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Sample records for initial microvessel density

  1. Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

    PubMed Central

    Jureidini, Ricardo; da Cunha, José Eduardo Monteiro; Takeda, Flavio; Namur, Guilherme Naccache; Ribeiro, Thiago Costa; Patzina, Rosely; Figueira, Estela RR; Ribeiro, Ulysses; Bacchella, Telesforo; Cecconello, Ivan

    2016-01-01

    OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma. PMID:27438564

  2. EGFR and microvessel density in canine malignant mammary tumours.

    PubMed

    Carvalho, Maria Isabel; Guimarães, Maria João; Pires, Isabel; Prada, Justina; Silva-Carvalho, Ricardo; Lopes, Carlos; Queiroga, Felisbina L

    2013-12-01

    The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r = 0.843; P < 0.001) was also observed. Results suggest that an over-expression of EGFR may contribute to increased angiogenesis and aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment. PMID:24091029

  3. Microvessel density is a prognostic marker of human gastric cancer

    PubMed Central

    Zhao, Hong-Chuan; Qin, Rong; Chen, Xiao-Xin; Sheng, Xia; Wu, Ji-Feng; Wang, Dao-Bin; Chen, Gui-Hua

    2006-01-01

    AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis. METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohistochemical staining. To assess tumor angiogenesis, MVD was determined by immunohistochemical staining of endothelial protein factor VIII-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer. PMID:17171787

  4. Tumor-associated antigen CAPERα and microvessel density in hepatocellular carcinoma

    PubMed Central

    Dai, Liping; Peng, Xuan-Xian; Tan, Eng M.; Zhang, Jian-Ying

    2016-01-01

    Purpose CAPERα, a tumor-associated antigen, was identified from a cDNA clone with autoantibody from a patient with hepatocellular carcinoma (HCC). It has been implicated, by way of alternative splicing of VEGF pre-mRNA, in the regulation of microvessel formation in Ewing's sarcoma. In this study, we looked for possible association of alterations in CAPERα with microvessel density in HCC. Methods Enzyme-linked immunosorbent assay using recombinant CAPERα as antigen were used to detect antibody against CAPERα. Immunohistochemistry (IHC) on liver sections was performed to analyze expression profiles of CAPERα, VEGF and CD34 in HCC and control tissues and was further used to assess the correlation of expression among CAPERα, VEGF and CD34 in HCC development. Results Autoantibody to CAPERα was highest in HCC (22/76, 28.9%), not detected in prostate cancer (0/79) and at 3.4% (3/88) in breast cancer. In immunohistochemical analysis of grades II and III HCC tissues, significantly decreased immunostaining for CAPERα was observed and this correlated directly with decreased immunostaining for VEGF (R=0.534, P=0.0003). Using CD34 immunostaining for detecting newly formed microvessels, strong staining was observed in grades II and III HCC. Normal liver sections, all of which have high expression of CAPERα were totally negative for CD34 immunostaining. A significant inverse correlation was seen between CAPERα and CD34 immunostaining (R=−0.481, P=0.0012). Conclusions Decreased expression of CAPERα appears to be correlated with appearance of microvessels. It would be of interest to elucidate the cause of altered CAPERα since new formation of microvessels is important in progression of HCC. PMID:26934653

  5. Expression of Endoglin (CD-105) and Microvessel Density in Oral Dysplasia and Squamous Cell Carcinoma

    PubMed Central

    SR, Shashikanth; BNVS, Satish

    2014-01-01

    Objective: To assess the expression of Endoglin (CD-105) and Microvessel Density in clinically normal oral mucosa of non-tobacco and tobacco habituated patients & also histopathologically confirmed cases of oral squamous cell carcinoma (OSCC) patients. Materials and Methods: Twenty cases of clinically normal oral mucosa with tobacco habituation in the form of chewing or smoking, 20 histopathologically confirmed cases of OSCC and twelve normal healthy oral mucosal cases without tobacco habituation in any form, served as control group, were immunohistochemically analysed for expression of Endoglin (CD-105). Chi-square test is used to determine statistical analysis and significance. Result & Conclusion: The finding of 65% of Endoglin CD - 105 positivity and microvessel density (MVD) in the mucosal specimens of tobacco users may be attributed as neoangiogenesis or angiogenic squamous dysplasia like phenomenon occurring as important pathological biomarker preceding oral cancer development, and may therefore be useful as a predictive marker of malignancy. PMID:25386532

  6. Engineered Microvessels with Strong Alignment and High Lumen Density Via Cell-Induced Fibrin Gel Compaction and Interstitial Flow

    PubMed Central

    Morin, Kristen T.; Dries-Devlin, Jessica L.

    2014-01-01

    The development of engineered microvessels with clinically relevant characteristics is a critical step toward the creation of engineered myocardium. Alignment is one such characteristic that must be achieved, as it both mimics native capillary beds and provides natural inlet and outlet sides for perfusion. A second characteristic that is currently deficient is cross-sectional lumen density, typically under 100 lumens/mm2; the equivalent value for human myocardium is 2000 lumens/mm2. Therefore, this study examined the effects of gel compaction and interstitial flow on microvessel alignment and lumen density. Strong microvessel alignment was achieved via mechanically constrained cell-induced fibrin gel compaction following vasculogenesis, and high lumen density (650 lumens/mm2) was achieved by the subsequent application of low levels of interstitial flow. Low interstitial flow also conferred microvessel barrier function. PMID:24083839

  7. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  8. Effect of hyperbaric oxygen treatment on irradiated oral mucosa: microvessel density.

    PubMed

    Svalestad, J; Hellem, S; Thorsen, E; Johannessen, A C

    2015-03-01

    The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on microvascular tissue and cell proliferation in the oral mucosa. Twenty patients, aged 51-78 years, were allocated randomly to a treatment or a control group. All had a history of radiotherapy (50-70 Gy) to the orofacial region 2-6 years previously. Tissue samples were taken from the irradiated buccal oral mucosa before HBOT and at 6 months after treatment. In the control group, tissue samples were taken on two occasions, 6 months apart. The samples were subjected to immunohistochemistry staining: double staining with CD31 and D2-40 for microvessels, or Ki-67 for the analysis of cell proliferation. Blood vessel density and area were significantly increased after HBOT (P=0.002-0.041). D2-40-positive lymphatic vessels were significantly increased in number and area in the sub-epithelial area (P=0.002 and P=0.019, respectively). No significant differences were observed in the control group. There were no significant differences in Ki-67-expressing epithelial cells between the two groups. It is concluded that the density and area of blood and lymphatic vessels in the irradiated mucosa are increased by HBOT 6 months after therapy. Epithelial cell proliferation is not affected by HBOT. PMID:25604154

  9. VEGFR1 and VEGFR2 in lip carcinogenesis and its association with microvessel density.

    PubMed

    Ariotti, Carla; Wagner, Vivian Petersen; Salvadori, Gabriela; Carrard, Vinicius Coelho; Martins, Marco Antônio Trevizani; da Cunha Filho, Joao Julio; Meurer, Luise; Martins, Manoela Domingues

    2015-09-01

    The aim of the present study was to determine the role of vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) in lip carcinogenesis, to investigate correlations between these markers with microvessel density (MVD) and clinicopathological aspects. Medical records from 27 cases of actinic cheilitis (AC) and 46 cases of lower lip squamous cell carcinoma (LLSCC) were analysed and submitted to immunohistochemistry. VEGFR1- and VEGFR2-immunostained sections were analysed based on percentage of positive epithelial and inflammatory cells, while CD31 was submitted to quantitative analysis to determine MVD. Different patterns of VGFR1 and VEGFR2 expression were observed between AC and LLSCC. VEGFR1 expression in epithelial and inflammatory cells and VEGFR2 expression in epithelial cells were higher in AC compared to LLSCC (p < 0.05). VEGFR1 expression in epithelial cells was higher in LLSCC compared to AC (p < 0.001). Expression of both receptors was not associated to MVD or clinicopathological aspects. A direct correlation was found between epithelial VEGFR1 and VEGFR2 expression (p = 0.02) and between VEGFR2 epithelial and inflammatory expression (p < 0.001). Our findings indicate that activation of VEGFR1 and VEGFR2 in epithelial and inflammatory cells appears to be an early event in lip carcinogenesis. PMID:25895461

  10. Prognostic Significance of Microvessel Density Determining by Endoglin in Stage II Rectal Carcinoma: A Retrospective Analysis

    PubMed Central

    Martinovic, Zeljko; Kovac, Drazen; Martinovic, Mia

    2015-01-01

    Background. The role of endoglin in the Dukes B rectal cancer is still unexplored. The aim of this study was to examine the expression of endoglin (CD105) in resected rectal cancer and to evaluate the relationship between microvessels density (MVD), clinicopathological factors, and survival rates. Methods. The study included 95 primary rectal adenocarcinomas, corresponding to 67 adjacent and 73 distant normal mucosa specimens from surgical resection samples. Tumor specimens were paraffin-embedded and immunohistochemical staining for the CD105 endothelial antigen was performed to count CD105-MVD. For exact measurement of the CD105-MVD used a computer-integrated system Alphelys Spot Browser 2 was used. Results. The intratumoral CD105-MVD was significantly higher compared with corresponding adjacent mucosa (P < 0.0001) and distant mucosa specimens (P < 0.0001). There was no significant difference in the CD105-MVD according to patients age, gender, tumor location, grade of differentiation, histological type, depth of tumor invasion, and tumor size. The overall survival rate was significantly higher in the low CD105-MVD group of patients than in the high CD105-MVD group of patients (log-rank test, P = 0.0406). Conclusion. CD105-assessed MVD could help to identify patients with possibility of poor survival in the group of stage II RC. PMID:26089870

  11. Clinicopathological significance of vascular endothelial growth factor, thymidine phosphorylase and microvessel density in colorectal cancer.

    PubMed

    Kimura, Yutaka; Morohashi, Satoko; Yoshizawa, Tadashi; Suzuki, Takahiro; Morohashi, Hajime; Sakamoto, Yoshiyuki; Koyama, Motoi; Murata, Akihiko; Kijima, Hiroshi; Hakamada, Kenichi

    2016-02-01

    Colorectal cancer is a common malignant disease, the incidence of which is increasing worldwide, therefore, identifying novel prognostic factors to improve adjuvant therapeutic strategies or postoperative monitoring is required. Angiogenesis, which is assessed by microvessel density (MVD), is significant in tumor growth and metastasis. However, the association between angiogenesis and clinical outcome remains controversial. In the present study, 84 surgically resected cases of colorectal cancer were examined to clarify the clinicopathological significance of vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cluster of differentiation (CD)34 expression levels. VEGF expression was identified to be significantly correlated with TP expression (r=0.45; P<0.0001) and MVD in the high VEGF expression group was observed to be significantly greater than that in the low VEGF expression group (P=0.0194). In the Dukes' stage D group, the MVD in the high TP expression group was significantly greater than that in the low TP expression group (P=0.0149). High VEGF expression was subsequently correlated with a short overall survival rate for patients exhibiting lymph node metastasis (P=0.0128); however, there was no significant difference in overall survival rate regarding the expression levels of TP and CD34. The results of the present study indicate that VEGF expression may serve as a prognostic factor for colorectal cancer patients exhibiting lymph node metastasis. Furthermore, angiogenesis, as assessed by MVD, is an important prognostic factor for tumor growth at the primary site. PMID:26676225

  12. Smaller Absolute Quantities but Greater Relative Densities of Microvessels Are Associated with Cerebellar Degeneration in Lurcher Mice

    PubMed Central

    Kolinko, Yaroslav; Cendelin, Jan; Kralickova, Milena; Tonar, Zbynek

    2016-01-01

    Degenerative affections of nerve tissues are often accompanied by changes of vascularization. In this regard, not much is known about hereditary cerebellar degeneration. In this study, we compared the vascularity of the individual cerebellar components and the mesencephalon of 3-month-old wild type mice (n = 5) and Lurcher mutant mice, which represent a model of hereditary olivocerebellar degeneration (n = 5). Paraformaldehyde-fixed brains were processed into 18-μm thick serial sections with random orientation. Microvessels were visualized using polyclonal rabbit anti-laminin antibodies. Then, the stacks comprised of three 5-μm thick optical sections were recorded using systematic uniform random sampling. Stereological assessment was conducted based on photo-documentation. We found that each of the cerebellar components has its own features of vascularity. The greatest number and length of vessels were found in the granular layer; the number of vessels was lower in the molecular layer, and the lowest number of vessels was observed in the cerebellar nuclei corresponding with their low volume. Nevertheless, the nuclei had the greatest density of blood vessels. The reduction of cerebellum volume in the Lurcher mice was accompanied by a reduction in vascularization in the individual cerebellar components, mainly in the cortex. Moreover, despite the lower density of microvessels in the Lurcher mice compared with the wild type mice, the relative density of microvessels in the cerebellar cortex and nuclei was greater in Lurcher mice. The complete primary morphometric data, in the form of continuous variables, is included as a supplement. Mapping of the cerebellar and midbrain microvessels has explanatory potential for studies using mouse models of neurodegeneration. PMID:27147979

  13. Quantitative evaluation of microvessel density using CD34 in clinical variants of ameloblastoma: An immunohistochemical study

    PubMed Central

    Pereira, Treville; Dodal, Shashibhushan; Tamgadge, Avinash; Bhalerao, Sudhir; Tamgadge, Sandhya

    2016-01-01

    Background: Odontogenic epithelium plays an important role in the histogenesis of odontogenic tumors of the jaws. Ameloblastomas, which arise from odontogenic epithelium, are considered benign with little tendency to metastasize. Tumors require an adequate supply of oxygen and a way to remove their waste products. This can be achieved by angiogenesis. In situ quantification of the microvessel density (MVD) is a usual method for assessing angiogenesis. Moreover, angiogenesis may differ in subtypes of ameloblastomas and could play a role in determining the pattern of tumor growth. Aim: The aim of the present study was to demonstrate the expression of cluster of differentiation (CD34) in variants of ameloblastomas and to correlate and compare their expression to the aggressive behavior. Materials and Methods: A retrospective cross-sectional study which included forty paraffin blocks was conducted after obtaining ethical committee clearance. Ten cases of pyogenic granuloma were used as a positive control and thirty cases were of solid multicystic ameloblastoma (SMA), unicystic ameloblastoma (UA) and desmoplastic ameloblastomas. Angiogenesis was assessed using CD34 antigen and was immunohistochemically localized. Statistical analysis was carried out for comparative analysis with the help of ANOVA test, Kolmogorov–Smirnov test and least significance difference test. Results: A significant correlation was obtained between the MVD of all the three variants, i.e., SMA, UA and desmoplastic ameloblastomas which was statistically significant (P < 0.05). Conclusion: Increased MVD in the three variants, i.e., SMA, UA and desmoplastic ameloblastoma seen in the present study could suggest that the angiogenesis has an important role in tumor progression and aggressiveness of ameloblastomas. PMID:27194862

  14. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    PubMed

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p < .001) and VEGF expression (r = .35, p < .001). For the prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies. PMID:26052072

  15. Study of the Impact of Uterine Artery Embolization (UAE) on Endometrial Microvessel Density (MVD) and Angiogenesis

    SciTech Connect

    Tan Guosheng; Xiang Xianhong; Guo Wenbo; Zhang Bing; Chen Wei; Yang Jianyong

    2013-08-01

    PurposeTo investigate the influence of uterine artery embolization (UAE) on endometrial microvessel density (MVD) and angiogenesis.MethodsSixty female guinea pigs were divided into two groups, the control group (n = 15) and the UAE treatment group (n = 45). In the UAE group, tris-acryl gelatin microspheres were used to generate embolization. Animals were further divided into three subgroups, A1, A2, and A3 (n = 15 for each subgroup), with uterine specimens collected at 7-15, 16-30, and 31-45 days after UAE, respectively. Immunostaining for factor VIII and CD105 was performed to identify total endometrial MVD (MVD{sub FVIII}) and CD105-positive angiogenesis (MVD{sub CD105}) at the indicated time points after UAE.ResultsQuantitative analysis revealed that MVD{sub FVIII} significantly decreased in the A1 (11.40 {+-} 2.76, p < 0.05) and A2 (15.37 {+-} 3.06, p < 0.05) groups compared to the control group (19.40 {+-} 2.50), and was restored to normal in the A3 group (18.77 {+-} 2.69). UAE caused a temporal up-regulation of MVD{sub CD105}-positive angiogenesis in the A1 group (9.33 {+-} 2.37, p < 0.05) and the A2 group (11.63 {+-} 1.56, p < 0.05) compared to the control group (7.12 {+-} 1.67), and the MVD{sub CD105} value returned to normal in the A3 group (8.07 {+-} 1.97).ConclusionUAE caused a temporal decrease in endometrial MVD that reversed over time as a result of the increase of CD105-positive angiogenesis. Although the UAE-induced reduction of endometrial MVD was reversible, its long-term effect on endometrial receptivity still needs further study.

  16. Development and Validation of a Histological Method to Measure Microvessel Density in Whole-Slide Images of Cancer Tissue.

    PubMed

    Marien, Koen M; Croons, Valerie; Waumans, Yannick; Sluydts, Ellen; De Schepper, Stefanie; Andries, Luc; Waelput, Wim; Fransen, Erik; Vermeulen, Peter B; Kockx, Mark M; De Meyer, Guido R Y

    2016-01-01

    Despite all efforts made to develop predictive biomarkers for antiangiogenic therapies, no unambiguous markers have been identified so far. This is due to among others the lack of standardized tests. This study presents an improved microvessel density quantification method in tumor tissue based on stereological principles and using whole-slide images. Vessels in tissue sections of different cancer types were stained for CD31 by an automated and validated immunohistochemical staining method. The stained slides were digitized with a digital slide scanner. Systematic, uniform, random sampling of the regions of interest on the whole-slide images was performed semi-automatically with the previously published applications AutoTag and AutoSnap. Subsequently, an unbiased counting grid was combined with the images generated with these scripts. Up to six independent observers counted microvessels in up to four cancer types: colorectal carcinoma, glioblastoma multiforme, ovarian carcinoma and renal cell carcinoma. At first, inter-observer variability was found to be unacceptable. However, after a series of consensus training sessions and interim statistical analysis, counting rules were modified and inter-observer concordance improved considerably. Every CD31-positive object was counted, with exclusion of suspected CD31-positive monocytes, macrophages and tumor cells. Furthermore, if interconnected, stained objects were considered a single vessel. Ten regions of interest were sufficient for accurate microvessel density measurements. Intra-observer and inter-observer variability were low (intraclass correlation coefficient > 0.7) if the observers were adequately trained. PMID:27583442

  17. LCN2 Promoter Methylation Status as Novel Predictive Marker for Microvessel Density and Aggressive Tumor Phenotype in Breast Cancer Patients.

    PubMed

    Meka, Phanni bhushann; Jarjapu, Sarika; Nanchari, Santhoshi Rani; Vishwakarma, Sandeep Kumar; Edathara, Prajitha Mohandas; Gorre, Manjula; Cingeetham, Anuradha; Vuree, Sugunakar; Annamaneni, Sandhya; Dunna, Nageswara Rao; Mukta, Srinivasulu; B, Triveni; Satti, Vishnupriya

    2015-01-01

    LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis in breast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreatic cancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvessels is poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation with microvessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylation status was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvessel density (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34 and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breast cancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylation status was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients. PMID:26163623

  18. Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: Results of RTOG 9505

    SciTech Connect

    Foote, Robert L. . E-mail: foote.robert@mayo.edu; Weidner, Noel; Harris, Jonathan; Hammond, Elizabeth; Lewis, Jean E.; Vuong, Te; Ang, K. Kian; Fu, Karen K.

    2005-03-01

    Purpose: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. Methods and materials: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin-stained section prepared at the block face. One representative section for tumor was stained for factor VIII-related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200x field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200x field. Using a breakpoint of MVD < 60 vs. {>=}60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. Results: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. Conclusions: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD < 60 vs. MVD {>=}60. The study was perhaps limited by the small size of the NPC samples.

  19. Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

    PubMed Central

    Chang, Yuan; Niu, Wei; Lian, Pei-Long; Wang, Xian-Qiang; Meng, Zhi-Xin; Liu, Yi; Zhao, Rui

    2016-01-01

    AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor (VEGF) and prognosis in gastric cancer. METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density (MVD) (endocan-MVD), VEGF and vascular endothelial growth factor receptor 2 (VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student’s t-test or an analysis of variance test. Spearman’s rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. Long-term survival of these patients was analysed using univariate and multivariate analyses. RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues (108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type (P > 0.05), while endocan-MVD was associated with tumour size, Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage (P < 0.05). According to the Spearman’s rank correlation analysis, endocan-MVD had a positive correlation with VEGF (r = 0.167, P = 0.047) and VEGFR2 (r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD (17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor. CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer. PMID:27340359

  20. Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study

    PubMed Central

    2010-01-01

    Background Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival. Methods Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400× magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis. Results The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD. Conclusion Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of

  1. Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAβ Mouse Model of Cerebral Amyloidosis

    PubMed Central

    Ielacqua, Giovanna D.; Schlegel, Felix; Füchtemeier, Martina; Xandry, Jael; Rudin, Markus; Klohs, Jan

    2016-01-01

    Alterations in density and morphology of the cerebral microvasculature have been reported to occur in Alzheimer's disease patients and animal models of the disease. In this study we compared magnetic resonance imaging (MRI) techniques for their utility to detect age-dependent changes of the cerebral vasculature in the arcAβ mouse model of cerebral amyloidosis. Dynamic susceptibility contrast (DSC)-MRI was performed by tracking the passage of a superparamagnetic iron oxide nanoparticle in the brain with dynamic gradient echo planar imaging (EPI). From this measurements relative cerebral blood volume [rCBV(DSC)] and relative cerebral blood flow (rCBF) were estimated. For the same animal maps of the relaxation shift index Q were computed from high resolution gradient echo and spin echo data that were acquired before and after superparamagnetic iron oxide (SPIO) nanoparticle injection. Q-values were used to derive estimates of microvessel density. The change in the relaxation rates ΔR2* obtained from pre- and post-contrast gradient echo data was used for the alternative determination of rCBV [rCBV(ΔR2*)]. Linear mixed effects modeling found no significant association between rCBV(DSC), rCBV(ΔR2*), rCBF, and Q with genotype in 13-month old mice [compared to age-matched non-transgenic littermates (NTLs)] for any of the evaluated brain regions. In 24-month old mice there was a significant association for rCBV(DSC) with genotype in the cerebral cortex, and for rCBV(ΔR2*) in the cerebral cortex and cerebellum. For rCBF there was a significant association in the cerebellum but not in other brain regions. Q-values in the olfactory bulb, cerebral cortex, striatum, hippocampus, and cerebellum in 24-month old mice were significantly associated with genotype. In those regions Q-values were reduced between 11 and 26% in arcAβ mice compared to age-matched NTLs. Vessel staining with CD31 immunohistochemistry confirmed a reduction of microvessel density in the old arcAβ mice

  2. The relationship between semaphorin 3C and microvessel density in the progression of breast and oral neoplasia.

    PubMed

    Cole-Healy, Zachary; Vergani, Patricia; Hunter, Keith; Brown, Nicola J; Reed, Malcolm W R; Staton, Carolyn A

    2015-08-01

    This study aimed to identify the expression of semaphorin 3C (SEMA3C) in the normal-metastatic spectrum of breast and oral cancers, and correlate expression with microvessel density (MVD, CD31), a surrogate marker of angiogenesis. Histological analysis revealed that SEMA3C expression was reduced in the development of oral cancer from normal oral tissue (P<0.0001) and expression was inversely correlated with MVD (r=-0.394, P=0.05). In contrast, SEMA3C expression increased in the transition from normal to invasive breast disease in epithelial/tumour cells (P=0.001) and endothelial cells (P=0.006), with both correlating weakly with MVD (r=0.35, p=0.03 and r=0.243, p=0.041 respectively). Furthermore, histological analysis of a breast cancer tissue microarray revealed a weak positive correlation with tumour grade (r=0.305, P=<0.001) and biological phenotype (r=0.237, p=0.004) with tumour cell expression of SEMA3C highest in triple negative and ER-, PR-, HER2+ subtypes. These data suggest that SEMA3C expression is differentially regulated in the development and progression of breast versus oral neoplasia, and that increased expression of SEMA3C may be modulating breast cancer progression and angiogenesis, and could represent a biomarker of metastatic disease. PMID:25910410

  3. Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images

    PubMed Central

    Kather, Jakob Nikolas; Marx, Alexander; Reyes-Aldasoro, Constantino Carlos; Schad, Lothar R.; Zöllner, Frank Gerrit; Weis, Cleo-Aron

    2015-01-01

    Blood vessels in solid tumors are not randomly distributed, but are clustered in angiogenic hotspots. Tumor microvessel density (MVD) within these hotspots correlates with patient survival and is widely used both in diagnostic routine and in clinical trials. Still, these hotspots are usually subjectively defined. There is no unbiased, continuous and explicit representation of tumor vessel distribution in histological whole slide images. This shortcoming distorts angiogenesis measurements and may account for ambiguous results in the literature. In the present study, we describe and evaluate a new method that eliminates this bias and makes angiogenesis quantification more objective and more efficient. Our approach involves automatic slide scanning, automatic image analysis and spatial statistical analysis. By comparing a continuous MVD function of the actual sample to random point patterns, we introduce an objective criterion for hotspot detection: An angiogenic hotspot is defined as a clustering of blood vessels that is very unlikely to occur randomly. We evaluate the proposed method in N=11 images of human colorectal carcinoma samples and compare the results to a blinded human observer. For the first time, we demonstrate the existence of statistically significant hotspots in tumor images and provide a tool to accurately detect these hotspots. PMID:26061817

  4. Is there any role of mast cell density and microvessel density in cervical squamous cell carcinoma? A histologic study with special reference to CD-34 immunomarker staining

    PubMed Central

    Mondal, Santosh Kumar; Dasgupta, Senjuti; Mandal, Palash Kumar; Chatterjee, Shankha; Chakraborty, Debdutta

    2014-01-01

    Background: Mast cells are involved in induction of angiogenesis in the early-stages of tumor development and in modulating blood vessel growth in the later stages of tumor progression. Aims and Objectives: This study was carried out to evaluate the association between mast cell density (MCD) and microvessel density (MVD) in carcinoma in situ (CIS), microinvasive carcinoma (CA) and invasive squamous cell CA of cervix. Materials and Methods: Six cases of CIS, four cases of microinvasive CA and 38 cases of invasive CA were studied over a period of 2 years from August, 2011 to June, 2013. Ten control samples were included in the study. Routine histologic examination was done. Toluidine blue stain was used for MCD determination. Immunohistochemical analysis with CD-34 was done for assessing MVD. Student's t-test was used to calculate the statistical significance of MCD and MVD. Results: Both MCD and MVD increased from normal samples through CIS to invasive cervical CA. In the four cases of microinvasive CA, the MCD and MVD were more than that of the control samples, but less than that of the six cases of CIS. Conclusion: There is a correlation between mast cell accumulation and angiogenesis in CIS, microinvasive CA and invasive cervical squamous cell CA. MCD and MVD in invasive CA exceed those in CIS and microinvasive CA. It gives us an opportunity to postulate that therapeutic strategies against mast cell mediators and angiogenesis may be of benefit in patients of early-stage cervical CA. PMID:25197180

  5. Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia

    PubMed Central

    Meier, Valeria; Guscetti, Franco; Roos, Malgorzata; Ohlerth, Stefanie; Pruschy, Martin; Rohrer Bley, Carla

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki

  6. Expression and localization of the vascular endothelial growth factor and changes of microvessel density during hair follicle development of Liaoning cashmere goats.

    PubMed

    Zhang, Q L; Li, J P; Li, Y M; Chang, Q; Chen, Y; Jiang, H Z; Zhao, Z H; Guo, D

    2013-01-01

    Vascular endothelial growth factors (VEGFs) play important roles in neovascularization, tissue development, and angiogenesis. In this study, changes in VEGF expression patterns and microvessel density (MVD), and their correlations, were investigated during hair follicle development in epidermal appendages of Liaoning cashmere goats. Polyclonal antibodies to VEGF and microvessels were used for monthly immunohistochemical examinations of normal skin specimens from adult female goats for one year. VEGF was expressed in the hair bulb of primary and secondary hair follicles, the outer and inner root sheaths, sebaceous glands (ductal and secretory portions), eccrine sweat glands (ductal and secretory portions), and the epidermis. Abundant expression of VEGF was observed in the follicular basement membrane zone surrounding the bulb matrix and in ductal and secretory portions of eccrine sweat glands. The change in VEGFs in primary hair follicles showed a bimodal pattern, with the first peak observed from March to May, and the second in August. Maximal expression in secondary hair follicles occurred in May and August. Therefore, VEGF expression in primary and secondary hair follicles is synchronized throughout the year, and is correlated to hair development. In the later telogen and anagen phases, VEGF expression was higher in the secondary, compared to the primary, hair follicle. Changes in MVD also showed a bimodal pattern with peaks in May and August. VEGF expression and MVD showed moderate and strongly positive correlation in the primary and secondary hair follicles, respectively. Therefore, MVD and VEGF are closely related to the processes involved in hair cycle regulation. PMID:24390991

  7. Synthesis of oxadiazole-morpholine derivatives and manifestation of the repressed CD31 Microvessel Density (MVD) as tumoral angiogenic parameters in Dalton's Lymphoma.

    PubMed

    Al-Ghorbani, Mohammed; Vigneshwaran, V; Ranganatha, V Lakshmi; Prabhakar, B T; Khanum, Shaukath Ara

    2015-06-01

    A series of oxadiazole derivatives possessing morpholine 6a-l were synthesized by nucleophilic substitution reaction of key intermediates [1,3,4]-oxadiazole-2-thiol derivatives 5a-l with 4-(2-chloroethyl) morpholine. Compounds 6a-l were evaluated for their in vitro and in vivo antitumor potential in Dalton's Lymphoma Ascites (DLA) tumor cells. Among 6a-l series, compound 6a with concentration ∼8.5μM have shown extensive cytotoxicity in vitro and 85% reduction in tumor volume in vivo, attributing an excellent anti-proliferative capability towards the cancer cells. Compound 6a has extensively inhibited the Microvessel Density (MVD) or tumoral neovasculature which was evident from the CD31 immuno staining and peritoneal H&E staining. The major reason for the antiproliferative activity of compound 6a was due to the repression of tumor vasculature. PMID:26005956

  8. Novel functional germline variants in the vascular endothelial growth factor receptor 2 gene and their effect on gene expression and microvessel density in lung cancer

    PubMed Central

    Glubb, Dylan M; Cerri, Elisa; Giese, Alexandra; Zhang, Wei; Mirza, Osman; Thompson, Emma E.; Chen, Peixian; Das, Soma; Jassem, Jacek; Rzyman, Witold; Lingen, Mark W.; Salgia, Ravi; Hirsch, Fred R.; Dziadziuszko, Rafal; Ballmer-Hofer, Kurt; Innocenti, Federico

    2011-01-01

    Purpose VEGFR-2 plays a crucial role in mediating angiogenic endothelial cell responses via the VEGF pathway and angiogenesis inhibitors targeting VEGFR-2 are in clinical use. As angiogenesis is a host-driven process, functional heritable variation in KDR, the gene encoding VEGFR-2, may affect VEGFR-2 function, and ultimately, the extent of tumor angiogenesis. Experimental Design We resequenced KDR using 24 DNAs each from healthy Caucasian, African American and Asian groups. Non-synonymous genetic variants were assessed for function using phosphorylation assays. Luciferase reporter gene assays were used to examine effects of variants on gene expression. KDR mRNA and protein expression, and microvessel density (MVD) were measured in non-small cell lung cancer (NSCLC) tumor samples and matching patient DNA samples were genotyped to test for associations with variants of interest. Results KDR resequencing led to the discovery of 120 genetic variants, of which 25 had not been previously reported. Q472H had increased VEGFR-2 protein phosphorylation and associated with increased MVD in NSCLC tumor samples. −2854C and −2455A increased luciferase expression and associated with higher KDR mRNA levels in NSCLC samples. −271A reduced luciferase expression and associated with lower VEGFR-2 levels in NSCLC samples. −906C and 23408G, associated with higher KDR mRNA levels in NSCLC samples. Conclusions This study has defined KDR genetic variation in three populations and identified common variants that impact on tumoral KDR expression and vascularization. These findings may have important implications for understanding the molecular basis of genetic associations between KDR variation and clinical phenotypes related to VEGFR-2 function. PMID:21712447

  9. Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1alpha (HIF-1alpha), and microvessel density in endometrial tissue in women with adenomyosis.

    PubMed

    Goteri, Gaia; Lucarini, Guendalina; Montik, Nina; Zizzi, Antonio; Stramazzotti, Daniela; Fabris, Guidalberto; Tranquilli, Andrea Luigi; Ciavattini, Andrea

    2009-03-01

    Adenomyosis is a disease with a mysterious pathogenesis, defined by an abnormal displacement of the eutopic endometrium deeply and haphazardly inside the myometrium. Angiogenesis has been indicated to play an important role and our aim was to investigate whether vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1alpha) expression and microvessel density (MVD) were different in women with and without adenomyosis. Immunohistochemistry was performed in endometrial tissues in 23 patients who underwent radical hysterectomy for adenomyosis (14) and for ovarian cysts and fibroids (9) at an Academic Hospital. Compared to women without the disease, VEGF expression was increased in endometrium with a normal location in patients with adenomyosis, although not associated to a significant increase of HIF-1alpha and MVD. Moreover, the endometrium with an abnormal location in patients with adenomyosis showed an increased VEGF and HIF-1alpha expression, particularly in the epithelial cells, associated to an increase of MVD, compared with the endometrium in a normal location in the same group of patients. Our present findings suggest that VEGF-mediated angiogenesis might be associated with the development of adenomyosis. In the ectopic foci the abnormal location might contribute to increased HIF-1a expression, stimulation of VEGF production, and increased vessel formation. In endometrium with a normal location, instead, where VEGF increased expression seems not to be correlated with HIF-1alpha increased expression nor with an increased MVD, other mechanisms might be reasonably postulated. Additional studies are required to explore new targeted and more effective treatment modalities. PMID:19188818

  10. The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas.

    PubMed

    Jelicic, Jelena; Balint, Milena Todorovic; Jovanovic, Maja Perunicic; Boricic, Novica; Micev, Marjan; Stojsic, Jelena; Antic, Darko; Andjelic, Bosko; Bila, Jelena; Balint, Bela; Pavlovic, Sonja; Mihaljevic, Biljana

    2016-07-01

    Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC >2.6 in DLBCL and ALC/AMC ≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p < 0.05). In DLBCL, MVD > 42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p < 0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p < 0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s). PMID:26750138

  11. Adrenergic receptors on cerebral microvessels in control and Parkinsonian subjects

    SciTech Connect

    Cash, R.; Lasbennes, F.; Sercombe, R.; Seylaz, J.; Agid, Y.

    1985-08-12

    The binding of adrenergic ligands (/sup 3/H-prazosin, /sup 3/H-clonidine, /sup 3/H-dihydroalprenolol) was studied on a preparation of cerebral microvessels in the prefrontal cortex and putamen of control and Parkinsonian subjects. The adrenergic receptor density in microvessels of control patients was less than 0.5% and 3.3% respectively of the total binding. A significant decrease in the number of alpha-1 binding sites was observed on microvessels in the putamen of patients with Parkinson's disease. 22 references, 2 tables.

