GTPase activating protein (GAP) activity towards Rab5 and Rab7. Then, using a model of latex bead phagosomes, we demonstrated that Ndk inhibits phagosome maturation and fusion with lysosomes in murine RAW 264.7 macrophages. Maturation arrest of phagosomes containing Ndk-beads was associated with the inactivation of both Rab5 and Rab7 as evidenced by the lack of recruitment of their respective effectors EEA1 (early endosome antigen 1) and RILP (Rab7-interacting lysosomal protein). Consistent with these findings, macrophage infection with an Ndk knocked-down BCG strain resulted in increased fusion of its phagosome with lysosomes along with decreased survival of the mutant. Conclusion Our findings provide evidence in support of the hypothesis that mycobacterial Ndk is a putative virulence factor that inhibits phagosome maturation and promotes survival of mycobacteria within the macrophage. PMID:20098737

  8. Isoform-Specific Upregulation of Palladin in Human and Murine Pancreas Tumors

    PubMed Central

    Goicoechea, Silvia M.; Bednarski, Brian; Stack, Christianna; Cowan, David W.; Volmar, Keith; Thorne, Leigh; Cukierman, Edna; Rustgi, Anil K.; Brentnall, Teresa; Hwang, Rosa F.; McCulloch, Christopher A. G.; Yeh, Jen Jen; Bentrem, David J.; Hochwald, Steven N.; Hingorani, Sunil R.

    2010-01-01

    Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a characteristic pattern of early metastasis, which is driving a search for biomarkers that can be used to detect the cancer at an early stage. Recently, the actin-associated protein palladin was identified as a candidate biomarker when it was shown that palladin is mutated in a rare inherited form of PDA, and overexpressed in many sporadic pancreas tumors and premalignant precursors. In this study, we analyzed the expression of palladin isoforms in murine and human PDA and explored palladin's potential use in diagnosing PDA. We performed immunohistochemistry and immunoblot analyses on patient samples and tumor-derived cells using an isoform-selective monoclonal antibody and a pan-palladin polyclonal antibody. Immunoblot and real-time quantitative reverse transcription-PCR were used to quantify palladin mRNA levels in human samples. We show that there are two major palladin isoforms expressed in pancreas: 65 and 85–90 kDa. The 65 kDa isoform is expressed in both normal and neoplastic ductal epithelial cells. The 85–90 kDa palladin isoform is highly overexpressed in tumor-associated fibroblasts (TAFs) in both primary and metastatic tumors compared to normal pancreas, in samples obtained from either human patients or genetically engineered mice. In tumor-derived cultured cells, expression of palladin isoforms follows cell-type specific patterns, with the 85–90 kDa isoform in TAFs, and the 65 kDa isoform predominating in normal and neoplastic epithelial cells. These results suggest that upregulation of 85–90 kDa palladin isoform may play a role in the establishment of the TAF phenotype, and thus in the formation of a desmoplastic tumor microenvironment. Thus, palladin may have a potential use in the early diagnosis of PDA and may have much broader significance in understanding metastatic behavior. PMID:20436683

  9. Anomalous Thermal Diffusivity in Bad Metals

    NASA Astrophysics Data System (ADS)

    Zhang, Jiecheng; Levenson-Falk, Eli M.; Ramshaw, Brad J.; Bonn, Douglas A.; Liang, Ruixing; Hardy, Walter N.; Hartnoll, Sean A.; Kapitulnik, Aharon

    Local measurements of thermal diffusivity are used to analyze the transport of heat in the bad metallic regime of several strongly correlated materials. In underdoped YBCO systems, we use the in-plane anisotropy to analyze transport in this system. Specifically, we find that the diffusivity anisotropy is comparable to reported values of the electrical resistivity anisotropy and drops sharply below the charge order transition, suggesting that both anisotropies have the same origin. We interpret our results through a strong electron-phonon scattering picture and find that both electronic and phononic contributions to the diffusivity exhibit a saturated scattering time of ℏ /kB T . Our results suggest that neither well-defined electron nor phonon quasiparticles are present in underdoped YBCO systems, and thermal transport exhibits a collective behavior of a ''soup'' of strongly coupled electrons and phonons which moves at a velocity that is smaller than the Fermi velocity, but larger than the speed of sound. We generalize this treatment to measurements of other bad metals and discuss its implications. Work supported by the Gordon and Betty Moore Foundation through the EPiQS Initiative, Grant GBMF4529, and by a Department of Energy Early Career Award (SAH).

  10. The Diffuse Light of the Universe

    NASA Astrophysics Data System (ADS)

    Bonnet-Bidaud, Jean-Marc

    2017-06-01

    In 1965, the discovery of a new type of uniform radiation, located between radiowaves and infrared light, was accidental. Known today as Cosmic Microwave background (CMB), this diffuse radiation is commonly interpreted as a fossil light released in an early hot and dense universe and constitutes today the main 'pilar' of the big bang cosmology. Considerable efforts have been devoted to derive fundamental cosmological parameters from the characteristics of this radiation that led to a surprising universe that is shaped by at least three major unknown components: inflation, dark matter and dark energy. This is an important weakness of the present consensus cosmological model that justifies raising several questions on the CMB interpretation. Can we consider its cosmological nature as undisputable? Do other possible interpretations exist in the context of other cosmological theories or simply as a result of other physical mechanisms that could account for it? In an effort to questioning the validity of scientific hypotheses and the under-determination of theories compared to observations, we examine here the difficulties that still exist on the interpretation of this diffuse radiation and explore other proposed tracks to explain its origin. We discuss previous historical concepts of diffuse radiation before and after the CMB discovery and underline the limit of our present understanding.

  11. Light diffusing fiber optic chamber

    DOEpatents

    Maitland, Duncan J.

    2002-01-01

    A light diffusion system for transmitting light to a target area. The light is transmitted in a direction from a proximal end to a distal end by an optical fiber. A diffusing chamber is operatively connected to the optical fiber for transmitting the light from the proximal end to the distal end and transmitting said light to said target area. A plug is operatively connected to the diffusing chamber for increasing the light that is transmitted to the target area.

  12. Embryo density and medium volume effects on early murine embryo development.

    PubMed

    Canseco, R S; Sparks, A E; Pearson, R E; Gwazdauskas, F C

    1992-10-01

    One-cell mouse embryos were used to determine the effects of drop size and number of embryos per drop for optimum development in vitro. Embryos were collected from immature C57BL6 female mice superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin and mated by CD1 males. Groups of 1, 5, 10, or 20 embryos were cultured in 5-, 10-, 20-, or 40-microliters drops of CZB under silicon oil at 37.5 degrees C in a humidified atmosphere of 5% CO2 and 95% air. Development score for embryos cultured in 10 microliters was higher than that of embryos cultured in 20 or 40 microliters. Embryos cultured in groups of 5, 10, or 20 had higher development scores than embryos cultured singly. The highest development score was obtained by the combination of 5 embryos per 10-microliters drop. The percentage of live embryos in 20 or 40 microliters was lower than that of embryos cultured in 10 microliters. Additionally, the percentage of live embryos cultured singly was lower than that of embryos cultured in groups. Our results suggest that a stimulatory interaction occurs among embryos possibly exerted through the secretion of growth factors. This effect can be diluted if the embryos are cultured in large drops or singly.

  13. Optical metabolic imaging measures early drug response in an allograft murine breast cancer model (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Sharick, Joe T.; Cook, Rebecca S.; Skala, Melissa C.

    2017-02-01

    Previous work has shown that cellular-level Optical Metabolic Imaging (OMI) of organoids derived from human breast cancer cell-line xenografts accurately and rapidly predicts in vivo response to therapy. To validate OMI as a predictive measure of treatment response in an immune-competent model, we used the polyomavirus middle-T (PyVmT) transgenic mouse breast cancer model. The PyVmT model includes intra-tumoral heterogeneity and a complex tumor microenvironment that can influence treatment responses. Three-dimensional organoids generated from primary PyVmT tumor tissue were treated with a chemotherapy (paclitaxel) and a PI3K inhibitor (XL147), each alone or in combination. Cellular subpopulations of response were measured using the OMI Index, a composite endpoint of metabolic response comprised of the optical redox ratio (ratio of the fluorescence intensities of metabolic co-enzymes NAD(P)H to FAD) as well as the fluorescence lifetimes of NAD(P)H and FAD. Combination treatment significantly decreased the OMI Index of PyVmT tumor organoids (p<0.0001) and in vivo tumors (p<0.0001) versus controls. Subpopulation analyses revealed a homogeneous response to combined therapy in both cultured organoids and in vivo tumors, while single agent treatment with XL147 alone or paclitaxel alone elicited heterogeneous responses in organoids. Tumor volume decreased with combination treatment through treatment day 30. These results indicate that OMI of organoids generated from PyVmT tumors can accurately reflect drug response in heterogeneous allografts with both innate and adaptive immunity. Thus, this method is promising for use in humans to predict long-term treatment responses accurately and rapidly, and could aid in clinical treatment planning.