  12. Review: in vitro microvessel models.

    PubMed

    Bogorad, Max I; DeStefano, Jackson; Karlsson, Johan; Wong, Andrew D; Gerecht, Sharon; Searson, Peter C

    2015-11-21

    A wide range of perfusable microvessel models have been developed, exploiting advances in microfabrication, microfluidics, biomaterials, stem cell technology, and tissue engineering. These models vary in complexity and physiological relevance, but provide a diverse tool kit for the study of vascular phenomena and methods to vascularize artificial organs. Here we review the state-of-the-art in perfusable microvessel models, summarizing the different fabrication methods and highlighting advantages and limitations. PMID:26364747

  13. Tumor microvessel density–associated mast cells in canine nodal lymphoma

    PubMed Central

    Mann, Elizabeth; Whittington, Lisa

    2014-01-01

    Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4) was significantly higher (p < 0.05) than that in the control (0.83 ± 0.3) and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009). Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended. PMID:26770752

  14. Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo

    NASA Astrophysics Data System (ADS)

    Fu, Bingmei M.; Yang, Jinlin; Cai, Bin; Fan, Jie; Zhang, Lin; Zeng, Min

    2015-10-01

    Tumor cell adhesion to the microvessel wall is a critical step during tumor metastasis. Vascular endothelial growth factor (VEGF), a secretion of tumor cells, can increase microvessel permeability and tumor cell adhesion in the microvessel. To test the hypothesis that inhibiting permeability increase can reduce tumor cell adhesion, we used in vivo fluorescence microscopy to measure both microvessel permeability and adhesion rates of human mammary carcinoma MDA-MB-231 cells in post-capillary venules of rat mesentery under the treatment of VEGF and a cAMP analog, 8-bromo-cAMP, which can decrease microvessel permeability. By immunostaining adherens junction proteins between endothelial cells forming the microvessel wall, we further investigated the structural mechanism by which cAMP abolishes VEGF-induced increase in microvessel permeability and tumor cell adhesion. Our results demonstrate that 1) Pretreatment of microvessels with cAMP can abolish VEGF-enhanced microvessel permeability and tumor cell adhesion; 2) Tumor cells prefer to adhere to the endothelial cell junctions instead of cell bodies; 3) VEGF increases microvessel permeability and tumor cell adhesion by compromising endothelial junctions while cAMP abolishes these effects of VEGF by reinforcing the junctions. These results suggest that strengthening the microvessel wall integrity can be a potential approach to inhibiting hematogenous tumor metastasis.

  15. Inosculation and perfusion of pre-vascularized tissue patches containing aligned human microvessels after myocardial infarction.

    PubMed

    Riemenschneider, Sonja B; Mattia, Donald J; Wendel, Jacqueline S; Schaefer, Jeremy A; Ye, Lei; Guzman, Pilar A; Tranquillo, Robert T

    2016-08-01

    A major goal of tissue engineering is the creation of pre-vascularized tissues that have a high density of organized microvessels that can be rapidly perfused following implantation. This is especially critical for highly metabolic tissues like myocardium, where a thick myocardial engineered tissue would require rapid perfusion within the first several days to survive transplantation. In the present work, tissue patches containing human microvessels that were either randomly oriented or aligned were placed acutely on rat hearts post-infarction and for each case it was determined whether rapid inosculation could occur and perfusion of the patch could be maintained for 6 days in an infarct environment. Patches containing self-assembled microvessels were formed by co-entrapment of human blood outgrowth endothelial cells and human pericytes in fibrin gel. Cell-induced gel contraction was mechanically-constrained resulting in samples with high densities of microvessels that were either randomly oriented (with 420 ± 140 lumens/mm(2)) or uniaxially aligned (with 940 ± 240 lumens/mm(2)) at the time of implantation. These patches were sutured onto the epicardial surface of the hearts of athymic rats following permanent ligation of the left anterior descending artery. In both aligned and randomly oriented microvessel patches, inosculation occurred and perfusion of the transplanted human microvessels was maintained, proving the in vivo vascularization potential of these engineered tissues. No difference was found in the number of human microvessels that were perfused in the randomly oriented (111 ± 75 perfused lumens/mm(2)) and aligned (173 ± 97 perfused lumens/mm(2)) patches. Our results demonstrate that tissue patches containing a high density of either aligned or randomly oriented human pre-formed microvessels achieve rapid perfusion in the myocardial infarct environment - a necessary first-step toward the creation of a thick, perfusable heart patch. PMID

  16. Recombinant human erythropoietin α modulates the effects of radiotherapy on colorectal cancer microvessels

    PubMed Central

    Ceelen, W; Boterberg, T; Smeets, P; Van Damme, N; Demetter, P; Zwaenepoel, O; Cesteleyn, L; Houtmeyers, P; Peeters, M; Pattyn, P

    2007-01-01

    Recent data suggest that recombinant human erythropoietin (rhEPO) modulates tumour growth and therapy response. The purpose of the present study was to examine the modulation of radiotherapy (RT) effects on tumour microvessels by rhEPO in a rat colorectal cancer model. Before and after 5 × 5 Gy of RT, dynamic contrast-enhanced -magnetic resonance imaging was performed and endothelial permeability surface product (PS), plasma flow (F), and blood volume (V) were modelled. Imaging was combined with pO2 measurements, analysis of microvessel density, microvessel diameter, microvessel fractal dimension, and expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 α (HIF-1α), Bax, and Bcl-2. We found that RT significantly reduced PS and V in control rats, but not in rhEPO-treated rats, whereas F was unaffected by RT. Oxygenation was significantly better in rhEPO-treated animals, and RT induced a heterogeneous reoxygenation in both groups. Microvessel diameter was significantly larger in rhEPO animals, whereas VEGF expression was significantly lower in the rhEPO group. No differences were observed in HIF-1α, Bax, or Bcl-2 expression. We conclude that rhEPO results in spatially heterogeneous modulation of RT effects on tumour microvessels. Direct effects of rhEPO on neoplastic endothelium are likely to explain these findings in addition to indirect effects induced by increased oxygenation. PMID:17299396

  17. A mathematical model for understanding fluid flow through engineered tissues containing microvessels.

    PubMed

    Morin, Kristen T; Lenz, Michelle S; Labat, Caroline A; Tranquillo, Robert T

    2015-05-01

    Knowledge is limited about fluid flow in tissues containing engineered microvessels, which can be substantially different in topology than native capillary networks. A need exists for a computational model that allows for flow through tissues dense in nonpercolating and possibly nonperfusable microvessels to be efficiently evaluated. A finite difference (FD) model based on Poiseuille flow through a distribution of straight tubes acting as point sources and sinks, and Darcy flow through the interstitium, was developed to describe fluid flow through a tissue containing engineered microvessels. Accuracy of the FD model was assessed by comparison to a finite element (FE) model for the case of a single tube. Because the case of interest is a tissue with microvessels aligned with the flow, accuracy was also assessed in depth for a corresponding 2D FD model. The potential utility of the 2D FD model was then explored by correlating metrics of flow through the model tissue to microvessel morphometric properties. The results indicate that the model can predict the density of perfused microvessels based on parameters that can be easily measured. PMID:25424905

  18. The viscosity of gaseous propane and its initial density dependence

    NASA Astrophysics Data System (ADS)

    Vogel, E.

    1995-11-01

    Results of five series of high-precision viscosity measurements on gaseous propane, each differing in density, are reported. The measurements were performed in a quartz oscillating-disk viscometer with small gaps from room temperature up to about 625 K and for densities between 0.01 and 0.05 mol · L-1. The experimental data were evaluated with a first-order expansion, in terms of density, for the viscosity. Reduced values of the second viscosity virial coefficients deduced from the zero-density and initial-density viscosity coefficients for propane and for further n-alkanes are in close agreement with the theoretical representation of the Rainwater-Friend theory for the potential parameter ratios by Bich and Vogel. A new representation of the viscosity of propane in the limit of zero density is provided using the new experimental data and some data sets from literature. The universal correlation based on the extended principle of corresponding states extends over the temperature range 293 to 625 K with an uncertainty of ±0.5 % and deviates from earlier representations by about 1 % at the upper temperature limit.

  19. The viscosity of gaseous propane and its initial density dependence

    SciTech Connect

    Vogel, E.

    1995-11-01

    Results of five series of high-precision viscosity measurements on gaseous propane, each differing in density, are reported. The measurements were performed in a quartz oscillating-disk viscometer with small gaps from room temperature up to about 625 K and for densities between 0.01 and 0.05 mol {center_dot} L{sup -1}. The experimental data were evaluated with a first-order expansion, in terms of density, for the viscosity. Reduced values of the second viscosity virial coefficients deduced from the zero-density and initial-density viscosity coefficients for propane and for further n-alkanes are in close agreement with the theoretical representation of the Rainwater-Friend theory for the potential parameter ratios by Bich and Vogel. A new representation of the viscosity of propane in the limit of zero density is provided using the new experimental data and some data sets from literature. The universal correlation based on the extended principle of corresponding states extends over the temperature range 293 to 625 K with an uncertainty of {plus_minus}0.5% and deviates from earlier representations by about 1% at the upper temperature limit.

  20. Relationship between Exploding Bridgewire & Spark Initiation of Low Density PETN

    NASA Astrophysics Data System (ADS)

    Lee, Elizabeth; Drake, Rod

    2015-06-01

    Recent work has shown that the energy delivered after bridgewire burst affects the function time of an EBW detonator. The spark which is formed post bridgewire burst is the means by which the remaining fireset energy is delivered into the detonator. Therefore, by studying the characteristics of spark-gap detonators insight into the contribution of spark initiation to the functioning of EBW detonators may be achieved. Spark initiation of low density explosives consists of; (i) spark formation, (ii) spark interaction with the bed, and (iii) ignition and growth of reaction. Experiments were performed in which beds of an inert simulant were used to study the formation and propagation of sparks. The effect of the spark on inert porous beds was studied over a limited delivered energy range. The disruption of the bed was found to be dependent on the particle size / pore structure of the bed. The effect of spark initiation on a low density PETN bed was then examined, the relationship between delivered energy and function time was found to be the same as for EBW detonators. This necessitated the development of electrical diagnostic techniques to measure the energy delivered to the spark.

  1. Chronic ethanol treatment changes the number of beta-receptors in rat brain microvessels

    SciTech Connect

    Lucchi, L.; Cazzaniga, A.; Picotti, G.B.; Covelli, V.; Magnoni, M.S.; Borriero, L.; Spano, P.F.; Trabucchi, M.

    1984-01-01

    The effect of chronic ethanol consumption on the binding (125I)-iodohydroxybenzylpindolol to beta-adrenergic receptors in rat brain microvessels has been studied. The results show that chronic ethanol treatment increases the number of beta-receptors present in brain microvessels without changing the binding affinity of the binding site for the beta-adrenoceptor ligand. This effect is apparently not associated with changes in peripheral adrenergic tone, since no differences in platelet epinephrine or norepinephrine concentrations were found between ethanol-treated and control animals. An increase in beta-receptor density in brain microvessels might contribute to the alterations of cerebral blood flow and oxygen consumption reported during chronic ethanol intoxication.

  2. Effect of antihypertensive drugs on the myocardial microvessels in rats with nitric oxide blockade.

    PubMed

    Meirelles Pereira, L M; Mandarim-de-Lacerda, C A

    2000-01-01

    In the present study, myocardial microvessels were investigated by stereology in rats with nitric oxide blockade and concomitant antihypertensive treatment for 40 days. The following five groups (10 rats each) were studied: control; L-NAME; L-NAME + spironolactone; L-NAME + enalapril; L-NAME + verapamil. The blood pressure (BP) increased every week in the L-NAME group; after an initial increase BP decreased in the treated groups and was not different from the control group. Compared to control animals, the myocardium had hypertrophied myocytes and capillary rarefaction; the tunica media and the tunica intima of small arteries were thickened, and an increase in collagen fibrils in L-NAME treated animals was noted. The enalapril, verapamil and spironolactone groups showed uniform myocardium, quite similar to the control group. The volume density of vessels, in comparison with the L-NAME group, was greater in the spironolactone group (57%), in the enalapril group (76%) and in the verapamil group (81%). The length density of vessels was, respectively, 56%, 50%, and 76% greater in the spironolactone, enalapril and verapamil groups than in the L-NAME group. The surface density of the vessels of the L-NAME group was, respectively, 88%, 96%, and 113% lower than in the spironolactone, enalapril and verapamil groups. These results are compatible with the occurrence of angiogenesis in the verapamil rats. PMID:10834387

  3. Shock-initiated Combustion of a Spherical Density Inhomogeneity

    NASA Astrophysics Data System (ADS)

    Haehn, Nicholas; Oakley, Jason; Rothamer, David; Anderson, Mark; Ranjan, Devesh; Bonazza, Riccardo

    2010-11-01

    A spherical density inhomogeneity is prepared using fuel and oxidizer at a stoichiometric ratio and Xe as a diluent that increases the overall density of the bubble mixture (55% Xe, 30% H2, 15% O2). The experiments are performed in the Wisconsin Shock Tube Laboratory in a 9.2 m vertical shock tube with a 25.4 cm x 25.4 cm square cross-section. An injector is used to generate a 5 cm diameter soap film bubble filled with the combustible mixture. The injector retracts flush into the side of the tube releasing the bubble into a state of free fall. The combustible bubble is accelerated by a planar shock wave in N2 (2.0 < M < 2.8). The mismatch of acoustic impedances results in shock-focusing at the downstream pole of the bubble. The shock focusing results in localized temperatures and pressures significantly larger than nominal conditions behind a planar shock wave, resulting in auto-ignition at the focus. Planar Mie scattering and chemiluminescence are used simultaneously to visualize the bubble morphology and combustion characteristics. During the combustion phase, both the span-wise and stream-wise lengths of the bubble are seen to increase compared to the non-combustible scenario. Additionally, smaller instabilities are observed on the upstream surface, which are absent in the non-combustible bubbles.

  4. JSR photolithography based microvessel scaffold fabrication and cell seeding.

    PubMed

    Wang, Gou-Jen; Hsu, Yi-Feng; Hsu, Shan-Hui; Horng, Ray Hua

    2006-03-01

    A simple and inexpensive lithograph approach, in which the PMMA polymer was selected to be the substrate, the negative photoresist JSR was employed to form the microchannel structure, was adopted to fabricate the microvessel scaffold. In addition, a soft PDMS based microvessel scaffold was built by using a mold that was made up of the negative photoresist JSR. With O(2) plasma treatment, the PDMS based microvessel scaffold became more hydrophilic such that the cell culture could be easier to conduct. During cell culture, it was found that the fabricated scaffold enabled the bovine endothelial cells (BEC) to statically grow. However, the overall exchange of nutrient and oxygen was inefficient. Dynamic seeding by a novel apparatus was further conducted to have better circulation of culture medium. The bovine endothelial cells could successfully be cultivated in the microvessel scaffold by dynamic seeding. PMID:16491327

  5. Structure-based algorithms for microvessel classification

    PubMed Central

    Smith, Amy F.; Secomb, Timothy W.; Pries, Axel R.; Smith, Nicolas P.; Shipley, Rebecca J.

    2014-01-01

    Objective Recent developments in high-resolution imaging techniques have enabled digital reconstruction of three-dimensional sections of microvascular networks down to the capillary scale. To better interpret these large data sets, our goal is to distinguish branching trees of arterioles and venules from capillaries. Methods Two novel algorithms are presented for classifying vessels in microvascular anatomical data sets without requiring flow information. The algorithms are compared with a classification based on observed flow directions (considered the gold standard), and with an existing resistance-based method that relies only on structural data. Results The first algorithm, developed for networks with one arteriolar and one venular tree, performs well in identifying arterioles and venules and is robust to parameter changes, but incorrectly labels a significant number of capillaries as arterioles or venules. The second algorithm, developed for networks with multiple inlets and outlets, correctly identifies more arterioles and venules, but is more sensitive to parameter changes. Conclusions The algorithms presented here can be used to classify microvessels in large microvascular data sets lacking flow information. This provides a basis for analyzing the distinct geometrical properties and modelling the functional behavior of arterioles, capillaries and venules. PMID:25403335

  6. Mesoscale simulation of blood flow in microvessels

    NASA Astrophysics Data System (ADS)

    Bagchi, Prosenjit

    2006-11-01

    Computational modeling of blood flow in microvessels (20--500 micron) is a major challenge. Blood in such vessels behaves as a multiphase suspension of deformable particles. Individual red blood cell (RBC), which is highly deformable, must be considered in the model. Multiple cells, often a few thousands in number, must also be considered. We present two dimensional computational simulation of blood flow in 20--300 micron vessels at discharge hematocrit of 10--60 percent taking into consideration the particulate nature of blood and cell deformation. The numerical model is based on the immersed boundary method, and the red blood cells are modeled as liquid capsules. A large RBC population of up to 2500 cells is simulated. Migration of the cells normal to the wall of the vessel and the formation of the cell- free layer are studied. Results on the trajectory and velocity traces of the RBCs are presented. Also presented are the plug flow velocity profile of blood, the apparent viscosity, and the Fahraeus-Lindqvist effect. The computational results are in good agreement with the experimental results of Bishop et al (2001, 2002) and Pries et al (1992).

  7. In vivo microscopy of microvessel oxygenation and network connections.

    PubMed

    Lee, Jennifer A; Kozikowski, Raymond T; Sorg, Brian S

    2015-03-01

    Abnormal or compromised microvascular function is a key component of various diseases. In vivo microscopy of microvessel function in preclinical models can be useful for the study of a disease state and effects of new treatments. Wide-field imaging of microvascular oxygenation via hemoglobin (Hb) saturation measurements has been applied in various applications alone and in combination with other measures of microvessel function, such as blood flow. However, most current combined imaging methods of microvessel function do not provide direct information on microvessel network connectivity or changes in connections and blood flow pathways. First-pass fluorescence (FPF) imaging of a systemically administered fluorescent contrast agent can be used to directly image blood flow pathways and connections relative to a local supplying arteriole in a quantitative manner through measurement of blood supply time (BST). Here, we demonstrate the utility of information produced by the combination of Hb saturation measurements via spectral imaging with BST measurements via FPF imaging for correlation of microvessel oxygenation with blood flow pathways and connections throughout a local network. Specifically, we show network pathway effects on oxygen transport in normal microvessels, dynamic changes associated with wound healing, and pathological effects of abnormal angiogenesis in tumor growth and development. PMID:25500481

  8. Endothelin stimulates phosphoinositide hydrolysis and PAF synthesis in brain microvessels.

    PubMed

    Catalán, R E; Martínez, A M; Aragonés, M D; Martínez, A; Díaz, G

    1996-11-01

    Treatment of brain microvessels with the three endothelin (ET) isoforms resulted in an increase of phosphoinositide turnover by activation of phospholipase C in a dose- and time-dependent manner. Both ET-1 and ET-2 are maximally effective, whereas the effect evoked by ET-3 was smaller. Concomitantly, there was an enhanced production of a platelet-activating factor (PAF)-like material. This was identified by standard and biological probes in platelets, such as induction of aggregation, phosphatidic acid (PA) production, increase of endogenous protein phosphorylation, and reversal of these responses by a PAF antagonist. The effects evoked by endothelins on phosphoinositide metabolism and PAF production were, to a certain extent, dependent on the presence of extracellular Ca2+. In addition, ET induced changes in Ca2+ dynamics, evoking an initial and rapid intracellular mobilization and influx of Ca2+ and, later, a maintained Ca2+ influx. These findings contribute to the understanding of the pathophysiological role of ET in the blood-brain barrier (BBB). PMID:8898708

  9. Erythrocyte hemodynamics in stenotic microvessels: A numerical investigation

    NASA Astrophysics Data System (ADS)

    Wang, T.; Xing, Z. W.

    2013-10-01

    This paper presents a two-dimensional numerical investigation of deformation and motion of erythrocytes in stenotic microvessels using the immersed boundary-fictitious domain method. The erythrocytes were modeled as biconcave-shaped closed membranes filled with cytoplasm. We studied the biophysical characteristics of human erythrocytes traversing constricted microchannels with the narrowest cross-sectional diameter as small as 3 μm. The effects of essential parameters, namely, stenosis severity, shape of the erythrocytes, and erythrocyte membrane stiffness, were simulated and analyzed in this study. Moreover, simulations were performed to discuss conditions associated with the shape transitions of the cells along with the relative effects of radial position and initial orientation of erythrocytes, membrane stiffness, and plasma environments. The simulation results were compared with existing experiment findings whenever possible, and the physical insights obtained were discussed. The proposed model successfully simulated rheological behaviors of erythrocytes in microscale flow and thus is applicable to a large class of problems involving fluid flow with complex geometry and fluid-cell interactions. Our study would be helpful for further understanding of pathology of malaria and some other blood disorders.

  10. Erythrocyte hemodynamics in stenotic microvessels: A numerical investigation

    NASA Astrophysics Data System (ADS)

    Wang, Tong; Xing, Zhongwen

    2014-03-01

    This paper presents a two-dimensional numerical investigation of deformation and motion of erythrocytes in stenotic microvessels using the immersed boundary-fictitious domain method. The erythrocytes were modeled as biconcave-shaped closed membranes filled with cytoplasm. We studied the biophysical characteristics of human erythrocytes traversing constricted microchannels with the narrowest cross-sectional diameter as small as 3 μm. The effects of essential parameters, namely, stenosis severity, shape of the erythrocytes, and erythrocyte membrane stiffness, were simulated and analyzed in this study. Moreover, simulations were performed to discuss conditions associated with the shape transitions of the cells along with the relative effects of radial position and initial orientation of erythrocytes, membrane stiffness, and plasma environments. The simulation results were compared with existing experiment findings whenever possible, and the physical insights obtained were discussed. The proposed model successfully simulated rheological behaviors of erythrocytes in microscale flow and thus is applicable to a large class of problems involving fluid flow with complex geometry and fluid-cell interactions. Our study would be helpful for further understanding of pathology of malaria and some other blood disorders.

  11. Model experiments on measuring flow in microvessels using tracers.

    PubMed

    Federspiel, W J; Malai, K

    1993-11-01

    Most techniques for measuring plasma or red cell flow velocity within microvessels rely on determining the transit time of a tracer to transverse the distance between two monitoring sites within a vessel. In principle, proper transit time determinations require flow-weighted sampling of the tracer at monitoring sites. In practical application of the tracer technique, however, trace sampling at monitoring sites is not flow-weighted but is area-weighted, and hence elapsed transient time can only be estimated from tracer data. We previously showed theoretically (Microvasc. Res. 40, 394-411, 1990) that the flow velocity determined under these conditions can differ appreciably from the actual mean flow velocity of the carrier fluid within the microvessel. Nevertheless, trace mean flow velocity does approach that of the fluid when tracer velocity is measured past a finite distance from the microvessel entrance. In this study, we examined the tracer measurement of flow experimentally using a physical model. We perfused single glass microvessels and simple fabricated microvessel networks with distilled water at physiological flow rates. Mean tracer velocity (Vd) was determined at several axial locations within the microvessels using injected Evans blue dye. At each location Vd was determined in a manner consistent with usual application of the tracer flow measurement technique. Actual mean flow velocity (Va) was determined from the measured effluent flow rates discharged from each microvessel. Our experimental results confirm the existence of an appreciable velocity measurement error (VME) associated with the tracer technique. The VME behavior was consistent with our original theoretical analysis. Vd was significantly smaller than Va within a finite length of vessel near the entrance, but approached and became equal to Va past this length. Furthermore, even under conditions where the VME was negligible at the end of a parent microvessel, a new and appreciable VME arose

  12. Ammonia inhibition on Arthrospira platensis in relation to the initial biomass density and pH.

    PubMed

    Markou, Giorgos; Vandamme, Dries; Muylaert, Koenraad

    2014-08-01

    In this study the combined effect of total ammoniacal nitrogen (TAN) concentration, initial biomass density and initial pH of the cultivation medium on growth of Arthrospira platensis was studied. The results indicate that TAN inhibition in relation to the initial biomass in unregulated pH cultures is neither a clearly biomass-independent nor biomass-dependent phenomenon. However, low biomass densities are more susceptible to ammonia inhibition than higher biomass densities. Higher biomass densities seems to mitigate ammonia inhibition through rapider assimilation of TAN. In all cases studied the growth rates were lower compared to the cultures with nitrate as nitrogen source. It was observed that at low TAN concentration, although no ammonia inhibition occured the growth rates were decreased due to nitrogen limitation. Low TAN concentration triggered the accumulation of carbohydrates affecting thus significantly the biomass composition. Ammonia losses from the cultivation system were also determined. Ammonia losses ranged between 17% and 80%. PMID:24926597

  13. Effects of wall shear stress and its gradient on tumor cell adhesion in curved microvessels

    PubMed Central

    Yan, W. W.; Cai, B.

    2016-01-01

    Tumor cell adhesion to vessel walls in the microcirculation is one critical step in cancer metastasis. In this paper, the hypothesis that tumor cells prefer to adhere at the microvessels with localized shear stresses and their gradients, such as in the curved microvessels, was examined both experimentally and computationally. Our in vivo experiments were performed on the microvessels (post-capillary venules, 30–50 μm diameter) of rat mesentery. A straight or curved microvessel was cannulated and perfused with tumor cells by a glass micropipette at a velocity of ~1mm/s. At less than 10 min after perfusion, there was a significant difference in cell adhesion to the straight and curved vessel walls. In 60 min, the averaged adhesion rate in the curved vessels (n = 14) was ~1.5-fold of that in the straight vessels (n = 19). In 51 curved segments, 45% of cell adhesion was initiated at the inner side, 25% at outer side, and 30% at both sides of the curved vessels. To investigate the mechanical mechanism by which tumor cells prefer adhering at curved sites, we performed a computational study, in which the fluid dynamics was carried out by the lattice Boltzmann method, and the tumor cell dynamics was governed by the Newton’s law of translation and rotation. A modified adhesive dynamics model that included the influence of wall shear stress/gradient on the association/dissociation rates of tumor celladhesion was proposed, in which the positive wall shear stress/gradient jump would enhance tumor cell adhesion while the negative wall shear stress/gradient jump would weaken tumor cell adhesion. It was found that the wall shear stress/gradient, over a threshold, had significant contribution to tumor cell adhesion by activating or inactivating cell adhesion molecules. Our results elucidated why the tumor cell adhesion prefers to occur at the positive curvature of curved microvessels with very low Reynolds number (in the order of 10−2) laminar flow. PMID:21818636

  14. RECONSTRUCTING THE INITIAL DENSITY FIELD OF THE LOCAL UNIVERSE: METHODS AND TESTS WITH MOCK CATALOGS

    SciTech Connect

    Wang Huiyuan; Mo, H. J.; Yang Xiaohu; Van den Bosch, Frank C.

    2013-07-20

    Our research objective in this paper is to reconstruct an initial linear density field, which follows the multivariate Gaussian distribution with variances given by the linear power spectrum of the current cold dark matter model and evolves through gravitational instabilities to the present-day density field in the local universe. For this purpose, we develop a Hamiltonian Markov Chain Monte Carlo method to obtain the linear density field from a posterior probability function that consists of two components: a prior of a Gaussian density field with a given linear spectrum and a likelihood term that is given by the current density field. The present-day density field can be reconstructed from galaxy groups using the method developed in Wang et al. Using a realistic mock Sloan Digital Sky Survey DR7, obtained by populating dark matter halos in the Millennium simulation (MS) with galaxies, we show that our method can effectively and accurately recover both the amplitudes and phases of the initial, linear density field. To examine the accuracy of our method, we use N-body simulations to evolve these reconstructed initial conditions to the present day. The resimulated density field thus obtained accurately matches the original density field of the MS in the density range 0.3{approx}<{rho}/ {rho}-bar {approx}<20 without any significant bias. In particular, the Fourier phases of the resimulated density fields are tightly correlated with those of the original simulation down to a scale corresponding to a wavenumber of {approx}1 h Mpc{sup -1}, much smaller than the translinear scale, which corresponds to a wavenumber of {approx}0.15 h Mpc{sup -1}.

  15. Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of nuclei and vessels

    PubMed Central

    Tsai, Philbert S.; Kaufhold, John P.; Blinder, Pablo; Friedman, Beth; Drew, Patrick J.; Karten, Harvey J.; Lyden, Patrick D.; Kleinfeld, David

    2016-01-01

    It is well known that the density of neurons varies within the adult brain. In neocortex, this includes variations in neuronal density between different lamina as well as between different regions. Yet the concomitant variation of the microvessels is largely uncharted. Here we present automated histological, imaging, and analysis tools to simultaneously map the locations of all neuronal and non-neuronal nuclei and the centerlines and diameters of all blood vessels within thick slabs of neocortex from mice. Based on total inventory measurements of different cortical regions (~ 107 cells vectorized across brains), these methods revealed: (1) In three dimensions, the mean distance of the center of neuronal somata to the closest microvessel was 14 μm. (2) Volume samples within lamina of a given region show that the density of microvessels does not match the strong laminar variation in neuronal density. This holds for both agranular and granular cortex. (3) Volume samples in successive radii from the midline to the ventral-lateral edge, where each volume summed the number of cells and microvessels from the pia to the white matter, show a significant correlation between neuronal and microvessel densities. These data show that while neuronal and vascular densities do not track each other on the 100 μm scale of cortical lamina, they do track each other on the 1 – 10 mm scale of the cortical mantle. The absence of a disproportionate density of blood vessels in granular lamina is argued to be consistent with the initial locus of functional brain imaging signals. PMID:19923289

  16. Effect of Initial Seeding Density on Human Umbilical Cord Mesenchymal Stromal Cells for Fibrocartilage Tissue Engineering

    PubMed Central

    Wang, Limin; Seshareddy, Kiran; Weiss, Mark L.

    2009-01-01

    Cells derived from Wharton's jelly from human umbilical cords (called umbilical cord mesenchymal stromal cells herein) are a novel cell source for musculoskeletal tissue engineering. In this study, we examined the effects of different seeding densities on seeding efficiency, cell proliferation, biosynthesis, mechanical integrity, and chondrogenic differentiation. Cells were seeded on non-woven polyglycolic acid (PGA) meshes in an orbital shaker at densities of 5, 25, or 50 million cells/mL and then statically cultured for 4 weeks in chondrogenic medium. At week 0, initial seeding density did not affect seeding efficiency. Throughout the 4-week culture period, absolute cell numbers of the 25 and 50 million-cells/mL (higher density) groups were significantly larger than in the 5 million-cells/mL (lower density) group. The presence of collagen types I and II and aggrecan was confirmed using immunohistochemical staining. Glycosaminoglycan and collagen contents per construct in the higher-density groups were significantly greater than in the lower-density group. Constructs in the high-density groups maintained their mechanical integrity, which was confirmed using unconfined compression testing. In conclusion, human umbilical cord cells demonstrated the potential for chondrogenic differentiation in three-dimensional tissue engineering, and higher seeding densities better promoted biosynthesis and mechanical integrity, and thus a seeding density of at least 25 million cells/mL is recommended for fibrocartilage tissue engineering with umbilical cord mesenchymal stromal cells. PMID:18759671

  17. Shock Initiation Experiments with Ignition and Growth Modeling on Low Density Composition B

    NASA Astrophysics Data System (ADS)

    Vandersall, Kevin S.; Garcia, Frank; Tarver, Craig M.

    2015-06-01

    Shock initiation experiments on low density (~1.2 and ~1.5 g/cm3) Composition B were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (~1.2 g/cm3) confined in Teflon rings or sample disks pressed to low density (~1.5 g/cm3) . The shock sensitivity was found to increase with decreasing density as expected. Ignition and Growth model parameters were derived that yielded reasonable agreement with the experimental data at both initial densities. The shock sensitivity at the tested densities will be compared to prior work published as near full density material. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. This work was funded in part by the Joint DoD-DOE Munitions Program.

  18. Rapidity profile of the initial energy density in heavy-ion collisions

    NASA Astrophysics Data System (ADS)

    Özönder, Şener; Fries, Rainer J.

    2014-03-01

    The rapidity dependence of the initial energy density in heavy-ion collisions is calculated from a three-dimensional McLerran-Venugopalan model introduced by Lam and Mahlon. This model is infrared safe since global color neutrality is enforced. In this framework, the nuclei have nonzero thickness in the longitudinal direction. This leads to Bjorken-x-dependent unintegrated gluon distribution functions, which in turn result in a rapidity-dependent initial energy density after the collision. These unintegrated distribution functions are substituted in the initial energy density expression, which has been derived for the boost-invariant case. We argue that using three-dimensional (x-dependent) unintegrated distribution functions together with the boost-invariant energy formula is consistent given that the overlap of the two nuclei lasts less than the natural time scale for the evolution of the fields (1/Qs) after the collision. The initial energy density and its rapidity dependence are important initial conditions for the quark gluon plasma and its hydrodynamic evolution.

  19. Critical sequences of phenomena in the progression of atherosclerotic lesions, with reference to the role of microvessels.

    PubMed

    Michael Munro, J; Path, F R C

    2012-10-01

    Atherosclerosis affects the inner layers of human arteries, and causes major problems by blocking, directly or indirectly, the flow of blood. This paper concerns the growth of atherosclerotic lesions (atherogenesis), in particular potential factors that may allow a form of 'positive feedback' that drives the development of lesions, and considers the role of microvessels. The lesions of atherosclerosis have previously been compared to, or thought of as, sites of inflammation, and involve the accumulation of cells, including large lipid-containing macrophages, and extracellular elements. In tissues other than arteries inflammation may involve, amongst other phenomena, a resolution stage with the removal or departure of macrophages via lymphatics. However, the inner aspects of large arteries do not normally demonstrate lymphatics or other microvessels, and there is evidence from animal work that the lack of vessels effectively contributes to the development of atherosclerosis, as this limits the egress of macrophages and other elements. Conversely, in humans microvessels have been suggested to play a key role in the progress of atherosclerotic lesions. The importance of microvessels is herein considered, in particular the potentially paradoxical situation where as stated the lack of microvessels can be considered to allow atherosclerosis, but on the other hand these structures are involved in lesion development - the explanation can be seen to relate to the relatively short length of time which is assessable in animal models, compared to the lengthy period over which lesions appear to develop in humans. In addition, consideration is given to other factors, including haemodynamic factors related to the physical presence of lesions, which could lead to phenomena that can be regarded as a vicious cycle of events that lead to growth of the lesion. Specifically initial inflammation may lead to scarring and anatomical distortion, which through haemodynamic and physical

  20. On the logistic equation subject to uncertainties in the environmental carrying capacity and initial population density

    NASA Astrophysics Data System (ADS)

    Dorini, F. A.; Cecconello, M. S.; Dorini, L. B.

    2016-04-01

    It is recognized that handling uncertainty is essential to obtain more reliable results in modeling and computer simulation. This paper aims to discuss the logistic equation subject to uncertainties in two parameters: the environmental carrying capacity, K, and the initial population density, N0. We first provide the closed-form results for the first probability density function of time-population density, N(t), and its inflection point, t*. We then use the Maximum Entropy Principle to determine both K and N0 density functions, treating such parameters as independent random variables and considering fluctuations of their values for a situation that commonly occurs in practice. Finally, closed-form results for the density functions and statistical moments of N(t), for a fixed t > 0, and of t* are provided, considering the uniform distribution case. We carried out numerical experiments to validate the theoretical results and compared them against that obtained using Monte Carlo simulation.

  1. Specific binding of atrial natriuretic factor in brain microvessels

    SciTech Connect

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-04-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

  2. Specific Binding of Atrial Natriuretic Factor in Brain Microvessels

    NASA Astrophysics Data System (ADS)

    Chabrier, Pierre E.; Roubert, Pierre; Braquet, Pierre

    1987-04-01

    Cerebral capillaries constitute the blood--brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. We examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using 125I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity (dissociation constant, ≈ 10-10 M) and with a binding capacity of 58 fmol/mg of protein. The binding of 125I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood--brain barrier function.

  3. LABORATORY CULTURE OF CHIRONOMUS TENTANS FOR USE IN TOXICITY TESTING: OPTIMUM INITIAL EGG STOCKING DENSITIES

    EPA Science Inventory

    This study was conducted to determine the effet of initial culture stocking density on: (1) post-hatch (larval) dry weight, body length and head-capsule width at 10 and 20 days; (2) time to emergence; (3) number and sex of emergent adults; (4) number of larvae and pupae at test t...

  4. Cold dissipationless collapse of spherical systems - Sensitivity to the initial density law

    NASA Technical Reports Server (NTRS)

    Cannizzo, John K.; Hollister, Timothy C.

    1992-01-01

    The collapse of cold, initially spherical systems with varying degrees of central condensation is investigated. The way in which the final shape of a collapsing system depends on the initial density law is examined. For an initial stellar number density rho varies as r exp -n, where n is in the range 0-2.5, the final, nearly prolate shape is given by a/c is approximately equal to 1.28(1 + 0.16 n), where a/c is the ratio of long to short axes of the inertia ellipsoid computed from the moment of inertia tensor of the most tightly bound 80 percent of the mass. The properties associated with the final states in the present computations are also studied. The collapsing systems develop an anisotropic halo dominated by radial orbits surrounding an isotropic core as predicted by Burkert (1990).