  14. Nitric Oxide-Mediated Tumoricidal Activity of Murine Microglial Cells12

    PubMed Central

    Brantley, Emily C; Guo, Lixia; Zhang, Chenyu; Lin, Qingtang; Yokoi, Kenji; Langley, Robert R; Kruzel, Ewa; Maya, Marva; Kim, Seung Wook; Kim, Sun-Jin; Fan, Dominic; Fidler, Isaiah J

    2010-01-01

    Experimental metastases in the brain of mice are infiltrated by microglia, and parabiosis experiments of green fluorescent protein (GFP+) and GFP- mice revealed that these microglia are derived from circulating monocytes (GFP+, F4/80+, and CD68+). These findings raised the question as to whether microglia (specialized macrophages) possess tumoricidal activity. C8-B4 murine microglia cells were incubated in vitro in medium (control) or in medium containing both lipopolysaccharide and interferon-γ. Control microglia were not tumoricidal against a number of murine and human tumor cells, whereas lipopolysaccharide/interferon-γ-activated microglia lysed murine and human tumor cells by release of nitric oxide. Parallel experiments with murine peritoneal macrophages produced identical results. Neither activated microglia nor activated macrophages lysed nontumorigenic murine or human cells. Collectively, these data demonstrate that brain metastasis-associated microglia are derived from circulating mononuclear cells and exhibit selective and specific tumoricidal activity. PMID:21151477

  15. On Diffusive Climatological Models.

    NASA Astrophysics Data System (ADS)

    Griffel, D. H.; Drazin, P. G.

    1981-11-01

    A simple, zonally and annually averaged, energy-balance climatological model with diffusive heat transport and nonlinear albedo feedback is solved numerically. Some parameters of the model are varied, one by one, to find the resultant effects on the steady solution representing the climate. In particular, the outward radiation flux, the insulation distribution and the albedo parameterization are varied. We have found an accurate yet simple analytic expression for the mean annual insolation as a function of latitude and the obliquity of the Earth's rotation axis; this has enabled us to consider the effects of the oscillation of the obliquity. We have used a continuous albedo function which fits the observed values; it considerably reduces the sensitivity of the model. Climatic cycles, calculated by solving the time-dependent equation when parameters change slowly and periodically, are compared qualitatively with paleoclimatic records.

  16. The diffuse interstellar medium

    NASA Technical Reports Server (NTRS)

    Cox, Donald P.

    1990-01-01

    The last 20 years of the efforts to understand the diffuse ISM are reviewed, with recent changes of fundamental aspects being highlighted. Attention is given to the interstellar pressure and its components, the weight of the ISM, the midplane pressure contributions, and pressure contributions at 1 kpc. What velocity dispersions, cosmic ray pressure, and magnetic field pressure that can be expected for a gas in a high magnetic field environment is addressed. The intercloud medium is described, with reference to the work of Cox and Slavin (1989). Various caveats are discussed and a number of areas for future investigation are identified. Steps that could be taken toward a successful phase segregation model are discussed.

  17. Diffusion in Jammed Particle Packs.

    PubMed

    Bolintineanu, Dan S; Grest, Gary S; Lechman, Jeremy B; Silbert, Leonardo E

    2015-08-21

    Using random walk simulations we explore diffusive transport through monodisperse sphere packings over a range of packing fractions ϕ in the vicinity of the jamming transition at ϕ(c). Various diffusion properties are computed over several orders of magnitude in both time and packing pressure. Two well-separated regimes of normal "Fickian" diffusion, where the mean squared displacement is linear in time, are observed. The first corresponds to diffusion inside individual spheres, while the latter is the long-time bulk diffusion. The intermediate anomalous diffusion regime and the long-time value of the diffusion coefficient are both shown to be controlled by particle contacts, which in turn depend on proximity to ϕ(c). The time required to recover normal diffusion t* scales as (ϕ-ϕ(c))(-0.5) and the long-time diffusivity D(∞)∼(ϕ-ϕ(c))0.5, or D(∞)∼1/t*. It is shown that the distribution of mean first passage times associated with the escape of random walkers between neighboring particles controls both t* and D(∞) in the limit ϕ→ϕ(c).

  18. The physical and biological basis of quantitative parameters derived from diffusion MRI

    PubMed Central

    2012-01-01

    Diffusion magnetic resonance imaging is a quantitative imaging technique that measures the underlying molecular diffusion of protons. Diffusion-weighted imaging (DWI) quantifies the apparent diffusion coefficient (ADC) which was first used to detect early ischemic stroke. However this does not take account of the directional dependence of diffusion seen in biological systems (anisotropy). Diffusion tensor imaging (DTI) provides a mathematical model of diffusion anisotropy and is widely used. Parameters, including fractional anisotropy (FA), mean diffusivity (MD), parallel and perpendicular diffusivity can be derived to provide sensitive, but non-specific, measures of altered tissue structure. They are typically assessed in clinical studies by voxel-based or region-of-interest based analyses. The increasing recognition of the limitations of the diffusion tensor model has led to more complex multi-compartment models such as CHARMED, AxCaliber or NODDI being developed to estimate microstructural parameters including axonal diameter, axonal density and fiber orientations. However these are not yet in routine clinical use due to lengthy acquisition times. In this review, I discuss how molecular diffusion may be measured using diffusion MRI, the biological and physical bases for the parameters derived from DWI and DTI, how these are used in clinical studies and the prospect of more complex tissue models providing helpful micro-structural information. PMID:23289085

  19. Early presentation of primary glioblastoma.

    PubMed

    Faguer, R; Tanguy, J-Y; Rousseau, A; Clavreul, A; Menei, P

    2014-08-01

    Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Detecting recurrent gene mutation in interaction network context using multi-scale graph diffusion.

    PubMed

    Babaei, Sepideh; Hulsman, Marc; Reinders, Marcel; de Ridder, Jeroen

    2013-01-23

    Delineating the molecular drivers of cancer, i.e. determining cancer genes and the pathways which they deregulate, is an important challenge in cancer research. In this study, we aim to identify pathways of frequently mutated genes by exploiting their network neighborhood encoded in the protein-protein interaction network. To this end, we introduce a multi-scale diffusion kernel and apply it to a large collection of murine retroviral insertional mutagenesis data. The diffusion strength plays the role of scale parameter, determining the size of the network neighborhood that is taken into account. As a result, in addition to detecting genes with frequent mutations in their genomic vicinity, we find genes that harbor frequent mutations in their interaction network context. We identify densely connected components of known and putatively novel cancer genes and demonstrate that they are strongly enriched for cancer related pathways across the diffusion scales. Moreover, the mutations in the clusters exhibit a significant pattern of mutual exclusion, supporting the conjecture that such genes are functionally linked. Using multi-scale diffusion kernel, various infrequently mutated genes are found to harbor significant numbers of mutations in their interaction network neighborhood. Many of them are well-known cancer genes. The results demonstrate the importance of defining recurrent mutations while taking into account the interaction network context. Importantly, the putative cancer genes and networks detected in this study are found to be significant at different diffusion scales, confirming the necessity of a multi-scale analysis.

  1. Turing instability in reaction-diffusion systems with nonlinear diffusion

    SciT

    Zemskov, E. P., E-mail: zemskov@ccas.ru

    2013-10-15

    The Turing instability is studied in two-component reaction-diffusion systems with nonlinear diffusion terms, and the regions in parametric space where Turing patterns can form are determined. The boundaries between super- and subcritical bifurcations are found. Calculations are performed for one-dimensional brusselator and oregonator models.

  2. Optical fiber spectroscopy measures perfusion of the brain in a murine Alzheimer's disease model

    NASA Astrophysics Data System (ADS)

    Ahn, Hyung Jin; Strickland, Sidney; Krueger, James; Gareau, Daniel

    2014-02-01

    Optical fiber spectroscopy is a versatile tool for measuring diffuse reflectance and extracting absorption information that can noninvasively quantify the presence of chromophores such as oxyhemoglobin and deoxy-hemoglobin in tissues. Cerebrovascular abnormalities were widely recognized in Alzheimer's disease (AD) patients. We analyzed blood volume fraction and level of oxygenated hemoglobin in Tg6799 mice, which are transgenic mice expressing five different familial Alzheimer disease-associated mutations in the human amyloid precursor protein and presenilin-1 genes. Diffuse reflectance spectra were iteratively fit as weighted sums of oxy- and deoxy-hemoglobin. Our observations showed slightly hypoxic conditions and significantly increased blood volume in the Alzheimer's mice versus wild type. These results suggest that hyperperfusion of our AD mice may be a compensating mechanism for impaired cerebral vascular function and somehow relevant with early stage of AD patients. Ongoing work focuses on developing a cannula fixture that allows measurement in awake, behaving animals.

  3. Murine models of osteosarcoma: A piece of the translational puzzle.

    PubMed

    Walia, Mannu K; Castillo-Tandazo, Wilson; Mutsaers, Anthony J; Martin, Thomas John; Walkley, Carl R

    2018-06-01

    Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. While our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear. Murine models of OS have now been demonstrated to be highly valid recapitulations of human OS. These models were originally based on the frequent disruption of p53 and Rb in familial OS syndromes, which are also common mutations in sporadic OS. They have been applied to significantly improve our understanding about the functions of recurrently mutated genes in disease. The murine models can be used as a platform for preclinical testing and identifying new therapeutic targets, in addition to testing the role of additional mutations in vivo. Most recently these models have begun to be used for discovery based approaches and screens, which hold significant promise in furthering our understanding of the genetic and therapeutic sensitivities of OS. In this review, we discuss the mouse models of OS that have been reported in the last 3-5 years and newly identified pathways from these studies. Finally, we discuss the preclinical utilization of the mouse models of OS for identifying and validating actionable targets to improve patient outcome. © 2017 Wiley Periodicals, Inc.

  4. Immunological impact of magnetic nanoparticles (Ferucarbotran) on murine peritoneal macrophages

    NASA Astrophysics Data System (ADS)

    Yeh, Chen-Hao; Hsiao, Jong-Kai; Wang, Jaw-Lin; Sheu, Fuu

    2010-01-01

    Ferucarbotran, a clinically used superparamagnetic iron oxide, is widely developed as a magnetic resonance imaging (MRI) contrast agent and has the potential to improve the monitoring of macrophage recirculation in vivo. However, the biological effect of Ferucarbotran or magnetic nanoparticles (MNPs) on macrophage is not clearly understood yet. This study is aimed to examine the immunological impact of Ferucarbotran toward murine peritoneal macrophages. Cells treated with Ferucarbotran demonstrated a dose-responsive increase of granularity in the cytoplasm. After 24 h of incubation, viability and cytotoxicity in macrophages treated with 200 μg Fe/mL of Ferucarbotran were not affected. Macrophages loaded with Ferucarbotran above 100 μg Fe/mL showed a significant ( p < 0.01) increase in cytokine (TNF-α, IL-1β, IL-6) secretion and mRNA expression, followed by nitric oxide (NO) secretion and iNOS mRNA expression. Chemotactic responses of Ferucarbotran-preloaded macrophages toward CX3CL1 were significantly ( p < 0.05) lower than those of untreated macrophages. Taking together, Ferucarbotran at high dose (100 μg Fe/mL) could induce murine peritoneal macrophages activation in pro-inflammatory cytokine secretion and NO production.

  5. Differential chemokine responses in the murine brain following lyssavirus infection.

    PubMed

    Hicks, D J; Núñez, A; Banyard, A C; Williams, A; Ortiz-Pelaez, A; Fooks, A R; Johnson, N

    2013-11-01

    The hallmark of lyssavirus infection is lethal encephalomyelitis. Previous studies have reported distinct lyssavirus isolate-related differences in severity of cellular recruitment into the encephalon in a murine model of infection following peripheral inoculation with rabies virus (RABV) and European bat lyssavirus (EBLV)-1 and -2. In order to understand the role of chemokines in this process, comparative studies of the chemokine pattern, distribution and production in response to infection with these lyssaviruses were undertaken. Expression of CCL2, CCL5 and CXCL10 was observed throughout the murine brain with a distinct caudal bias in distribution, similar to both inflammatory changes and virus antigen distribution. CCL2 immunolabelling was localized to neuronal and astroglial populations. CCL5 immunolabelling was only detected in the astroglia, while CXCL10 labelling, although present in the astroglia, was more prominent in neurons. Isolate-dependent differences in the amount of chemokine immunolabelling in specific brain regions and chemokine production by neurons in vitro were observed, with a greater expression of CCL5 in vivo and CXCL10 production in vitro after EBLV infection. Additionally, strong positive associations between chemokine immunolabelling and perivascular cuffing and, to a lesser extent, virus antigen score were also observed. These differences in chemokine expression may explain the variation in severity of encephalitic changes observed in animals infected with different lyssavirus isolates. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  6. Adaptive Immunity Restricts Replication of Novel Murine Astroviruses

    PubMed Central

    Yokoyama, Christine C.; Loh, Joy; Zhao, Guoyan; Stappenbeck, Thaddeus S.; Wang, David; Huang, Henry V.

    2012-01-01

    The mechanisms of astrovirus pathogenesis are largely unknown, in part due to a lack of a small-animal model of disease. Using shotgun sequencing and a custom analysis pipeline, we identified two novel astroviruses capable of infecting research mice, murine astrovirus (MuAstV) STL1 and STL2. Subsequent analysis revealed the presence of at least two additional viruses (MuAstV STL3 and STL4), suggestive of a diverse population of murine astroviruses in research mice. Complete genomic characterization and subsequent phylogenetic analysis showed that MuAstV STL1 to STL4 are members of the mamastrovirus genus and are likely members of a new mamastrovirus genogroup. Using Rag1−/− mice deficient in B and T cells, we demonstrate that adaptive immunity is required to control MuAstV infection. Furthermore, using Stat1−/− mice deficient in innate signaling, we demonstrate a role for the innate immune response in the control of MuAstV replication. Our results demonstrate that MuAstV STL permits the study of the mechanisms of astrovirus infection and host-pathogen interactions in a genetically manipulable small-animal model. Finally, we detected MuAstV in commercially available mice, suggesting that these viruses may be present in academic and commercial research mouse facilities, with possible implications for interpretation of data generated in current mouse models of disease. PMID:22951832

  7. Activation of DNA damage repair pathways by murine polyomavirus

    SciT

    Heiser, Katie; Nicholas, Catherine; Garcea, Robert

    Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which are thought to detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. We investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, and DNAPK. We found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK signaling.more » ATR inhibition did not reduce the total amount of viral DNA accumulated, but affected the amount of virus produced, indicating a defect in virus assembly. These results suggest that MuPyV may utilize a subset of DDR proteins or non-canonical DDR signaling pathways in order to efficiently replicate and assemble. -- Highlights: •Murine polyomavirus activates and recruits DNA damage repair (DDR) proteins to replication centers. •Large T-antigen mediates recruitment of DDR proteins to viral replication centers. •Inhibition or knockout of CHK1, CHK2, DNA-PK or H2AX do not affect viral titers. •Inhibition of ATR activity reduces viral titers, but not viral DNA accumulation.« less

  8. Dynamic Determination of Oxygenation and Lung Compliance in Murine Pneumonectomy

    PubMed Central

    Gibney, Barry; Lee, Grace S.; Houdek, Jan; Lin, Miao; Miele, Lino; Chamoto, Kenji; Konerding, Moritz A.; Tsuda, Akira; Mentzer, Steven J.

    2012-01-01

    Thoracic surgical procedures in mice have been applied to a wide range of investigations, but little is known about the murine physiologic response to pulmonary surgery. Using continuous arterial oximetry monitoring and the FlexiVent murine ventilator, we investigated the effect of anesthesia and pneumonectomy on mouse oxygen saturation and lung mechanics. Sedation resulted in a dose-dependent decline of oxygen saturation that ranged from 55–82%. Oxygen saturation was restored by mechanical ventilation with increased rate and tidal volumes. In the mouse strain studied, optimal ventilatory rates were a rate of 200/minute and a tidal volume of 10ml/kg. Sustained inflation pressures, referred to as a "recruitment maneuver," improved lung volumes, lung compliance and arterial oxygenation. In contrast, positive end expiratory pressure (PEEP) had a detrimental effect on oxygenation; an effect that was ameliorated after pneumonectomy. Our results confirm that lung volumes in the mouse are dynamically determined and suggest a threshold level of mechanical ventilation to maintain perioperative oxygen saturation. PMID:21574875

  9. Correlation between experimental human and murine skin sensitization induction thresholds.

    PubMed

    Api, Anne Marie; Basketter, David; Lalko, Jon

    2015-01-01

    Quantitative risk assessment for skin sensitization is directed towards the determination of levels of exposure to known sensitizing substances that will avoid the induction of contact allergy in humans. A key component of this work is the predictive identification of relative skin sensitizing potency, achieved normally by the measurement of the threshold (the "EC3" value) in the local lymph node assay (LLNA). In an extended series of studies, the accuracy of this murine induction threshold as the predictor of the absence of a sensitizing effect has been verified by conduct of a human repeated insult patch test (HRIPT). Murine and human thresholds for a diverse set of 57 fragrance chemicals spanning approximately four orders of magnitude variation in potency have been compared. The results confirm that there is a useful correlation, with the LLNA EC3 value helping particularly to identify stronger sensitizers. Good correlation (with half an order of magnitude) was seen with three-quarters of the dataset. The analysis also helps to identify potential outlier types of (fragrance) chemistry, exemplified by hexyl and benzyl salicylates (an over-prediction) and trans-2-hexenal (an under-prediction).

  10. Effects of the murine skull in optoacoustic brain microscopy.

    PubMed

    Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

    2016-01-01

    Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. β-Arrestin2 mediates progression of murine primary myelofibrosis.

    PubMed

    Rein, Lindsay Am; Wisler, James W; Kim, Jihee; Theriot, Barbara; Huang, LiYin; Price, Trevor; Yang, Haeyoon; Chen, Minyong; Chen, Wei; Sipkins, Dorothy; Fedoriw, Yuri; Walker, Julia Kl; Premont, Richard T; Lefkowitz, Robert J

    2017-12-21

    Primary myelofibrosis is a myeloproliferative neoplasm associated with significant morbidity and mortality, for which effective therapies are lacking. β-Arrestins are multifunctional adaptor proteins involved in developmental signaling pathways. One isoform, β-arrestin2 (βarr2), has been implicated in initiation and progression of chronic myeloid leukemia, another myeloproliferative neoplasm closely related to primary myelofibrosis. Accordingly, we investigated the relationship between βarr2 and primary myelofibrosis. In a murine model of MPLW515L-mutant primary myelofibrosis, mice transplanted with donor βarr2-knockout (βarr2-/-) hematopoietic stem cells infected with MPL-mutant retrovirus did not develop myelofibrosis, whereas controls uniformly succumbed to disease. Although transplanted βarr2-/- cells homed properly to marrow, they did not repopulate long-term due to increased apoptosis and decreased self-renewal of βarr2-/- cells. In order to assess the effect of acute loss of βarr2 in established primary myelofibrosis in vivo, we utilized a tamoxifen-induced Cre-conditional βarr2-knockout mouse. Mice that received Cre (+) donor cells and developed myelofibrosis had significantly improved survival compared with controls. These data indicate that lack of antiapoptotic βarr2 mediates marrow failure of murine hematopoietic stem cells overexpressing MPLW515L. They also indicate that βarr2 is necessary for progression of primary myelofibrosis, suggesting that it may serve as a novel therapeutic target in this disease.