  5. Determination of an Initial Mesh Density for Finite Element Computations via Data Mining

    SciTech Connect

    Kanapady, R; Bathina, S K; Tamma, K K; Kamath, C; Kumar, V

    2001-07-23

    Numerical analysis software packages which employ a coarse first mesh or an inadequate initial mesh need to undergo a cumbersome and time consuming mesh refinement studies to obtain solutions with acceptable accuracy. Hence, it is critical for numerical methods such as finite element analysis to be able to determine a good initial mesh density for the subsequent finite element computations or as an input to a subsequent adaptive mesh generator. This paper explores the use of data mining techniques for obtaining an initial approximate finite element density that avoids significant trial and error to start finite element computations. As an illustration of proof of concept, a square plate which is simply supported at its edges and is subjected to a concentrated load is employed for the test case. Although simplistic, the present study provides insight into addressing the above considerations.

  6. Motion of red blood cells near microvessel walls: effects of a porous wall layer

    PubMed Central

    HARIPRASAD, DANIEL S.; SECOMB, TIMOTHY W.

    2013-01-01

    A two-dimensional model is used to simulate the motion and deformation of a single mammalian red blood cell (RBC) flowing close to the wall of a microvessel, taking into account the effects of a porous endothelial surface layer (ESL) lining the vessel wall. Migration of RBCs away from the wall leads to the formation of a cell-depleted layer near the wall, which has a large effect on the resistance to blood flow in microvessels. The objective is to examine the mechanical factors causing this migration, including the effects of the ESL. The vessel is represented as a straight parallel-sided channel. The RBC is represented as a set of interconnected viscoelastic elements, suspended in plasma, a Newtonian fluid. The ESL is represented as a porous medium, and plasma flow in the layer is computed using the Brinkman approximation. It is shown that an initially circular cell positioned close to the ESL in a shear flow is deformed into an asymmetric shape. This breaking of symmetry leads to migration away from the wall. With increasing hydraulic resistivity of the layer, the rate of lateral migration increases. It is concluded that mechanical interactions of RBCs flowing in microvessels with a porous wall layer may reduce the rate of lateral migration and hence reduce the width of the cell-depleted zone external to the ESL, relative to the cell-depleted zone that would be formed if the interface between the ESL and free-flowing plasma were replaced by an impermeable boundary. PMID:23493820

  7. Role of initial cell density of algal bioassay of toxic chemicals.

    PubMed

    Singh, Prashant Kumar; Shrivastava, Alok Kumar

    2016-07-01

    A variety of toxicants such as, metal ions, pesticides, dyes, etc. are continuously being introduced anthropogenically in the environment and adversely affect to the biotic component of the ecosystem. Therefore, the assessment of negative effects of these toxicants is required. However, toxicity assessment anticipated by chemical analysis are extremely poor, therefore the application of the living systems for the same is an excellent approach. Concentration of toxicant as well as cell density both influenced the result of the algal toxicity assay. Here, Scenedesmus sp, a very fast growing green microalgae was selected for study the effects of initial cell densities on the toxicity of Cu(II), Cd(II), Zn(II), paraquat and 2,4-D. Results demonstrated concentration dependent decrease in biomass and specific growth rate of Scenedesmus sp. on exposure of abovesaid toxicants. Paraquat and 2,4-D emerged as extremely toxic to the test alga which reflected from the lowest EC value and very steep decline in biomass was evident with increasing concentration of paraquat and 2,4-D in the medium. Result also demonstrated that initial cell density is a very important parameter than specific growth rate for algal bioassay of various toxicants. Present study clearly illustrated that the use of smaller cell density is always recommended for assaying toxicity of chemicals in algal assays. PMID:26593761

  8. Effect of viscoelasticity and RBC migration phenomena in stenotic microvessels

    NASA Astrophysics Data System (ADS)

    Dimakopoulos, Yiannis; Syrakos, Alexandros; Georgiou, Georgios; Tsamopoulos, John

    2014-11-01

    This study deals with the numerical simulation of the hemodynamics in stenotic microvessels. The blood flow in microvessels differs significantly from that in large arteries and veins, because the Red Blood Cells (RBCs) are comparable in size with the radius of the microvessels and, consequently, local effects such as cell interaction and migration are more pronounced. In terms of complexity of the flow, viscoelasticity along with stress-gradient induced migration effects have a more dominant role, which exceeds the viscous, inertial and transient effects. Recently, a non-homogeneous viscoelastic model has been proposed by Moyers-Gonzalez et al. (2008), which can accurately predict the Fahraeus effects. We developed a numerical algorithm for the time-integration of the set of differential equations that arise from the coupling of momentum, mass, and population balances for RBCs and aggregates with the constitutive laws for both species. The simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness. Along this layer, the shear stresses are almost Newtonian because of the plasma, but the normal stresses that are exerted on the wall are high due to the contribution of the individual RBCs and rouleaux.

  9. Influence of Initial Population Densities of Meloidogyne incognita on Three Chile Cultivars.

    PubMed

    Lindsey, D L; Clayshulte, M S

    1982-07-01

    The effects of Meloidogyne incognita on the Big Jim, Jalapeno, and New Mexico No. 6 chile (Capsicum annuum) cultivars were investigated in microplots for two growing seasons. All three cultivars were susceptible to M. incognita and reacted similarly to different initial populations of this nematode. Severe stunting and yield suppressions occurred at all initial M. incognita densities tested ranging from 385 to 4,230 eggs and larvae/500 cm(3) soil. Regression analysis of the microplot data from a sandy loam soil showed yield losses of 31% for the 1978 season and 25% for the 1979 season for the three cultivars for each 10-fold increase in the initial population of M. incognita. PMID:19295720

  10. Fluids density functional theory and initializing molecular dynamics simulations of block copolymers

    NASA Astrophysics Data System (ADS)

    Brown, Jonathan R.; Seo, Youngmi; Maula, Tiara Ann D.; Hall, Lisa M.

    2016-03-01

    Classical, fluids density functional theory (fDFT), which can predict the equilibrium density profiles of polymeric systems, and coarse-grained molecular dynamics (MD) simulations, which are often used to show both structure and dynamics of soft materials, can be implemented using very similar bead-based polymer models. We aim to use fDFT and MD in tandem to examine the same system from these two points of view and take advantage of the different features of each methodology. Additionally, the density profiles resulting from fDFT calculations can be used to initialize the MD simulations in a close to equilibrated structure, speeding up the simulations. Here, we show how this method can be applied to study microphase separated states of both typical diblock and tapered diblock copolymers in which there is a region with a gradient in composition placed between the pure blocks. Both methods, applied at constant pressure, predict a decrease in total density as segregation strength or the length of the tapered region is increased. The predictions for the density profiles from fDFT and MD are similar across materials with a wide range of interfacial widths.

  11. Strain energy density and thermodynamic entropy as prognostic measures of crack initiation in aluminum

    NASA Astrophysics Data System (ADS)

    Ontiveros, Victor Luis

    A critical challenge to the continued use of engineering structures as they are asked to perform longer than their design life is the prediction of an initiating crack and the prevention of damage, estimation of remaining useful life, schedule maintenance and to reduce costly downtimes and inspections. The research presented in this dissertation explores the cumulative plastic strain energy density and thermodynamic entropy generation up to crack initiation. Plastic strain energy density and thermodynamic entropy generation are evaluated to investigate whether they would be capable of providing a physical basis for fatigue life and structural risk and reliability assessments. Navy aircraft, specifically, the Orion P-3C, which represent an engineered structure currently being asked to perform past is design life, which are difficult and time consuming to inspect from carrier based operations and are currently evaluated using an empirically based damage index the, fatigue life expended, is used as an example in this investigation. A set of experimental results for aluminum alloy 7075-T651, used in airframe structures, are presented to determine the correlation between plastic strain energy dissipation and the thermodynamic entropy generation versus fatigue crack initiation over a wide range of fatigue loadings. Cumulative plastic strain energy and thermodynamic entropy generation measured from hysteresis energy and temperature rise proved to be valid physical indices for estimation of the probability of crack initiation. Crack initiation is considered as a major evidence of fatigue damage and structural integrity risk. A Bayesian estimation and validation approach is used to determine systematic errors in the developed models as well as other model uncertainties. Comparisons of the energy-based and entropy-based models are presented and benefits of using one over the other are discussed.

  12. A simple method to calculate first-passage time densities with arbitrary initial conditions

    NASA Astrophysics Data System (ADS)

    Nyberg, Markus; Ambjörnsson, Tobias; Lizana, Ludvig

    2016-06-01

    Numerous applications all the way from biology and physics to economics depend on the density of first crossings over a boundary. Motivated by the lack of general purpose analytical tools for computing first-passage time densities (FPTDs) for complex problems, we propose a new simple method based on the independent interval approximation (IIA). We generalise previous formulations of the IIA to include arbitrary initial conditions as well as to deal with discrete time and non-smooth continuous time processes. We derive a closed form expression for the FPTD in z and Laplace-transform space to a boundary in one dimension. Two classes of problems are analysed in detail: discrete time symmetric random walks (Markovian) and continuous time Gaussian stationary processes (Markovian and non-Markovian). Our results are in good agreement with Langevin dynamics simulations.

  13. Current initiation in low-density foam z-pinch plasmas

    SciTech Connect

    Derzon, M.; Nash, T.; Allshouse, G.

    1996-07-01

    Low density agar and aerogel foams were tested as z-pinch loads on the SATURN accelerator. In these first experiments, we studied the initial plasma conditions by measuring the visible emission at early times with a framing camera and 1-D imaging. At later time, near the stagnation when the plasma is hotter, x-ray imaging and spectral diagnostics were used to characterize the plasma. Filamentation and arcing at the current contacts was observed. None of the implosions were uniform along the z-axis. The prime causes of these problems are believed to be the electrode contacts and the current return configuration and these are solvable. Periodic phenomena consistent with the formation of instabilities were observed on one shot, not on others, implying that there may be a way of controlling instabilities in the pinch. Many of the issues involving current initiation may be solvable. Solutions are discussed.

  14. Reduction of damage initiation density in fused silica optics via UV laser conditioning

    DOEpatents

    Peterson, John E.; Maricle, Stephen M.; Brusasco, Raymond M.; Penetrante, Bernardino M.

    2004-03-16

    The present invention provides a method for reducing the density of sites on the surface of fused silica optics that are prone to the initiation of laser-induced damage, resulting in optics which have far fewer catastrophic defects and are better capable of resisting optical deterioration upon exposure for a long period of time to a high-power laser beam having a wavelength of about 360 nm or less. The initiation of laser-induced damage is reduced by conditioning the optic at low fluences below levels that normally lead to catastrophic growth of damage. When the optic is then irradiated at its high fluence design limit, the concentration of catastrophic damage sites that form on the surface of the optic is greatly reduced.

  15. CYCLOOXYGENASE PRODUCTS STIMULATE CARBON MONOXIDE PRODUCTION BY PIGLET CEREBRAL MICROVESSELS

    PubMed Central

    Kanu, Alie; Gilpin, David; Fedinec, Alexander L.

    2005-01-01

    Products of arachidonic acid (AA) metabolism by cyclooxygenase (COX) are important in regulation of neonatal cerebral circulation. The brain and cerebral microvessels also express heme oxygenase (HO) that metabolizes heme to carbon monoxide (CO), biliverdin, and iron. The purpose of this study in newborn pig cerebral microvessels was to address the hypothesis that COX products affect HO activity and HO products affect COX activity. AA (2.0-20μM) increased PGE2 measured by RIA and also CO measured by gas chromatography/mass spectrometry (GC-MS). Further, indomethacin (10-4M), that inhibited COX, reduced both AA and heme-induced CO production. Conversely, neither exogenous heme (2×10-6M), that markedly increased CO production, nor the inhibitor of HO, chromium mesoporphyrin, altered PGE2 synthesis. Because AA metabolism by COX generates both prostanoids and superoxides, we determined the effects of the predominant prostanoid and superoxide on CO production. While PGE2 caused a small increase in CO production, xanthine oxidase plus hypoxanthine that produces superoxide strongly stimulated the production of CO by cerebral microvessels. This increase was mildly attenuated by catalase. These data suggest that COX catalyzed AA metabolite(s), most likely superoxide, H2O2, and / or a subsequent reactive oxygen species increases cerebrovascular CO production. This increase appears to be due, at least in part, to the elevation of HO-2 catalytic activity. Conversely, COX activity is not affected by HO-catalyzed heme metabolites. These data suggest that some cerebrovascular functions attributable to COX activity could be mediated by CO. PMID:16446494

  16. Flow-driven assembly of VWF fibres and webs in in vitro microvessels.

    PubMed

    Zheng, Ying; Chen, Junmei; López, José A

    2015-01-01

    Several systemic diseases, including thrombotic thrombocytopenic purpura, manifest much of their pathology through activation of endothelium and thrombotic occlusion of small blood vessels, often leading to multi-organ failure and death. Modelling these diseases is hampered by the complex three-dimensional architecture and flow patterns of the microvasculature. Here, we employ engineered microvessels of complex geometry to examine the pathological responses to endothelial activation. Our most striking finding is the capacity of endothelial-secreted von Willebrand factor (VWF) to assemble into thick bundles or complex meshes, depending on the vessel geometry and flow characteristics. Assembly is greatest in vessels of diameter ≤300 μm, with high shear stress or strong flow acceleration, and with sharp turns. VWF bundles and webs bind platelets, leukocytes and erythrocytes, obstructing blood flow and sometimes shearing passing erythrocytes. Our findings uncover the biophysical requirements for initiating microvascular thrombosis and suggest mechanisms for the onset and progression of microvascular diseases. PMID:26223854

  17. Statistics of initial density perturbations in heavy ion collisions and their fluid dynamic response

    NASA Astrophysics Data System (ADS)

    Floerchinger, Stefan; Wiedemann, Urs Achim

    2014-08-01

    An interesting opportunity to determine thermodynamic and transport properties in more detail is to identify generic statistical properties of initial density perturbations. Here we study event-by-event fluctuations in terms of correlation functions for two models that can be solved analytically. The first assumes Gaussian fluctuations around a distribution that is fixed by the collision geometry but leads to non-Gaussian features after averaging over the reaction plane orientation at non-zero impact parameter. In this context, we derive a three-parameter extension of the commonly used Bessel-Gaussian event-by-event distribution of harmonic flow coefficients. Secondly, we study a model of N independent point sources for which connected n-point correlation functions of initial perturbations scale like 1 /N n-1. This scaling is violated for non-central collisions in a way that can be characterized by its impact parameter dependence. We discuss to what extent these are generic properties that can be expected to hold for any model of initial conditions, and how this can improve the fluid dynamical analysis of heavy ion collisions.

  18. Percolation of randomly distributed growing clusters: the low initial density regime

    NASA Astrophysics Data System (ADS)

    Tsakiris, N.; Maragakis, M.; Kosmidis, K.; Argyrakis, P.

    2011-06-01

    We investigate the problem of growing clusters, which is modeled by two dimensional disks and three dimensional droplets. In this model we place a number of seeds on random locations on a lattice with an initial occupation probability, p. The seeds simultaneously grow with a constant velocity to form clusters. When two or more clusters eventually touch each other they immediately stop their growth. The probability that such a system will result in a percolating cluster depends on the density of the initially distributed seeds and the dimensionality of the system. For very low values of p we find a power law behavior for several properties that we investigate, namely for the size of the largest and second largest cluster, for the probability for a spanning cluster to occur, and for the mean radius of the finally formed droplets. We report the values of the corresponding scaling exponents. Finally, we show that for very low initial concentration of seeds the final coverage takes a constant value which depends on the system dimensionality.

  19. Adhesion of malignant mammary tumor cells MDA-MB-231 to microvessel wall increases microvascular permeability via degradation of endothelial surface glycocalyx

    PubMed Central

    Cai, Bin; Fan, Jie; Zeng, Min; Zhang, Lin

    2012-01-01

    To investigate the effect of tumor cell adhesion on microvascular permeability (P) in intact microvessels, we measured the adhesion rate of human mammary carcinoma MDA-MB-231, the hydraulic conductivity (Lp), the P, and reflection coefficient (σ) to albumin of the microvessels at the initial tumor cell adhesion and after ∼45 min cell perfusion in the postcapillary venules of rat mesentery in vivo. Rats (Sprague-Dawley, 250–300 g) were anesthetized with pentobarbital sodium given subcutaneously. A midline incision was made in the abdominal wall, and the mesentery was gently taken out and arranged on the surface of a glass coverslip for the measurement. An individual postcapillary venule was perfused with cells at a rate of ∼1 mm/s, which is the mean blood flow velocity in this type of microvessels. At the initial tumor cell adhesion, which was defined as one adherent cell in ∼100- to 145-μm vessel segment, Lp was 1.5-fold and P was 2.3-fold of their controls, and σ decreased from 0.92 to 0.64; after ∼45-min perfusion, the adhesion increased to ∼5 adherent cells in ∼100- to 145-μm vessel segment, while Lp increased to 2.8-fold, P to 5.7-fold of their controls, and σ decreased from 0.92 to 0.42. Combining these measured data with the predictions from a mathematical model for the interendothelial transport suggests that tumor cell adhesion to the microvessel wall degrades the endothelial surface glycocalyx (ESG) layer. This suggestion was confirmed by immunostaining of heparan sulfate of the ESG on the microvessel wall. Preserving of the ESG by a plasma glycoprotein orosomucoid decreased the P to albumin and reduced the tumor cell adhesion. PMID:22858626

  20. Quantitative study on appearance of microvessels in spectral endoscopic imaging

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Hiroshi; Saito, Takaaki; Shiraishi, Yasushi; Arai, Fumihito; Morimoto, Yoshinori; Yuasa, Atsuko

    2015-03-01

    Increase in abnormal microvessels in the superficial mucosa is often relevant to diagnostic findings of neoplasia in digestive endoscopy; hence, observation of superficial vasculature is crucial for cancer diagnosis. To enhance the appearance of such vessels, several spectral endoscopic imaging techniques have been developed, such as narrow-band imaging and blue laser imaging. Both techniques exploit narrow-band blue light for the enhancement. The emergence of such spectral imaging techniques has increased the importance of understanding the relation of the light wavelength to the appearance of superficial vasculature, and thus a new method is desired for quantitative analysis of vessel visibility in relation to the actual structure in the tissue. Here, we developed microvessel-simulating phantoms that allowed quantitative evaluation of the appearance of 15-μm-thick vessels. We investigated the relation between the vascular contrast and light wavelength by the phantom measurements and also verified it in experiments with swine, where the endoscopically observed vascular contrast was investigated together with its real vascular depth and diameter obtained by microscopic observation of fluorescence-labeled vessels. Our study indicates that changing the spectral property even in the wavelength range of blue light may allow selective enhancement of the vascular depth for clinical use.

  1. Magnetic resonance imaging of microvessels using iron-oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Olamaei, N.; Cheriet, F.; Martel, S.

    2013-03-01

    The visualization of microstructures including blood vessels with an inner overall cross-sectional area below approximately 200 μm remains beyond the capabilities of current clinical imaging modalities. But with magnetic resonance (MR) imaging, magnetic entities cause susceptibility artifacts in the images by disrupting the homogeneous magnetic field in a much larger scale than their actual size. As validated in this paper through simulation and in-vitro experiments, these artifacts can serve as a source of contrast, enabling microvessels with an inner diameter below the spatial resolution of any medical imaging modalities to be visualized using a clinical MR scanner. For such experiments, micron-sized agglomerations of iron-oxide (Fe3O4) nanoparticles were injected in microchannels with internal diameters of 200 and 50 μm equivalent to a narrower artery or a larger arteriole, and down to a smaller arteriole, respectively. The results show the feasibility of the proposed method for micro-particle detection and the visualization of microvessels using a 1.5 T clinical MR scanner. It was confirmed that the method is reproducible and accurate at the sub-pixel level.

  2. High latitude proton precipitation and light-ion density profiles during the magnetic storm initial phase

    NASA Technical Reports Server (NTRS)

    Burch, J. L.

    1973-01-01

    Measurements of precipitating protons and light ion densities by experiments on OGO-4 indicate that widespread proton precipitation occurs in predawn hours during the magnetic storm initial phase from the latitude of the high-latitude ion trough, or plasmapause , up to Lambda 75 deg. A softening of the proton spectrum is apparent as the plasmapause is approached. The separation of the low-latitude precipitation boundaries for 7.3 kev and 23.8 kev protons is approximately 1 deg, compared with a 3.6 deg separation which has been computed using the formulas of Gendrin and Eather and Carovillano. Consideration of probable proton drift morphology leads to the conclusion that protons ase injected in predawn hours, with widespread precipitation occurring in the region outside the plasmapause. Protons less energetic than approximately 7 kev drift eastward, while the more energetic protons drift westward, producing the observed dawn-dusk asymmetry for the lower-energy protons.

  3. The Role of Surface Receptor Density in Surface-Initiated Polymerizations for Cancer Cell Isolation.

    PubMed

    Lilly, Jacob L; Berron, Brad J

    2016-06-01

    Fluid biopsies potentially offer a minimally invasive alternative to traditional tissue biopsies for the continual monitoring of metastatic cancer. Current established technologies for isolating circulating tumor cells (CTCs) suffer from poor purity and yield and require fixatives that preclude the collection of viable cells for longitudinal analyses of biological function. Antigen specific lysis (ASL) is a rapid, high-purity method of cell isolation based on targeted protective coatings on antigen-presenting cells and lysis depletion of unprotected antigen-negative cells. In ASL, photoinitiators are specifically labeled on cell surfaces that enable subsequent surface-initiated polymerization. Critically, the significant determinants of process yield have yet to be investigated for this emerging technology. In this work, we show that the labeling density of photoinitiators is strongly correlated with the yield of intact cells during ASL by flow cytometry analysis. Results suggest ASL is capable of delivering ∼25% of targeted cells after isolation using traditional antibody labeling approaches. Monomer formulations of two molecular weights of PEG-diacrylate (Mn ∼ 575 and 3500) are examined. The gelation response during ASL polymerization is also investigated via protein microarray analogues on planar glass. Finally, a density threshold of photoinitiator labeling required for protection during lysis is determined for both monomer formulations. These results indicate ASL is a promising technology for high yield CTC isolation for rare-cell function assays and fluid biopsies. PMID:27206735

  4. Shock initiation studies of low density HMX using electromagnetic particle velocity and PVDF stress gauges

    SciTech Connect

    Sheffield, S.A.; Gustavsen, R.L.; Alcon, R.R.; Graham, R.A.; Anderson, M.U.

    1993-09-01

    Magnetic particle velocity and PVDF stress rate gauges have been used to measure the shock response of low density octotetramethylene tetranitramine (HMX) (1.24 &/cm{sup 3}). In experiments done at LANL, magnetic particle velocity gauges were located on both sides of the explosive. In nearly identical experiments done at SNL, PVDF stress rate gauges were located at the same positions so both particle velocity and stress histories were obtained for a particular experimental condition. Unreacted Hugoniot data were obtained and an EOS was developed by combining methods used by Hayes, Sheffield and Mitchell (for describing the Hugoniot of HNS at various densities) with Hermann`s P-{alpha} model. Using this technique, it is only necessary to know some thermodynamic constants or the Hugoniot of the initially solid material and the porous material sound speed to obtain accurate unreacted Hugoniots for the porous explosive. Loading and reaction paths were established in the stress-particle velocity plane for some experimental conditions. This information was used to determine a global reaction rate of {approx} 0.13 {mu}s{sup {minus}1} for porous HMX shocked to 0.8 GPa. At low input stresses the transmitted wave profiles had long rise times (up to 1 {mu}s) due to the compaction processes.

  5. Self-similar space-time evolution of an initial density discontinuity

    SciTech Connect

    Rekaa, V. L.; Pécseli, H. L.; Trulsen, J. K.

    2013-07-15

    The space-time evolution of an initial step-like plasma density variation is studied. We give particular attention to formulate the problem in a way that opens for the possibility of realizing the conditions experimentally. After a short transient time interval of the order of the electron plasma period, the solution is self-similar as illustrated by a video where the space-time evolution is reduced to be a function of the ratio x/t. Solutions of this form are usually found for problems without characteristic length and time scales, in our case the quasi-neutral limit. By introducing ion collisions with neutrals into the numerical analysis, we introduce a length scale, the collisional mean free path. We study the breakdown of the self-similarity of the solution as the mean free path is made shorter than the system length. Analytical results are presented for charge exchange collisions, demonstrating a short time collisionless evolution with an ensuing long time diffusive relaxation of the initial perturbation. For large times, we find a diffusion equation as the limiting analytical form for a charge-exchange collisional plasma, with a diffusion coefficient defined as the square of the ion sound speed divided by the (constant) ion collision frequency. The ion-neutral collision frequency acts as a parameter that allows a collisionless result to be obtained in one limit, while the solution of a diffusion equation is recovered in the opposite limit of large collision frequencies.

  6. Density Functional Theory Study on OH-Initiated Atmospheric Oxidation of m-Xylene

    SciTech Connect

    Fan, Jiwen; Zhang, Renyi

    2008-05-08

    The OH-initiated oxidation reactions of m-xylene are investigated using density functional theory. The structures, energetics, and relative stability of the OH-m-xylene reaction intermediate radicals have been determined, and their activation barriers have been analyzed to assess the energetically favorable pathways to propagate the oxidation. OH addition occurs preferentially at the two ortho positions with the branching ratios of 0.97, 0.02, and 0.01 for ortho, meta, and ipso additions, respectively. The results reveal that the OH-m-xylene-O2 peroxy radicals preferentially cyclize to form bicyclic radicals under atmospheric conditions rather than reacting with NO to lead to ozone formation, and the decomposition to O2 and the hydroxyl m-xylene adduct is competitive with the cyclization process. The bicyclic radicals of m-xylene formed from the major OH-addition pathways (i.e., ortho positions) are more probable to form bicyclic peroxy radicals by reacting with O2. This study provides thermochemical and kinetic data of the OH-initiated reactions of m-xylene for assessment of the role of aromatic hydrocarbons in photochemical production of ozone, toxic products, and secondary organic aerosols.

  7. Effects of interferon-gamma on primary cultures of human brain microvessel endothelial cells.

    PubMed Central

    Huynh, H. K.; Dorovini-Zis, K.

    1993-01-01

    Primary cultures of human brain microvessel endothelial cells were used to study the effects of human recombinant interferon-gamma (IFN-gamma) on cerebral endothelium in vitro. Incubation of monolayers with various concentrations of IFN-gamma (10 to 200 U/ml) for 12 to 96 hours induced surface expression of class II major histocompatibility complex (Ia) antigen in a time- and concentration-dependent manner. In immunogold-stained cultures, labeling was observed as early as 12 hours, was maximal after 48 hours, and persisted at plateau levels in the continuous presence of the cytokine. Expression was blocked by coincubation with anti-IFN-gamma antibody and was reversed 4 days following removal of IFN-gamma from the culture media. Endothelial cells treated with IFN-gamma for 3 to 4 days became spindle-shaped, extensively overlapped, and frequently formed cellular whorls. These changes did not occur in the presence of anti-IFN-gamma antibody and reversed upon removal of IFN-gamma from the media. The morphological alterations were associated with increased permeability of confluent monolayers to macromolecules as compared with untreated cultures. The results of these studies indicate that human brain microvessel endothelial cells respond to in vitro cytokine stimulation by undergoing profound morphological, functional, and permeability changes. We conclude that cerebral endothelium may play an important role in the initiation and regulation of lymphocyte traffic across the blood-brain barrier in inflammatory disorders of the human central nervous system. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 PMID:8475997

  8. Initial Energy Density in Heavy Ion Collisions from a Color Neutral Three-Dimensional Color Glass Condensate Model of QCD

    NASA Astrophysics Data System (ADS)

    Ozonder, Sener

    In the ultrarelativistic heavy-ion collisions at the Relativistic Heavy Ion Collider (RHIC), Brookhaven National Lab (BNL) and the Large Hadron Collider (LHC), CERN, hot, dense and strongly interacting Quark Gluon Plasma has been created. After the Quark Gluon Plasma reaches local thermal equilibrium, the fireball expands rapidly. Relativistic hydrodynamics successfully captures this evolution given the initial energy and initial entropy densities, along with the equation of state. This is followed by freeze-out of the plasma into hadrons, which are finally recorded at the detectors. The final multiplicity of the detected particles as well as their distribution in transverse momentum and rapidity are determined by the initial conditions of the hydrodynamic evolution of the Quark Gluon Plasma. In this thesis, the initial energy density of heavy-ion collisions is calculated in the framework of an effective model based on Quantum Chromodynamics. An overview of heavy ion collisions and Quark Gluon Plasma is given first. Then, the three-dimensional, color neutral McLerran-Venugopalan model is introduced and its parameters are fixed from the data on gluon distribution functions. Finally, we apply this model to Au-Au (at RHIC) and Pb-Pb (at LHC) collisions to calculate the initial energy density. The most important result of the work presented here is calculation of the rapidity profile of the initial energy density. Finally we compare our results on the energy density profile with that is used in hydrodynamic simulations.

  9. Characterization of nerve and microvessel damage and recovery in type 1 diabetic mice after permanent femoral artery ligation.

    PubMed

    Lozeron, Pierre; Mantsounga, Chris S; Broqueres-You, Dong; Dohan, Anthony; Polivka, Marc; Deroide, Nicolas; Silvestre, Jean-Sébastien; Kubis, Nathalie; Lévy, Bernard I

    2015-09-01

    Neuropathy is the most common complication of the peripheral nervous system during the progression of diabetes. The pathophysiology is unclear but may involve microangiopathy, reduced endoneurial blood flow, and tissue ischemia. We used a mouse model of type 1 diabetes to study parallel alterations of nerves and microvessels following tissue ischemia. We designed an easily reproducible model of ischemic neuropathy induced by irreversible ligation of the femoral artery. We studied the evolution of behavioral function, epineurial and endoneurial vessel impairment, and large nerve myelinated fiber as well as small cutaneous unmyelinated fiber impairment for 1 month following the onset of ischemia. We observed a more severe hindlimb dysfunction and delayed recovery in diabetic animals. This was associated with reduced density of large arteries in the hindlimb and reduced sciatic nerve epineurial blood flow. A reduction in sciatic nerve endoneurial capillary density was also observed, associated with a reduction in small unmyelinated epidermal fiber number and large myelinated sciatic nerve fiber dysfunction. Moreover, vascular recovery was delayed, and nerve dysfunction was still present in diabetic animals at day 28. This easily reproducible model provides clear insight into the evolution over time of the impact of ischemia on nerve and microvessel homeostasis in the setting of diabetes. © 2015 Wiley Periodicals, Inc. PMID:25944265

  10. High-latitude proton precipitation and light ion density profiles during the magnetic storm initial phase.

    NASA Technical Reports Server (NTRS)

    Burch, J. L.

    1973-01-01

    Measurements of precipitating protons and light ion densities by experiments on Ogo 4 indicate that widespread proton precipitation occurs in predawn hours during the magnetic storm initial phase from the latitude of the high-latitude ion trough, or plasmapause, up to latitudes greater than 75 deg. A softening of the proton spectrum is apparent as the plasmapause is approached. The separation of the low-latitude precipitation boundaries for 7.3-keV and 23.8-keV protons is less than about 1 deg, compared with a 3.6-deg separation that has been computed by using the formulas of Gendrin and Eather and Carovillano. Consideration of probable proton drift morphology leads to the conclusion that protons are injected in predawn hours, widespread precipitation occurring in the region outside the plasmapause. Protons less energetic than 7 keV drift eastward, whereas the more energetic protons drift westward, producing the observed dawn-dusk asymmetry for the lower-energy protons.

  11. Blood flow structure related to red cell flow: determinant of blood fluidity in narrow microvessels.

    PubMed

    McHedlishvili, G; Maeda, N

    2001-02-01

    The review article deals with phenomena of the blood flow structure (structuring) in narrow microvessels-capillaries and the adjacent arterioles and venules. It is particularly focused on the flow behavior of red blood cells (RBCs), namely, on their specific arrangements of mutual interaction while forming definite patterns of self-organized microvascular flow. The principal features of the blood flow structure in microvessels, including capillaries, include axial RBC flow and parietal plasma layer, velocity profile in larger microvessels, plug (or bolus) flow in narrow capillaries, and deformation and specific behavior of the RBCs in the flow. The actual blood flow structuring in microvessels seems to be a most significant factor in the development of pathological conditions, including arterial hypertension, brain and cardiac infarctions, inflammation, and many others. The blood flow structuring might become a basic concept in determining the blood rheological properties and disorders in the narrow microvessels. No solid theoretical (biorheological) basis of the blood flow structuring in microvessel has been found, but in the future it might become a foundation for a better understanding of the mechanisms of these properties under normal and pathological conditions in the narrowest microvessels 5 to 25 microm large. It is also a topic for further biorheological research directed to find the background of actual physiopathological phenomena in the microcirculation. PMID:11281993

  12. Widefield in vivo spectral and fluorescence imaging microscopy of microvessel blood supply and oxygenation

    NASA Astrophysics Data System (ADS)

    Lee, Jennifer; Kozikowski, Raymond; Wankhede, Mamta; Sorg, Brian S.

    2011-02-01

    Abnormal microvascular function and angiogenesis are key components of various diseases that can contribute to the perpetuation of the disease. Several skin diseases and ophthalmic pathologies are characterized by hypervascularity, and in cancer the microvasculature of tumors is structurally and functionally abnormal. Thus, the microvasculature can be an important target for treatment of diseases characterized by abnormal microvasculature. Motivated largely by cancer research, significant effort has been devoted to research on drugs that target the microvasculature. Several vascular targeting drugs for cancer therapy are in clinical trials and approved for clinical use, and several off-label uses of these drugs have been reported for non-cancer diseases. The ability to image and measure parameters related to microvessel function preclinically in laboratory animals can be useful for development and comparison of vascular targeting drugs. For example, blood supply time measurements give information related to microvessel morphology and can be measured with first-pass fluorescence imaging. Hemoglobin saturation measurements give an indication of microvessel oxygen transport and can be measured with spectral imaging. While each measurement individually gives some information regarding microvessel function, the measurements together may yield even more information since theoretically microvessel morphology can influence microvessel oxygenation, especially in metabolically active tissue like tumors. However, these measurements have not yet been combined. In this study, we report the combination of blood supply time imaging and hemoglobin saturation imaging of microvessel networks in tumors using widefield fluorescence and spectral imaging, respectively. The correlation between the measurements in a mouse mammary tumor is analyzed.

  13. Microperfusion Technique to Investigate Regulation of Microvessel Permeability in Rat Mesentery.

    PubMed

    Curry, Fitz-Roy E; Clark, Joyce F; Adamson, Roger H

    2015-01-01

    Experiments to measure the permeability properties of individually perfused microvessels provide a bridge between investigation of molecular and cellular mechanisms regulating vascular permeability in cultured endothelial cell monolayers and the functional exchange properties of whole microvascular beds. A method to cannulate and perfuse venular microvessels of rat mesentery and measure the hydraulic conductivity of the microvessel wall is described. The main equipment needed includes an intravital microscope with a large modified stage that supports micromanipulators to position three different microtools: (1) a beveled glass micropipette to cannulate and perfuse the microvessel; (2) a glass micro-occluder to transiently block perfusion and enable measurement of transvascular water flow movement at a measured hydrostatic pressure, and (3) a blunt glass rod to stabilize the mesenteric tissue at the site of cannulation. The modified Landis micro-occlusion technique uses red cells suspended in the artificial perfusate as markers of transvascular fluid movement, and also enables repeated measurements of these flows as experimental conditions are changed and hydrostatic and colloid osmotic pressure difference across the microvessels are carefully controlled. Measurements of hydraulic conductivity first using a control perfusate, then after re-cannulation of the same microvessel with the test perfusates enable paired comparisons of the microvessel response under these well-controlled conditions. Attempts to extend the method to microvessels in the mesentery of mice with genetic modifications expected to modify vascular permeability were severely limited because of the absence of long straight and unbranched microvessels in the mouse mesentery, but the recent availability of the rats with similar genetic modifications using the CRISPR/Cas9 technology is expected to open new areas of investigation where the methods described herein can be applied. PMID:26436435

  14. Beetle and plant density as cues initiating dispersal in two species of adult predaceous diving beetles.

    PubMed

    Yee, Donald A; Taylor, Stacy; Vamosi, Steven M

    2009-05-01

    Dispersal can influence population dynamics, species distributions, and community assembly, but few studies have attempted to determine the factors that affect dispersal of insects in natural populations. Consequently, little is known about how proximate factors affect the dispersal behavior of individuals or populations, or how an organism's behavior may change in light of such factors. Adult predaceous diving beetles are active dispersers and are important predators in isolated aquatic habitats. We conducted interrelated studies to determine how several factors affected dispersal in two common pond-inhabiting species in southern Alberta, Canada: Graphoderus occidentalis and Rhantus sericans. Specifically, we (1) experimentally tested the effect of plant and beetle densities on dispersal probabilities in ponds; (2) surveyed ponds and determined the relationships among beetle densities and plant densities and water depth; and (3) conducted laboratory trials to determine how beetle behavior changed in response to variation in plant densities, conspecific densities, food, and water depth. Our field experiment determined that both species exhibited density dependence, with higher beetle densities leading to higher dispersal probabilities. Low plant density also appeared to increase beetle dispersal. Consistent with our experimental results, densities of R. sericans in ponds were significantly related to plant density and varied also with water depth; G. occidentalis densities did not vary with either factor. In the laboratory, behavior varied with plant density only for R. sericans, which swam at low density but were sedentary at high density. Both species responded to depth, with high beetle densities eliciting beetles to spend more time in deeper water. The presence of food caused opposite responses for G. occidentalis between experiments. Behavioral changes in response to patch-level heterogeneity likely influence dispersal in natural populations and are expected

  15. Bone Mineral Density Changes Among Women Initiating Blood Pressure Lowering Drugs: A SWAN Cohort Study

    PubMed Central

    Solomon, Daniel H.; Ruppert, Kristine; Zhao, Zhenping; Lian, YinJuan; Kuo, I-Hsin; Greendale, Gail A.; Finkelstein, Joel S.

    2016-01-01

    Purpose Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women’s Health Across the Nation. Methods We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14-years of observation were compared with non-users. Results Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of non-users. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (−0.28% vs −0.88%; p = 0.008) and the spine (−0.74% vs −1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in non-users. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (−0.35% vs −0.60%; p = 0.08) and a similar trend at the FN (−0.39% vs −0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (−0.48% vs −0.82%; p = 0.02), but not at the spine (−0.40% vs −0.56%; p = 0.23). Conclusions Neither ACEi nor BB were associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with non-users, as well as compared with ACEi and BB. PMID:26449354

  16. The dynamics of superclusters - Initial determination of the mass density of the universe at large scales

    NASA Technical Reports Server (NTRS)

    Ford, H. C.; Ciardullo, R.; Harms, R. J.; Bartko, F.

    1981-01-01

    The radial velocities of cluster members of two rich, large superclusters have been measured in order to probe the supercluster mass densities, and simple evolutionary models have been computed to place limits upon the mass density within each supercluster. These superclusters represent true physical associations of size of about 100 Mpc seen presently at an early stage of evolution. One supercluster is weakly bound, the other probably barely bound, but possibly marginally unbound. Gravity has noticeably slowed the Hubble expansion of both superclusters. Galaxy surface-density counts and the density enhancement of Abell clusters within each supercluster were used to derive the ratio of mass densities of the superclusters to the mean field mass density. The results strongly exclude a closed universe.

  17. Spectral imaging reveals microvessel physiology and function from anastomoses to thromboses

    NASA Astrophysics Data System (ADS)

    Wankhede, Mamta; Agarwal, Nikita; Fraga-Silva, Rodrigo A.; Dedeugd, Casey; Raizada, Mohan K.; Oh, S. Paul; Sorg, Brian S.

    2010-01-01

    Abnormal microvascular physiology and function is common in many diseases. Numerous pathologies include hypervascularity, aberrant angiogenesis, or abnormal vascular remodeling among the characteristic features of the disease, and quantitative imaging and measurement of microvessel function can be important to increase understanding of these diseases. Several optical techniques are useful for direct imaging of microvascular function. Spectral imaging is one such technique that can be used to assess microvascular oxygen transport function with high spatial and temporal resolution in microvessel networks through measurements of hemoglobin saturation. We highlight novel observation made with our intravital microscopy spectral imaging system employed with mouse dorsal skin-fold window chambers for imaging hemoglobin saturation in microvessel networks. Specifically, we image acute oxygenation fluctuations in a tumor microvessel network, the development of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia, and the formation of spontaneous and induced microvascular thromboses and occlusions.

  18. Flow of Red Blood Cells in Stenosed Microvessels.

    PubMed

    Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

    2016-01-01

    A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis. PMID:27319318

  19. Flow of Red Blood Cells in Stenosed Microvessels

    NASA Astrophysics Data System (ADS)

    Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

    2016-06-01

    A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis.

  20. Flow of Red Blood Cells in Stenosed Microvessels

    PubMed Central

    Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

    2016-01-01

    A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis. PMID:27319318

  1. Initial energy density and gluon distribution from the glasma in heavy-ion collisions

    NASA Astrophysics Data System (ADS)

    Fujii, Hirotsugu; Fukushima, Kenji; Hidaka, Yoshimasa

    2009-02-01

    We estimate the energy density and the gluon distribution associated with the classical fields describing the early-time dynamics of heavy-ion collisions. In the McLerran-Venugopalan model, we first decompose the energy density into the momentum components exactly, with the use of the Wilson line correlators. Then we evolve the energy density with the free-field equation, which is justified by the dominance of the ultraviolet modes near the collision point. We also discuss the improvement that occurs with the inclusion of nonlinear terms into the time evolution. Our numerical results at RHIC energy are fairly consistent with the empirical values.

  2. Initial energy density and gluon distribution from the glasma in heavy-ion collisions

    SciTech Connect

    Fujii, Hirotsugu; Fukushima, Kenji; Hidaka, Yoshimasa

    2009-02-15

    We estimate the energy density and the gluon distribution associated with the classical fields describing the early-time dynamics of heavy-ion collisions. In the McLerran-Venugopalan model, we first decompose the energy density into the momentum components exactly, with the use of the Wilson line correlators. Then we evolve the energy density with the free-field equation, which is justified by the dominance of the ultraviolet modes near the collision point. We also discuss the improvement that occurs with the inclusion of nonlinear terms into the time evolution. Our numerical results at RHIC energy are fairly consistent with the empirical values.

  3. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  4. Relation of initial spacing and relative stand density indices to stand characteristics in a Douglas-fir plantation spacing trial

    USGS Publications Warehouse

    Curtis, Robert O.; Bansal, Sheel; Harrington, Constance A.

    2016-01-01

    This report presents updated information on a 1981 Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii) plantation spacing trial at 33 years from planting. Stand statistics at the most recent measurement were compared for initial spacing of 1 through 6 meters and associated relative densities. There was no clear relationship of spacing to top height. Diameter, live crown ratio, and percent survival increased with spacing; basal area and relative density decreased with increase in spacing. Volume in trees ≥ 4 cm diameter was greatest at 2 m spacing, while utilizable volume (trees ≥20 cm dbh) was greatest at 4 m spacing. Live crown ratio decreased and total crown projectional area increased with increasing relative density indices. Total crown projectional area was more closely related to relative density than to basal area.

  5. Targeted disruption of deep-lying neocortical microvessels in rat using ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Nishimura, Nozomi; Schaffer, Christopher B.; Friedman, Beth; Tsai, Philbert S.; Lyden, Patrick D.; Kleinfeld, David

    2004-06-01

    The study of neurovascular diseases such as vascular dementia and stroke require novel models of targeted vascular disruption in the brain. We describe a model of microvascular disruption in rat neocortex that uses ultrashort laser pulses to induce localized injury to specific targeted microvessels and uses two-photon microscopy to monitor and guide the photodisruption process. In our method, a train of high-intensity, 100-fs laser pulses is tightly focused into the lumen of a blood vessel within the upper 500 μm of cortex. Photodisruption induced by these laser pulses creates injury to a single vessel located at the focus of the laser, leaving the surrounding tissue intact. This photodisruption results in three modalities of localized vascular injury. At low power, blood plasma extravasation can be induced. The vessel itself remains intact, while serum is extravasated into the intercellular space. Localized ischemia caused by an intravascular clot results when the photodisruption leads to a brief disturbance of the vascular walls that initiates an endogenous clotting cascade. The formation of a localized thrombus stops the blood flow at the location of the photodisruption. A hemorrhage, defined as a large extravasation of blood including plasma and red blood cells, results when higher laser power is used. The targeted vessel does not remain intact.

  6. Effect of Initial Nematode Population Density on the Interaction of Pratylenchus penetrans and Verticillium dahliae on 'Russet Burbank' Potato.

    PubMed

    Saeed, I A; Macguidwin, A E; Rouse, D I

    1998-03-01

    Four similar growth chamber experiments were conducted to test the hypothesis that the initial population density (Pi) of Pratylenchus penetrans influences the severity of interactive effects of P. penetrans and Verticillium dahliae on shoot growth, photosynthesis, and tuber yield of Russet Burbank potato. In each experiment, three population densities of P. penetrans with and without concomitant inoculation with V. dahliae were compared with nematode-free controls. The three specific Pi of JR penetrans tested varied from experiment to experiment but fell in the ranges 0.8-2.5, 1.8-3.9, 2.1-8.8, and 7.5-32.4 nematodes/cm(3) soil. Inoculum of V. dahliaewas mixed into soil, and the assayed density was 5.4 propagules/gram dry soil. Plants were grown 60 to 80 days in a controlled environment. Plant growth parameters in two experiments indicated significant interactions between P. penetrans and V. dahliae. In the absence of V. dahliae, P. penetrans did not reduce plant growth and tuber yield below that of the nematode-free control or did so only at the highest one or two population densities tested. In the presence of K dahliae, the lowest population density significantly reduced shoot weight and photosynthesis in three and four experiments, respectively. Higher densities had no additional effect on shoot weight and caused additional reductions in photosynthesis in only one experiment. Population densities of 0.8 and 7.5 nematodes/cm(3) soil reduced tuber yield by 51% and 45%, whereas higher densities had no effect or a 15% additional effect, respectively. These data indicate that interactive effects between P. penetrans and V. dahliae on Russet Burbank potato are manifested at P. penetrans population densities less than 1 nematode/cm(3) soil and that the nematode population density must be substantially higher before additional effects are apparent. PMID:19274204

  7. The Effect of Air Density on Atmospheric Electric Fields Required for Lightning Initiation from a Long Airborne Object

    NASA Technical Reports Server (NTRS)

    Bazelyan, E. M.; Aleksandrov, N. L.; Raizer, Yu. Pl.; Konchankov, A. M.

    2006-01-01

    The purpose of the work was to determine minimum atmospheric electric fields required for lightning initiation from an airborne vehicle at various altitudes up to 10 km. The problem was reduced to the determination of a condition for initiation of a viable positive leader from a conductive object in an ambient electric field. It was shown that, depending on air density and shape and dimensions of the object, critical atmospheric fields are governed by the condition for leader viability or that for corona onset. To establish quantitative criteria for reduced air densities, available observations of spark discharges in long laboratory gaps were analyzed, the effect of air density on leader velocity was discussed and evolution in time of the properties of plasma in the leader channel was numerically simulated. The results obtained were used to evaluate the effect of pressure on the quantitative relationships between the potential difference near the leader tip, leader current and its velocity; based on these relationships, criteria for steady development of a leader were determined for various air pressures. Atmospheric electric fields required for lightning initiation from rods and ellipsoidal objects of various dimensions were calculated at different air densities. It was shown that there is no simple way to extend critical ambient fields obtained for some given objects and pressures to other objects and pressures.

  8. Effects of equation of state on nuclear suppression and the initial entropy density of quark gluon plasma

    NASA Astrophysics Data System (ADS)

    Mazumder, Surasree; Alam, Jan-e.

    2012-04-01

    We study the effects of the equation of state on the nuclear suppression of heavy flavors in quark gluon plasma and estimate the initial entropy density of the system produced in Au + Au collision at the highest Relativistic Heavy Ion Collider (RHIC) energy. For this purpose the experimental data on the charged-particle multiplicity and the nuclear suppression of single-electron spectra originating from the semileptonic decays of open charm and beauty mesons have been employed. We have used inputs from lattice QCD to minimize the model dependence of the results. We obtain the value of the initial entropy density, which varies from 20 to 59/fm3 depending on the value of the velocity of sound that one uses for the analysis. Our investigation leads to a conservative value of the initial entropy density of ˜20/fm3 with a corresponding initial temperature of ˜210 MeV, which is well above the value of the transition temperature predicted by lattice QCD.

  9. Colonisation of the Non-Indigenous Pacific Oyster Crassostrea gigas Determined by Predation, Size and Initial Settlement Densities

    PubMed Central

    Hedge, Luke H.; Johnston, Emma L.

    2014-01-01

    Survival of incipient non-indigenous populations is dramatically altered by early predation on new colonisers. These effects can be influenced by morphological traits, such as coloniser size and density. The Australian non-native Pacific Oyster Crassostrea gigas is generally more fecund and faster growing compared to the native Saccostrea glomerata found in the same habitat. It is therefore important to quantify how the two species differ in survival across coloniser density and predation gradients. This information could become pertinent to the management of wild and aquaculture populations of the non-native C. gigas. Using a field-based factorial experiment we model the survival of incipient populations of both the native S. glomerata and the non-indigenous C. gigas as a function of coloniser density, predator reduction and individual size. Unexpectedly, survival of the non-indigenous C. gigas increased compared to S. glomerata when individuals were larger. The proportional survival of newly colonised oyster populations also increased with larger initial populations, regardless of species identity. Further, predator reduction resulted in increased survival of both oyster species, irrespective of coloniser size or initial density. Here we quantitatively demonstrate the effects of recruit density and size on enhancing the survivability of incipient oyster populations. PMID:24663029

  10. Reactive flow modeling of initial density effect on divergence JB-9014 detonation driving

    NASA Astrophysics Data System (ADS)

    Yu, Xin; Huang, Kuibang; Zheng, Miao

    2016-06-01

    A serious of experiments were designed and the results were represented in this paper, in which 2mm thickness cooper shells were impacted by explosives named JB-9014 with different densities, and the surface velocities of the OFHC shells were measured. The comparison of experimental data shows the free surface velocity of the OFHC shell increase with the IHE density. Numerical modeling, which occupied phenomenological reactive flow rate model using the two-dimensional Lagrange hydrodynamic code, were carried out to simulate the above experiments, and empirical adjustments on detonation velocity and pressure and Pier Tang's adjustments on EOS of detonation products were both introduced in our numerical simulation work. The computational results agree well with that of experiments, and the numerical results with original parameters of products and the adjusted ones of JB-9014 could describe the density effect distinctly.

  11. Analysis of correlation between initial alveolar bone density and apical root resorption after 12 months of orthodontic treatment without extraction

    PubMed Central

    Scheibel, Paula Cabrini; Ramos, Adilson Luiz; Iwaki, Lilian Cristina Vessoni; Micheletti, Kelly Regina

    2014-01-01

    OBJECTIVE: The aim of the present study was to investigate the correlation between initial alveolar bone density of upper central incisors (ABD-UI) and external apical root resorption (EARR) after 12 months of orthodontic movement in cases without extraction. METHODS: A total of 47 orthodontic patients 11 years old or older were submitted to periapical radiography of upper incisors prior to treatment (T1) and after 12 months of treatment (T2). ABD-UI and EARR were measured by means of densitometry. RESULTS: No statistically significant correlation was found between initial ABD-UI and EARR at T2 (r = 0.149; p = 0.157). CONCLUSION: Based on the present findings, alveolar density assessed through periapical radiography is not predictive of root resorption after 12 months of orthodontic treatment in cases without extraction. PMID:25715722

  12. Initiation of conidiation in Erysiphe necator is regulated by prior vegetative growth, inoculum density and light

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Initiation of asexual sporulation in powdery mildews is preceded by a period of superficial vegetative growth of mildew colonies. We found evidence of signaling in Erysiphe necator that was promulgated at the colony center as early as five days after inoculation and stimulated sporulation throughout...

  13. Influence of initial pesticide concentrations and plant population density on dimethomorph toxicity and removal by two duckweed species.

    PubMed

    Dosnon-Olette, Rachel; Couderchet, Michel; El Arfaoui, Achouak; Sayen, Stéphanie; Eullaffroy, Philippe

    2010-04-15

    Aquatic plants take up, transform and sequester organic contaminants and may therefore be used in phytoremediation for the removal of pollutants from wastewaters. A better understanding of factors affecting the rate of contaminant uptake by aquatic plants is needed to improve engineered systems for removal of pollutants from wastewaters. This work focused on the influence of initial concentrations of pesticide and population density of plants on toxicity and uptake of the fungicide dimethomorph by two duckweed species. An increased sensitivity to dimethomorph was observed with increasing duckweed population density. Less light, due to crowding, may explain this higher sensitivity and reduced removal rate. A positive relationship was also found between toxicity or contaminant uptake and initial pesticide concentration with a maximal removal of 41 and 26 microg g(-1) fresh weight of dimethomorph (at 600 microg L(-1) of dimethomorph and an initial density of 0.10g E-flask(-1)) by Lemna minor and Spirodela polyrhiza, respectively. This research also indicated that these aquatic plants can efficiently eliminate organic contaminants and may ultimately serve as phytoremediation agents in the natural environment. PMID:20156640

  14. Visualization of Microvessels in Skin by Three-Dimensional Ultrasound Microscope

    NASA Astrophysics Data System (ADS)

    Saijo, Y.; Kobayashi, K.; Hozumi, N.; Tanaka, A.; Sakai, S.

    A non-invasive imaging technique capable of visualizing microvessels through epidermis to subdermis has been strongly desired. A PVDF ultrasonic transducer with the central frequency of 100 MHz and the focal length of 3.2 mm was mechanically scanned over the objects by two linear servo motors controlled by a personal computer. A microvessel model was made of a tungsten wire with a diameter of 100-microns and placed in the water tank. The microvessel model was clearly visualized by 3D ultrasound microscope. In cases of skin imaging, conventional echo gel was used as the coupling medium between transducer and skin surface. In vivo 3D skin morphology was also clearly visualized. In dermis, a microvessel may be shown as small, round, lucent echo areas continuously observed in the serial sections. 3D structure of hair-follicle was also visualized from the skin surface to the bud of hair-follicle in dermis. The 3D ultrasound microscope noninvasively provides important information on the distribution of microvessels in skin.

  15. Flow of a circulating tumor cell and red blood cells in microvessels

    NASA Astrophysics Data System (ADS)

    Takeishi, Naoki; Imai, Yohsuke; Yamaguchi, Takami; Ishikawa, Takuji

    2015-12-01

    Quantifying the behavior of circulating tumor cells (CTCs) in the blood stream is of fundamental importance for understanding metastasis. Here, we investigate the flow mode and velocity of CTCs interacting with red blood cells (RBCs) in various sized microvessels. The flow of leukocytes in microvessels has been described previously; a leukocyte forms a train with RBCs in small microvessels and exhibits margination in large microvessels. Important differences in the physical properties of leukocytes and CTCs result from size. The dimensions of leukocytes are similar to those of RBCs, but CTCs are significantly larger. We investigate numerically the size effects on the flow mode and the cell velocity, and we identify similarities and differences between leukocytes and CTCs. We find that a transition from train formation to margination occurs when (R -a ) /tR≈1 , where R is the vessel radius, a is the cell radius, and tR is the thickness of RBCs, but that the motion of RBCs differs from the case of leukocytes. Our results also show that the velocities of CTCs and leukocytes are larger than the average blood velocity, but only CTCs move faster than RBCs for microvessels of R /a ≈1.5 -2.0 . These findings are expected to be useful not only for understanding metastasis, but also for developing microfluidic devices.

  16. Strain energy density-distance criterion for the initiation of stress corrosion cracking of alloy X-750

    SciTech Connect

    Hall, M.M. Jr.; Symons, D.M.

    1996-05-01

    A strain energy density-distance criterion was previously developed and used to correlate rising-load K{sub c} initiation data for notched and fatigue precracked specimens of hydrogen precharged Alloy X-750. This criterion, which was developed for hydrogen embrittlement (HE) cracking, is used here to correlate static-load stress corrosion cracking (SCC) initiation times obtained for smooth geometry, notched and fatigue precracked specimens. The onset of SCC crack growth is hypothesized to occur when a critical strain, which is due to environment-enhanced creep, is attained within the specimen interior. For notched and precracked specimens, initiation is shown by analysis to occur at a variable distance from notch and crack tips. The initiation site varies from very near the crack tip, for highly loaded sharp cracks, to a site that is one grain diameter from the notch, for lower loaded, blunt notches. The existence of hydrogen gradients, which are due to strain-induced hydrogen trapping in the strain fields of notch and crack tips, is argued to be controlling the site for initiation of cracking. By considering the sources of the hydrogen, these observations are shown to be consistent with those from the previous HE study, in which the characteristic distance for crack initiation was found to be one grain diameter from the notch tip, independent of notch radius, applied stress intensity factor and hydrogen level.

  17. An experimental investigation of the dynamics of submarine leveed channel initiation as sediment-laden density currents experience sudden unconfinement

    SciTech Connect

    Rowland, Joel C; Hilley, George E; Fildani, Andrea

    2009-01-01

    Leveed submarine channels play a critical role in the transfer of sediment from the upper continental slopes to interslope basins and ultimately deepwater settings. Despite a reasonable understanding of how these channels grow once established, how such channels initiate on previously unchannelized portions of the seafloor remains poorly understood. We conducted a series of experiments that elucidate the influence of excess density relative to flow velocity on the dynamics of, and depositional morphologies arising from, density currents undergoing sudden unconfinement across a sloped bed. Experimental currents transported only suspended sediment across a non-erodible substrate. Under flow conditions ranging from supercritical to subcritical (bulk Richardson numbers of 0.02 to 1.2) our experiments failed to produce deposits resembling or exhibiting the potential to evolve into self-formed leveed channels. In the absence of excess density, a submerged sediment-laden flow produced sharp crested lateral deposits bounding the margins of the flow for approximately a distance of two outlet widths down basin. These lateral deposits terminated in a centerline deposit that greatly exceeded marginal deposits in thickness. As excess density increased relative to the outlet velocity, the rate of lateral spreading of the flow increased relative to the downstream propagation of the density current, transitioning from a narrow flow aligned with the channel outlet to a broad radially expanding flow. Coincident with these changes in flow dynamics, the bounding lateral deposits extended for shorter distances, had lower, more poorly defined crests that were increasingly wider in separation than the initial outlet, and progressively became more oblong rather than linear. Based on our results, we conclude that leveed channels cannot initiate from sediment-laden density currents under strictly depositional conditions. Partial confinement of these currents appears to be necessary to

  18. LIPUS promotes spinal fusion coupling proliferation of type H microvessels in bone

    PubMed Central

    Xu, Ximing; Wang, Fei; Yang, Yahong; Zhou, Xiaoyi; Cheng, Yajun; Wei, Xianzhao; Li, Ming

    2016-01-01

    Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate spinal fusion. Type H microvessels are found in close relation with bone development. We analyzed the role of type H vessels in rat spinal fusion model intervened by LIPUS. It was found LIPUS could significantly accelerate bone fusion rate and enlarge bone callus. Osteoblasts were specifically located on the bone meshwork of the allograft, and were surrounded by type H microvessels. LIPUS could significantly increase the quantity of osteoblasts during spine fusion, which process was coupled with elevated angiogenesis of type H microvessels. Our results suggest that LIPUS may be a noninvasive adjuvant treatment modality in spinal fusion for clinical use. The treatment is recommended for usage for at least one month. PMID:26830666

  19. Correlates of Initiation of Antifracture Therapy in Older Women with Low Bone Mineral Density

    PubMed Central

    2006-01-01

    The National Osteoporosis Foundation recommends treating certain postmenopausal women with low bone density (BMD). Do physicians and patients adopt these recommendations? We used the Health, Aging, and Body Composition Study, in which older women, and their doctors, received a copy of their dual x-ray absorptiometry scan. After 2 years, only 30% of those at risk started antifracture therapy; use was far less in black women, even after adjustment for BMD. This may reflect physicians' or patients' uncertainties about the value of treating low BMD, and the lack of data supporting antifracture medicine use in nonwhites. Improving osteoporosis treatment may require patient-specific and provider-targeted interventions in the clinic setting.

  20. Initial assessment of radiation behavior of very-high-density low-enriched-uranium fuels.

    SciTech Connect

    Hofman, G. L.; Meyer, M. L.; Snelgrove, J. L.; Dietz, M. L.; Strain, R. V.; Kim, K. H.

    1999-10-01

    Results from the postirradiation examinations of microplates irradiated in the RERTR-1 and -2 experiments in the ATR have shown several binary and ternary U-Mo alloys to be promising candidates for use in aluminum-based dispersion fuels with uranium densities up to 8 to 9 g/cm{sup 3}. Ternary alloys of uranium, niobium, and zirconium performed poorly, however, both in terms of fuel/matrix reaction and fission-gas-bubble behavior, and have been dropped from further study. Since irradiation temperatures achieved in the present experiments (approximately 70 C)are considerably lower than might be experienced in a high-performance reactor, a new experiment is being planned with beginning-of-cycle temperatures greater than 200 C in 8-g U/cm{sup 3} fuel.

  1. Temperature and initial curvature effects in low-density panel flutter

    NASA Technical Reports Server (NTRS)

    Resende, Hugo B.

    1992-01-01

    The panel flutter phenomenon is studied assuming free-molecule flow. This kind of analysis is relevant in the case of hypersonic flight vehicles traveling at high altitudes, especially in the leeward portion of the vehicle. In these conditions the aerodynamic shear can be expected to be considerably larger than the pressure at a given point, so that the effects of such a loading are incorporated into the structural model. Both the pressure and shear loadings are functions of the panel temperature, which can lead to great variations on the location of the stability boundaries for parametric studies. Different locations can, however, be 'collapsed' onto one another by using as ordinate an appropriately normalized dynamic pressure parameter. This procedure works better for higher values of the panel temperature for a fixed undisturbed flow temperature. Finally, the behavior of the system is studied when the panel has some initial curvature. This leads to the conclusion that it may be unrealistic to try to distinguish between a parabolic or sinusoidal initial shape.

  2. Accurate measurement of reduced glutathione in gamma-glutamyltransferase-rich brain microvessel fractions.

    PubMed

    Maguin Gaté, Katy; Lartaud, Isabelle; Giummelly, Philippe; Legrand, Romain; Pompella, Alfonso; Leroy, Pierre

    2011-01-19

    Investigation of the redox status in the cerebral circulation is of great importance in order to evaluate intensity of oxidative stress-related diseases and the corresponding therapeutic effects. Changes in levels of reduced glutathione (GSH) are a major indicator of oxidative stress conditions. However, an important limitation for measurement of GSH as a biomarker is the possible presence in samples of gamma-glutamyltransferase (GGT) activity, i.e., the enzyme catalysing GSH breakdown. An accurate assay for the measurement of GSH in rat brain microvessels was developed, taking into account the high GGT activity expressed in this tissue compartment. Based on a sensitive fluorescence-based microtiter plate method using 2,3-naphthalenedicarboxyaldehyde as GSH-selective fluorogenic probe, the assay was applied to brain microvessels isolated from individual male Wistar rats. Pooling of microvessel fractions from several animals, as required by other procedures, could thus be avoided. In order to prevent GSH consumption via GGT activity, serine-boric acid complex (SBC) was added as inhibitor all along the microvessels isolation process. In the absence of GGT inhibition GSH in isolated brain microvessels was below the limit of quantification. Addition of SBC almost completely suppressed GGT activity, thus allowing GSH quantification (4.4±1.6 nmol.mg(-1) protein, n=3). Following the administration of a GSH depletor (diethyl maleate, 1g.kg(-1), i.p.), decreased GSH levels were measured in liver, brain tissue and brain microvessels as well, thus confirming the reliability of the method for safe GSH measurements in small-sized, individual samples presenting high GGT activity. PMID:21047497

  3. Clostridium perfringens epsilon-toxin increases permeability of single perfused microvessels of rat mesentery.

    PubMed

    Adamson, R H; Ly, J C; Fernandez-Miyakawa, M; Ochi, S; Sakurai, J; Uzal, F; Curry, F E

    2005-08-01

    Epsilon-toxin, the primary virulence factor of Clostridium perfringens type D, causes mortality in livestock, particularly sheep and goats, in which it induces an often-fatal enterotoxemia. It is believed to compromise the intestinal barrier and then enter the gut vasculature, from which it is carried systemically, causing widespread vascular endothelial damage and edema. Here we used single perfused venular microvessels in rat mesentery, which enabled direct observation of permeability properties of the in situ vascular wall during exposure to toxin. We determined the hydraulic conductivity (L(p)) of microvessels as a measure of the response to epsilon-toxin. We found that microvessels were highly sensitive to toxin. At 10 microg ml(-1) the L(p) increased irreversibly to more than 15 times the control value by 10 min. At 0.3 microg ml(-1) no increase in L(p) was observed for up to 90 min. The toxin-induced increase in L(p) was consistent with changes in ultrastructure of microvessels exposed to the toxin. Those microvessels exhibited gaps either between or through endothelial cells where perfusate had direct access to the basement membrane. Many endothelial cells appeared necrotic, highly attenuated, and with dense cytoplasm. We showed that epsilon-toxin, in a time- and dose-dependent manner, rapidly and irreversibly compromised the barrier function of venular microvessel endothelium. The results conformed to the hypothesis that epsilon-toxin interacts with vascular endothelial cells and increases the vessel wall permeability by direct damage of the endothelium. PMID:16041001

  4. Determination of size distribution of elliptical microvessels from size distribution measurement of their section profiles.

    PubMed

    Krasnoperov, R A; Gerasimov, A N

    2003-01-01

    In transmission electron microscopy, microvessels (MVs) are studied as profiles on ultrathin sections. To determine MV sizes from measurements made on MV profiles, an assumption must be made about MV shape, a circular cylinder being used to approximate the latter on limited lengths. However, this model is irrelevant in case MVs have some flatness. The elliptical cylinder model is preferable, although relationships between the cylinder profile (two-dimensional; 2D) and its true (three-dimensional; 3D) sizes are not yet known. We have obtained the 2D/3D functions that express the relationships between such profile sizes as the minor radius (Y), major radius (X), axial ratio (X/Y), area (S), and perimeter (P) on the one hand, and the corresponding MV sizes (Y(0), X(0), X(0)/Y(0), S(0), and P(0)) on the other. The 2D/3D functions make it possible to derive elliptical MV sizes from section profile size distributions, probability density functions (PDFs) for the latter being determined. We have applied the 2D/3D functions in studying axial ratios of thyroid hemocapillaries. A factual X/Y frequency histogram has been constructed and fitted by theoretical X/Y PDFs plotted for different sets of capillary sizes. The thyroid capillaries have been revealed to be clustered, 72.7% of them having X(0)/Y(0) approximately 1.6, 17.6%, X(0)/Y(0) approximately 1.0, and 9.7%, X(0)/Y(0) approximately 3.2. The proposed technique is instrumental in precise modeling of microcirculatory network geometry. PMID:12524478

  5. Planar Laser Induced Fluorescence of Shock Initiated Combustion of a Spherical Density Inhomogeneity

    NASA Astrophysics Data System (ADS)

    Haehn, Nicholas; Weber, Chris; Oakley, Jason; Anderson, Mark; Rothamer, Dave; Bonazza, Riccardo

    2009-11-01

    A spherical density inhomogeneity with a stoichiometric mixture of H2, O2, and a diluent such as Xe is ignited with a planar shock wave. When a heavy bubble, such as Xe, is shock accelerated in a lighter ambient gas, such as Ar, the shock wave at the exterior periphery of the bubble travels faster than the interior transmitted wave, resulting in shock-focusing at the downstream pole of the bubble. The shock wave convergence results in a temperature much higher than the one behind the transmitted shock and auto ignition may occur at this location. For non-point source ignition experiments, the temperature is raised by a second shock acceleration from the planar shock that reflects from the shock tube's end-wall. These experiments shed light on the combustion characteristics under both turbulent and non-turbulent conditions. In addition, results are used for validating hydrodynamic codes with chemical reactions. The experiments are performed at the Wisconsin Shock Tube Laboratory in a 6 m vertical shock tube with a 25.4x25.4 cm^2 square cross-section. Diagnostics are performed using planar laser induced fluorescence of the OH^- molecule present during the combustion process. A Nd:Yag pumped dye laser at a wavelength of 283 nm excites the (1,0) band of the OH^- molecule.

  6. High-Density Transcriptional Initiation Signals Underline Genomic Islands in Bacteria

    PubMed Central

    Huang, Qianli; Cheng, Xuanjin; Cheung, Man Kit; Kiselev, Sergey S.; Ozoline, Olga N.; Kwan, Hoi Shan

    2012-01-01

    Genomic islands (GIs), frequently associated with the pathogenicity of bacteria and having a substantial influence on bacterial evolution, are groups of “alien” elements which probably undergo special temporal–spatial regulation in the host genome. Are there particular hallmark transcriptional signals for these “exotic” regions? We here explore the potential transcriptional signals that underline the GIs beyond the conventional views on basic sequence composition, such as codon usage and GC property bias. It showed that there is a significant enrichment of the transcription start positions (TSPs) in the GI regions compared to the whole genome of Salmonella enterica and Escherichia coli. There was up to a four-fold increase for the 70% GIs, implying high-density TSPs profile can potentially differentiate the GI regions. Based on this feature, we developed a new sliding window method GIST, Genomic-island Identification by Signals of Transcription, to identify these regions. Subsequently, we compared the known GI-associated features of the GIs detected by GIST and by the existing method Islandviewer to those of the whole genome. Our method demonstrates high sensitivity in detecting GIs harboring genes with biased GI-like function, preferred subcellular localization, skewed GC property, shorter gene length and biased “non-optimal” codon usage. The special transcriptional signals discovered here may contribute to the coordinate expression regulation of foreign genes. Finally, by using GIST, we detected many interesting GIs in the 2011 German E. coli O104:H4 outbreak strain TY-2482, including the microcin H47 system and gene cluster ycgXEFZ-ymgABC that activates the production of biofilm matrix. The aforesaid findings highlight the power of GIST to predict GIs with distinct intrinsic features to the genome. The heterogeneity of cumulative TSPs profiles may not only be a better identity for “alien” regions, but also provide hints to the special

  7. Miscible gravitational instability of initially stable horizontal interface in a porous medium: Non-monotonic density profiles

    NASA Astrophysics Data System (ADS)

    Kim, Min Chan

    2014-11-01

    To simulate a CO2 sequestration process, some researchers employed a water/propylene glycol (PPG) system which shows a non-monotonic density profile. Motivated by this fact, the stability of the diffusion layer of two miscible fluids saturated in a porous medium is analyzed. For a non-monotonic density profile system, linear stability equations are derived in a global domain, and then transformed into a system of ordinary differential equations in an infinite domain. Initial growth rate analysis is conducted without the quasi-steady state approximation (QSSA) and shows that initially the system is unconditionally stable for the least stable disturbance. For the time evolving case, the ordinary differential equations are solved applying the eigen-analysis and numerical shooting scheme with and without the QSSA. To support these theoretical results, direct numerical simulations are conducted using the Fourier spectral method. The results of theoretical linear stability analyses and numerical simulations validate one another. The present linear and nonlinear analyses show that the water/PPG system is more unstable than the CO2/brine one, and the flow characteristics of these two systems are quite different from each other.

  8. Gaussian beam in two-photon fluorescence imaging of rat brain microvessel

    PubMed Central

    Shi, Lingyan; Rodríguez-Contreras, Adrián; Alfano, Robert R.

    2014-01-01

    Abstract. The critical optical properties of a Gaussian laser beam in two-photon or multiphoton fluorescence imaging, including the beam spot size, depth of focus, and intensity profile, are investigated for spatially locating nanoscale solutes in and surrounding the microvessels of rat brain. PMID:25490048

  9. OBSERVATIONS OF TRANSLATION AND JETTING OF ULTRASOUND-ACTIVATED MICROBUBBLES IN MESENTERIC MICROVESSELS

    PubMed Central

    Chen, Hong; Brayman, Andrew A.; Kreider, Wayne; Bailey, Michael R.; Matula, Thomas J.