  12. Lessons learned: Optimization of a murine small bowel resection model

    PubMed Central

    Taylor, Janice A.; Martin, Colin A.; Nair, Rajalakshmi; Guo, Jun; Erwin, Christopher R.; Warner, Brad W.

    2008-01-01

    Background/Purpose Central to the use of murine models of disease is the ability to derive reproducible data. The purpose of this study was to determine factors contributing to variability in our murine model of small bowel resection (SBR). Methods Male C57Bl/6 mice were randomized to sham or 50% SBR. The effect of housing type (pathogen-free versus standard housing), nutrition (reconstituted powder versus tube feeding formulation), and correlates of intestinal morphology with gene expression changes were investigated Multiple linear regression modeling or one-way ANOVA was used for data analysis. Results Pathogen-free mice had significantly shorter ileal villi at baseline and demonstrated greater villus growth after SBR compared to mice housed in standard rooms. Food type did not affect adaptation. Gene expression changes were more consistent and significant in isolated crypt cells that demonstrated adaptive growth when compared with crypts that did not deepen after SBR. Conclusion Maintenance of mice in pathogen-free conditions and restricting gene expression analysis to individual animals exhibiting morphologic adaptation enhances sensitivity and specificity of data derived from this model. These refinements will minimize experimental variability and lead to improved understanding of the complex process of intestinal adaptation. PMID:18558176

  13. Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

    NASA Astrophysics Data System (ADS)

    Pissuwan, Dakrong; Valenzuela, Stella M.; Killingsworth, Murray C.; Xu, Xiaoda; Cortie, Michael B.

    2007-12-01

    Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (˜1×105 to 1×1010 W/m2). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5×102 W/m2 being sufficient, provided that a total fluence of ˜30 J/cm2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.

  14. Orthotopic lung cancer murine model by nonoperative transbronchial approach.

    PubMed

    Nakajima, Takahiro; Anayama, Takashi; Matsuda, Yasushi; Hwang, David M; McVeigh, Patrick Z; Wilson, Brian C; Zheng, Gang; Keshavjee, Shaf; Yasufuku, Kazuhiro

    2014-05-01

    The aim of this work was to establish a novel orthotopic human non-small cell lung cancer (NSCLC) murine xenograft model by a nonsurgical, transbronchial approach. Male athymic nude mice and human NSCLC cell lines, including A549, H460, and H520 were used. Under direct visualization of the vocal cords, a 23-gauge blunt-tip slightly curved metal catheter was introduced into the trachea to the bronchus, and 2.5×10(5) tumor cells mixed with Matrigel (BD Biosciences, Mississauga, Ontario, Canada) were administered into the lung. Mice were monitored using weekly microcomputed tomography scans for tumor formation. When the tumor size reached more than 4 mm in diameter, the animals were euthanized, and the tumor tissue was evaluated histopathologically. Of 37 mice studied, 34 were confirmed to have tumor formation: 29 developed solitary tumors and 5 had multifocal lesions. There was no evidence of extrapleural dissemination or effusion. Transbronchial delivery of tumor cells enabled the establishment of a novel orthotopic human NSCLC murine xenograft model. This clinically relevant preclinical model bearing a solitary nodule is of value for a variety of in vivo research studies. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Facilitated Diffusion of Transcription Factor Proteins with Anomalous Bulk Diffusion.

    PubMed

    Liu, Lin; Cherstvy, Andrey G; Metzler, Ralf

    2017-02-16

    What are the physical laws of the diffusive search of proteins for their specific binding sites on DNA in the presence of the macromolecular crowding in cells? We performed extensive computer simulations to elucidate the protein target search on DNA. The novel feature is the viscoelastic non-Brownian protein bulk diffusion recently observed experimentally. We examine the influence of the protein-DNA binding affinity and the anomalous diffusion exponent on the target search time. In all cases an optimal search time is found. The relative contribution of intermittent three-dimensional bulk diffusion and one-dimensional sliding of proteins along the DNA is quantified. Our results are discussed in the light of recent single molecule tracking experiments, aiming at a better understanding of the influence of anomalous kinetics of proteins on the facilitated diffusion mechanism.

  16. Pre-seizure state identified by diffuse optical tomography

    PubMed Central

    Zhang, Tao; Zhou, Junli; Jiang, Ruixin; Yang, Hao; Carney, Paul R.; Jiang, Huabei

    2014-01-01

    In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a “pre-seizure” state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways. PMID:24445927

  17. Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

    NASA Astrophysics Data System (ADS)

    Rollakanti, Kishore Reddy

    Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

  18. Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models.

    PubMed

    Bruner-Tran, Kaylon L; Gnecco, Juan; Ding, Tianbing; Glore, Dana R; Pensabene, Virginia; Osteen, Kevin G

    2017-03-01

    Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new "Organ-on-Chip" models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Exposure to the Environmental Endocrine Disruptor TCDD and Human Reproductive Dysfunction: Translating Lessons from Murine Models

    PubMed Central

    Bruner-Tran, Kaylon L.; Gnecco, Juan; Ding, Tianbing; Glore, Dana R.; Pensabene, Virginia; Osteen, Kevin G.

    2016-01-01

    Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new “Organ-on-Chip” models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease. PMID:27423904

  20. Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

    NASA Astrophysics Data System (ADS)

    Joshi, Bishnu P.; Miller, Sharon J.; Lee, Cameron; Gustad, Adam; Seibel, Eric J.; Wang, Thomas D.

    2012-02-01

    We demonstrate a multi-spectral scanning fiber endoscope (SFE) that collects fluorescence images in vivo from three target peptides that bind specifically to murine colonic adenomas. This ultrathin endoscope was demonstrated in a genetically engineered mouse model of spontaneous colorectal adenomas based on somatic Apc (adenomatous polyposis coli) gene inactivation. The SFE delivers excitation at 440, 532, 635 nm with <2 mW per channel. The target 7-mer peptides were conjugated to visible organic dyes, including 7-Diethylaminocoumarin-3-carboxylic acid (DEAC) (λex=432 nm, λem=472 nm), 5-Carboxytetramethylrhodamine (5-TAMRA) (λex=535 nm, λem=568 nm), and CF-633 (λex=633 nm, λem=650 nm). Target peptides were first validated using techniques of pfu counting, flow cytometry and previously established methods of fluorescence endoscopy. Peptides were applied individually or in combination and detected with fluorescence imaging. The ability to image multiple channels of fluorescence concurrently was successful for all three channels in vitro, while two channels were resolved simultaneously in vivo. Selective binding of the peptide was evident to adenomas and not to adjacent normal-appearing mucosa. Multispectral wide-field fluorescence detection using the SFE is achievable, and this technology has potential to advance early cancer detection and image-guided therapy in human patients by simultaneously visualizing multiple over expressed molecular targets unique to dysplasia.

  1. Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract.

    PubMed

    Koenigsknecht, Mark J; Theriot, Casey M; Bergin, Ingrid L; Schumacher, Cassie A; Schloss, Patrick D; Young, Vincent B

    2015-03-01

    Clostridium difficile infection (CDI) following antibiotic therapy is a major public health threat. While antibiotic disruption of the indigenous microbiota underlies the majority of cases of CDI, the early dynamics of infection in the disturbed intestinal ecosystem are poorly characterized. This study defines the dynamics of infection with C. difficile strain VPI 10463 throughout the gastrointestinal (GI) tract using a murine model of infection. After inducing susceptibility to C. difficile colonization via antibiotic administration, we followed the dynamics of spore germination, colonization, sporulation, toxin activity, and disease progression throughout the GI tract. C. difficile spores were able to germinate within 6 h postchallenge, resulting in the establishment of vegetative bacteria in the distal GI tract. Spores and cytotoxin activity were detected by 24 h postchallenge, and histopathologic colitis developed by 30 h. Within 36 h, all infected mice succumbed to infection. We correlated the establishment of infection with changes in the microbiota and bile acid profile of the small and large intestines. Antibiotic administration resulted in significant changes to the microbiota in the small and large intestines, as well as a significant shift in the abundance of primary and secondary bile acids. Ex vivo analysis suggested the small intestine as the site of spore germination. This study provides an integrated understanding of the timing and location of the events surrounding C. difficile colonization and identifies potential targets for the development of new therapeutic strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. 4D optical coherence tomography of aortic valve dynamics in a murine mouse model ex vivo

    NASA Astrophysics Data System (ADS)

    Schnabel, Christian; Jannasch, Anett; Faak, Saskia; Waldow, Thomas; Koch, Edmund

    2015-07-01

    The heart and its mechanical components, especially the heart valves and leaflets, are under enormous strain during lifetime. Like all highly stressed materials, also these biological components undergo fatigue and signs of wear, which impinge upon cardiac output and in the end on health and living comfort of affected patients. Thereby pathophysiological changes of the aortic valve leading to calcific aortic valve stenosis (AVS) as most frequent heart valve disease in humans are of particular interest. The knowledge about changes of the dynamic behavior during the course of this disease and the possibility of early stage diagnosis could lead to the development of new treatment strategies and drug-based options of prevention or therapy. ApoE-/- mice as established model of AVS versus wildtype mice were introduced in an ex vivo artificially stimulated heart model. 4D optical coherence tomography (OCT) in combination with high-speed video microscopy were applied to characterize dynamic behavior of the murine aortic valve and to characterize dynamic properties during artificial stimulation. OCT and high-speed video microscopy with high spatial and temporal resolution represent promising tools for the investigation of dynamic behavior and their changes in calcific aortic stenosis disease models in mice.