    2011-01-01

    High-speed photomicrography was used to study the translational dynamics of single microbubbles in microvessels of ex vivo rat mesenteries. The microbubbles were insonated by a single 2 μs ultrasound pulse with a center frequency of 1 MHz and peak negative pressures spanning the range of 0.8–4 MPa. The microvessel diameters ranged from 10 – 80 μm. The high-speed image sequences show evidence of ultrasound-activated microbubble translation away from the nearest vessel wall; no microbubble showed a net translation toward the nearest vessel wall. Microbubble maximum translational displacements exceeded 20 μm. Microjets with the direction of the jets identifiable were also observed; all microjets appear to have been directed away from the nearest vessel wall. These observations appear to be characteristic of a strong coupling between ultrasound-driven microbubbles and compliant microvessels. Although limited to mesenteric tissues, these observations provide an important step in understanding the physical interactions between microbubbles and microvessels. PMID:22036639

  10. Quantifying Single Microvessel Permeability in Isolated Blood-perfused Rat Lung Preparation

    PubMed Central

    Kandasamy, Kathirvel; Parthasarathi, Kaushik

    2014-01-01

    The isolated blood-perfused lung preparation is widely used to visualize and define signaling in single microvessels. By coupling this preparation with real time imaging, it becomes feasible to determine permeability changes in individual pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse them with autologous blood. Then, we outline steps to infuse fluorophores or agents via a microcatheter into a small lung region. Using these procedures described, we determined permeability increases in rat lung microvessels in response to infusions of bacterial lipopolysaccharide. The data revealed that lipopolysaccharide increased fluid leak across both venular and capillary microvessel segments. Thus, this method makes it possible to compare permeability responses among vascular segments and thus, define any heterogeneity in the response. While commonly used methods to define lung permeability require postprocessing of lung tissue samples, the use of real time imaging obviates this requirement as evident from the present method. Thus, the isolated lung preparation combined with real time imaging offers several advantages over traditional methods to determine lung microvascular permeability, yet is a straightforward method to develop and implement. PMID:25045895

  11. A Biodegradable Microvessel Scaffold as a Framework to Enable Vascular Support of Engineered Tissues

    PubMed Central

    Ye, Xiaofeng; Lu, Liang; Kolewe, Martin E.; Park, Hyoungshin; Larson, Benjamin L.; Kim, Ernest S.; Freed, Lisa E.

    2013-01-01

    A biodegradable microvessel scaffold comprised of distinct parenchymal and vascular compartments separated by a permeable membrane interface was conceptualized, fabricated, cellularized, and implanted. The device was designed with perfusable microfluidic channels on the order of 100 µm to mimic small blood vessels, and high interfacial area to an adjacent parenchymal space to enable transport between the compartments. Poly(glycerol sebacate) (PGS) elastomer was used to construct the microvessel framework, and various assembly methods were evaluated to ensure robust mechanical integrity. In vitro studies demonstrated the differentiation of human skeletal muscle cells cultured in the parenchymal space, a 90% reduction in muscle cell viability due to trans-membrane transport of a myotoxic drug from the perfusate, and microvessel seeding with human endothelial cells. In vivo studies of scaffolds implanted subcutaneously and intraperitoneally, without or with exogenous cells, into nude rats demonstrated biodegradation of the membrane interface and host blood cell infiltration of the microvessels. This modular, implantable scaffold could serve as a basis for building tissue constructs of increasing scale and clinical relevance. PMID:24079890

  12. Women's Health Initiative diet intervention did not increase macular pigment optical density in an ancillary study of a subsample of the Women's Health Initiative.

    PubMed

    Moeller, Suzen M; Voland, Rick; Sarto, Gloria E; Gobel, Vicki L; Streicher, Sharyn L; Mares, Julie A

    2009-09-01

    In this study, we examined the impact of long-term (>8 y), low-fat, high-fruit and -vegetable diets on levels of lutein and zeaxanthin in the macula of the retina, as indicated by the OD of macular pigment. Macular pigment OD, measured by heterochromatic flicker photometry, was compared in women aged 60-87 y, who, 7-18 mo earlier (median 12 mo), had been in the dietary modification intervention (n = 158) or comparison (n = 236) groups of the Women's Health Initiative (WHI) at the Madison, WI site for a mean of 8.5 y. Women in the intervention group ate more fruits and vegetables (mean +/- SEM) (6.1 +/- 0.2 vs. 4.6 +/- 0.2 servings/d; P < 0.0001) and had higher intakes of lutein and zeaxanthin from foods and supplements (2.7 +/- 0.2 vs. 2.1 +/- 0.1 mg/d; P = 0.0003) than the comparison group. However, macular pigment density did not differ between the intervention (0.36 +/- 0.02 OD units) and comparison (0.35 +/- 0.01 OD units) groups. It tended to be higher (11%; P = 0.11) in women consuming lutein and zeaxanthin in the highest compared with the lowest quintile (median 6.4 vs. 1.1 mg/d). The increase in fruit and vegetable intake among dietary modification participants of this WHI subsample was not of sufficient magnitude to alter the mean density of retinal carotenoids, given other existing dietary conditions in this sample. PMID:19587126

  13. Effects of algal concentration and initial density on the population growth of Diaphanosoma celebensis Stingelin (Crustacea, Cladocera)

    NASA Astrophysics Data System (ADS)

    Wang, Yan; Xie, Ningxia; Wang, Weiliang

    2009-09-01

    The effects of algal concentration and initial density on the population growth of the estuarine cladocera, Diaphanosoma celebensis Stingelin, were evaluated in an indoor experiment. A 2 × 4 layout that included two algal concentrations ( Chlorella pyrenoidosa, 1 × 106 and 3 × 106 cell/mL) and four inoculation densities (100, 200, 300 and 400 ind./L) were established. Diaphanosoma celebensis were reared in 150 mL flasks containing 50 mL of algal medium at 22°C, under salinity of 10 and a photoperiod of 12 h L: 12 h D. The lag phase required to initiate continuous population growth following inoculation was shorter for D. celebensis fed 1 × 106 cell/mL and inoculated at 300 or 400 ind./L than that for D. celebensis fed 3 × 106 cell/mL and inoculated at 100 or 200 ind./L. However, D. celebensis fed 3 × 106 cell/mL and inoculated at 100 or 200 ind./L exhibited longer periods of positive population growth. The maximum population densities were 5 875 ± 324, 6 690 ± 691, 7 735 ± 1,121 and 6 365 ± 691 ind./L for D. celebensis fed 1 × 106 cell/mL and inoculated at 100, 200, 300 and 400 ind./L, respectively, and 15 070 ± 379, 12 215 ± 648, 11 960 ± 2,551 and 16 130 ± 880 ind./L for D. celebensis fed 3 × 106 cell/mL and inoculated at 100, 200, 300 and 400 ind./L, respectively. The average daily increasing rates of population were 0.076 ± 0.001, 0.065 ± 0.002, 0.055 ± 0.002 and 0.048 ± 0.003 for D. celebensis fed 1×106 cell/mL and inoculated at 100, 200, 300 and 400 ind./L, respectively, and 0.098 ± 0.001, 0.078 ± 0.002, 0.072 ± 0.003 and 0.067 ± 0.003 for D. celebensis fed 3 × 106 cell/mL and inoculated at 100, 200, 300 and 400 ind./L, respectively. The maximum population density and average daily increasing rate of population increased as the algal concentration increased, whereas an increase in the inoculation density led to a linear decrease in the daily increasing rate of population under both algal concentrations. The results of the present

  14. Dependence of optimal initial density on laser parameters for multi-keV x-ray radiators generated by nanosecond laser-produced underdense plasma

    NASA Astrophysics Data System (ADS)

    Tu, Shao-yong; Yuan, Yong-teng; Hu, Guang-yue; Miao, Wen-yong; Zhao, Bin; Zheng, Jian; Jiang, Shao-en; Ding, Yong-kun

    2016-01-01

    Efficient multi-keV x-ray sources can be produced using nanosecond laser pulse-heated middle-Z underdense plasmas generated using gas or foam. Previous experimental results show that an optimal initial target density exists for efficient multi-keV x-ray emission at which the laser ionization wave is supersonic. Here we explore the influence of the laser intensity and the pulse duration on this optimal initial target density via a one-dimensional radiation hydrodynamic simulation. The simulation shows that the optimal initial density is sensitive to both the laser intensity and the pulse duration. However, the speed of the supersonic ionization wave at the end of the laser irradiation is always maintained at 1.5 to 1.7 times that of the ion acoustic wave under the optimal initial density conditions.

  15. Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

    PubMed Central

    Yang, Yu; Bai, Wenkun; Chen, Yini; Nan, Shuliang; Lin, Yanduan; Ying, Tao; Hu, Bing

    2016-01-01

    The aim of the present study was to investigate whether low-frequency ultrasound (US)-mediated microvessel disruption combined with docetaxel (DTX) can be used as a novel type of chemoembolization. Mice were assigned to four groups: i) The USMB group, treated with low-frequency US combined with microbubbles (USMB); ii) the DTX group, treated with DTX; iii) the USMB + DTX group, treated with combined therapy; and iv) the control group, which was untreated. Immediately after the first treatment, the average peak intensity (API) on contrast-enhanced US was calculated, and tumors were excised for hematoxylin and eosin (HE) staining. At 2 weeks post-treatment, the tumor volumes and wet weights were calculated, and tumors were excised for immunohistochemistry to calculate apoptotic index (AI), proliferative index (PI) and microvessel density (MVD) values. Immediately after the first treatment, in the DTX and control groups, the tumors demonstrated abundant perfusion enhancement, while in the USMB + DTX and USMB groups, blood perfusion of the tumors was interrupted. Compared with that of the control group, the API was significantly lower in the USMB + DTX USMB groups (all P<0.001). HE staining showed that tumor microvasculature was disrupted into flaky hematomas and severely dilated microvessels in the USMB + DTX and USMB groups. In the DTX and control groups, there was no distinct evidence of the disruption and dilation of blood microvessels. At the end of the treatment, the mean tumor inhibition ratio was 73.33, 46.67 and 33.33% for the USMB + DTX, DTX and USMB groups, respectively. The USMB + DTX group had the highest AI, and the lowest PI and MVD compared with the other groups, although the difference between the USMB + DTX and DTX groups with regard to PI and MVD was not significant (USMB + DTX vs. DTX group, P=0.345 and P=0.059, respectively). In conclusion, as a novel type of chemoembolization, USMB combined with DTX is more effective than USMB or DTX alone in

  16. Ultra-high Speed Optical Imaging of Ultrasound-activated Microbubbles in Mesenteric Microvessels

    NASA Astrophysics Data System (ADS)

    Chen, Hong

    Ultrasound contrast agent microbubbles have gained widespread applications in diagnostic and therapeutic ultrasound. Animal studies of bioeffects induced by ultrasound-activated microbubbles have demonstrated that microbubbles can cause microvessel damage. Much scientific attention has been attracted to such microvascular bioeffects, not only because of the related safety concerns, but also because of the potential useful applications of microbubbles in the intravascular delivery of drugs and genetic materials into target tissues. A significant challenge in using microbubbles in medical ultrasound is the lack of knowledge about how the microbubbles behave in blood vessels when exposed to ultrasound and how their interactions with ultrasound cause vascular damage. Although extensive studies were performed in the past to study the dynamics of microbubbles, most of those studies were performed in vitro and did not directly address the clinical environment in which microbubbles are injected into blood vessels. In this thesis work, a synchronized optical-acoustic system was set up for ultrahigh speed imaging of insonated microbubbles in microvessels. The recorded images revealed the formation of microjets penetrating the microbubbles, as well as vessel distention (motion outward against the surrounding tissue) and vessel invagination (motion inward toward the lumen) caused by the expansion and collapse of the microbubbles, respectively. Contrary to current paradigms which propose that microbubbles damage vessels either by distending them or by forming liquid jets impinging on them, microbubbles translation and jetting were in the direction away from the nearest vessel wall; furthermore, invagination typically exceeded distention in arterioles and venules. Vessel invagination was found to be associated with vascular damage. These studies suggest that vessel invagination may be a newly discovered potential mechanism for vascular damage by ultrasound-activated microbubbles

  17. Effects of rearing density, age, sex, and food deprivation on flight initiation of the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effects of rearing density, adult density and sex ratio in the flight chamber, adult age, sex, presence or absence of food, and duration of food deprivation on rate of and time to flight initiation of the red flour beetle, Tribolium castaneum (Herbst), were studied in the laboratory. Rates of flight...

  18. Characterization of the Cell-Free Layer in a Microvessel by Computer Simulation

    NASA Astrophysics Data System (ADS)

    Jee, Sol Keun; Freund, Jonathon; Moser, Robert

    2006-11-01

    The cell-free layer between the erythrocyte-rich core of a micro-vessel and the vessel wall is a significant component of the hydrodynamics of the microcirculation. To investigate the mechanics of the cell-free layer, we simulate a two-dimensional periodic blood flow in a microvessel containing numerous erythrocytes, modeled as capsules with elastic shell membranes using the boundary integral method. Cell-cell interactions are mediated with an interaction potential which represents aggregation forces. Our model successfully recreates in-vivo hemodynamic properties such as blunt velocity profile and Fahraeus effect. The cell-free layer has a thickness of order one erythrocyte radius which is consistent with experimental results. To investigate the mechanics of the cell-free layer a number of numerical experiments were conducted, in which the effects of aggregation forces, and lubrication forces are investigated, by varying the aggregation potential, introducing artificial body forces and changing boundary condition.

  19. Effect of heat transfer on rotating electroosmotic flow through a micro-vessel: haemodynamical applications

    NASA Astrophysics Data System (ADS)

    Sinha, A.; Mondal, A.; Shit, G. C.; Kundu, P. K.

    2016-08-01

    This paper theoretically analyzes the heat transfer characteristics associated with electroosmotic flow of blood through a micro-vessel having permeable walls. The analysis is based on the Debye-Hückel approximation for charge distributions and the Navier-Stokes equations are assumed to represent the flow field in a rotating system. The velocity slip condition at the vessel walls is taken into account. The essential features of the rotating electroosmotic flow of blood and associated heat transfer characteristics through a micro-vessel are clearly highlighted by the variation in the non-dimensional flow velocity, volumetric flow rate and non-dimensional temperature profiles. Moreover, the effect of Joule heating parameter and Prandtl number on the thermal transport characteristics are discussed thoroughly. The study reveals that the flow of blood is appreciably influenced by the elctroosmotic parameter as well as rotating Reynolds number.

  20. Microvessel reactivity changes in light-diode irradiation of blood (470 to 980 nm)

    NASA Astrophysics Data System (ADS)

    Petrishchev, Nikolai N.; Yantareva, Ludmila I.

    1998-01-01

    The effects of distant light diode irradiation with various spectrums of the trunk vessels on reactivity of microvessels in the small intestine mesentery treated with threshold doses of norepinephrine (NoE) are compared. The character of changes in reactivity of microvessels to NoE was found to depend on the wave length and irradiation dose. Ultraviolet irradiation (470 nm, 0.03 J/sm2) was noticed to increase reactivity of the vessels to NoE (vasoconstriction increase). In green light irradiation (540 nm, 0.3 J/sm2 sm2) no changes in reactivity were observed. Red light irradiation (670 nm, 2.0 J/sm2), infrared particular (980 nm, 1.0 J/sm2), lowered reactivity to NoE. Thus, noninvasive light-diode irradiation of the blood results in different systemic changes of endothelial dependent reactivity of microcirculation due to specify of photochemical processes involved.

  1. In Vitro Recapitulation of Functional Microvessels for the Study of Endothelial Shear Response, Nitric Oxide and [Ca2+]i

    PubMed Central

    He, Pingnian; Liu, Yuxin

    2015-01-01

    Microfluidic technologies enable in vitro studies to closely simulate in vivo microvessel environment with complexity. Such method overcomes certain constrains of the statically cultured endothelial monolayers and enables the cells grow under physiological range of shear flow with geometry similar to microvessels in vivo. However, there are still existing knowledge gaps and lack of convincing evidence to demonstrate and quantify key biological features of the microfluidic microvessels. In this paper, using advanced micromanufacturing and microfluidic technologies, we presented an engineered microvessel model that mimicked the dimensions and network structures of in vivo microvessels with a long-term and continuous perfusion capability, as well as high-resolution and real-time imaging capability. Through direct comparisons with studies conducted in intact microvessels, our results demonstrated that the cultured microvessels formed under perfused conditions recapitulated certain key features of the microvessels in vivo. In particular, primary human umbilical vein endothelial cells were successfully cultured the entire inner surfaces of the microchannel network with well-developed junctions indicated by VE-cadherin staining. The morphological and proliferative responses of endothelial cells to shear stresses were quantified under different flow conditions which was simulated with three-dimensional shear dependent numerical flow model. Furthermore, we successfully measured agonist-induced changes in intracellular Ca2+ concentration and nitric oxide production at individual endothelial cell levels using fluorescence imaging. The results were comparable to those derived from individually perfused intact venules. With in vivo validation of its functionalities, our microfluidic model demonstrates a great potential for biological applications and bridges the gaps between in vitro and in vivo microvascular research. PMID:25965067

  2. The fabrication of PLGA microvessel scaffolds with nano-patterned inner walls.

    PubMed

    Wang, Gou-Jen; Lin, Yan-Cheng; Hsu, Shan-Hui

    2010-10-01

    Poly (lactic-co-glycolic acid) (PLGA) is one of the most commonly used biodegradable, biocompatible materials. Nanostructured PLGA has immense potential for application in tissue engineering. In this article we discuss a novel approach for the fabrication of PLGA microvessel scaffolds with nanostructured inner walls. In this novel nano-patterning approach, the thermal reflow technique is first adapted to fabricate a semi-cylindrical photoresist master mold. A thin film of titanium and a thin film of aluminum are sputtered in sequence on the semi-cylindrical microvessel network. Aluminum foil anodization is then executed to transform the aluminum thin film into a porous anodic aluminum oxide (AAO) film. During the casting process a PLGA solution is cast on the AAO film to build up semi-cylindrical PLGA microstructures with nanostructured inner walls after which inductive coupled plasma (ICP) is implemented to assist bonding of the two PLGA structures. The result is the building of a network of microchannels with nano-patterned inner walls. Bovine endothelial cells (BECs) are carefully cultured in the scaffold via semi-dynamic seeding for 7 days. Observations show that the BECs grew more separately in a nano-patterned microvessel scaffold than they did in a smooth surface scaffold. PMID:20532635

  3. Identification and characterization of the insulin receptor of bovine retinal microvessels

    SciTech Connect

    Haskell, J.F.; Meezan, E.; Pillion, D.J.

    1984-08-01

    The presence of specific, high affinity receptors for insulin has been demonstrated in purified preparations of bovine retinal microvessels. The binding of (/sup 125/I)insulin to isolated retinal microvessels was inhibited by unlabeled insulin, but not by other peptide hormones. Scatchard analysis of the (/sup 125/I)insulin binding data gave a curvilinear plot similar to that exhibited by insulin receptors in known insulin-sensitive tissues such as adipocytes and hepatocytes. Binding of (/sup 125/I)insulin to retinal microvessels, followed by covalent cross-linking of the bound ligand to the alpha-subunit of the insulin receptor with the bifunctional reagent disuccinimidyl suberate, yielded a prominent specific (/sup 125/I)insulin-labeled band when analyzed by sodium dodecyl sulfate-gel electrophoresis followed by autoradiography, and this band had a mobility identical to that of the corresponding complex obtained with rat liver plasma membranes (mol wt, 125,000). These results demonstrate for the first time that the retinal microvasculature, a major site of pathological injury in diabetes mellitus, contains insulin receptors that are similar to those present in known insulin-sensitive tissues, such as liver, fat, and muscle.

  4. The Mechanical Effects of Ultrasound Contrast Agents on Micro-vessels

    NASA Astrophysics Data System (ADS)

    Hosseinkhah, N.; Hynynen, K.

    2011-09-01

    Ultrasound activated contrast agents inside microvessels induce mechanical effects on the vessel wall. It is important to use the bubbles safely and avoid rupturing the vessels. The objective of this work was to develop a three dimensional model of a bubble, blood and micro-vessels in order to investigate the mechanical effects (mainly the fluid shear stress and the circumferential stress) by a non-inertial microbubble on the vessel wall. A finite element method was used to solve for this model numerically. The blood vessel was simulated as having a viscoelastic, elastic or a rigid wall. Acoustic pressure and frequency were varied and the values for fluid shear stress and circumferential stress on the vessel wall were calculated. The circumferential stress could exceed the vascular strength in rigid microvessels if the applied acoustic pressure is above 260 kPa. Also the values for fluid shear stress are large enough to induce hemolysis or damage the cell membrane close to the oscillating bubble. Next, the streamlines and stagnation points are obtained for a rigid and a flexible vessel.

  5. Initial hepatic removal of chylomicron remnants is unaffected but endocytosis is delayed in mice lacking the low density lipoprotein receptor.

    PubMed Central

    Herz, J; Qiu, S Q; Oesterle, A; DeSilva, H V; Shafi, S; Havel, R J

    1995-01-01

    Two endocytic receptors, the low density lipoprotein (LDL) receptor (LDLR) and the LDLR-related protein (LRP), are thought to act in concert in the hepatic uptake of partially metabolized dietary lipoproteins, the chylomicron remnants. We have evaluated the role of these two receptors in the hepatic metabolism of chylomicron remnants in normal mice and in LDLR-deficient [LDLR (-/-)] mice. The rate of chylomicron remnant removal by the liver was normal up to 30 min after intravenous injection of chylomicrons into LDLR (-/-) mice and was unaffected by receptor-associated protein (RAP), a potent inhibitor of ligand binding to LRP. In contrast, endocytosis of the remnants by the hepatocytes, measured by their accumulation in the endosomal fraction and by the rate of hydrolysis of component cholesteryl esters, was dramatically reduced in the absence of the LDLR. Coadministration of RAP prevented the continuing hepatic removal of chylomicron remnants in LDL (-/-) mice after 30 min, consistent with blockade of the slow endocytosis by a RAP-sensitive process. Taken together with previous studies, our results are consistent with a model in which the initial hepatic removal of chylomicron remnants is primarily mediated by mechanisms that do not include LDLR or LRP, possibly involving glycosaminoglycan-bound hepatic lipase and apolipoprotein E. After the remnants bind to these alternative sites on the hepatocyte surface, endocytosis is predominantly mediated by the LDLR and also by a slower and less efficient backup process that is RAP sensitive and therefore most likely involves LRP. PMID:7753850

  6. Thrombin mitogenic responses and protein phosphorylation are different in cultured human endothelial cells derived from large and microvessels

    SciTech Connect

    Dupuy, E.; Bikfalvi, A.; Rendu, F.; Toledano, S.L.; Tobelem, G. )

    1989-12-01

    It is well established that thrombin induces various biological responses in endothelial cells derived from large vessels. However, little is known about the effects of thrombin on the microvasculature. Protein phosphorylation may be one of the mechanisms by which an extracellular stimulus initiates cellular events like proliferation. Therefore, we have compared the effects of either human alpha-thrombin or phorbol esters (TPA) on the proliferation or protein phosphorylation in endothelial cells derived from large vessels (umbilical vein, HUVEC) or microvessels (omental tissue, HOMEC). In HOMEC, thrombin did not stimulate cell proliferation and protein phosphorylation while TPA slightly reduced the cell proliferation and induced the phosphorylation of a 27-kDa protein. In contrast, in HUVEC, thrombin or TPA markedly enhanced the cell proliferation and stimulated the phosphorylation of a 59-kDa protein. These data indicate that endothelial cells from large and small vessels respond differently to thrombin and there is a complex and as yet unclear relationship between the proliferation and the protein phosphorylation induced by thrombin.

  7. Monocarboxylate Transporter 1 is Deficient on Microvessels in the Human Epileptogenic Hippocampus

    PubMed Central

    Lauritzen, Fredrik; de Lanerolle, Nihal C.; Lee, Tih-Shih W.; Spencer, Dennis D.; Kim, Jung H.; Bergersen, Linda H.; Eid, Tore

    2010-01-01

    Monocarboxylate transporter 1 (MCT1) facilitates the transport of important metabolic fuels (lactate, pyruvate and ketone bodies) and possibly also acidic drugs such as valproic acid across the blood brain barrier. Because an impaired brain energy metabolism and resistance to antiepileptic drugs are common features of temporal lobe epilepsy (TLE), we sought to study the expression of MCT1 in the brain of patients with this disease. Immunohistochemistry and immunogold electron microscopy were used to assess the distribution of MCT1 in brain specimens from patients with TLE and concomitant hippocampal sclerosis (referred to as mesial TLE or MTLE (n = 15)), patients with TLE and no hippocampal sclerosis (non-MTLE, n = 13) and neurologically normal autopsy subjects (n = 8). MCT1 was present on an extensive network of microvessels throughout the hippocampal formation in autopsy controls and to a lesser degree in non-MTLE. Patients with MTLE were markedly deficient in MCT1 on microvessels in several areas of the hippocampal formation, especially CA1, which exhibited a 37 to 48% loss of MCT1 on the plasma membrane of endothelial cells when compared with non-MTLE. These findings suggest that the uptake of blood-derived monocarboxylate fuels and possibly also acidic drugs, such as valproic acid, is perturbed in the epileptogenic hippocampus, particularly in MTLE. We hypothesize that the loss of MCT1 on brain microvessels is mechanistically involved in the pathophysiology of drug-resistant TLE, and propose that re-expression of MCT1 may represent a novel therapeutic approach for this disease. PMID:21081165

  8. Photoacoustic simulation of microvessel bleeding: spectral analysis and its implication for monitoring vascular-targeted treatments

    NASA Astrophysics Data System (ADS)

    Fadhel, Muhannad N.; Hysi, Eno; Zalev, Jason; Kolios, Michael C.

    2016-03-01

    The destruction of blood vessels is a commonly used cancer therapeutic strategy. Bleeding consequently follows and leads to the accumulation of blood in the interstitium. Photoacoustic (PA) imaging is well positioned to detect bleeding due to its sensitivity to hemoglobin. After treatment vascular disruption can occur within just a few hours, which leads to bleeding which might be detected using PA to assess therapeutic effectiveness. Deep micro-vessels cannot typically be resolved using acoustic-resolution PA. However, spectral analysis of PA signals may still permit assessment of bleeding. This paper introduces a theoretical model to simulate the PA signals from disrupted vessels using a fractal model. The fractal model uses bifurcated-cylinder bases to represent vascular trees. Vessels have circular absorption cross-sections. To mimic bleeding from blood vessels, the diffusion of hemoglobin from micro-vessels was simulated. The PA signals were computed and in the simulations were detected using a linear array transducer (30 MHz center frequency) for four different vascular trees (at 256 axial spatial locations/tree). The Fourier Transform of each beam-formed PA signal was computed and the power spectra were fitted to a straight line within the -6 dB bandwidth of the receiving transducer. When comparing the power spectra before and after simulated bleeding, the spectral slope and mid-band fit (MBF) parameters decreased by 0.12 dB/MHz and 2.12 dB, while the y-intercept did not change after 1 hour of simulated bleeding. The results suggest that spectral PA analysis is sensitive to changes in the concentration and spatial distribution of hemoglobin in tissue, and changes due to bleeding can be detected without the need to resolve individual vessels. The simulations support the applicability of PA imaging in cancer treatment monitoring by detecting micro-vessel disruption.

  9. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Huls, M. H.; Sams, Clarence F.

    1989-01-01

    In view of the suggestions by Chabrier et al. (1987) and Steardo and Nathanson (1987) that atrial natriuretic peptide (ANP) may play a role in the fluid homeostasis of the brain, the ANP receptors in primary cultures of bovine brain microvessel endothelian cells were quantitated and characterized. Results of partition binding studies and the effect of cGMP additions indicated the presence of at least two types of ANP receptors, with the majority of the receptors being the nonguanylate cyclase coupled receptors. The presence of at least two ANP receptor types suggests an active role for ANP in regulating brain endothelial cell function.

  10. High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

    SciTech Connect

    Wolfe, Adam R.; Atkinson, Rachel L.; Reddy, Jay P.; Debeb, Bisrat G.; Larson, Richard; Li, Li; Masuda, Hiroko; Brewer, Takae; Atkinson, Bradley J.; Brewster, Abeena; Ueno, Naoto T.; Woodward, Wendy A.

    2015-04-01

    Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

  11. Structure and ultrastructure of microvessels in the kidney seen by the corrosion casting method.

    PubMed

    Sangiorgi, Simone; Manelli, Alessandro; Protasoni, Marina; Reguzzoni, Marcella; Congiu, Terenzio; Raspanti, Mario

    2004-01-01

    Scanning electron microscopic observation of corrosion casts is the finest technique to describe spatial patterns of microvessels in many organs, giving a readily interpreted representation of their vascular architecture without interference from surrounding tissues. We focused on the renal cortex of guinea pigs to make an in-depth morphological analysis of structural and ultrastructural details left by the cells on the resin cast. In addition, we made a qualitative description of normal variants usually observed in glomerular disposition, arteriolar morphology or capillary arrangement in the space to shed more light on the relationship between vascular tissue and surrounding cells. The study also disclosed some examples of vascular adaption to physiological and pathological conditions occurring in renal microvessels such as many systems essential to flow regulation, filtration and excretory processes. At lower magnification, all major vessels can be readily distinguished: interlobar, arciform and interlobular arteries and veins, along with a web of peritubular and capsular capillaries. At higher magnification, the glomeruli become visible and the afferent and efferent arteries and the tortuosity the inner vessels can be distinguished. In some of them, the resin, due to the narrowing sizes, suddenly stopped leaving a half-casted glomerulus. This helped to reveal its internal circulation characterized by thin capillaries with a high degree of bi or trifurcation. In addition, we confirmed the close correspondence between cellular ultrastructural detail (pores, corrugations of cellular membrane, perivascular cell branches) and the impressions left on the resin visible only at high magnifications. PMID:15141474

  12. A standalone perfusion platform for drug testing and target validation in micro-vessel networks

    PubMed Central

    Zhang, Boyang; Peticone, Carlotta; Murthy, Shashi K.; Radisic, Milica

    2013-01-01

    Studying the effects of pharmacological agents on human endothelium includes the routine use of cell monolayers cultivated in multi-well plates. This configuration fails to recapitulate the complex architecture of vascular networks in vivo and does not capture the relationship between shear stress (i.e. flow) experienced by the cells and dose of the applied pharmacological agents. Microfluidic platforms have been applied extensively to create vascular systems in vitro; however, they rely on bulky external hardware to operate, which hinders the wide application of microfluidic chips by non-microfluidic experts. Here, we have developed a standalone perfusion platform where multiple devices were perfused at a time with a single miniaturized peristaltic pump. Using the platform, multiple micro-vessel networks, that contained three levels of branching structures, were created by culturing endothelial cells within circular micro-channel networks mimicking the geometrical configuration of natural blood vessels. To demonstrate the feasibility of our platform for drug testing and validation assays, a drug induced nitric oxide assay was performed on the engineered micro-vessel network using a panel of vaso-active drugs (acetylcholine, phenylephrine, atorvastatin, and sildenafil), showing both flow and drug dose dependent responses. The interactive effects between flow and drug dose for sildenafil could not be captured by a simple straight rectangular channel coated with endothelial cells, but it was captured in a more physiological branching circular network. A monocyte adhesion assay was also demonstrated with and without stimulation by an inflammatory cytokine, tumor necrosis factor-α. PMID:24404058

  13. Sphingosine-1-phosphate Maintains Normal Vascular Permeability by Preserving Endothelial Surface Glycocalyx in Intact Microvessels

    PubMed Central

    Zhang, Lin; Zeng, Min; Fan, Jie; Tarbell, John, M.; Curry, Fitz-Roy E.; Fu, Bingmei M.

    2016-01-01

    Objective Sphingosine-1-phosphate (S1P) was found to protect the endothelial surface glycocalyx (ESG) by inhibiting matrix metalloproteinase (MMP) activity-dependent shedding of ESG in cultured endothelial cell studies. We aimed to further test that S1P contributes to the maintenance of normal vascular permeability by protecting the ESG in intact microvessels. Methods We quantified the ESG in post-capillary venules of rat mesentery and measured the vascular permeability to albumin in the presence and absence of 1 μM S1P. We also measured permeability to albumin in the presence of MMP inhibitors and compared the measured permeability with those predicted by a transport model for the inter-endothelial cleft. Results We found that in the absence of S1P, the fluorescence intensity of the FITC-anti-heparan sulfate labeled ESG was ~10% of that in the presence of S1P, while the measured permeability to albumin was ~6.5 fold that in the presence of S1P. Similar results were observed with MMP inhibition. The predictions by the mathematical model further confirmed that S1P maintains microvascular permeability by preserving ESG. Conclusions Our results show that S1P contributes to the maintenance of normal vascular permeability by protecting the ESG in intact microvessels, consistent with parallel observation in cultured endothelial monolayers. PMID:27015105

  14. Magnetic targeting in the impermeable microvessel with two-phase fluid model--non-Newtonian characteristics of blood.

    PubMed

    Shaw, Sachin; Murthy, P V S N

    2010-09-01

    The present investigation deals with finding the trajectories of the drug dosed magnetic carrier particle in a microvessel with two-phase fluid model which is subjected to the external magnetic field. The radius of the microvessel is divided into the endothelial glycocalyx layer in which the blood is assumed to obey Newtonian character and a core and plug regions where the blood obeys the non-Newtonian Herschel-Bulkley character which is suitable for the microvessel of radius 50 microm. The carrier particles, bound with nanoparticles and drug molecules are injected into the vascular system upstream from malignant tissue, and captured at the tumor site using a local applied magnetic field. The applied magnetic field is produced by a cylindrical magnet positioned outside the body and near the tumor position. The expressions for the fluidic force for the carrier particle traversing in the two-phase fluid in the microvessel and the magnetic force due to the external magnetic field are obtained. Several factors that influence the magnetic targeting of the carrier particles in the microvasculature, such as the size of the carrier particle, the volume fraction of embedded magnetic nanoparticles, and the distance of separation of the magnet from the axis of the microvessel are considered in the present problem. An algorithm is given to solve the system of coupled equations for trajectories of the carrier particle in the invasive case. The trajectories of the carrier particle are found for both invasive and noninvasive targeting systems. A comparison is made between the trajectories in these cases. Also, the present results are compared with the data available for the impermeable microvessel with single-phase fluid flow. Also, a prediction of the capture of therapeutic magnetic nanoparticle in the impermeable microvasculature is made for different radii, distances and volume fractions in both the invasive and noninvasive cases. PMID:20478317

  15. Prostaglandin release from isolated rabbit cerebral cortex micro-vessels--comparison of 6-keto PGF1 alpha and PGE2 release from micro-vessels incubated in 100% O2, room air and 95% N2:5% CO2.

    PubMed

    Rodrigues, A M; Gerritsen, M E

    1984-01-01

    Prostaglandin release from microvessels isolated from the rabbit cerebral cortex was determined under three different atmospheric conditions: 100% O2 ("O2") room air, and 95% N2:5% CO2 ("N2-CO2"). Initial studies with homogenates prepared from rabbit cerebral microvessels (RCMV) indicated two pathways of enzymatic PGH2 transformation, namely PGI2 synthase and GSH-dependent PGH-PGE isomerase. We measured the release of the principal products of these pathways, 6-keto PGF1 alpha and PGE2 from freshly prepared RCMV. The release of 6-keto PGF1 alpha exceeded that of PGE2 in all three protocols. RCMV incubated in "N2-CO2" exhibited a reduction in the release of 6-keto PGF1 alpha compared to room air or "O2" incubated RCMV, evident at 30-60 min of incubation. No significant differences in the release of PGE2 were observed among the three incubation protocols. In all three incubation protocols the ratio of 6-keto PGF1 alpha to PGE2 did not differ during the initial 10 minutes of each incubation. After 30 to 60 min of incubation, this ratio did not change from the "O2" or room air treated RCMV, but decreased significantly for the "N2-CO2" treated group. To determine the reversibility of the apparent "N2-CO2" induced decline in 6-keto PGF1 alpha release, microvessels were removed from the nitrogen atmosphere and incubated in room air. Release was measured during the initial 10 min following reintroduction to room air and was compared to room air pretreated controls treated in an identical manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6431653

  16. Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

    NASA Astrophysics Data System (ADS)

    Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

    1995-07-01

    Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

  17. Population age and initial density in a patchy environment affect the occurrence of abrupt transitions in a birth-and-death model of Taylor's law

    USGS Publications Warehouse

    Jiang, Jiang; DeAngelis, Donald L.; Zhang, B.; Cohen, J.E.