  3. Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality

    PubMed Central

    Al-Griw, M.A.; Alghazeer, R.O.; Al-Azreg, S.A.; Bennour, E.M.

    2016-01-01

    Exposures to a wide variety of environmental substances are negatively associated with many biological cell systems both in humans and rodents. Trichloroethane (TCE), a ubiquitous environmental toxicant, is used in large quantities as a dissolvent, metal degreaser, chemical intermediate, and component of consumer products. This increases the likelihood of human exposure to these compounds through dermal, inhalation and oral routes. The present in vivo study was aimed to investigate the possible cellular and molecular etiology of liver abnormality induced by early exposure to TCE using a murine model. The results showed a significant increase in liver weight. Histopathological examination revealed a TCE-induced hepatotoxicity which appeared as heavily congested central vein and blood sinusoids as well as leukocytic infiltration. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates hepatocellular apoptosis was evident in the treated mice compared to control. TCE was also found to induce oxidative stress as indicated by an increase in the levels of lipid peroxidation, an oxidative stress marker. There was also a significant decrease in the DNA content of the hepatocytes of the treated groups compared to control. Agarose gel electrophoresis also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation in the liver cells, indicating oxidative stress as the cause of DNA damage. These results suggest the need for a complete risk assessment of any new chemical prior to its arrival into the consumer market. PMID:27800299

  4. Enzyme Replacement for Craniofacial Skeletal Defects and Craniosynostosis in Murine Hypophosphatasia

    PubMed Central

    Liu, Jin; Campbell, Cassie; Nam, Hwa Kyung; Caron, Alexandre; Yadav, Manisha C; Millán, José Luis; Hatch, Nan E.

    2015-01-01

    Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl−/− mice exhibit many characteristics seen in infantile HPP including long bone and tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous reports demonstrated that a mineral-targeted form of TNAP rescues long bone, verterbral and tooth mineralization defects in Alpl−/− mice. Here we report that enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents craniosynostosis (the premature fusion of cranial bones) and additional craniofacial skeletal abnormalities in Alpl−/− mice. Craniosynostosis, cranial bone volume and density, and craniofacial shape abnormalities were assessed by microsocopy, histology, digital caliper measurements and micro CT. We found that craniofacial shape defects, cranial bone mineralization and craniosynostosis were corrected in Alpl−/− mice injected daily subcutaneously starting at birth with recombinant enzyme. Analysis of Alpl−/− calvarial cells indicates that TNAP deficiency leads to aberrant osteoblastic gene expression and diminished proliferation. Some but not all of these cellular abnormalities were rescued by treatment with inorganic phosphate. These results confirm an essential role for TNAP in craniofacial skeletal development and demonstrate the efficacy of early postnatal mineral-targeted enzyme replacement for preventing craniofacial abnormalities including craniosynostosis in murine infantile HPP. PMID:25959417

  5. Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a murine pneumonia model.

    PubMed

    Thomsen, K; Christophersen, L; Bjarnsholt, T; Jensen, P Ø; Moser, C; Høiby, N

    2016-03-01

    Oral prophylactic therapy by gargling with pathogen-specific egg yolk immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive immunization and we investigated the effects of anti-P. aeruginosa IgY antibodies on bacterial eradication in a murine pneumonia model. P. aeruginosa pneumonia was established in Balb/c mice and the effects of prophylactic IgY administration on lung bacteriology, clinical parameters and subsequent inflammation were compared to controls. Prophylactic administration of IgY antibodies targeting P. aeruginosa significantly reduced the bacterial burden by 2-log 24h post-infection compared to controls and was accompanied by significantly reduced clinical symptom scores and successive inflammatory cytokine profile indicative of diminished lung inflammation. Passive immunization by anti-P. aeruginosa IgY therapy facilitates promptly bacterial clearance and moderates inflammation in P. aeruginosa lung infection and may serve as an adjunct to antibiotics in reducing early colonization. Copyright © 2015. Published by Elsevier B.V.

  6. Interferon-γ-Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients

    PubMed Central

    Zhou, Jing; Qin, Lingfeng; Yi, Tai; Ali, Rahmat; Li, Qingle; Jiao, Yang; Li, Guangxin; Tobiasova, Zuzana; Huang, Yan; Zhang, Jiasheng; Yun, James J.; Sadeghi, Mehran M.; Giordano, Frank J.; Pober, Jordan S.; Tellides, George

    2015-01-01

    Rationale Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors. Objective To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients. Methods and Results We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon-γ and other Th1-type cytokines, and showed both systemic and intra-lesional activation of leukocytes, particularly T helper cells. Serologic neutralization of interferon-γ after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host. Conclusions Our study reveals that sustained activation of the immune system due to chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients. PMID:26399469

  7. Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury.

    PubMed

    Llacuna, Laura; Marí, Montserrat; Garcia-Ruiz, Carmen; Fernandez-Checa, José C; Morales, Albert

    2006-09-01

    The molecular mechanisms of hepatic ischemia/reperfusion (I/R) damage are incompletely understood. We investigated the role of ceramide in a murine model of warm hepatic I/R injury. This sphingolipid induces cell death and participates in tumor necrosis factor (TNF) signaling. Hepatic ceramide levels transiently increased after the reperfusion phase of the ischemic liver in mice, because of an early activation of acidic sphingomyelinase (ASMase) followed by acid ceramidase stimulation. In vivo administration of an ASMase inhibitor, imipramine, or ASMase knockdown by siRNA decreased ceramide generation during I/R, and attenuated serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation. ASMase-induced ceramide generation activated JNK resulting in BimL phosphorylation and translocation to mitochondria, as the inhibition of ASMase by imipramine prevented these events. In contrast, blockade of ceramide catabolism by N-oleyolethanolamine (NOE), a ceramidase inhibitor, enhanced ceramide levels and potentiated I/R injury compared with vehicle-treated mice. Pentoxifylline treatment prevented TNF upregulation and ASMase activation. Furthermore, 9 of 11 mice treated with imipramine survived 7 days after total liver ischemia, compared with 4 of 12 vehicle-treated mice, whereas 8 of 8 NOE-treated mice died within 2 days of total liver ischemia. In conclusion, ceramide generated from ASMase plays a key role in I/R-induced liver damage, and its modulation may be of therapeutic relevance.

  8. Assaying macrophage activity in a murine model of inflammatory bowel disease using fluorine-19 MRI

    PubMed Central

    Kadayakkara, Deepak K; Ranganathan, Sarangarajan; Young, Won-Bin; Ahrens, Eric T

    2012-01-01

    Macrophages have an important role in the pathogenesis of most chronic inflammatory diseases. A means of non-invasively quantifying macrophage migration would contribute significantly towards our understanding of chronic inflammatory processes and aid the evaluation of novel therapeutic strategies. We describe the use of a perfluorocarbon tracer reagent and in vivo 19F magnetic resonance imaging (MRI) to quantify macrophage burden longitudinally. We apply these methods to evaluate the severity and three-dimensional distribution of macrophages in a murine model of inflammatory bowel disease (IBD). MRI results were validated by histological analysis, immunofluorescence and quantitative real-time polymerase chain reaction. Selective depletion of macrophages in vivo was also performed, further validating that macrophage accumulation of perfluorocarbon tracers was the basis of 19F MRI signals observed in the bowel. We tested the effects of two common clinical drugs, dexamethasone and cyclosporine A, on IBD progression. Whereas cyclosporine A provided mild therapeutic effect, unexpectedly dexamethasone enhanced colon inflammation, especially in the descending colon. Overall, 19F MRI can be used to evaluate early-stage inflammation in IBD and is suitable for evaluating putative therapeutics. Due to its high macrophage specificity and quantitative ability, we envisage 19F MRI having an important role in evaluating a wide range of chronic inflammatory conditions mediated by macrophages. PMID:22330343

  9. Podocytic PKC-Alpha Is Regulated in Murine and Human Diabetes and Mediates Nephrin Endocytosis

    PubMed Central

    Tossidou, Irini; Teng, Beina; Menne, Jan; Shushakova, Nelli; Park, Joon-Keun; Becker, Jan U.; Modde, Friedrich; Leitges, Michael; Haller, Hermann; Schiffer, Mario

    2010-01-01

    Background Microalbuminuria is an early lesion during the development of diabetic nephropathy. The loss of high molecular weight proteins in the urine is usually associated with decreased expression of slit diaphragm proteins. Nephrin, is the major component of the glomerular slit diaphragm and loss of nephrin has been well described in rodent models of experimental diabetes as well as in human diabetic nephropathy. Methodology/Principal Findings In this manuscript we analyzed the role of PKC-alpha (PKCα) on endocytosis of nephrin in podocytes. We found that treatment of diabetic mice with a PKCα-inhibitor (GÖ6976) leads to preserved nephrin expression and reduced proteinuria. In vitro, we found that high glucose stimulation would induce PKCα protein expression in murine and human podocytes. We can demonstrate that PKCα mediates nephrin endocytosis in podocytes and that overexpression of PKCα leads to an augmented endocytosis response. After PKC-activation, we demonstrate an inducible association of PKCα, PICK1 and nephrin in podocytes. Moreover, we can demonstrate a strong induction of PKCα in podocytes of patients with diabetic nephropathy. Conclusions/Significance We therefore conclude that activation of PKCα is a pathomechanistic key event during the development of diabetic nephropathy. PKCα is involved in reduction of nephrin surface expression and therefore PKCα inhibition might be a novel target molecule for anti-proteinuric therapy. PMID:20419132

  10. Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation.

    PubMed

    Langer, Diana; Martianov, Igor; Alpern, Daniel; Rhinn, Muriel; Keime, Céline; Dollé, Pascal; Mengus, Gabrielle; Davidson, Irwin

    2016-03-30

    TAF4 (TATA-binding protein-associated factor 4) and its paralogue TAF4b are components of the TFIID core module. We inactivated the murine Taf4a gene to address Taf4 function during embryogenesis. Here we show that Taf4a(-/-) embryos survive until E9.5 where primary germ layers and many embryonic structures are identified showing Taf4 is dispensable for their specification. In contrast, Taf4 is required for correct patterning of the trunk and anterior structures, ventral morphogenesis and proper heart positioning. Overlapping expression of Taf4a and Taf4b during embryogenesis suggests their redundancy at early stages. In agreement with this, Taf4a(-/-) embryonic stem cells (ESCs) are viable and comprise Taf4b-containing TFIID. Nevertheless, Taf4a(-/-) ESCs do not complete differentiation into glutamatergic neurons and cardiomyocytes in vitro due to impaired preinitiation complex formation at the promoters of critical differentiation genes. We define an essential role of a core TFIID TAF in differentiation events during mammalian embryogenesis.

  11. Immunostimulating activity of maysin isolated from corn silk in murine RAW 264.7 macrophages.

    PubMed

    Lee, Jisun; Kim, Sun-Lim; Lee, Seul; Chung, Mi Ja; Park, Yong Il

    2014-07-01

    Corn silk (CS) has long been consumed as a traditional herb in Korea. Maysin is a major flavonoid of CS. The effects of maysin on macrophage activation were evaluated, using the murine macrophage RAW 264.7 cells. Maysin was isolated from CS by methanol extraction, and preparative C18 reverse phase column chromatography. Maysin was nontoxic up to 100 μg/ml, and dose-dependently increased TNF-α secretion and iNOS production by 11.2- and 4.2-fold, respectively, compared to untreated control. The activation and subsequent nuclear translocation of NF-κB was substantially enhanced upon treatment with maysin (1-100 μg/ml). Maysin also stimulated the phosphorylation of Akt and MAPKs (ERK, JNK). These results indicated that maysin activates macrophages to secrete TNF-α and induce iNOS expression, via the activation of the Akt, NF-κB and MAPKs signaling pathways. These results suggest for the first time that maysin can be a new immunomodulator, enhancing the early innate immunity.

  12. Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus

    PubMed Central

    Carrillo-Salinas, F. J.; Mestre, L.; Mecha, M.; Feliú, A.; del Campo, R.; Villarrubia, N.; Espejo, C.; Montalbán, X.; Álvarez-Cermeño, J. C.; Villar, L. M.; Guaza, C.

    2017-01-01

    Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice. PMID:28290524

  13. Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation

    PubMed Central

    Langer, Diana; Martianov, Igor; Alpern, Daniel; Rhinn, Muriel; Keime, Céline; Dollé, Pascal; Mengus, Gabrielle; Davidson, Irwin

    2016-01-01

    TAF4 (TATA-binding protein-associated factor 4) and its paralogue TAF4b are components of the TFIID core module. We inactivated the murine Taf4a gene to address Taf4 function during embryogenesis. Here we show that Taf4a−/− embryos survive until E9.5 where primary germ layers and many embryonic structures are identified showing Taf4 is dispensable for their specification. In contrast, Taf4 is required for correct patterning of the trunk and anterior structures, ventral morphogenesis and proper heart positioning. Overlapping expression of Taf4a and Taf4b during embryogenesis suggests their redundancy at early stages. In agreement with this, Taf4a−/− embryonic stem cells (ESCs) are viable and comprise Taf4b-containing TFIID. Nevertheless, Taf4a−/− ESCs do not complete differentiation into glutamatergic neurons and cardiomyocytes in vitro due to impaired preinitiation complex formation at the promoters of critical differentiation genes. We define an essential role of a core TFIID TAF in differentiation events during mammalian embryogenesis. PMID:27026076

  14. Transduction of Schistosoma mansoni by vesicular stomatitis virus glycoprotein-pseudotyped Moloney murine leukemia retrovirus.

    PubMed

    Kines, Kristine J; Mann, Victoria H; Morales, Maria E; Shelby, Bryan D; Kalinna, Bernd H; Gobert, Geoffrey N; Chirgwin, Sharon R; Brindley, Paul J

    2006-04-01

    Retroviral transduction of cultured schistosomes offers a potential means to establish transgenic lines of schistosomes and thereby to facilitate the elucidation of schistosome gene function and expression. The Moloney murine leukemia retroviral (MMLV) vector pLNHX was modified to incorporate EGFP or luciferase reporter genes under control of schistosome endogenous gene promoters from the spliced leader RNA and HSP70 genes. These constructs and a plasmid encoding vesicular stomatitis virus glycoprotein (VSVG) were utilized along with GP2-293 cells to produce replication incompetent retrovirus particles pseudotyped with the VSVG envelope. Exposure of several developmental stages, including sporocysts, of Schistosoma mansoni to these virions was facilitated by incubation with polybrene and/or by centrifugation. The early stages of binding and uptake of virus to the parasite tegument were demonstrated by the immunofluorescence colocalization of VSVG envelope and retroviral capsid proteins. Southern hybridization analysis indicated the integration of proviral forms of the MMLV constructs in genomic DNA isolated from the virus exposed schistosomes. Furthermore, analysis of RNA isolated from virus treated parasites demonstrated the presence of transcripts encoding reporter transgenes. Together these results indicated productive transduction by VSVG pseudotyped MMLV of cultured schistosomes, and suggest a tractable route forward towards heritable schistosome transgenesis.

  15. A longitudinal magnetic resonance elastography study of murine brain tumors following radiation therapy

    NASA Astrophysics Data System (ADS)

    Feng, Y.; Clayton, E. H.; Okamoto, R. J.; Engelbach, J.; Bayly, P. V.; Garbow, J. R.

    2016-08-01

    An accurate and noninvasive method for assessing treatment response following radiotherapy is needed for both treatment monitoring and planning. Measurement of solid tumor volume alone is not sufficient for reliable early detection of therapeutic response, since changes in physiological and/or biomechanical properties can precede tumor volume change following therapy. In this study, we use magnetic resonance elastography to evaluate the treatment effect after radiotherapy in a murine brain tumor model. Shear modulus was calculated and compared between the delineated tumor region of interest (ROI) and its contralateral, mirrored counterpart. We also compared the shear modulus from both the irradiated and non-irradiated tumor and mirror ROIs longitudinally, sampling four time points spanning 9-19 d post tumor implant. Results showed that the tumor ROI had a lower shear modulus than that of the mirror ROI, independent of radiation. The shear modulus of the tumor ROI decreased over time for both the treated and untreated groups. By contrast, the shear modulus of the mirror ROI appeared to be relatively constant for the treated group, while an increasing trend was observed for the untreated group. The results provide insights into the tumor properties after radiation treatment and demonstrate the potential of using the mechanical properties of the tumor as a biomarker. In future studies, more closely spaced time points will be employed for detailed analysis of the radiation effect.

  16. IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics.

    PubMed

    Sasaki, Masato; Knobbe, Christiane B; Munger, Joshua C; Lind, Evan F; Brenner, Dirk; Brüstle, Anne; Harris, Isaac S; Holmes, Roxanne; Wakeham, Andrew; Haight, Jillian; You-Ten, Annick; Li, Wanda Y; Schalm, Stefanie; Su, Shinsan M; Virtanen, Carl; Reifenberger, Guido; Ohashi, Pamela S; Barber, Dwayne L; Figueroa, Maria E; Melnick, Ari; Zúñiga-Pflücker, Juan-Carlos; Mak, Tak W

    2012-08-30

    Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.

  17. Osmosis and Diffusion Conceptual Assessment

    ERIC Educational Resources Information Center

    Fisher, Kathleen M.; Williams, Kathy S.; Lineback, Jennifer Evarts

    2011-01-01

    Biology student mastery regarding the mechanisms of diffusion and osmosis is difficult to achieve. To monitor comprehension of these processes among students at a large public university, we developed and validated an 18-item Osmosis and Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered items, some adopted or modified…

  18. Consequences of Diffusion of Innovations.

    ERIC Educational Resources Information Center

    Goss, Kevin F.

    1979-01-01

    The article traces evolution of diffusion theory; illustrates undesirable consequences in a cross-cultural setting, reviews criticisms of several scholars; considers distributional effects and unanticipated consequences for potential ameliorative impact on diffusion theory; and codifies these factors into a framework for research into consequences…

  19. Demonstrating Diffusion: Why the Confusion?

    ERIC Educational Resources Information Center

    Panizzon, Debra Lee

    1998-01-01

    Examines the principles of diffusion and how it may be confused with convection. Suggests that educators may be misleading students and clouding their understanding of the process. Provides two contemporary examples to explain the process of diffusion and how it differs from convection. (Author/CCM)

  20. Diffusion in jammed particle packs

    NASA Astrophysics Data System (ADS)

    Bolintineanu, Dan S.; Silbert, Leonardo E.; Grest, Gary S.; Lechman, Jeremy B.