    2014-01-01

    Taylor's power law describes an empirical relationship between the mean and variance of population densities in field data, in which the variance varies as a power, b, of the mean. Most studies report values of b varying between 1 and 2. However, Cohen (2014a) showed recently that smooth changes in environmental conditions in a model can lead to an abrupt, infinite change in b. To understand what factors can influence the occurrence of an abrupt change in b, we used both mathematical analysis and Monte Carlo samples from a model in which populations of the same species settled on patches, and each population followed independently a stochastic linear birth-and-death process. We investigated how the power relationship responds to a smooth change of population growth rate, under different sampling strategies, initial population density, and population age. We showed analytically that, if the initial populations differ only in density, and samples are taken from all patches after the same time period following a major invasion event, Taylor's law holds with exponent b=1, regardless of the population growth rate. If samples are taken at different times from patches that have the same initial population densities, we calculate an abrupt shift of b, as predicted by Cohen (2014a). The loss of linearity between log variance and log mean is a leading indicator of the abrupt shift. If both initial population densities and population ages vary among patches, estimates of b lie between 1 and 2, as in most empirical studies. But the value of b declines to ~1 as the system approaches a critical point. Our results can inform empirical studies that might be designed to demonstrate an abrupt shift in Taylor's law.

  18. Early Osteogenic Signal Expression of Rat Bone Marrow Stromal Cells is Influenced by Both Hydroxyapatite Nanoparticle Content and Initial Cell Seeding Density in Biodegradable Nanocomposite Scaffolds

    PubMed Central

    Kim, Kyobum; Dean, David; Lu, Anqi; Mikos, Antonios G.; Fisher, John P.

    2010-01-01

    Incorporation of hydroxyapatite (HA) within a degradable polymeric scaffold may provide a favorable synthetic microenvironment that more closely mimics natural bone tissue physiology. Both incorporation of HA nanoparticles and alteration of paracrine cell-cell signaling distances may affect the intercellular signaling mechanism and facilitate the enhanced osteogenic signal expressions among the implanted cell population. In this study, we investigate the effect of the incorporation of HA nanoparticles into poly(propylene fumarate) (PPF) scaffolds on the surface properties of composite scaffolds and early osteogenic growth factor gene expression in relation to initial cell seeding density. The result of surface characterization indicated that HA addition improved surface properties of PPF/HA composite scaffolds by showing increased roughness, hydrophilicity, protein adsorption, and initial cell attachment. Rat bone marrow stromal cells (BMSCs), which were CD34(−), CD45(−), CD29(+), and CD90(+), were cultured on 3D macroporous PPF/HA scaffolds with two different initial cell seeding densities (0.33 and 1.00 million cells per scaffold) for 8 days. Results demonstrated that endogenous osteogenic signal expression profiles, including bone morphogenetic protein-2, fibroblast growth factor-2, and transforming growth factor-β1, as well as the transcriptional factor Runx2 were affected by both HA amount and initial cell seeding density. Upregulated expression of osteogenic growth factor genes was related to subsequent osteoblastic differentiation of rat BMSCs on 3D scaffolds, as characterized by alkaline phosphatase activity, osteocalcin mRNA expression, and calcium deposition. Thus PPF/HA composite scaffold construction parameters, including incorporated HA amount and initial cell seeding density, may be utilized to induce the osteoblastic differentiation of transplanted rat BMSCs. PMID:21074640

  19. Direct phase selection of initial phases from single-wavelength anomalous dispersion (SAD) for the improvement of electron density and ab initio structure determination

    SciTech Connect

    Chen, Chung-De; Huang, Yen-Chieh; Chiang, Hsin-Lin; Hsieh, Yin-Cheng; Guan, Hong-Hsiang; Chuankhayan, Phimonphan; Chen, Chun-Jung

    2014-09-01

    A novel direct phase-selection method to select optimized phases from the ambiguous phases of a subset of reflections to replace the corresponding initial SAD phases has been developed. With the improved phases, the completeness of built residues of protein molecules is enhanced for efficient structure determination. Optimization of the initial phasing has been a decisive factor in the success of the subsequent electron-density modification, model building and structure determination of biological macromolecules using the single-wavelength anomalous dispersion (SAD) method. Two possible phase solutions (ϕ{sub 1} and ϕ{sub 2}) generated from two symmetric phase triangles in the Harker construction for the SAD method cause the well known phase ambiguity. A novel direct phase-selection method utilizing the θ{sub DS} list as a criterion to select optimized phases ϕ{sub am} from ϕ{sub 1} or ϕ{sub 2} of a subset of reflections with a high percentage of correct phases to replace the corresponding initial SAD phases ϕ{sub SAD} has been developed. Based on this work, reflections with an angle θ{sub DS} in the range 35–145° are selected for an optimized improvement, where θ{sub DS} is the angle between the initial phase ϕ{sub SAD} and a preliminary density-modification (DM) phase ϕ{sub DM}{sup NHL}. The results show that utilizing the additional direct phase-selection step prior to simple solvent flattening without phase combination using existing DM programs, such as RESOLVE or DM from CCP4, significantly improves the final phases in terms of increased correlation coefficients of electron-density maps and diminished mean phase errors. With the improved phases and density maps from the direct phase-selection method, the completeness of residues of protein molecules built with main chains and side chains is enhanced for efficient structure determination.

  20. Ultraviolet/Ozone as a Tool To Control Grafting Density in Surface-Initiated Controlled-Radical Polymerizations via Ablation of Bromine.

    PubMed

    Sheridan, Richard J; Orski, Sara V; Muramoto, Shin; Stafford, Christopher M; Beers, Kathryn L

    2016-08-16

    We used an ultraviolet-ozone (UVO) cleaner to create substrates for atom-transfer radical polymerization (ATRP) with varying surface initiator coverage. We collected complementary time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) measurements to investigate the precise chemical origin of the variation in grafting density. At short exposure times, the atomic composition underwent minor changes except for the relative amount of bromine. At longer UVO exposure times, there is clear evidence of exposure-dependent surface initiator oxidation. We interpret these data as evidence of a bromine ablation process within the UVO cleaner, with additional oxidative modification of the rest of the surface. We then used these substrates to create a series of poly(methyl methacrylate) (PMMA) brushes varying in grafting density, demonstrating the utility of this tool for the control of polymer brush density. The measured brush grafting densities were correlated with the bromine concentration measured by both ToF-SIMS and XPS. XPS and brush thicknesses correlated strongly, following an exponential decay with a half-life of 18 ± 1 s. PMID:27442615

  1. Application of image restoration and three-dimensional visualization techniques to frog microvessels in-situ loaded with fluorescent indicators

    NASA Astrophysics Data System (ADS)

    Pagakis, Stamatis N.; Curry, Fitz-Roy E.; Lenz, Joyce F.

    1993-07-01

    In situ experiments on microvessels require image sensors of wide dynamic range due to large variations of the intensity in the scene, and 3D visualization due to the thickness of the preparation. The images require restoration because of the inherent tissue movement, out-of- focus-light contamination, and blur. To resolve the above problems, we developed an imaging system for quantitative imaging based on a 12 bits/pixel cooled CCD camera and a PC based digital imaging system. We applied the optical sectioning technique with image restoration using a modified nearest neighbor algorithm and iterative constrained deconvolution on each of the 2D optical sections. For the 3D visualization of the data, a volume rendering software was used. The data provided 3D images of the distribution of fluorescent indicators in intact microvessels. Optical cross sections were also compared with cross sections of the same microvessels examined in the electron microscope after their luminal surfaces were labeled with a tracer which was both electron dense and fluorescent. This procedure enabled precise identification of the endothelial cells in the microvessel wall as the principal site of accumulation of the fluorescent calcium indicator, fura-2, during microperfusion experiments.

  2. LASER BIOLOGY AND MEDICINE: Recording of lymph flow dynamics in microvessels using correlation properties of scattered coherent radiation

    NASA Astrophysics Data System (ADS)

    Fedosov, I. V.; Tuchin, Valerii V.; Galanzha, E. I.; Solov'eva, A. V.; Stepanova, T. V.

    2002-11-01

    The direction-sensitive method of microflow velocity measurements based on the space — time correlation properties of the dynamic speckle field is described and used for in vivo monitoring of lymph flow in the vessels of rat mesentery. The results of measurements are compared with the data obtained from functional video microscopy of the microvessel region.

  3. Micropinocytic Ingestion of Glycosylated Albumin by Isolated Microvessels: Possible Role in Pathogenesis of Diabetic Microangiopathy

    NASA Astrophysics Data System (ADS)

    Williams, Stuart K.; Devenny, James J.; Bitensky, Mark W.

    1981-04-01

    Microvessels isolated from rat epididymal fat exhibit differential vesicular ingestion rates for unmodified and nonenzymatically glycosylated rat albumin. While unmodified rat albumin is excluded from ingestion by endothelial micropinocytic vesicles, glycosylated albumin is avidly taken up by endocytosis. Interaction of albumin and glycosylated albumin with endothelium was studied with a double-label fluorescence assay of micropinocytosis. When glycosylated albumin was present at a concentration of 6% with respect to total albumin (the level found in ``non diabetic'' serum), only glycosylated albumin was ingested. At higher concentrations of glycosylated albumin (those found in diabetic serum), both albumin and glycosylated albumin are ingested. Glycosylation of endothelial membrane components results in stimulated ingestion of glycosylated albumin, persistent exclusion of unmodified albumin, and unaltered micropinocytic ingestion of native ferritin. These results indicate that nonenzymatic glycosylation of serum albumin may result in rapid vesicle-mediated extravasation of albumin. Chronic microvascular leakage of glycosylated albumin could contribute to the pathogenesis of diabetic microangiopathy.

  4. Modifying mixing and instability growth through the adjustment of initial conditions in a high-energy-density counter-propagating shear experiment on OMEGA

    DOE PAGESBeta

    Merritt, E. C.; Doss, F. W.; Loomis, E. N.; Flippo, K. A.; Kline, J. L.

    2015-06-24

    Counter-propagating shear experiments conducted at the OMEGA Laser Facility have been evaluating the effect of target initial conditions, specifically the characteristics of a tracer foil located at the shear boundary, on Kelvin-Helmholtz instability evolution and experiment transition toward nonlinearity and turbulence in the high-energy-density (HED) regime. Experiments are focused on both identifying and uncoupling the dependence of the model initial turbulent length scale in variable-density turbulence models of k-ϵ type on competing physical instability seed lengths as well as developing a path toward fully developed turbulent HED experiments. We present results from a series of experiments controllably and independently varyingmore » two initial types of scale lengths in the experiment: the thickness and surface roughness (surface perturbation scale spectrum) of a tracer layer at the shear interface. We show that decreasing the layer thickness and increasing the surface roughness both have the ability to increase the relative mixing in the system, and thus theoretically decrease the time required to begin transitioning to turbulence in the system. In addition, we also show that we can connect a change in observed mix width growth due to increased foil surface roughness to an analytically predicted change in model initial turbulent scale lengths.« less

  5. Modifying mixing and instability growth through the adjustment of initial conditions in a high-energy-density counter-propagating shear experiment on OMEGA

    SciTech Connect

    Merritt, E. C.; Doss, F. W.; Loomis, E. N.; Flippo, K. A.; Kline, J. L.

    2015-06-24

    Counter-propagating shear experiments conducted at the OMEGA Laser Facility have been evaluating the effect of target initial conditions, specifically the characteristics of a tracer foil located at the shear boundary, on Kelvin-Helmholtz instability evolution and experiment transition toward nonlinearity and turbulence in the high-energy-density (HED) regime. Experiments are focused on both identifying and uncoupling the dependence of the model initial turbulent length scale in variable-density turbulence models of k-ϵ type on competing physical instability seed lengths as well as developing a path toward fully developed turbulent HED experiments. We present results from a series of experiments controllably and independently varying two initial types of scale lengths in the experiment: the thickness and surface roughness (surface perturbation scale spectrum) of a tracer layer at the shear interface. We show that decreasing the layer thickness and increasing the surface roughness both have the ability to increase the relative mixing in the system, and thus theoretically decrease the time required to begin transitioning to turbulence in the system. In addition, we also show that we can connect a change in observed mix width growth due to increased foil surface roughness to an analytically predicted change in model initial turbulent scale lengths.

  6. Modifying mixing and instability growth through the adjustment of initial conditions in a high-energy-density counter-propagating shear experiment on OMEGA

    SciTech Connect

    Merritt, E. C. Doss, F. W.; Loomis, E. N.; Flippo, K. A.; Kline, J. L.

    2015-06-15

    Counter-propagating shear experiments conducted at the OMEGA Laser Facility have been evaluating the effect of target initial conditions, specifically the characteristics of a tracer foil located at the shear boundary, on Kelvin-Helmholtz instability evolution and experiment transition toward nonlinearity and turbulence in the high-energy-density (HED) regime. Experiments are focused on both identifying and uncoupling the dependence of the model initial turbulent length scale in variable-density turbulence models of k-ϵ type on competing physical instability seed lengths as well as developing a path toward fully developed turbulent HED experiments. We present results from a series of experiments controllably and independently varying two initial types of scale lengths in the experiment: the thickness and surface roughness (surface perturbation scale spectrum) of a tracer layer at the shear interface. We show that decreasing the layer thickness and increasing the surface roughness both have the ability to increase the relative mixing in the system, and thus theoretically decrease the time required to begin transitioning to turbulence in the system. We also show that we can connect a change in observed mix width growth due to increased foil surface roughness to an analytically predicted change in model initial turbulent scale lengths.

  7. Mediastinal micro-vessels clipping during lymph node dissection may contribute to reduce postoperative pleural drainage

    PubMed Central

    Yan, Shi; Wang, Xing; Lv, Chao; Phan, Kevin; Wang, Yuzhao; Wang, Jia; Yang, Yue

    2016-01-01

    Background Postoperative pleural drainage markedly influences the length of postoperative stay and financial costs of medical care. The aim of this study is to retrospectively investigate potentially predisposing factors related to pleural drainage after curative thoracic surgery and to explore the impact of mediastinal micro-vessels clipping on pleural drainage control after lymph node dissection. Methods From February 2012 to November 2013, 322 consecutive cases of operable non-small cell lung cancers (NSCLC) undergoing lobectomy and mediastinal lymph node dissection with or without application of clipping were collected. Total and daily postoperative pleural drainage were recorded. Propensity score matching (1:2) was applied to balance variables potentially impacting pleural drainage between group clip and group control. Analyses were performed to compare drainage volume, duration of chest tube and postoperative hospital stay between the two groups. Variables linked with pleural drainage in whole cohort were assessed using multivariable logistic regression analysis. Results Propensity score matching resulted in 197 patients (matched cohort). Baseline patient characteristics were matched between two groups. Group clip showed less cumulative drainage volume (P=0.020), shorter duration of chest tube (P=0.031) and postoperative hospital stay (P=0.022) compared with group control. Risk factors significantly associated with high-output drainage in multivariable logistic regression analysis were being male, age >60 years, bilobectomy/sleeve lobectomy, pleural adhesion, the application of clip applier, duration of operation ≥220 minutes and chylothorax (P<0.05). Conclusions This study suggests that mediastinal micro-vessels clipping during lymph node dissection may reduce postoperative pleural drainage and thus shorten hospital stay. PMID:27076936

  8. Autonomic nerves terminating on microvessels in the pineal organs of various submammalian vertebrates.

    PubMed

    Frank, C L; Czirok, Szabina J; Vincze, Csilla; Rácz, G; Szél, A; Vígh, B

    2005-01-01

    In earlier works we have found that in the mammalian pineal organ, a part of autonomic nerves--generally thought to mediate light information from the retina--form vasomotor endings on smooth muscle cells of vessels. We supposed that they serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. In the present work, we investigated whether peripheral nerves present in the photoreceptive pineal organs of submammalians form similar terminals on microvessels. In the cyclostome, fish, amphibian, reptile and bird species investigated, autonomic nerves accompany vessels entering the arachnoidal capsule and interfollicular meningeal septa of the pineal organ. The autonomic nerves do not enter the pineal tissue proper but remain in the perivasal meningeal septa isolated by basal lamina. They are composed of unmyelinated and myelinated fibers and form terminals around arterioles, veins and capillaries. The terminals contain synaptic and granular vesicles. Comparing various vertebrates, more perivasal terminals were found in reptiles and birds than in the cyclostome, fish and amphibian pineal organs. Earlier, autonomic nerves of the pineal organs were predominantly investigated in connection with the innervation of pineal tissue. The perivasal terminals found in various submammalians show that a part of the pineal autonomic fibers are vasomotoric in nature, but the vasosensor function of some fibers cannot be excluded. We suppose that the vasomotor regulation of the pineal microvessels in the photosensory submamalian pineal--like in mammals--may serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. The higher number of perivasal terminals in reptiles and birds may correspond to the higher metabolic activity of the tissues in more differentiated species. PMID:15813212

  9. Chronic lead treatment accelerates photochemically induced platelet aggregation in cerebral microvessels of mice, in vivo

    SciTech Connect

    Al Dhaheri, A.H.; El-Sabban, F.; Fahim, M.A.

    1995-04-01

    Effects of two chronic treatment levels with lead on platelet aggregation in cerebral (pial) microcirculation of the mouse were investigated. Exposure to lead was made by subcutaneous injections for 7 days of lead acetate dissolved in 5% glucose solution, vehicle. Two doses of lead were used, a low dose of 0.1 mg/kg and a high dose of 1.0 mg/kg. Adult male mice were divided into three groups, 10 each; one group was injected with vehicle (control), another was injected with the low dose, and the third was injected with the high dose. Additional mice were used for the determination of hematological parameters and for the lead level in serum of the three groups. On the eighth day, platelet aggregation in pial microvessels of these groups of mice was carried out in vivo. Animals were anesthetized (urethane, 1-2 mg/g, ip), the trachea was intubated, and a craniotomy was performed. Platelet aggregation in pial microvessels was induced photochemically, by activation of circulating sodium fluorescein (0.1 mg/25 g, iv) with an intense mercury light. The time required for the first platelet aggregate to appear in pial arterioles was significantly shorter in the lead-treated mice than in control. This effect was in a dose-dependent manner; 113 {+-} 44 sec for low dose and 71 {+-} 18 sec for high dose vs 155 {+-} 25 sec for control, P < 0.02 and P < 0.001, respectively. Between the two lead-treated groups, the high dose significantly (P < 0.05) shortened the time to first aggregate. These data evidenced an increased susceptibility to cerebrovascular thrombosis as a result of exposure to lead. 26 refs., 4 figs., 2 tabs.

  10. Initial association of fresh microbial products to soil particles: a joint density fractionation and NanoSIMS study

    NASA Astrophysics Data System (ADS)

    Hatton, Pierre-Joseph; Remusat, Laurent; Brewer, Elizabeth; Derrien, Delphine

    2014-05-01

    While soil microorganisms are increasingly seen as shaping stable soil organic matter (OM) formation, the mechanisms controlling the attachment of microbial metabolites to soil particles are not fully understood yet. We investigate the spatial distribution of freshly produced microbial products among density-isolated fractions of soil using stable C and N isotopes and Nano-scale secondary ion mass spectrometry (NanoSIMS). A surface forest soil was amended with uniformly 13C/15N labeled glycine and incubated for 8 hours in gamma-irradiated and non-sterile soils. Sequential density fractionation was then performed to isolate various classes of aggregates and of single mineral particles. Eight hours after the labeled glycine addition, 7 % of the 13C and 15N was tightly bound to soil assemblages. Comparison of sterile and non-sterile treatments revealed that microbial activity was almost completely responsible for this rapid association (>85 %). The distributions of glycine-derived 13C and 15N, considered as markers of new microbial products, were mapped on particles of the non-sterile treatment using NanoSIMS. New microbial products were heterogeneously distributed and spatially decoupled at the surface of on soil particles. 13C microbial products were scarce and presumably within or in the vicinity of microbial cells. In contrast, 15N microbial products seemed evenly spread at the surface of soil particles, likely as soluble exoenzymes diffusing away from their parent cell. Macroscopic measurements among density fractions suggested that the diffusion of such 15N microbial products was spatially limited yet, because of pore space architecture. NanoSIMS images further allowed gaining insight into the attachment of the new microbial products on particle surfaces already covered by OM, in a multilayer fashion. Using an internal calibration method to determine C/N ratios of NanoSIMS images, we showed the preferential attachment of soluble microbial N-metabolites to N

  11. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

    PubMed Central

    2011-01-01

    Background AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP) enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels. Methods Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP) or Δ9-tetrahydrocannabinol (Δ9-THC). Results After ex vivo exposure to TCDD (a highly potent AhR ligand) for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold) and Cyp1b1 protein (2-fold) in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo) strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression Conclusions Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation. PMID:21867498

  12. Power densities and microbial communities of brewery wastewater-fed microbial fuel cells according to the initial substrates.

    PubMed

    Yu, Jaecheul; Park, Younghyun; Kim, Byunggoon; Lee, Taeho

    2015-01-01

    Single-chamber microbial fuel cells (MFCs) acclimated with glucose, butyrate, propionate, acetate, and a mixture of the four were operated with brewery wastewater (BWW) under a fed-batch mode. Glucose-fed MFC (GW-MFC) showed the highest maximum power density (PDmax) of 1,519 mW/m(2), followed in order by acetate-fed MFC (AW-MFC), mixed substrates-fed MFC (MW-MFC), butyrate-fed MFC (BW-MFC), and propionate-fed MFC (PW-MFC). After changing to BWW, power production was decreased for all MFCs. MFC acclimated with glucose showed the highest PDmax of 890 ± 12 mW/m(2), followed in order by MW-MFC, AW-MFC, BW-MFC, and PW-MFC. The PDmax in BWW-MFC, which was acclimated and operated with BWW, of 552 mW/m(2) was less than that of GW-MFC and MW-MFC but more than that of AW-MFC, BW-MFC, and PW-MFC. MFCs with fermentable substrates were less affected by the BWW. Gammaproteobacteria, including Pseudomonas sp., Acinetobacter sp. and Xanthomonas axonopodis, were found in all MFCs with pure substrates and Rubrivivax benzoatilyticus, thiobacillus sp. and Denitratisoma oestradiolicum belonging to Betaproteobacteria were newly detected in all MFCs when the substrate was changed to BWW. PMID:24973903

  13. High energy emission of GRB 130821A: Constraining the density profile of the circum-burst medium as well as the initial Lorentz factor of the outflow

    SciTech Connect

    Liang, Yun-Feng; Zhou, Bei; He, Hao-Ning; Fan, Yi-Zhong; Wei, Da-Ming; Tam, Pak-Hin Thomas

    2014-02-01

    GRB 130821A was detected by Fermi-GBM/LAT, Konus-WIND, SPI-ACS/INTEGRAL, RHESSI and Mars Odyssey-HEND. Although the data of GRB 130821A are very limited, we show in this work that the high energy γ-ray emission (i.e., above 100 MeV) alone imposes tight constraint on the density profile of the circum-burst medium as well as the initial Lorentz factor of the outflow. The temporal behavior of the high energy γ-ray emission is consistent with the forward shock synchrotron radiation model, and the circum-burst medium likely has a constant-density profile. The Lorentz factor is about a few hundred, similar to other bright GRBs.

  14. Bone Mineral Density Changes Among Women Initiating Proton Pump Inhibitors or H2 Receptor Antagonists: A SWAN Cohort Study

    PubMed Central

    Solomon, Daniel H; Diem, Susan J; Ruppert, Kristine; Juan Lian, Yin; Liu, Chih-Chin; Wohlfart, Alyssa; Greendale, Gail A; Finkelstein, Joel S

    2015-01-01

    Proton pump inhibitors (PPIs) have been associated with diminished bone mineral density (BMD) and an increased risk of fracture; however, prior studies have not yielded consistent results, and many have suboptimal ascertainment of both PPI use and BMD. We used data from the Study of Women’s Health Across the Nation (SWAN), a multicenter, multi-ethnic, community-based longitudinal cohort study of women across the menopause transition to examine the association between annualized BMD changes and new use of PPIs. We compared changes in BMD in new PPI users with changes in BMD in new users of histamine 2 receptor antagonists (H2RAs) and with changes in BMD in subjects who did not use either class of medications. Mixed linear regression models included recognized risk factors for osteoporosis, including demographics, menopausal transition stage, body mass index (BMI), lifestyle factors, as well as comorbidities and concomitant medications. To provide further evidence for the validity of our analytic approach, we also examined the effects of hormone-replacement therapy (HT), a class of medications that should reduce bone loss, on changes in BMD as an internal positive control group. We identified 207 new users of PPIs, 185 new users of H2RAs, and 1,676 non-users. Study subjects had a mean age of 50 years and were followed for a median of 9.9 years. Adjusted models found no difference in the annualized BMD change at the lumbar spine, femoral neck, or total hip in PPI users compared with H2RA users or non-users. These results were robust to sensitivity analyses. BMD increased as expected in HT users, supporting the validity of our study design. These longitudinal analyses plus similar prior studies argue against an association between PPI use and BMD loss. PMID:25156141

  15. Sensitivity of mesoscale-model forecast skill to some initial-data characteristics, data density, data position, analysis procedure and measurement error

    NASA Technical Reports Server (NTRS)

    Warner, Thomas T.; Key, Lawrence E.; Lario, Annette M.

    1989-01-01

    The effects of horizontal and vertical data resolution, data density, data location, different objective analysis algorithms, and measurement error on mesoscale-forecast accuracy are studied with observing-system simulation experiments. Domain-averaged errors are shown to generally decrease with time. It is found that the vertical distribution of error growth depends on the initial vertical distribution of the error itself. Larger gravity-inertia wave noise is produced in forecasts with coarser vertical data resolution. The use of a low vertical resolution observing system with three data levels leads to more forecast errors than moderate and high vertical resolution observing systems with 8 and 14 data levels. Also, with poor vertical resolution in soundings, the initial and forecast errors are not affected by the horizontal data resolution.

  16. Microbubble oscillating in a microvessel filled with viscous fluid: A finite element modeling study.

    PubMed

    Chen, Chuyi; Gu, Yuyang; Tu, Juan; Guo, Xiasheng; Zhang, Dong

    2016-03-01

    Understanding the dynamics of coated-microbubble oscillating in an elastic microvessel is important for effective and safe applications of ultrasound contrast agents (UCAs) in imaging and therapy. Numerical simulations are performed based on a two-dimensional (2D) asymmetric finite element model to investigate the influences of both acoustic driving parameters (e.g., pressure and frequency) and material properties (vessel size, microbubble shell visco-elastic parameters and fluid viscosity) on the dynamic interactions in the bubble-blood-vessel system. The results show that, the constrained effect of the blood vessel along the radial direction will induce the asymmetric bubble oscillation and vessel deformation, as well as shifting the bubble resonance frequency toward the higher frequency range. For a bubble (1.5-μm radius) activated by 1-MHz ultrasound pulses in a microvessel with a radius varying between 2 and 6.5 μm, up to 26.95 kPa shear stress could be generated on the vessel wall at a driving pressure of 0.2 MPa, which should be high enough to damage the vascular endothelial cells. The asymmetrical oscillation ratio of the bubble can be aggravated from 0.12% to 79.94% with the increasing acoustic driving pressure and blood viscosity, or the decreasing vessel size and microbubble shell visco-elastic properties. The maximum compression velocity on the bubble shell will be enhanced from 0.19 to 22.79 m/s by the increasing vessel size and acoustic pressure, or the decreasing microbubble shell visco-elasticity and blood viscosity. As the results, the peak values of microstreaming-induced shear stress on the vessel wall increases from 0.003 to 26.95 kPa and the deformation degree of vessel is raised from 1.01 to 1.49, due to the enhanced acoustic amplitude, or the decreasing vessel size, blood viscosity and microbubble shell visco-elasticity. Moreover, it also suggests that, among above impact parameters, microbubble resonance frequency and UCA shell elasticity

  17. Vascular Mechanics in Decellularized Aortas and Coronary Resistance Microvessels in Type 2 Diabetic db/db Mice.

    PubMed

    Anghelescu, Mircea; Tonniges, Jeffrey R; Calomeni, Ed; Shamhart, Patricia E; Agarwal, Gunjan; Gooch, Keith J; Trask, Aaron J

    2015-11-01

    We previously reported differences in stiffness between macro- and micro-vessels in type 2 diabetes (T2DM). The aim of this study was to define the mechanical properties of the ECM independent of vascular cells in coronary resistance micro-vessels (CRMs) and macro-vessels (aorta) in control Db/db and T2DM db/db mice. Passive vascular remodeling and mechanics were measured in both intact and decellularized CRMs and aortas from 0 to 125 mmHg. We observed no differences in intact control and diabetic aortic diameters, wall thicknesses, or stiffnesses (p > 0.05). Aortic decellularization caused a significant increase in internal and external diameters and incremental modulus over a range of pressures that occurred to a similar degree in T2DM. Differences in aortic diameters due to decellularization occurred at lower pressures (0-75 mmHg) and converged with intact aortas at higher, physiological pressures (100-125 mmHg). In contrast, CRM decellularization caused increased internal diameter and incremental modulus only in the db/db mice, but unlike the aorta, the intact and decellularized CRM curves were more parallel. These data suggest that (1) micro-vessels may be more sensitive to early adverse consequences of diabetes than macro-vessels and (2) the ECM is a structural limit in aortas, but not CRMs. PMID:25986954

  18. Temporal and spatial variations of wall shear stress in the entrance region of microvessels.

    PubMed

    Oulaid, Othmane; Zhang, Junfeng

    2015-06-01

    Using a simplified two-dimensional divider-channel setup, we simulate the development process of red blood cell (RBC) flows in the entrance region of microvessels to study the wall shear stress (WSS) behaviors. Significant temporal and spatial variation in WSS is noticed. The maximum WSS magnitude and the strongest variation are observed at the channel inlet due to the close cell-wall contact. From the channel inlet, both the mean WSS and variation magnitude decrease, with a abrupt drop in the close vicinity near the inlet and then a slow relaxation over a relatively long distance; and a relative stable state with approximately constant mean and variation is established when the flow is well developed. The correlations between the WSS variation features and the cell free layer (CFL) structure are explored, and the effects of several hemodynamic parameters on the WSS variation are examined. In spite of the model limitations, the qualitative information revealed in this study could be useful for better understanding relevant processes and phenomena in the microcirculation. PMID:25781004

  19. Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells.

    PubMed

    Brown, Rachel C; Morris, Andrew P; O'Neil, Roger G

    2007-01-26

    Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions. PMID:17169347

  20. The Wall-stress Footprint of Blood Cells Flowing in Microvessels

    PubMed Central

    Freund, Jonathan B.; Vermot, Julien

    2014-01-01

    It is well known that mechanotransduction of hemodynamic forces mediates cellular processes, particularly those that lead to vascular development and maintenance. Both the strength and space-time character of these forces have been shown to affect remodeling and morphogenesis. However, the role of blood cells in the process remains unclear. We investigate the possibility that in the smallest vessels blood’s cellular character of itself will lead to forces fundamentally different than the time-averaged forces usually considered, with fluctuations that may significantly exceed their mean values. This is quantitated through the use of a detailed simulation model of microvessel flow in two principal configurations: a diameter D=6.5μm tube—a model for small capillaries through which red blood cells flow in single-file—and a D=12μm tube—a model for a nascent vein or artery through which the cells flow in a confined yet chaotic fashion. Results in both cases show strong sensitivity to the mean flow speed U. Peak stresses exceed their means by greater than a factor of 10 when U/D≲10 s−1, which corresponds to the inverse relaxation time of a healthy red blood cell. This effect is more significant for smaller D cases. At faster flow rates, including those more commonly observed under normal, nominally static physiological conditions, the peak fluctuations are more comparable with the mean shear stress. Implications for mechanotransduction of hemodynamic forces are discussed. PMID:24507616

  1. Contribution of selectins to leucocyte sequestration in pulmonary microvessels by intravital microscopy in rabbits.

    PubMed Central

    Kuebler, W M; Kuhnle, G E; Groh, J; Goetz, A E

    1997-01-01

    1. Sequestration of leucocytes in the lung is the net result of leucocyte rolling and sticking in pulmonary arterioles and venules and their retention in alveolar capillaries. 2. In order to investigate whether adhesion molecules of the selectin family contribute to these phenomena the effects of fucoidin (an inhibitor of L- and P-selectin) on microhaemodynamics and leucocyte kinetic were studied in pulmonary arterioles, capillaries and venules by means of intravital fluorescence microscopy in a rabbit model. 3. Fucoidin reduced leucocyte rolling in pulmonary arterioles and venules by 75 and 83%, respectively, without affecting leucocyte sticking. In alveolar capillaries, fucoidin reduced leucocyte retention and accelerated leucocyte passage, thus reducing the alveolar transit time of leucocytes by 62%. 4. It is concluded that rolling of leucocytes in pulmonary microvessels is mediated by selectins, whereas sticking relies on selectin-independent mechanisms. 5. Leucocyte retention in alveolar capillaries is not due solely to mechanical hindrance of leucocyte passage through narrow vessel segments, as previously hypothesized, but also depends on interaction of leucocytes with the capillary endothelium. PMID:9192309

  2. The wall traction induced by flowing red blood cells in model microvessels and its potential mechanotransduction

    NASA Astrophysics Data System (ADS)

    Freund, Jonathan; Vermot, Julien

    2013-11-01

    There is evidence in early embryonic development, even well before advective oxygen transport is important, that the presence of red bloods cells per se trigger essential steps of normal vascular development. For example, showed that sequestration of blood cells early in the development of a mouse, such that the hematocrit is reduced, suppresses normal vascular network development. Vascular development also provides a model for remodeling and angiogenesis. We consider the transient stresses associated with blood cells flowing in model microvessels of comparable diameter to those at early stages of development (6 μm to 12 μm). A detailed simulation tool is used to show that passing blood cells present a significant fluctuating traction signature on the vessel wall, well above the mean stresses. This is particularly pronounced for slow flows (<= 50 μm/s) or small diameters (<= 7 μm), for which root-mean-square wall traction fluctuations can exceed their mean. These events potentially present mechanotranduction triggers that direct development or remodeling. Attenuation of such fluctuating tractions by a viscoelastic endothelial glycocalyx layer is also considered. NSF supported.

  3. Control of in vivo microvessel ingrowth by modulation of biomaterial local architecture and chemistry

    SciTech Connect

    Sanders, Joan E.; Baker, Aaron B.; Golledge, Stephen

    2002-04-01

    We developed a method for controlling local architecture and chemistry simultaneously in biomaterial implants to control microvessel ingrowth in vivo. Porous polypropylene disks (5 mm in diameter and 40 um thick) were plasma-coated with a fluoropolymer and then laser-drilled with 50-*m-diameter holes through their thickness. We then oxidized the disks to create hydroxyl functionality on the exposed polypropylene (inside the holes). Acrylamide was grafted to the hydroxyl groups through polymerization in the presence of activating ceric ions. Staining with toluidine blue O demonstrated that grafting occurred only inside the holes. We used the Hoffman degradation reaction to convert the amide groups of acrylamide to amine groups, and then we used ethylene glycol diglycidyl ether to attach biomolecules of interest inside the holes: secreted protein acidic and rich in cysteine (SPARC) peptide Lys-Gly-His-Lys (KGHK; angiogenic), thrombospondin-2 (TSP; antiangiogenic), or albumin (rat; neutral). In vivo testing in a rat subcutaneous dorsum model for a 3-week interval demonstrated a greater vessel surface area (p = 0.032) and a greater number of vessels (p = 0.043) in tissue local to the holes with KGHKimmobilized disks than with TSP-immobilized disks. However, differences between KGHK-immobilized and albuminimmobilized disks were less significant (p = 0.120 and p = 0.289 for the vessel surface area and number of vessels, respectively). The developed methods have potential applications in biomaterial design applications for which selective neovascularization is desired.

  4. Dispersion characteristics of blood during nanoparticle assisted drug delivery process through a permeable microvessel.

    PubMed

    Shaw, Sachin; Ganguly, Suvankar; Sibanda, Precious; Chakraborty, Suman

    2014-03-01

    Nanoparticle assisted drug delivery holds considerable promise as a means of next generation of medicine that allows for the intravascular delivery of drugs and contrast agents. We analyze the dispersion characteristics of blood during a nanoparticle-assisted drug delivery process through a permeable microvessel. The contribution of molecular and convective diffusion is based on Taylor's theory of shear dispersion. The aggregation of red blood cells in blood flowing through small tubes (less than 40 μm) leads to the two-phase flow with a core of rouleaux surrounded by a cell-depleted peripheral layer. The core region models as a non-Newtonian Casson fluid and the peripheral region acts as a Newtonian fluid. We investigate the influence of the nanoparticle volume fraction, the permeability of the blood vessel, pressure distribution, yield stress and the radius of the nanoparticle on the effective dispersion. We show that the effective diffusion of the nanoparticles reduces with an increase in nanoparticle volume fraction. The permeability of the blood vessels increases the effective dispersion at the inlet. The present study contributes to the fundamental understanding on how the particulate nature of blood influences nanoparticle delivery, and is of particular significance in nanomedicine design for targeted drug delivery applications. PMID:24406843

  5. Elucid—exploring the local universe with the reconstructed initial density field. I. Hamiltonian Markov chain Monte Carlo method with particle mesh dynamics

    SciTech Connect

    Wang, Huiyuan; Mo, H. J.; Yang, Xiaohu; Lin, W. P.; Jing, Y. P.

    2014-10-10

    Simulating the evolution of the local universe is important for studying galaxies and the intergalactic medium in a way free of cosmic variance. Here we present a method to reconstruct the initial linear density field from an input nonlinear density field, employing the Hamiltonian Markov Chain Monte Carlo (HMC) algorithm combined with Particle-mesh (PM) dynamics. The HMC+PM method is applied to cosmological simulations, and the reconstructed linear density fields are then evolved to the present day with N-body simulations. These constrained simulations accurately reproduce both the amplitudes and phases of the input simulations at various z. Using a PM model with a grid cell size of 0.75 h {sup –1} Mpc and 40 time steps in the HMC can recover more than half of the phase information down to a scale k ∼ 0.85 h Mpc{sup –1} at high z and to k ∼ 3.4 h Mpc{sup –1} at z = 0, which represents a significant improvement over similar reconstruction models in the literature, and indicates that our model can reconstruct the formation histories of cosmic structures over a large dynamical range. Adopting PM models with higher spatial and temporal resolutions yields even better reconstructions, suggesting that our method is limited more by the availability of computer resource than by principle. Dynamic models of structure evolution adopted in many earlier investigations can induce non-Gaussianity in the reconstructed linear density field, which in turn can cause large systematic deviations in the predicted halo mass function. Such deviations are greatly reduced or absent in our reconstruction.

  6. The Effects of Taoren-Honghua Herb Pair on Pathological Microvessel and Angiogenesis-Associated Signaling Pathway in Mice Model of CCl4-Induced Chronic Liver Disease.

    PubMed

    Xi, Shengyan; Yue, Lifeng; Shi, Mengmeng; Peng, Ying; Xu, Yangxinzi; Wang, Xinrong; Li, Qian; Kang, Zhijun; Li, Hanjing; Wang, Yanhui

    2016-01-01

    Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0.1 mg/kg), (4) THHP (5.53, 2.67, and 1.33 g/kg), and (5) Tao Hong Siwu Decoction (THSWD) (8.50 g/kg). Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF) were measured with ELISA. VEGF, kinase insert domain-containing receptor (KDR), Flt-1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt-1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis-associated VEGF and its upstream and downstream signaling pathways. PMID:27293456

  7. The Effects of Taoren-Honghua Herb Pair on Pathological Microvessel and Angiogenesis-Associated Signaling Pathway in Mice Model of CCl4-Induced Chronic Liver Disease

    PubMed Central

    Xi, Shengyan; Yue, Lifeng; Shi, Mengmeng; Peng, Ying; Xu, Yangxinzi; Wang, Xinrong; Li, Qian; Kang, Zhijun; Li, Hanjing; Wang, Yanhui

    2016-01-01

    Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0.1 mg/kg), (4) THHP (5.53, 2.67, and 1.33 g/kg), and (5) Tao Hong Siwu Decoction (THSWD) (8.50 g/kg). Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF) were measured with ELISA. VEGF, kinase insert domain-containing receptor (KDR), Flt-1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt-1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis-associated VEGF and its upstream and downstream signaling pathways. PMID:27293456

  8. Model-based Characterization of the Parameters of Dissimilatory Sulfate Reduction Under the Effect of Different Initial Density of Desulfovibrio piger Vib-7 Bacterial Cells.

    PubMed

    Kushkevych, Ivan; Bolis, Marco; Bartos, Milan

    2015-01-01

    The objective of this study was to design a model of dissimilatory sulfate reduction process using the Verhulst function, with a particular focus on the kinetics of bacterial growth, sulfate and lactate consumption, and accumulation of hydrogen sulfide and acetate. The effect of the initial density (0.12±0.011, 0.25±0.024, 0.5±0.048 and 1.0±0.096 mg cells/ml of medium) of the sulfate-reducing bacteria Desulfovibrio piger Vib-7 on the growth and dissimilatory sulfate reduction was studied. The exponential growth phase of the D. piger Vib-7 was observed for 72 hours of cultivation at the (0.12 and 0.25 mg/ml) initial concentration of bacterial cells. Sulfate and lactate were consumed incompletely during this time. The increase in the initial concentration of cells to 0.5 and 1 mg/ml led to a shortening of the exponential bacterial growth phase and a shift to the stationary phase of the growth. In the case of 0.5 mg/ml seeding, the stationary growth phase was observed in the 36(th) hour of cultivation. The increase in the initial concentration of cells to 1 mg/ml led to the beginning of the stationary growth phase in 24th hours of cultivation. Under these conditions, sulfate and lactate were consumed completely in the 48th hour of cultivation. The kinetic analysis of the curves of bacterial growth and the process of dissimilatory sulfate reduction by D. piger Vib-7 was carried out. PMID:26668663

  9. Emergent molecular theory of initiation of detonation: the effect of molecular and crystal structure on thermal stability of high density energy materials

    NASA Astrophysics Data System (ADS)

    Kukla, Maija; Tsyshevsky, Roman; Sharia, Onise

    The sensitivity to detonation initiation of high density energy materials along with their performance are two most important criteria for choosing the best material for explosive formulations, booster engines, detonators, etc. After numerous experimental and theoretical attempts to develop a single parameter describing sensitivity of different classes of energetic materials, one concludes that the complexity of physical and chemical explosive properties cannot be trivialized. We report here the results of our theoretical and computational studies of thermal decomposition mechanisms and kinetics of five classes of EM: pentaerythritol tetranitrate (PETN), nitramine cyclotetramethylene-tetranitramine (HMX), diamino-dinitroethene (DADNE), bis-(nitrofurazano)-furoxane (BNFF) and benchmark triamino-trinitrobenzene (TATB). Our modeling reveals how the thermal stability depends on the molecular structure of the material and how the crystal structure may additionally hinder or catalyze decomposition reactions. We will also discuss an effect of crystalline defects on sensitivity and performance of materials.

  10. Initial stages of ITO/Si interface formation: In situ x-ray photoelectron spectroscopy measurements upon magnetron sputtering and atomistic modelling using density functional theory

    SciTech Connect

    Løvvik, O. M.; Diplas, S.; Ulyashin, A.; Romanyuk, A.

    2014-02-28

    Initial stages of indium tin oxide (ITO) growth on a polished Si substrate upon magnetron sputtering were studied experimentally using in-situ x-ray photoelectron spectroscopy measurements. The presence of pure indium and tin, as well as Si bonded to oxygen at the ITO/Si interface were observed. The experimental observations were compared with several atomistic models of ITO/Si interfaces. A periodic model of the ITO/Si interface was constructed, giving detailed information about the local environment at the interface. Molecular dynamics based on density functional theory was performed, showing how metal-oxygen bonds are broken on behalf of silicon-oxygen bonds. These theoretical results support and provide an explanation for the present as well as previous ex-situ and in-situ experimental observations pointing to the creation of metallic In and Sn along with the growth of SiO{sub x} at the ITO/Si interface.

  11. Non-Newtonian characteristics of peristaltic flow of blood in micro-vessels

    NASA Astrophysics Data System (ADS)

    Maiti, S.; Misra, J. C.

    2013-08-01

    Of concern in the paper is a generalized theoretical study of the non-Newtonian characteristics of peristaltic flow of blood through micro-vessels, e.g. arterioles. The vessel is considered to be of variable cross-section and blood to be a Herschel-Bulkley type of fluid. The progressive wave front of the peristaltic flow is supposed sinusoidal/straight section dominated (SSD) (expansion/contraction type); Reynolds number is considered to be small with reference to blood flow in the micro-circulatory system. The equations that govern the non-Newtonian peristaltic flow of blood are considered to be non-linear. The objective of the study has been to examine the effect of amplitude ratio, mean pressure gradient, yield stress and the power law index on the velocity distribution, wall shear stress, streamline pattern and trapping. It is observed that the numerical estimates for the aforesaid quantities in the case of peristaltic transport of blood in a channel are much different from those for flow in an axisymmetric vessel of circular cross-section. The study further shows that peristaltic pumping, flow velocity and wall shear stress are significantly altered due to the non-uniformity of the cross-sectional radius of blood vessels of the micro-circulatory system. Moreover, the magnitude of the amplitude ratio and the value of the fluid index are important parameters that affect the flow behaviour. Novel features of SSD wave propagation that affect the flow behaviour of blood have also been discussed.

  12. Three-dimensional computational modeling of multiple deformable cells flowing in microvessels

    NASA Astrophysics Data System (ADS)

    Doddi, Sai K.; Bagchi, Prosenjit

    2009-04-01

    Three-dimensional (3D) computational modeling and simulation are presented on the motion of a large number of deformable cells in microchannels. The methodology is based on an immersed boundary method, and the cells are modeled as liquid-filled elastic capsules. The model retains two important features of the blood flow in the microcirculation, that is, the particulate nature of blood and deformation of the erythrocytes. The tank-treading and tumbling motion and the lateral migration, as observed for erythrocytes in dilute suspension, are briefly discussed. We then present results on the motion of multiple cells in semidense suspension and study how their collective dynamics leads to various physiologically relevant processes such as the development of the cell-free layer and the Fahraeus-Lindqvist effect. We analyze the 3D trajectory and velocity fluctuations of individual cell in the suspension and the plug-flow velocity profile as functions of the cell deformability, hematocrit, and vessel size. The numerical results allow us to directly obtain various microrheological data, such as the width of the cell-free layer, and the variation in the apparent blood viscosity and hematocrit over the vessel cross section. We then use these results to calculate the core and plasma-layer viscosity and show that the two-phase (or core-annular) model of blood flow in microvessels underpredicts the blood velocity obtained in the simulations by as much as 40%. Based on a posteriori analysis of the simulation data, we develop a three-layer model of blood flow by taking into consideration the smooth variation in viscosity and hematocrit across the interface of the cell-free layer and the core. We then show that the blood velocity predicted by the three-layer model agrees very well with that obtained from the simulations.

  13. Evidence for a non-universal stellar initial mass function in low-redshift high-density early-type galaxies

    NASA Astrophysics Data System (ADS)

    Dutton, Aaron A.; Mendel, J. Trevor; Simard, Luc

    2012-05-01

    We determine an absolute calibration of stellar mass-to-light ratios for the densest ≃3 per cent of early-type galaxies in the local Universe (redshift z≃ 0.08) from Sloan Digital Sky Survey (SDSS) Data Release 7. This sample of ˜4000 galaxies has, assuming a Chabrier initial mass function (IMF), effective stellar surface densities Σe > 2500 M⊙ pc-2, stellar population synthesis (SPS) stellar masses log10(MSPS/M⊙) < 10.8 and aperture velocity dispersions of ? (68 per cent range). In contrast to typical early-type galaxies, we show that these dense early-type galaxies follow the virial Fundamental Plane, which suggests that mass follows light. With the additional assumption that any dark matter does not follow the light, the dynamical masses of dense galaxies provide a direct measurement of stellar masses. Our dynamical masses (Mdyn), obtained from the spherical Jeans equations, are only weakly sensitive to the choice of anisotropy (β) due to the relatively large aperture of the SDSS fibre for these galaxies: Rap≃ 1.5Re. Assuming isotropic orbits (β= 0), we find a median log10(Mdyn/MSPS) = 0.233 ± 0.003, consistent with a Salpeter IMF, while more bottom-heavy IMFs and standard Milky Way IMFs are strongly disfavoured. Our results are consistent with, but do not require, a dependence of the IMF on dynamical mass or velocity dispersion. We find evidence for a colour dependence to the IMF such that redder galaxies have heavier IMFs with Mdyn/MSPS∝ (g-r)1.13 ± 0.09. This may reflect a more fundamental dependence of the IMF on the age or metallicity of a stellar population, or the density at which the stars formed.

  14. In Situ Observation of Initial Stage in Dielectric Growth and Deposition of Ultrahigh Nucleation Density Dielectric on Two-Dimensional Surfaces.

    PubMed

    Park, Jun Hong; Movva, Hema C P; Chagarov, Evgeniy; Sardashti, Kasra; Chou, Harry; Kwak, Iljo; Hu, Kai-Ting; Fullerton-Shirey, Susan K; Choudhury, Pabitra; Banerjee, Sanjay K; Kummel, Andrew C

    2015-10-14

    Several proposed beyond-CMOS devices based on two-dimensional (2D) heterostructures require the deposition of thin dielectrics between 2D layers. However, the direct deposition of dielectrics on 2D materials is challenging due to their inert surface chemistry. To deposit high-quality, thin dielectrics on 2D materials, a flat lying titanyl phthalocyanine (TiOPc) monolayer, deposited via the molecular beam epitaxy, was employed to create a seed layer for atomic layer deposition (ALD) on 2D materials, and the initial stage of growth was probed using in situ STM. ALD pulses of trimethyl aluminum (TMA) and H2O resulted in the uniform deposition of AlOx on the TiOPc/HOPG. The uniformity of the dielectric is consistent with DFT calculations showing multiple reaction sites are available on the TiOPc molecule for reaction with TMA. Capacitors prepared with 50 cycles of AlOx on TiOPc/graphene display a capacitance greater than 1000 nF/cm(2), and dual-gated devices have current densities of 10(-7)A/cm(2) with 40 cycles. PMID:26393281

  15. Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom

    PubMed Central

    2013-01-01

    Introduction In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom. Methods The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine. Results The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes. Conclusions We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used. PMID:24286540

  16. Weight and Lean Body Mass Change with Antiretroviral Initiation and Impact on Bone Mineral Density: AIDS Clinical Trials Group Study A5224s

    PubMed Central

    Erlandson, Kristine Mace; Kitch, Douglas; Tierney, Camlin; Sax, Paul E.; Daar, Eric S.; Tebas, Pablo; Melbourne, Kathleen; Ha, Belinda; Jahed, Nasreen C.; Mccomsey, Grace A.

    2014-01-01

    Objective To compare the effect initiating different antiretroviral therapy (ART) regimens have on weight, body mass index (BMI), and lean body mass (LBM) and explore how changes in body composition are associated with bone mineral density (BMD). Methods A5224s was a substudy of A5202, a prospective trial of 1857 ART-naïve participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). All subjects underwent dual-energy absorptiometry (DXA) and abdominal CT for body composition. Analyses used 2-sample t-tests and linear regression. Results A5224s included 269 subjects: 85% male, 47% white non-Hispanic, median age 38 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 233 cells/µL. Overall, significant gains occurred in weight, BMI, and LBM at 96 weeks post randomization (all p<0.001). Assignment to ATV/r (vs EFV) resulted in significantly greater weight (mean difference 3.35 kg) and BMI gain (0.88 kg/m2; both p=0.02), but not LBM (0.67 kg; p=0.15), while ABC/3TC and TDF/FTC were not significantly different (p≥0.10). In multivariable analysis, only lower baseline CD4 count and higher HIV-1 RNA were associated with greater increase in weight, BMI, or LBM. In multivariable analyses, increased LBM was associated with an increased hip BMD. Conclusions ABC/3TC vs. TDF/FTC did not differ in change in weight, BMI, or LBM; ATV/r vs. EFV resulted in greater weight and BMI gain but not LBM. A positive association between increased LBM and increased hip BMD should be further investigated through prospective interventional studies to verify the impact of increased LBM on hip BMD. PMID:24384588

  17. Initial implementation of the conversion from the energy-subtracted CT number to electron density in tissue inhomogeneity corrections: An anthropomorphic phantom study of radiotherapy treatment planning

    SciTech Connect

    Tsukihara, Masayoshi; Noto, Yoshiyuki; Sasamoto, Ryuta; Hayakawa, Takahide; Saito, Masatoshi

    2015-03-15

    Purpose: To achieve accurate tissue inhomogeneity corrections in radiotherapy treatment planning, the authors had previously proposed a novel conversion of the energy-subtracted computed tomography (CT) number to an electron density (ΔHU–ρ{sub e} conversion), which provides a single linear relationship between ΔHU and ρ{sub e} over a wide range of ρ{sub e}. The purpose of this study is to present an initial implementation of the ΔHU–ρ{sub e} conversion method for a treatment planning system (TPS). In this paper, two example radiotherapy plans are used to evaluate the reliability of dose calculations in the ΔHU–ρ{sub e} conversion method. Methods: CT images were acquired using a clinical dual-source CT (DSCT) scanner operated in the dual-energy mode with two tube potential pairs and an additional tin (Sn) filter for the high-kV tube (80–140 kV/Sn and 100–140 kV/Sn). Single-energy CT using the same DSCT scanner was also performed at 120 kV to compare the ΔHU–ρ{sub e} conversion method with a conventional conversion from a CT number to ρ{sub e} (Hounsfield units, HU–ρ{sub e} conversion). Lookup tables for ρ{sub e} calibration were obtained from the CT image acquisitions for tissue substitutes in an electron density phantom (EDP). To investigate the beam-hardening effect on dosimetric uncertainties, two EDPs with different sizes (a body EDP and a head EDP) were used for the ρ{sub e} calibration. Each acquired lookup table was applied to two radiotherapy plans designed using the XiO TPS with the superposition algorithm for an anthropomorphic phantom. The first radiotherapy plan was for an oral cavity tumor and the second was for a lung tumor. Results: In both treatment plans, the performance of the ΔHU–ρ{sub e} conversion was superior to that of the conventional HU–ρ{sub e} conversion in terms of the reliability of dose calculations. Especially, for the oral tumor plan, which dealt with dentition and bony structures, treatment

  18. A high-density wireless underground sensor network (WUSN) to quantify hydro-ecological interactions for a UK floodplain; project background and initial results

    NASA Astrophysics Data System (ADS)

    Verhoef, A.; Choudhary, B.; Morris, P. J.; McCann, J.

    2012-04-01

    Floodplain meadows support some of the most diverse vegetation in the UK, and also perform key ecosystem services, such as flood storage and sediment retention. However, the UK now has less than 1500 ha of this unique habitat remaining. In order to conserve and better exploit the services provided by this grassland, an improved understanding of its functioning is essential. Vegetation functioning and species composition are known to be tightly correlated to the hydrological regime, and related temperature and nutrient regime, but the mechanisms controlling these relationships are not well established. The FUSE* project aims to investigate the spatiotemporal variability in vegetation functioning (e.g. photosynthesis and transpiration) and plant community composition in a floodplain meadow near Oxford, UK (Yarnton Mead), and their relationship to key soil physical variables (soil temperature and moisture content), soil nutrient levels and the water- and energy-balance. A distributed high density Wireless Underground Sensor Network (WUSN) is in the process of being established on Yarnton Mead. The majority, or ideally all, of the sensing and transmitting components will be installed below-ground because Yarnton Mead is a SSSI (Site of Special Scientific Interest, due to its unique plant community) and because occasionally sheep or cattle are grazing on it, and that could damage the nodes. This prerequisite has implications for the maximum spacing between UG nodes and their communications technologies; in terms of signal strength, path losses and requirements for battery life. The success of underground wireless communication is highly dependent on the soil type and water content. This floodplain environment is particularly challenging in this context because the soil contains a large amount of clay near the surface and is therefore less favourable to EM wave propagation than sandy soils. Furthermore, due to high relative saturation levels (as a result of high

  19. Fucoidan Extracted from Hijiki Protects Brain Microvessel Endothelial Cells Against Diesel Exhaust Particle Exposure-Induced Disruption.

    PubMed

    Choi, Young-Sook; Eom, Sang-Yong; Kim, In-Soo; Ali, Syed F; Kleinman, Michael T; Kim, Yong-Dae; Kim, Heon

    2016-05-01

    This study was performed to evaluate the protective effects of fucoidan against the decreased function of primary cultured bovine brain microvessel endothelial cells (BBMECs) after exposure to diesel exhaust particles (DEPs). BBMECs were extracted from bovine brains and cultured until confluent. To evaluate the function of BBMECs, we performed a permeability test using cell-by-cell equipment and by Western blot analysis for zonular occludens-1 (ZO-1), which is a tight junction protein of BMECs, and evaluated oxidative stress in BBMECs using the DCFH-DA assay and the CUPRAC-BCS assay. The increased oxidative stress in BBMECs following DEP exposure was suppressed by fucoidan. In addition, permeability of BBMECs induced by DEP exposure was decreased by fucoidan treatment. Our results showed that fucoidan protects against BBMEC disruption induced by DEP exposure. This study provides evidence that fucoidan might protect the central nervous system (CNS) against DEP exposure. PMID:27152978

  20. Influence of polymer content in Ca-deficient hydroxyapatite-polycaprolactone nanocomposites on the formation of microvessel-like structures.

    PubMed

    Fuchs, S; Jiang, X; Gotman, I; Makarov, C; Schmidt, H; Gutmanas, E Y; Kirkpatrick, C J

    2010-08-01

    Calcium phosphate (CaP) ceramics are widely used in bone tissue engineering due to their good osteoconductivity. The mechanical properties of CaP can be modified by the addition of small volume fractions of biodegradable polymers such as polycaprolactone (PCL). Nevertheless, it is also important to evaluate how the polymer content influences cell-material or cell-cell interactions because of potential consequences for bone regeneration and vascularization. In this study we assessed the general biocompatibilty of Ca-deficient hydroxyapatite (CDHA)-PCL disks containing nominally 11 and 24% polycaprolactone using human umbilical vein endothelial cells and human primary osteoblasts. Confocal microscopy showed that both CDHA-PCL variants supported the growth of both cell types. In terms of the endothelial cells grown on CDHA-PCL nanocomposites with 24% PCL, an increased expression of the endothelial marker vWF compared to CDHA-PCL with 11% PCL was observed in real-time polymerase chain reaction analysis. In addition to monocultures, co-cultures of outgrowth endothelial cells, derived from peripheral blood, and primary osteoblasts were assessed as an example of a more complex test system for bone regeneration and vascularization. Constructs based on CDHA with different PCL contents were investigated with regard to the formation of microvessel-like structures induced by the co-culture process using confocal microscopy and quantitative image analysis. Furthermore, the osteogenic differentiation of the co-culture was assessed. As a result, more pre-vascular structures were observed after 1 week on the CDHA-PCL disks with 24% PCL, whereas after 4 weeks of culture the extent of microvessel-like structure formation was slightly higher on the CDHA with 11% PCL. In contrast to this, variation of PCL content had no effect on the osteogenic differentiation in the co-culture. PMID:20144913

  1. Generation of Bioactive Oxylipins from Exogenously Added Arachidonic, Eicosapentaenoic and Docosahexaenoic Acid in Primary Human Brain Microvessel Endothelial Cells.

    PubMed

    Aukema, Harold M; Winter, Tanja; Ravandi, Amir; Dalvi, Siddhartha; Miller, Donald W; Hatch, Grant M

    2016-05-01

    The human blood-brain barrier (BBB) is the restrictive barrier between the brain parenchyma and the circulating blood and is formed in part by microvessel endothelial cells. The brain contains significant amounts of arachidonic acid (ARA), and docosahexaenoic acid (DHA), which potentially give rise to the generation of bioactive oxylipins. Oxylipins are oxygenated fatty acid metabolites that are involved in an assortment of biological functions regulating neurological health and disease. Since it is not known which oxylipins are generated by human brain microvessel endothelial cells (HBMECs), they were incubated for up to 30 min in the absence or presence of 0.1-mM ARA, eicosapentaenoic acid (EPA) or DHA bound to albumin (1:1 molar ratio), and the oxylipins generated were examined using high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Of 135 oxylipins screened in the media, 63 were present at >0.1 ng/mL at baseline, and 95 were present after incubation with fatty acid. Oxylipins were rapidly generated and reached maximum levels by 2-5 min. While ARA, EPA and DHA each stimulated the production of oxylipins derived from these fatty acids themselves, ARA also stimulated the production of oxylipins from endogenous 18- and 20-carbon fatty acids, including α-linolenic acid. Oxylipins generated by the lipoxygenase pathway predominated both in resting and stimulated states. Oxylipins formed via the cytochrome P450 pathway were formed primarily from DHA and EPA, but not ARA. These data indicate that HBMECs are capable of generating a plethora of bioactive lipids that have the potential to modulate BBB endothelial cell function. PMID:26439837

  2. Silane-initiated nucleation in chemically active plasmas: validation of density functionals, mechanisms, and pressure-dependent variational transition state calculations.

    PubMed

    Bao, Junwei Lucas; Truhlar, Donald G

    2016-04-21

    The growth of anionic silicon hydride clusters is a critically important process in nanodusty plasmas. In the current study, we focus on the formation of homologs of silylene (Sin+1H2n+2(-), n = 3, 4) and silyl (SinH2n+1(-), n = 4, 5) anions via anion-neutral reaction pathways. Species like silyl or silylene anions and their related elementary reactions, which are involved in the formation of silicon hydride clusters, were not used in developing exchange-correlation (xc) density functionals (i.e., they were not included in the training set of semiempirical density functionals); therefore, we explored the accuracy of various widely used xc density functionals based on reaction energies and barrier heights. Among the 21 density functionals we tested, M06-2X has the best performance for a hybrid functional, and MN15-L has the best performance for a local functional. Thermal rate constants of the elementary reactions involved in the reaction mechanism are calculated using M06-2X and multistructural canonical variational transition state theory with the small-curvature tunneling approximation (MS-CVT/SCT). The pressure dependence of unimolecular isomerization reactions is treated with system-specific quantum RRK theory (SS-QRRK) and the Lindemann-Hinshelwood mechanism. PMID:27009479

  3. Dynamics of Gram-negative bacteria population density in a soil in the course of the succession initiated by chitin and cellulose

    NASA Astrophysics Data System (ADS)

    Konstantin, Ivanov; Lubov, Polyanskaya

    2014-05-01

    The functions of actinomycetes in polymer destruction in soil traditionally considered as the dominant, compare to another groups of bacteria. Gram-positive bacteria also have ecological functions in destruction of soil organic matter. The role of Gram-negative bacteria has been researched in the microbial succession in terms of polymers destruction, which are widely spreads in soils: chitin and cellulose. The method with nalidixic acid as an inhibitor of DNA division of Gram-negative bacteria was modified. By modified method microbial succession of Gram-negative bacteria in the different horizons of a chernozem under aerobic and anaerobic conditions was researched. Chitin and cellulose as the source of nutrients with moistening was used in experiments. The introduction of chitin had no positive effect on the population density of Gram-negative bacteria in a chernozem, but it advanced the date of their appearance in microbial succession: the maximum of Gram-negative bacteria population density was registered on the 3rd- 7th day of the experiment with adding chitin. Compare to the control, which one was without any nutrient adding this dynamics registered much earlier. Consequently, the introduction of chitin as an additional source of nutrition promoted revealing of the Gram-negative bacteria in soil already at the early stages of the succession. In the course of the succession, when the fungal mycelium begins to die off, the actinomycetic mycelium increases in length, i.e., Gram-negative bacteria are replaced at this stage with Gram-positive ones, the leading role among which belongs to actinomycetes. The growth rate of Gram-negative bacteria is higher than that of actinomycetes, so they start chitin utilization at the early stages of the succession, whereas actinomycetes dominate at the late stages. The population density of Gram-negative bacteria was lower under the anaerobic conditions as compared with that in the aerobic ones. The population density of Gram

  4. Fluctuations in the population density of Gram-negative bacteria in a chernozem in the course of a succession initiated by moistening and chitin and cellulose introduction

    NASA Astrophysics Data System (ADS)

    Polyanskaya, L. M.; Ivanov, K. E.; Zvyagintsev, D. G.

    2012-10-01

    The role has been studied of Gram-negative bacteria in the destruction of polymers widely spread in soils: chitin and cellulose. The introduction of chitin had no positive effect on the population density of Gram-negative bacteria, but it advanced the date of their appearance: the maximum population density of Gram-negative bacteria was recorded not on the 7th-15th day as in the control but much earlier, on the 3rd-7th day of the experiment. Consequently, the introduction of chitin as an additional source of nutrition promoted revealing of the Gram-negative bacteria already at the early stages of the succession. In the course of the succession, when the fungal mycelium begins to die off, the actinomycetic mycelium increases in length, i.e., Gram-negative bacteria are replaced at this stage with Gram-positive ones, the leading role among which belongs to actinomycetes. The growth rate of Gram-negative bacteria is higher than that of actinomycetes, so they start chitin utilization at the early stages of the succession, whereas actinomycetes dominate at the late stages. The population density of Gram-negative bacteria was lower under the anaerobic conditions as compared with that in the aerobic ones. The population density of Gram-negative bacteria in the lower layer of the A horizon and in the B horizon was slightly higher only in the case of the chitin introduction. When cellulose was introduced into the soil under aerobic conditions, the population density of Gram-negative bacteria in all the layers of the A horizon was maximal from the 14th to the 22nd day of the experiment. Cellulose was utilized in the soil mostly by fungi, and this was suggested by the increase of the length of the fungal mycelium. Simultaneously, an increase in the length of the actinomycetal mycelium was observed, as these organisms also perform cellulose hydrolysis in soils. The Gram-negative bacteria began to develop at the stage of the fungal mycelium destruction, which indirectly

  5. Inhibition of endothelial nitric oxide synthase decreases breast cancer cell MDA-MB-231 adhesion to intact microvessels under physiological flows.

    PubMed

    Zhang, Lin; Zeng, Min; Fu, Bingmei M

    2016-06-01

    Nitric oxide (NO) at different concentrations may promote or inhibit tumor growth and metastasis under various conditions. To test the hypothesis that tumor cells prefer to adhere to the locations with a higher endothelial NO production in intact microvessels under physiological flows and to further test that inhibiting NO production decreases tumor cell adhesion, we used intravital fluorescence microscopy to measure NO production and tumor cell adhesion in postcapillary venules of rat mesentery under normal and reduced flow conditions, and in the presence of an endothelial nitric oxide synthase (eNOS) inhibitor, N(G)-monomethyl-l-arginine (l-NMMA). Rats (SD, 250-300 g) were anesthetized. A midline incision (∼2 inch) was made in the abdominal wall, and the mesentery was taken out from the abdominal cavity and spread over a coverslip for the measurement. An individual postcapillary venule (35-50 μm) was first loaded with 4,5-diaminofluorescein diacetate (DAF-2 DA), a fluorescent indictor for NO. Then the DAF-2 intensity was measured for 30 min under a normal or reduced flow velocity, with and without perfusion with MDA-MB-231 breast cancer cells, and in the presence of l-NMMA. We found that tumor cells prefer to adhere to the microvessel locations with a higher NO production such as curved portions. Inhibition of eNOS by l-NMMA attenuated the flow-induced NO production and reduced tumor cell adhesion. We also found that l-NMMA treatment for ∼40 min reduced microvessel permeability to albumin. Our results suggest that inhibition of eNOS is a good approach to preventing tumor cell adhesion to intact microvessels under physiological flows. PMID:27059076

  6. Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion

    PubMed Central

    Schaffer, Chris B; Friedman, Beth; Nishimura, Nozomi; Schroeder, Lee F; Tsai, Philbert S; Ebner, Ford F; Lyden, Patrick D

    2006-01-01

    A highly interconnected network of arterioles overlies mammalian cortex to route blood to the cortical mantle. Here we test if this angioarchitecture can ensure that the supply of blood is redistributed after vascular occlusion. We use rodent parietal cortex as a model system and image the flow of red blood cells in individual microvessels. Changes in flow are quantified in response to photothrombotic occlusions to individual pial arterioles as well as to physical occlusions of the middle cerebral artery (MCA), the primary source of blood to this network. We observe that perfusion is rapidly reestablished at the first branch downstream from a photothrombotic occlusion through a reversal in flow in one vessel. More distal downstream arterioles also show reversals in flow. Further, occlusion of the MCA leads to reversals in flow through approximately half of the downstream but distant arterioles. Thus the cortical arteriolar network supports collateral flow that may mitigate the effects of vessel obstruction, as may occur secondary to neurovascular pathology. PMID:16379497

  7. Spectral imaging based in vivo model system for characterization of tumor microvessel response to vascular targeting agents

    NASA Astrophysics Data System (ADS)

    Wankhede, Mamta

    Functional vasculature is vital for tumor growth, proliferation, and metastasis. Many tumor-specific vascular targeting agents (VTAs) aim to destroy this essential tumor vasculature to induce indirect tumor cell death via oxygen and nutrition deprivation. The tumor angiogenesis-inhibiting anti-angiogenics (AIs) and the established tumor vessel targeting vascular disrupting agents (VDAs) are the two major players in the vascular targeting field. Combination of VTAs with conventional therapies or with each other, have been shown to have additive or supra-additive effects on tumor control and treatment. Pathophysiological changes post-VTA treatment in terms of structural and vessel function changes are important parameters to characterize the treatment efficacy. Despite the abundance of information regarding these parameters acquired using various techniques, there remains a need for a quantitative, real-time, and direct observation of these phenomenon in live animals. Through this research we aspired to develop a spectral imaging based mouse tumor system for real-time in vivo microvessel structure and functional measurements for VTA characterization. A model tumor system for window chamber studies was identified, and then combinatorial effects of VDA and AI were characterized in model tumor system. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

  8. Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels.

    PubMed

    Arrigoni, Chiara; Bongio, Matilde; Talò, Giuseppe; Bersini, Simone; Enomoto, Junko; Fukuda, Junji; Moretti, Matteo

    2016-07-01

    A major challenge in the development of clinically relevant 3D tissue constructs is the formation of vascular networks for oxygenation, nutrient supply, and waste removal. To this end, this study implements a multimodal approach for the promotion of vessel-like structures formation in stiff fibrin hydrogels. Computational simulations have been performed to identify the easiest microchanneled configuration assuring normoxic conditions throughout thick cylindrical hydrogels (8 mm height, 6 mm ∅), showing that in our configuration a minimum of three microchannels (600 μm ∅), placed in a non-planar disposition, is required. Using small hydrogel bricks with oxygen distribution equal to the microchanneled configuration, this study demonstrates that among different culture conditions, co-culture of mesenchymal and endothelial cells supplemented with ANG-1 and VEGF leads to the most developed vascular network. Microchanneled hydrogels have been then cultured in the same conditions both statically and in a bioreactor for 7 d. Unexpectedly, the combination between shear forces and normoxic conditions is unable to promote microvascular networks formation in three-channeled hydrogels. Differently, application of either shear forces or normoxic conditions alone results in microvessels outgrowth. These results suggest that to induce angiogenesis in engineered constructs, complex interactions between several biochemical and biophysical parameters have to be modulated. PMID:27191352

  9. Parvocellular and magnocellular contributions to the initial generators of the visual evoked potential: high-density electrical mapping of the "C1" component.