    2015-03-01

    Diffusive transport in jammed particle packs is of interest for a number of applications, as well as being a potential indicator of structural properties near the jamming point. To this end, we report stochastic simulations of equilibrium diffusion through monodisperse sphere packs near the jamming point in the limit of a perfectly insulating surrounding medium. The time dependence of various diffusion properties is resolved over several orders of magnitude. Two time regimes of expected Fickian diffusion are observed, separated by an intermediate regime of anomalous diffusion. This intermediate regime grows as the particle volume fraction approaches the critical jamming transition. The diffusion behavior is fully controlled by the extent of the contacts between neighboring particles, which in turn depend on proximity to the jamming point. In particular, the mean first passage time associated with the escape of random walkers between neighboring particles is shown to control both the time to recover Fickian diffusion and the long time diffusivity. Scaling laws are established that relate these quantities to the difference between the actual and critical jamming volume fractions. Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE- AC04-94AL85000.

  1. Fractional diffusion on bounded domains

    DOE PAGES

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; ...

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  2. Enhancement of diffusers BRDF accuracy

    NASA Astrophysics Data System (ADS)

    Otter, Gerard; Bazalgette Courrèges-Lacoste, Gregory; van Brug, Hedser; Schaarsberg, Jos Groote; Delwart, Steven; del Bello, Umberto

    2017-11-01

    This paper reports the result of an ESA study conducted at TNO to investigate properties of various diffusers. Diffusers are widely used in space instruments as part of the on-board absolute calibration. Knowledge of the behaviour of the diffuser is therefore most important. From measurements of launched instruments in-orbit it has been discovered that when a diffuser is used in the vacuum of space the BRDF can change with respect to the one in ambient conditions. This is called the air/vacuum effect and has been simulated in this study by measuring the BRDF in a laboratory in ambient as well as vacuum conditions. Another studied effect is related to the design parameters of the optical system and the scattering properties of the diffuser. The effect is called Spectral Features and is a noise like structure superimposed on the diffuser BRDF. Modern space spectrometers, which have high spectral resolution and/or a small field of view (high spatial resolution) are suffering from this effect. The choice of diffuser can be very critical with respect to the required absolute radiometric calibration of an instrument. Even if the Spectral Features are small it can influence the error budget of the retrieval algorithms for the level 2 products. in this presentation diffuser trade-off results are presented and the Spectral Features model applied to the optical configuration of the MERIS instrument is compared to in-flight measurements of MERIS.

  3. pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

    PubMed

    Wang, Enfeng; Wu, Yin; Cheung, Jerry S; Zhou, Iris Yuwen; Igarashi, Takahiro; Zhang, XiaoAn; Sun, Phillip Zhe

    2017-10-01

    Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P < 0.01). Although there was no significant difference in perfusion and diffusion between the kurtosis lesion and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P < 0.05). Moreover, pH in the kurtosis lesion and kurtosis/diffusion mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.

  4. Survival and characteristics of murine leukaemic and normal stem cells after hyperthermia: a murine model for human bone marrow purging.

    PubMed

    Gidáli, J; Szamosvölgyi, S; Fehér, I; Kovács, P

    1990-01-01

    The effect of hyperthermia in vitro on the survival and leukaemogenic effectiveness of WEHI 3-B cells and on the survival and transplantation efficiency of bone marrow cells was compared in a murine model system. Normal murine clonogenic haemopoietic cells (day 9 CFU-S and CFU-GM) proved to be significantly less sensitive to 42.5 degrees C hyperthermia (Do values: 54.3 and 41.1 min, respectively) than leukaemic clonogenic cells (CFU-L) derived from suspension culture or from bone marrow of leukaemic mice (Do: 17.8 min). Exposure for 120 min to 42.5 degrees C reduced the surviving fraction of CFU-L to 0.002 and that of CFU-S to 0.2. If comparable graft sizes were transplanted from normal or heat exposed bone marrow, 60-day survival of supralethally irradiated mice was similar. Surviving WEHI 3-B cells were capable of inducing leukaemia in vivo. The two log difference in the surviving fraction of CFU-L and CFU-S after 120 min exposure to 42.5 degrees C suggests that hyperthermia ex vivo may be a suitable purging method for autologous bone marrow transplantation.

  5. Portable vapor diffusion coefficient meter

    DOEpatents

    Ho, Clifford K [Albuquerque, NM

    2007-06-12

    An apparatus for measuring the effective vapor diffusion coefficient of a test vapor diffusing through a sample of porous media contained within a test chamber. A chemical sensor measures the time-varying concentration of vapor that has diffused a known distance through the porous media. A data processor contained within the apparatus compares the measured sensor data with analytical predictions of the response curve based on the transient diffusion equation using Fick's Law, iterating on the choice of an effective vapor diffusion coefficient until the difference between the predicted and measured curves is minimized. Optionally, a purge fluid can forced through the porous media, permitting the apparatus to also measure a gas-phase permeability. The apparatus can be made lightweight, self-powered, and portable for use in the field.

  6. Heat transfer, diffusion, and evaporation

    NASA Technical Reports Server (NTRS)

    Nusselt, Wilhelm

    1954-01-01

    Although it has long been known that the differential equations of the heat-transfer and diffusion processes are identical, application to technical problems has only recently been made. In 1916 it was shown that the speed of oxidation of the carbon in iron ore depends upon the speed with which the oxygen of the combustion air diffuses through the core of gas surrounding the carbon surface. The identity previously referred to was then used to calculate the amount of oxygen diffusing to the carbon surface on the basis of the heat transfer between the gas stream and the carbon surface. Then in 1921, H. Thoma reversed that procedure; he used diffusion experiments to determine heat-transfer coefficients. Recently Lohrisch has extended this work by experiment. A technically very important application of the identity of heat transfer and diffusion is that of the cooling tower, since in this case both processes occur simultaneously.

  7. Moist, Double-diffusive convection

    NASA Astrophysics Data System (ADS)

    Oishi, Jeffrey; Burns, Keaton; Brown, Ben; Lecoanet, Daniel; Vasil, Geoffrey

    2017-11-01

    Double-diffusive convection occurs when the competition between stabilizing and a destabilizing buoyancy source is mediated by a difference in the diffusivity of each source. Such convection is important in a wide variety of astrophysical and geophysical flows. However, in giant planets, double-diffusive convection occurs in regions where condensation of important components of the atmosphere occurs. Here, we present preliminary calculations of moist, double-diffusive convection using the Dedalus pseudospectral framework. Using a simple model for phase change, we verify growth rates for moist double diffusive convection from linear calculations and report on preliminary relationships between the ability to form liquid phase and the resulting Nusselt number in nonlinear simulations.

  8. Neighbor of Punc E 11: expression pattern of the new hepatic stem/progenitor cell marker during murine liver development.

    PubMed

    Schievenbusch, Stephanie; Sauer, Elisabeth; Curth, Harald-Morten; Schulte, Sigrid; Demir, Münevver; Toex, Ulrich; Goeser, Tobias; Nierhoff, Dirk

    2012-09-20

    We have previously identified Neighbor of Punc E 11 (Nope) as a specific cell surface marker of stem/progenitor cells in the murine fetal liver that is also expressed in hepatocellular carcinoma. Here, we focus on the differential expression pattern of Nope during murine fetal and postnatal liver development as well as in a normal and regenerating adult liver including oval cell activation. In the fetal liver, Nope shows a constantly high expression level and is a useful surface marker for the identification of Dlk, E-cadherin, and CD133-positive hepatoblasts by flow cytometry. Postnatally, Nope expression declines rapidly and remains barely detectable in the adult liver as shown by quantitative real-time reverse-transcriptase polymerase chain reaction and western blot analyses. Immunohistochemically, costainings for Nope- and epithelial-specific markers (E-cadherin), markers of early hepatoblasts (alpha-fetoprotein), and biliary marker proteins (CK19) demonstrate that Nope is initially expressed on bipotent hepatoblasts and persists thereafter on commited hepatocytic as well as cholangiocytic progenitor cells during late fetal liver development. Postnatally, Nope loses its circular expression pattern and is specifically directed to the sinusoidal membrane of early hepatocytes. While Nope is only weakly expressed on cholangiocytes in the normal adult liver, activated stem/progenitor (oval) cells clearly coexpress Nope together with the common markers A6, EpCAM, and CD24 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model. In conclusion, Nope should be most useful in future research to define the differentiation stage of hepatic-specified cells of various sources and is a promising candidate to identify and isolate hepatic stem cells from the adult liver.

  9. Diffuse gamma radiation

    NASA Technical Reports Server (NTRS)

    Fichtel, C. E.; Simpson, G. A.; Thompson, D. J.

    1977-01-01

    An examination of the intensity, energy spectrum, and spatial distribution of the diffuse gamma-radiation observed by SAS-2 satellite away from the galactic plane in the energy range above 35 MeV has shown that it consists of two components. One component is generally correlated with galactic latitudes, the atomic hydrogen column density was deduced from 21 cm measurements, and the continuum radio emission, believed to be synchrotron emission. It has an energy spectrum similar to that in the plane and joins smoothly to the intense radiation from the plane. It is therefore presumed to be of galactic origin. The other component is apparently isotropic, at least on a coarse scale, and has a steep energy spectrum. No evidence is found for a cosmic ray halo surrounding the galaxy in the shape of a sphere or oblate spheroid with galactic dimensions. Constraints for a halo model with significantly larger dimensions are set on the basis of an upper limit to the gamma-ray anisotropy.

  10. Handheld Diffusion Test Cells

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This photo shows the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells (inside the plastic box) will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

  11. Handheld Diffusion Test Cells

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This photo shows an individual cell from the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

  12. Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant

    PubMed Central

    Yang, Xu; Ricciardi, Benjamin F.; Dvorzhinskiy, Aleksey; Brial, Caroline; Lane, Zachary; Bhimani, Samrath; Burket, Jayme C.; Hu, Bin; Sarkisian, Alexander M.; Ross, F. Patrick; van der Meulen, Marjolein C.H.; Bostrom, Mathias P.G.

    2015-01-01

    Background: Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. Methods: Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. Results: Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher

  13. Lacosamide improves outcome in a murine model of traumatic brain injury.

    PubMed

    Wang, Bo; Dawson, Hana; Wang, Haichen; Kernagis, Dawn; Kolls, Brad J; Yao, Lucy; Laskowitz, Daniel T

    2013-08-01

    Use of antiepileptic drugs (AED's) is common in the neurocritical care setting. However, there remains a great deal of controversy regarding the optimal agent. Studies associating the prophylactic use of AED's with poor outcomes are heavily biased by the prevalent use of phenytoin, an agent highly associated with deleterious effects. In the current study, we evaluate lacosamide for neuroprotective properties in a murine model of closed head injury. Mice were subjected to moderate closed head injury using a pneumatic impactor, and then treated with either low-dose (6 mg/kg) or high-dose (30 mg/kg) lacosamide or vehicle at 30 min post-injury, and twice daily for 3 days after injury. Motor and cognitive functional assessments were performed following injury using rotarod and Morris Water Maze, respectively. Neuronal injury and microglial activation were measured by flourojade-B, NeuN, and F4/80 staining at 1 and 7 days post-injury. Timm's staining was also performed to assess lacosamide effects on mossy fiber axonal sprouting. To evaluate possible mechanisms of lacosamide effects on the inflammatory response to injury, an RNA expression array was used to evaluate for alterations in differential gene expression patterns in injured mice following lacosamide or vehicle treatments. High-dose lacosamide was associated with improved functional outcome on both the rotarod and Morris Water Maze. High-dose lacosamide was also associated with a reduction of neuronal injury at 24 h post-injury. However, the reduction in neuronal loss observed early did not result in greater neuronal density at 31 days post-injury based on unbiased stereology of NeuN staining. High-dose lacosamide was also associated with a significant reduction in microglial activation at 7 days post-injury. The therapeutic effects of lacosamide are associated with a delay in injury-related changes in RNA expression of a subset of inflammatory mediator genes typically seen at 24 h post-injury. Administration of

  14. Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant.

    PubMed

    Yang, Xu; Ricciardi, Benjamin F; Dvorzhinskiy, Aleksey; Brial, Caroline; Lane, Zachary; Bhimani, Samrath; Burket, Jayme C; Hu, Bin; Sarkisian, Alexander M; Ross, F Patrick; van der Meulen, Marjolein C H; Bostrom, Mathias P G

    2015-07-01

    Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the i

  15. Growth and metabolism of murine and bovine embryos in bovine uterine flushing-supplemented culture media.

    PubMed Central

    Rondeau, M; Guay, P; Goff, A K; Cooke, G M

    1996-01-01

    The aim of this study was to compare the development and metabolic activity of cultured murine and bovine embryos in 2 standard media (HAM F-10 and RPMI) in the presence or absence of bovine uterine flushings. Murine morulae (n = 653) and day 7 bovine embryos (n = 273) were cultured for 18 h or 36 h in either HAM F-10 or RPMI in the presence or absence of bovine uterine flushings. After culture, the development, quality, and metabolic activity (glucose utilization or methionine uptake and incorporation) of embryos was assessed. It was found that HAM F-10 (without uterine flushings) was a more suitable medium than RPMI for optimal development and metabolism of murine and bovine embryos. Poor quality and development, as well as decreased metabolism, were evident after culture of murine embryos in RPMI; in contrast, this medium had no adverse effects on bovine embryos in culture. Supplementation of HAM F-10 with bovine uterine flushings improved the growth of murine embryos and the protein synthesis (as measured by an increased methionine incorporation) for both murine and bovine embryos. However, supplementation with bovine uterine flushings could not overcome deficiencies of an inappropriate medium (RPMI) for murine embryos. Supplementation of a well-defined culture medium with uterine flushings increased metabolism of embryos in culture, and thus might help to increase pregnancy rates after transfer of such embryos to recipient cows. PMID:8825988

  16. Transdermal diffusion of xenon in vitro using diffusion cells

    NASA Astrophysics Data System (ADS)

    Verkhovsky, A.; Petrov, E.

    2015-11-01

    The aim of this research was to study the diffusion rate of xenon through guinea pig skin and how viscosity of cosmetic component capryl/capric triglyceride (CCT) facilitates to deliver xenon to surface of skin patches. They were placed in Franz cell for 24 hours and diffusion rate and permeability of xenon were calculated. Thus diffusion rate was 0.031 mg/hour*cm2 and permeability was 0.003 cm/hour. Using Brookfield viscometer it was shown that viscosity of CCT decreased upon increasing xenon concentration. Obtained results can be utilized in developing of new xenon containing drugs for topical administration.

  17. b matrix errors in echo planar diffusion tensor imaging

    PubMed Central

    Boujraf, Saïd; Luypaert, Robert; Osteaux, Michel

    2001-01-01

    Diffusion‐weighted magnetic resonance imaging (DW‐MRI) is a recognized tool for early detection of infarction of the human brain. DW‐MRI uses the signal loss associated with the random thermal motion of water molecules in the presence of magnetic field gradients to derive parameters that reflect the translational mobility of the water molecules in tissues. If diffusion‐weighted images with different values of b matrix are acquired during one individual investigation, it is possible to calculate apparent diffusion coefficient maps that are the elements of the diffusion tensor. The diffusion tensor elements represent the apparent diffusion coefficient of protons of water molecules in each pixel in the corresponding sample. The relation between signal intensity in the diffusion‐weighted images, diffusion tensor, and b matrix is derived from the Bloch equations. Our goal is to establish the magnitude of the error made in the calculation of the elements of the diffusion tensor when the imaging gradients are ignored. PACS number(s): 87.57. –s, 87.61.–c PMID:11602015

  18. Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis.

    PubMed

    Want, Muzamil Y; Islammudin, Mohammad; Chouhan, Garima; Ozbak, Hani A; Hemeg, Hassan A; Chattopadhyay, Asoke P; Afrin, Farhat

    2017-01-01

    Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania . Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box-Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC 50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL.

  19. Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

    PubMed Central

    Want, Muzamil Y; Islammudin, Mohammad; Chouhan, Garima; Ozbak, Hani A; Hemeg, Hassan A; Chattopadhyay, Asoke P; Afrin, Farhat

    2017-01-01

    Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of −27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL. PMID:28356736

  20. Focal Solute Trapping and Global Glymphatic Pathway Impairment in a Murine Model of Multiple Microinfarcts

    PubMed Central

    Wang, Minghuan; Ding, Fengfei; Deng, SaiYue; Guo, Xuequn; Wang, Wei

    2017-01-01

    Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease. However, the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer's disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid β and tau. We investigated whether glymphatic pathway function is impaired in a murine model of multiple microinfarcts induced by intraarterial injection of cholesterol crystals. The analysis showed that multiple microinfarcts markedly impaired global influx of CSF along the glymphatic pathway. Although suppression of global glymphatic function was transient, resolving within 2 weeks of injury, CSF tracers also accumulated within tissue associated with microinfarcts. The effect of diffuse microinfarcts on global glymphatic pathway function was exacerbated in the mice aged 12 months compared with the 2- to 3-month-old mice. These findings indicate that glymphatic function is focally disrupted around microinfarcts and that the aging brain is more vulnerable to this disruption than the young brain. These observations suggest that microlesions may trap proteins and other interstitial solutes within the brain parenchyma, increasing the risk of amyloid plaque formation. SIGNIFICANCE STATEMENT Microinfarcts, small (<1 mm) ischemic lesions, are strongly associated with age-related dementia. However, how these microscopic lesions affect global cognitive function and predispose to Alzheimer's disease is unclear. The glymphatic system is a brain-wide network of channels surrounding brain blood vessels that allows CSF to exchange with interstitial fluid, clearing away cellular wastes such as amyloid β. We observed that, in mice, microinfarcts impaired

  1. Focal Solute Trapping and Global Glymphatic Pathway Impairment in a Murine Model of Multiple Microinfarcts.

    PubMed

    Wang, Minghuan; Ding, Fengfei; Deng, SaiYue; Guo, Xuequn; Wang, Wei; Iliff, Jeffrey J; Nedergaard, Maiken

    2017-03-15

    Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease. However, the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer's disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid β and tau. We investigated whether glymphatic pathway function is impaired in a murine model of multiple microinfarcts induced by intraarterial injection of cholesterol crystals. The analysis showed that multiple microinfarcts markedly impaired global influx of CSF along the glymphatic pathway. Although suppression of global glymphatic function was transient, resolving within 2 weeks of injury, CSF tracers also accumulated within tissue associated with microinfarcts. The effect of diffuse microinfarcts on global glymphatic pathway function was exacerbated in the mice aged 12 months compared with the 2- to 3-month-old mice. These findings indicate that glymphatic function is focally disrupted around microinfarcts and that the aging brain is more vulnerable to this disruption than the young brain. These observations suggest that microlesions may trap proteins and other interstitial solutes within th