    PubMed

    Foxe, John J; Strugstad, E Cathrine; Sehatpour, Pejman; Molholm, Sophie; Pasieka, Wren; Schroeder, Charles E; McCourt, Mark E

    2008-09-01

    The C1 component of the VEP is considered to index initial afference of retinotopic regions of human visual cortex (V1 and V2). C1 onsets over central parieto-occipital scalp between 45 and 60 ms, peaks between 70 and 100 ms, and then resolves into the following P1 component. By exploiting isoluminant and low-contrast luminance stimuli, we assessed the relative contributions of the Magnocellular (M) and Parvocellular (P) pathways to generation of C1. C1 was maximal at 88 ms in a 100% luminance contrast condition (which stimulates both P and M pathways) and at 115 ms in an isoluminant chromatic condition (which isolates contributions of the P pathway). However, in a 4% luminance contrast condition (which isolates the M pathway), where the stimuli were still clearly perceived, C1 was completely absent. Absence of C1 in this low contrast condition is unlikely to be attributable to lack of stimulus energy since a robust P1-N1 complex was evoked. These data therefore imply that C1 may be primarily parvocellular in origin. The data do not, however, rule out some contribution from the M system at higher contrast levels. Nonetheless, that the amplitude of C1 to P-isolating isoluminant chromatic stimuli is equivalent to that evoked by 100% contrast stimuli suggests that even at high contrast levels, the P system is the largest contributor. These data are related to intracranial recordings in macaque monkeys that have also suggested that the initial current sink in layer IV may not propagate effectively to the scalp surface when M-biased stimuli are used. We also discuss how this finding has implications for a long tradition of attention research that has used C1 as a metric of initial V1 afference in humans. C1 has been repeatedly interrogated for potential selective attentional modulations, particularly in spatial attentional designs, under the premise that modulation of this component, or lack thereof, would be evidence for or against selection at the initial inputs to

  10. Quantitative analysis of microvessels in rat circumventricular organs and pituitary gland

    SciTech Connect

    Fenstermacher, J.; Gross, P.; Sposito, N.; Pettersen, S.; Blasberg, R.; Patlak, C.; Butler, A.

    1986-03-01

    The cerebral circumventricular organs (CVOs) and pituitary gland (PG) purportedly have dense, highly permeable capillary beds which allow for ready blood-tissue exchange of messenger molecules. Quantitation of various morphological and physiological features of the capillaries with CVOs and PG plus some brain structures which have tight or blood-brain barrier (BBB) capillaries was undertaken in rats using several radiolabeled markers, quantitative autoradiography, image analysis, and light and electron microscopic morphometry. Microvascular blood volumes in CVOs and PG were several times larger than in other brain areas (54-70 ..mu../g and 5-8 ..mu../g, respectively). Capillary density and surface area were generally much greater in CVOs and PG than in gray matter; however the highest values for these two parameters were found for the pituitary neural lobe (NL) and supraoptic nucleus (SON), which has BBB capillaries. The rate of capillary blood flow was highest in NL and was similar in the subfornical organ, median eminence, cerebral cortex and SON (1.5 ml/g/min). The transcapillary exchange of several markers was 200-500 times greater in CVOs and NL than in BBB capillaries.

  11. Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction.

    PubMed

    Huber, B R; Meabon, J S; Hoffer, Z S; Zhang, J; Hoekstra, J G; Pagulayan, K F; McMillan, P J; Mayer, C L; Banks, W A; Kraemer, B C; Raskind, M A; McGavern, D B; Peskind, E R; Cook, D G

    2016-04-01

    Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. Microglial/macrophage activation was specifically associated with these restricted microdomains, as evidenced by rapid microglial process retraction, increased ameboid morphology, and escape of blood-borne Q-dot tracers that were internalized in microglial/macrophage cell bodies and phagosome-like compartments. Microdomains of cortical vascular disruption and microglial/macrophage activation were also associated with aberrant tight junction morphology that was more prominent after repetitive (3×) blast exposure. Repetitive, but not single, BOPs also caused TNFα elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuroinflammatory responses. PMID:26777891

  12. Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration

    PubMed Central

    Hoehme, Stefan; Brulport, Marc; Bauer, Alexander; Bedawy, Essam; Schormann, Wiebke; Hermes, Matthias; Puppe, Verena; Gebhardt, Rolf; Zellmer, Sebastian; Schwarz, Michael; Bockamp, Ernesto; Timmel, Tobias; Hengstler, Jan G.; Drasdo, Dirk

    2010-01-01

    Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl4, a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16 days regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named “hepatocyte-sinusoid alignment” (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues. PMID:20484673

  13. Retinal Microvessels Reflect Familial Vulnerability to Psychotic Symptoms: A Comparison of Twins Discordant for Psychotic Symptoms and Controls

    PubMed Central

    Meier, Madeline H.; Gillespie, Nathan A.; Hansell, Narelle K.; Hewitt, Alex W.; Hickie, Ian B.; Lu, Yi; McGrath, John; MacGregor, Stuart; Medland, Sarah E.; Sun, Cong; Wong, Tien Y.; Wright, Margaret J.; Zhu, Gu; Martin, Nicholas G.; Mackey, David A.

    2015-01-01

    Mounting evidence suggests that individuals with schizophrenia have an underlying vulnerability to cardiovascular disease, and a recent study suggested that this vulnerability might be reflected in the retinal microvasculature. The purpose of this study was to test the hypothesis that the retinal microvessels reflect familial vulnerability to psychotic symptoms. Participants were 531 adolescent and young adult twins who took part in the Brisbane Longitudinal Twin Study and the Twins Eye Study in Tasmania. The twins had photographs taken of their retina when they were adolescents or young adults (M age=20.6 years), and retinal vessel diameter was assessed using computer software. The twins completed an assessment of psychosis symptoms approximately six years later. We compared retinal venular diameters of individuals with one or more symptoms of psychosis (n=45), their unaffected co-twins (n=24), and controls (n=462). Individuals with one or more symptoms of psychosis had wider venules (standardized mean=0.29) than controls (standardized mean=-0.04; p=.03), and unaffected co-twins had venular diameters that were intermediate (standardized mean=0.13) between the two groups, suggesting that wide venules may represent a proxy marker of familial vulnerability to psychosis symptoms. Consistent with previous work, there were no differences in arteriolar diameter between individuals with and without symptoms of psychosis. Findings suggest that wide retinal venules may serve as a proxy marker of familial liability to psychosis symptoms. The pathophysiological mechanisms linking psychosis and cardiovascular disease may be operative from early in life, possibly at the level of the microvasculature. PMID:25694186

  14. In Vivo Correlation of Glucose Metabolism, Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI

    PubMed Central

    Kubiessa, Klaus; Boehm, Andreas; Barthel, Henryk; Kluge, Regine; Kahn, Thomas; Sabri, Osama; Stumpp, Patrick

    2015-01-01

    Objective To demonstrate the feasibility of simultaneous acquisition of 18F-FDG-PET, diffusion-weighted imaging (DWI) and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE) in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC) and to investigate possible correlations between these parameters. Methods 17 patients that had given informed consent (15 male, 2 female) with biopsy-proven HNSCC underwent simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE. SUVmax, SUVmean, ADCmean, ADCmin and Ktrans, kep and ve were measured for each tumour and correlated using Spearman’s ρ. Results Significant correlations were observed between SUVmean and Ktrans (ρ = 0.43; p ≤ 0.05); SUVmean and kep (ρ = 0.44; p ≤ 0.05); Ktrans and kep (ρ = 0.53; p ≤ 0.05); and between kep and ve (ρ = -0.74; p ≤ 0.01). There was a trend towards statistical significance when correlating SUVmax and ADCmin (ρ = -0.35; p = 0.08); SUVmax and Ktrans (ρ = 0.37; p = 0.07); SUVmax and kep (ρ = 0.39; p = 0.06); and ADCmean and ve (ρ = 0.4; p = 0.06). Conclusion Simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density. PMID:26270054

  15. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station

    PubMed Central

    Takano, Yoshio; Yoshimitsu, Kazuhiro; Omoto, Masayuki; Hashida, Ryuki; Tagawa, Yoshihiko; Inada, Tomohisa; Yamada, Shin; Ohshima, Hiroshi

    2015-01-01

    . Conclusions These results showed the orbital operation capability and utility, and the preventive effect of HTS for an astronaut’s musculoskeletal atrophy. The initial flight data together with the ground data obtained so far will be utilized in the future planning of human space exploration. PMID:26296204

  16. A three dimensional model of an ultrasound contrast agent gas bubble and its mechanical effects on microvessels

    PubMed Central

    Hosseinkhah, N.; Hynynen, K.

    2012-01-01

    Ultrasound contrast agents inside a microvessel, when driven by ultrasound, oscillate and induce mechanical stresses on the vessel wall. These mechanical stresses can produce beneficial therapeutic effects but also induce vessel rupture if the stresses are too high. Therefore, it is important to use sufficiently low pressure amplitudes to avoid rupturing the vessels while still inducing the desired therapeutic effects. In this work, we developed a comprehensive three dimensional model of a confined microbubble inside a vessel while considering the bubble shell properties, blood viscosity, vessel wall curvature and the mechanical properties of the vessel wall. Two bubble models with the assumption of a spherical symmetric bubble and a simple asymmetrical bubble were simulated. This work was validated with previous experimental results and enabled us to evaluate the microbubbles’ behaviour and the resulting mechanical stresses induced on the vessel walls. In this study the fluid shear and circumferential stresses were evaluated as indicators of the mechanical stresses. The effects of acoustical parameters, vessel viscoelasticity and rigidity, vessel/bubble size and off-center bubbles on bubble behaviour and stresses on the vessel were investigated. The fluid shear and circumferential stresses acting on the vessel varied with time and location. As the frequency changed, the microbubble oscillated with the highest amplitude at its resonance frequency which was different from the resonance frequency of an unbound bubble. The bubble resonance frequency increased as the rigidity of a flexible vessel increased. The fluid shear and circumferential stresses peaked at frequencies above the bubble’s resonance frequency. The more rigid the vessels were, the more damped the bubble oscillations. The synergistic effect of acoustic frequency and vessel elasticity had also been investigated, since the circumferential stress showed either an increasing trend or a decreasing one

  17. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies.

    PubMed

    Yu, Grace Z; Aye, Christina Y L; Lewandowski, Adam J; Davis, Esther F; Khoo, Cheen P; Newton, Laura; Yang, Cheng T; Al Haj Zen, Ayman; Simpson, Lisa J; O'Brien, Kathryn; Cook, David A; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M; Watt, Suzanne M; Leeson, Paul

    2016-09-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (-17.7±16.4% versus -9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth. PMID:27456522

  18. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies

    PubMed Central

    Yu, Grace Z.; Aye, Christina Y.L.; Lewandowski, Adam J.; Davis, Esther F.; Khoo, Cheen P.; Newton, Laura; Yang, Cheng T.; Al Haj Zen, Ayman; Simpson, Lisa J.; O’Brien, Kathryn; Cook, David A.; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M.; Watt, Suzanne M.

    2016-01-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (−17.7±16.4% versus −9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth. PMID:27456522

  19. Reduced vascular endothelial growth factor and capillary density in the occipital cortex in dementia with Lewy bodies.

    PubMed

    Miners, Scott; Moulding, Hayley; de Silva, Rohan; Love, Seth

    2014-07-01

    In dementia with Lewy bodies (DLB), blood flow tends to be reduced in the occipital cortex. We previously showed elevated activity of the endothelin and angiotensin pathways in Alzheimer's disease (AD). We have measured endothelin-1 (ET-1) level and angiotensin-converting enzyme (ACE) activity in the occipital cortex in DLB and control brains. We also measured vascular endothelial growth factor (VEGF); factor VIII-related antigen (FVIIIRA) to indicate microvessel density; myelin-associated glycoprotein (MAG), a marker of ante-mortem hypoperfusion; total α-synuclein (α-syn) and α-synuclein phosphorylated at Ser129 (α-syn-p129). In contrast to findings in AD, ACE activity and ET-1 level were unchanged in DLB compared with controls. VEGF and FVIIIRA levels were, however, significantly lower in DLB. VEGF correlated positively with MAG concentration (in keeping with a relationship between reduction in VEGF and hypoperfusion), and negatively with α-syn and α-syn-p129 levels. Both α-syn and α-syn-p129 levels increased in human SH-SY5Y neuroblastoma cells after oxygen-glucose deprivation (OGD), and VEGF level was reduced in SH-SY5Y cells overexpressing α-syn. Taken together, our findings suggest that reduced microvessel density rather than vasoconstriction is responsible for lower occipital blood flow in DLB, and that the loss of microvessels may result from VEGF deficiency, possible secondary to the accumulation of α-syn. PMID:24521289

  20. Exogenous arachidonic acid mediates permeability of human brain microvessel endothelial cells through prostaglandin E2 activation of EP3 and EP4 receptors.

    PubMed

    Dalvi, Siddhartha; Nguyen, Hieu H; On, Ngoc; Mitchell, Ryan W; Aukema, Harold M; Miller, Donald W; Hatch, Grant M

    2015-12-01

    The blood-brain barrier, formed by microvessel endothelial cells, is the restrictive barrier between the brain parenchyma and the circulating blood. Arachidonic acid (ARA; 5,8,11,14-cis-eicosatetraenoic acid) is a conditionally essential polyunsaturated fatty acid [20:4(n-6)] and is a major constituent of brain lipids. The current study examined the transport processes for ARA in confluent monolayers of human brain microvascular endothelial cells (HBMEC). Addition of radioactive ARA to the apical compartment of HBMEC cultured on Transwell(®) inserts resulted in rapid incorporation of radioactivity into the basolateral medium. Knock down of fatty acid transport proteins did not alter ARA passage into the basolateral medium as a result of the rapid generation of prostaglandin E2 (PGE2 ), an eicosanoid known to facilitate opening of the blood-brain barrier. Permeability following ARA or PGE2 exposure was confirmed by an increased movement of fluorescein-labeled dextran from apical to basolateral medium. ARA-mediated permeability was attenuated by specific cyclooxygenase-2 inhibitors. EP3 and EP4 receptor antagonists attenuated the ARA-mediated permeability of HBMEC. The results indicate that ARA increases permeability of HBMEC monolayers likely via increased production of PGE2 which acts upon EP3 and EP4 receptors to mediate permeability. These observations may explain the rapid influx of ARA into the brain previously observed upon plasma infusion with ARA. The blood-brain barrier, formed by microvessel endothelial cells, is a restrictive barrier between the brain parenchyma and the circulating blood. Radiolabeled arachidonic acid (ARA) movement across, and monolayer permeability in the presence of ARA, was examined in confluent monolayers of primary human brain microvessel endothelial cells (HBMECs) cultured on Transwell(®) plates. Incubation of HBMECs with ARA resulted in a rapid increase in HBMEC monolayer permeability. The mechanism was mediated, in part

  1. The permeation of dynorphin A 1–6 across the blood brain barrier and its effect on bovine brain microvessel endothelial cell monolayer permeability

    PubMed Central

    Sloan, Courtney D. Kuhnline; Audus, Kenneth L.; Aldrich, Jane V.; Lunte, Susan M.

    2012-01-01

    Dynorphin A 1–17 (Dyn A 1–17) is an endogenous neuropeptide known to act at the kappa opioid receptor; it has been implicated in a number of neurological disorders, including neuropathic pain, stress, depression, and Alzheimer’s and Parkinson’s diseases. The investigation of Dyn A 1–17 metabolism at the blood-brain barrier (BBB) is important since the metabolites exhibit unique biological functions compared to the parent compound. In this work, Dyn A 1–6 is identified as a metabolite of Dyn A 1–17 in the presence of bovine brain microvessel endhothelial cells (BBMECs), using LC-MS/MS. The transport of Dyn A 1–6 at the BBB was examined using this in vitro cell culture model of the BBB. Furthermore, the permeation of the BBB by the low molecular weight, permeability marker fluorescein was characterized in the presence and absences of Dyn A 1–6. PMID:23046728

  2. Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo.

    PubMed

    Zimmerer, Rüdiger M; Matthiesen, Peter; Kreher, Fritjof; Kampmann, Andreas; Spalthoff, Simon; Jehn, Philipp; Bittermann, Gido; Gellrich, Nils-Claudius; Tavassol, Frank

    2016-03-01

    Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation. In this study, the influence of cancer stem cells on initial angiogenesis was evaluated for the metastatic melanoma cell line D10. Following flow cytometry, CD133+ and CD133- cells were isolated using magnetic cell separation and different cell fractions were transferred to porcine gelatin sponges, which were implanted into the dorsal skinfold chamber of immunocompromised mice. Angiogenesis was analyzed based on microvessel density over a 10-day period using in vivo fluorescence microscopy, and the results were verified using immunohistology. CD133+ D10 cells showed a significant induction of early angiogenesis in vivo, contrary to CD133- D10 cells, unsorted D10 cells, and negative control. Neovascularization was confirmed by visualizing endothelial cells by immunohistology using an anti-CD31 antibody. Because CD133+ cells are rare in clinical specimens and hardly amenable to functional assays, the D10 cell line provides a suitable model to study the angiogenic potential of putative cancer stem cells and the leukocyte-endothelial cell interaction in the dorsal skinfold chamber in vivo. This cancer stem cell model might be useful in the development and evaluation of therapeutic agents targeting tumors. PMID:26656667

  3. Early increase precedes a depletion of endothelin-1 but not of von Willebrand factor in cutaneous microvessels of diabetic patients. A quantitative immunohistochemical study.

    PubMed

    Properzi, G; Terenghi, G; Gu, X H; Poccia, G; Pasqua, R; Francavilla, S; Polak, J M

    1995-02-01

    Endothelin-1 (ET-1) is a vasoconstrictor peptide which is produced by endothelial cells. The subcellular distribution of ET-1 in human skin and the variation of immunostaining for ET-1 by light microscopy in skin biopsies of diabetic patients have been analysed using immunohistochemistry and image analysis quantification. Skin biopsies were collected from 17 patients with type 1 diabetes of different durations and with presence or absence of microangiopathy in the retina; skin biopsies of healthy subjects were utilized as controls. The distribution of ET-1 immunoreactivity (IR) at both light and electron microscopy was compared to that of von Willebrand factor (vWf), a general marker of total cutaneous microvessels. Immunohistochemistry revealed that in controls the distribution of immunostaining was similar for ET-1 and vWf, being localized to microvessels in all areas of the skin. However, at the electron microscopical level ET-1-IR was localized in the endothelial cytoplasm rather than in specific organelles, while vWf immunostaining was associated with Weibel-Palade bodies. ET-1-IR was observed in 4/8 (50 per cent) biopsies from healthy subjects; this increased to 81.8 per cent in biopsies of patients affected by diabetes for less than 10 years and decreased to 16.6 per cent in patients with diabetes for more than 10 years. Quantification of ET-1 staining showed a significant decrease of ET-1-IR in patients affected by diabetes for more than 10 years compared with those affected by diabetes for less than 10 years (P < 0.05). Also, the percentage of biopsies showing positive ET-1 staining was lower in patients with retinopathy than in patients without retinopathy. On the contrary, vWf-IR was observed in all skin specimens and its quantification showed no differences between diabetic patients and controls. These changes are not related to variations in the number of blood vessels, and it is suggested that they reflect a possible functional alteration of the

  4. Density Visualization

    ERIC Educational Resources Information Center

    Keiter, Richard L.; Puzey, Whitney L.; Blitz, Erin A.

    2006-01-01

    Metal rods of high purity for many elements are now commercially available and may be used to construct a display of relative densities. We have constructed a display with nine metal rods (Mg, Al, Ti, V, Fe, Cu, Ag, Pb, and W) of equal mass whose densities vary from 1.74 to 19.3 g cm[superscript -3]. The relative densities of the metals may be…

  5. No Identical "Mesenchymal Stem Cells" at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels.

    PubMed

    Sacchetti, Benedetto; Funari, Alessia; Remoli, Cristina; Giannicola, Giuseppe; Kogler, Gesine; Liedtke, Stefanie; Cossu, Giulio; Serafini, Marta; Sampaolesi, Maurilio; Tagliafico, Enrico; Tenedini, Elena; Saggio, Isabella; Robey, Pamela G; Riminucci, Mara; Bianco, Paolo

    2016-06-14

    A widely shared view reads that mesenchymal stem/stromal cells ("MSCs") are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as "MSCs" based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called "MSCs," with important applicative implications. The data also support the view that rather than a uniform class of "MSCs," different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin. PMID:27304917

  6. Re-evaluation of the role of P-glycoprotein in in vitro drug permeability studies with the bovine brain microvessel endothelial cells.

    PubMed

    Hakkarainen, Jenni J; Rilla, Kirsi; Suhonen, Marjukka; Ruponen, Marika; Forsberg, Markus M

    2014-03-01

    1.  Currently available in vitro blood-brain barrier models all have recognized restrictions. In addition to leakiness, inconsistent data about P-glycoprotein mediated efflux limit the attractiveness of the primary bovine brain microvessel endothelial cells (BBMECs). Therefore, we re-evaluated the role of P-glycoprotein mediated efflux with two culture conditions in BBMECs for prediction of drug permeability of potential P-glycoprotein substrates. 2.  BBMECs were monocultured on filters on petri dishes and on filter inserts, and expression and localization of P-glycoprotein were compared by using western blot and confocal microscopy, respectively. The functionality of P-glycoprotein was assessed by using cellular uptake, calcein-AM and bidirectional transport assays. 3.  P-glycoprotein expression was higher in BBMECs cultured on filter inserts decreasing the permeability of digoxin and paclitaxel, but not the permeability of vinblastine. However, the monocultured BBMECs were not able to demonstrate efflux in the bidirectional transport assays. Under certain culture conditions, occludin may not be correctly located, perhaps explaining in part the leakiness of BBMECs. 4.  In conclusion, BBMECs, despite possessing a functional P-glycoprotein, under certain culture conditions may not be a suitable in vitro model for the bidirectional transport assays and for predicting the permeability of drugs and xenobiotics that are potential P-glycoprotein substrates. PMID:23924297

  7. Research Initiatives

    Cancer.gov

    This page provides detailed information about currently funded RFA initiatives both led by DCCPS, and those led by other NIH Institutes and Centers (I/Cs) that include DCCPS as a partner. Each initiative includes a table of funded grants and a map that shows the location of funded institutions.

  8. Bone Density

    MedlinePlus

    ... bone health. It compares your bone density, or mass, to that of a healthy person who is ... Whether your osteoporosis treatment is working Low bone mass that is not low enough to be osteoporosis ...

  9. Anatomic Distribution of Nerves and Microvascular Density in the Human Anterior Vaginal Wall: Prospective Study

    PubMed Central

    Li, Ting; Liao, Qinping; Zhang, Hong; Gao, Xuelian; Li, Xueying; Zhang, Miao

    2014-01-01

    Background The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina) remains controversial. We explored the histomorphological basis of the G-spot. Methods Biopsies were drawn from a 12 o’clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5–immunoreactive nerves and smooth muscle actin–immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay. Results Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p = 0.002). Conclusions Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction. PMID:25379731

  10. Low Bone Density

    MedlinePlus

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  11. Multiparametric PET/CT-perfusion does not add significant additional information for initial staging in lung cancer compared with standard PET/CT

    PubMed Central

    2014-01-01

    Background The purpose of this study was to assess the relationship of CT-perfusion (CTP), 18F-FDG-PET/CT and histological parameters, and the possible added value of CTP to FDG-PET/CT in the initial staging of lung cancer. Methods Fifty-four consecutive patients (median age 65 years, 15 females, 39 males) with suspected lung cancer were evaluated prospectively by CT-perfusion scan and 18F-FDG-PET/CT scan. Overall, 46 tumors were identified. CTP parameters blood flow (BF), blood volume (BV), and mean transit time (MTT) of the tumor tissue were calculated. Intratumoral microvessel density (MVD) was assessed quantitatively. Differences in CTP parameters concerning tumor type, location, PET positivity of lymph nodes, TNM status, and UICC stage were analyzed. Spearman correlation analyses between CTP and 18F-FDG-PET/CT parameters (SUVmax, SUVmean, PETvol, and TLG), MVD, tumor size, and tumor stage were performed. Results The mean BF (mL/100 mL min-1), BV (mL/100 mL), and MTT (s) was 35.5, 8.4, and 14.2, respectively. The BF and BV were lower in tumors with PET-positive lymph nodes (p = 0.02). However, the CTP values were not significantly different among the N stages. The CTP values were not different, depending on tumor size and location. No significant correlation was found between CTP parameters and MVD. Conclusions Overall, the CTP information showed only little additional information for the initial staging compared with standard FDG-PET/CT. Low perfusion in lung tumors might possibly be associated with metabolically active regional lymph nodes. Apart from that, both CTP and 18F-FDG-PET/CT parameter sets may reflect different pathophysiological mechanisms in lung cancer. PMID:24450990

  12. Modelling ionospheric density structures

    NASA Technical Reports Server (NTRS)

    Schunk, R. W.; Sojka, J. J.

    1989-01-01

    Large-scale density structures are a common feature in the high-latitude ionsphere. The structures were observed in the dayside cusp, polar cap, and nocturnal auroral region over a range of altitudes, including the E-region, F-region and topside ionosphere. The origins, lifetimes and transport characteristics of large-scale density structures were studied with the aid of a three-dimensional, time-dependent ionospheric model. Blob creation due to particle precipitation, the effect that structured electric fields have on the ionosphere, and the lifetimes and transport characteristics of density structures for different seasonal, solar cycle, and interplanetary magnetic field (IMF) conditions were studied. The main conclusions drawn are: (1) the observed precipitation energy fluxes are sufficient for blob creation if the plasma is exposed to the precipitation for 5 to 10 minutes; (2) structured electric fields produce structured electron densities, ion temperatures, and ion composition; (3) the lifetime of an F-region density structure depends on several factors, including the initial location where it was formed, the magnitude of the perturbation, season, solar cycle and IMF; and (4) depending on the IMF, horizontal plasma convection can cause an initial structure to break up into multiple structures of various sizes, remain as a single distorted structure, or become stretched into elongated segments.

  13. Recombinant interleukin-1β dilates steelhead trout coronary microvessels: effect of temperature and role of the endothelium, nitric oxide and prostaglandins

    PubMed Central

    Costa, Isabel A. S. F.; Hein, Travis W.; Secombes, Christopher J.; Gamperl, A. Kurt

    2015-01-01

    ABSTRACT Interleukin (IL)-1β is associated with hypotension and cardiovascular collapse in mammals during heat stroke, and the mRNA expression of this pro-inflammatory cytokine increases dramatically in the blood of Atlantic cod (Gadus morhua) at high temperatures. These data suggest that release of IL-1β at high temperatures negatively impacts fish cardiovascular function and could be a primary determinant of upper thermal tolerance in this taxa. Thus, we measured the concentration-dependent response of isolated steelhead trout (Oncorhynchus mykiss) coronary microvessels (<150 μm in diameter) to recombinant (r) IL-1β at two temperatures (10 and 20°C). Recombinant IL-1β induced a concentration-dependent vasodilation with vessel diameter increasing by approximately 8 and 30% at 10−8 and 10−7 mol l−1, respectively. However, this effect was not temperature dependent. Both vessel denudation and cyclooxygenase blockade (by indomethacin), but not the nitric oxide (NO) antagonist L-NIO, inhibited the vasodilator effect of rIL-1β. In contrast, the concentration-dependent dilation caused by the endothelium-dependent calcium ionophore A23187 was completely abolished by L-NIO and indomethacin, suggesting that both NO and prostaglandin signaling mechanisms exist in the trout coronary microvasculature. These data: (1) are the first to demonstrate a functional link between the immune and cardiovascular systems in fishes; (2) suggest that IL-1β release at high temperatures may reduce systemic vascular resistance, and thus, the capacity of fish to maintain blood pressure; and (3) provide evidence that both NO and prostaglandins play a role in regulating coronary vascular tone, and thus, blood flow. PMID:26026045

  14. Adhesion and migration of polymorphonuclear leukocytes across human brain microvessel endothelial cells are differentially regulated by endothelial cell adhesion molecules and modulate monolayer permeability.

    PubMed

    Wong, Donald; Prameya, Rukmini; Dorovini-Zis, Katerina

    2007-03-01

    The mechanisms by which polymorphonuclear leukocytes (PMN) cross the human blood-brain barrier have not been fully elucidated. Using a well characterized in vitro model of the human BBB, we examined the role of endothelial cell adhesion molecules on the adhesion and transendothelial migration of PMN across primary cultures of human brain microvessel endothelial cells (HBMEC). A small number of PMN (0.06%) adhered to unstimulated HBMEC, and the basal adhesion was not affected by anti-adhesion molecule antibodies. Treatment of HBMEC with tumor necrosis factor (TNF)-alpha resulted in increased PMN adhesion that was significantly inhibited by blocking antibodies to E-selectin and ICAM-1, but not VCAM-1 or PECAM-1. A very small number of adherent PMN migrated across unstimulated HBMEC monolayers. Migration increased 2 to 20 fold following stimulation of HBMEC with TNF-alpha. Monoclonal antibody blocking studies showed that PMN used ICAM-1, but not VCAM-1, E-selectin or PECAM-1 to move across activated monolayers. Anti-adhesion molecule antibodies did not diminish the basal PMN migration. Ultrastructurally, PMN often aggregated on top and between adjacent endothelial cells and adhered by first extending pseudopodia along the apical endothelial surface. They then flattened and inserted themselves between endothelial cells in order to migrate across the monolayers. At the end of the migration period, the cultures resumed their continuity with no evidence of disruption. Transendothelial migration of PMN decreased the transendothelial electrical resistance and increased the permeability to horseradish peroxidase, which penetrated alongside the migrating leukocytes. A blocking antibody to ICAM-1 that greatly decreased migration, had no effect on the permeability changes. These studies provide insights into the mechanisms that regulate the entry of PMN into the brain and the increased permeability of the BBB in CNS inflammation. PMID:17291598

  15. Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design

    PubMed Central

    YANG, YU; BAI, WENKUN; CHEN, YINI; LIN, YANDUAN; HU, BING

    2015-01-01

    The present study aimed to provide a complete exploration of the effect of sound intensity, frequency, duty cycle, microbubble volume and irradiation time on low-frequency low-intensity ultrasound (US)-mediated microvessel disruption, and to identify an optimal combination of the five factors that maximize the blockage effect. An orthogonal experimental design approach was used. Enhanced US imaging and acoustic quantification were performed to assess tumor blood perfusion. In the confirmatory test, in addition to acoustic quantification, the specimens of the tumor were stained with hematoxylin and eosin and observed using light microscopy. The results revealed that sound intensity, frequency, duty cycle, microbubble volume and irradiation time had a significant effect on the average peak intensity (API). The extent of the impact of the variables on the API was in the following order: Sound intensity; frequency; duty cycle; microbubble volume; and irradiation time. The optimum conditions were found to be as follows: Sound intensity, 1.00 W/cm2; frequency, 20 Hz; duty cycle, 40%; microbubble volume, 0.20 ml; and irradiation time, 3 min. In the confirmatory test, the API was 19.97±2.66 immediately subsequent to treatment, and histological examination revealed signs of tumor blood vessel injury in the optimum parameter combination group. In conclusion, the Taguchi L18 (3)6 orthogonal array design was successfully applied for determining the optimal parameter combination of API following treatment. Under the optimum orthogonal design condition, a minimum API of 19.97±2.66 subsequent to low-frequency and low-intensity mediated blood perfusion blockage was obtained. PMID:26722279

  16. Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells.

    PubMed

    Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Rice, Kenner C; Gannon, Brenda M; Fantegrossi, William E; Gonzalez, Carmen; Paule, Merle G; Ali, Syed F

    2016-08-26

    Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as "bath salts." These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5mM-2.5mM) for 24h. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5mM, with similar effects observed after MDPV exposures starting at 1mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1mM and disruption of the monolayer at 2.5mM. MDMA induced disruption of the endothelial monolayer from 1mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses ≥0.5mM without vacuole formation; at 2.5mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants alter monoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic. PMID:27320055

  17. Nanomolar aluminum induces expression of the inflammatory systemic biomarker C-reactive protein (CRP) in human brain microvessel endothelial cells (hBMECs).

    PubMed

    Alexandrov, Peter N; Kruck, Theodore P A; Lukiw, Walter J

    2015-11-01

    C-reactive protein (CRP; also known as pentraxin 1, PTX1), a 224 amino acid soluble serum protein organized into a novel pentameric ring-shaped structure, is a highly sensitive pathogenic biomarker for systemic inflammation. High CRP levels are found in practically every known inflammatory state, and elevated CRP levels indicate an increased risk for several common age-related human degenerative disorders, including cardiovascular disease, cancer, diabetes, and Alzheimer's disease (AD). While the majority of CRP is synthesized in the liver for secretion into the systemic circulation, it has recently been discovered that an appreciable amount of CRP is synthesized in highly specialized endothelial cells that line the vasculature of the brain and central nervous system (CNS). These highly specialized cells, the major cell type lining the human CNS vasculature, are known as human brain microvessel endothelial cells (hBMECs). In the current pilot study we examined (i) CRP levels in human serum obtained from AD and age-matched control patients; and (ii) analyzed the effects of nanomolar aluminum sulfate on CRP expression in primary hBMECs. The three major findings in this short communication are: (i) that CRP is up-regulated in AD serum; (ii) that CRP serum levels increased in parallel with AD progression; and (iii) for the first time show that nanomolar aluminum potently up-regulates CRP expression in hBMECs to many times its 'basal abundance'. The results suggest that aluminum-induced CRP may in part contribute to a pathophysiological state associated with a chronic systemic inflammation of the human vasculature. PMID:26265215

  18. The relationship between microvessel count and the expression of vascular endothelial growth factor, p53, and K-ras in non-small cell lung cancer.

    PubMed Central

    Kang, Y. H.; Kim, K. S.; Yu, Y. K.; Lim, S. C.; Kim, Y. C.; Park, K. O.

    2001-01-01

    Using immunohistochemical staining, we studied the relationship between the microvessel count (MC) and the expression of K-ras, mutant p53 protein, and vascular endothelial growth factor (VEGF) in 61 surgically resected non-small cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of the tumors with lymph node (LN) metastasis was significantly higher than that of tumors without LN metastasis (66.1+/-23.1 vs. 33.8+/-13.1, p<0.05). VEGF was positive in 54 patients (88.5%). MC was 58.1+/-25.2 (mean+/-S.D.) in a x200 field, and it was significantly higher in VEGF(+) tumors than in VEGF(-) tumors (61.4+/-23.7 vs. 32.9+/-23.8, p<0.05). VEGF expression was higher in K-ras-positive or mutant p53-positive tumors than in negative tumors (p<0.05). MC was significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did not differ according to the level of mutant p53 protein expression. Survival did not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In conclusion, there is a flow of molecular alterations from K-ras and p53, to VEGF expression, leading to angiogenesis and ultimately lymph node metastasis. Correlations between variables in close approximation and the lack of prognostic significance of individual molecular alterations suggest that tumorigenesis and metastasis are multifactorial processes. PMID:11511786

  19. SCB initiator

    DOEpatents

    Bickes, Jr., Robert W.; Renlund, Anita M.; Stanton, Philip L.

    1994-01-01

    A detonator for high explosives initiated by mechanical impact includes a cylindrical barrel, a layer of flyer material mechanically covering the barrel at one end, and a semiconductor bridge ignitor including a pair of electrically conductive pads connected by a semiconductor bridge. The bridge is in operational contact with the layer, whereby ignition of said bridge forces a portion of the layer through the barrel to detonate the explosive. Input means are provided for igniting the semiconductor bridge ignitor.

  20. SCB initiator

    DOEpatents

    Bickes Jr., Robert W.; Renlund, Anita M.; Stanton, Philip L.

    1994-11-01

    A detonator for high explosives initiated by mechanical impact includes a cylindrical barrel, a layer of flyer material mechanically covering the barrel at one end, and a semiconductor bridge ignitor including a pair of electrically conductive pads connected by a semiconductor bridge. The bridge is in operational contact with the layer, whereby ignition of said bridge forces a portion of the layer through the barrel to detonate the explosive. Input means are provided for igniting the semiconductor bridge ignitor.

  1. Catalytic degradation of high-density polyethylene on an ultrastable-Y zeolite. Nature of initial polymer reactions, pattern of formation of gas and liquid products, and temperature effects

    SciTech Connect

    Manos, G.; Garforth, A.; Dwyer, J.

    2000-05-01

    The catalytic degradation of high-density polyethylene (hdPE) over ultrastable Y zeolite in a semibatch reactor was studied at different heating rates and reaction temperatures. Catalytic degradation of the polymer occurred at much lower temperatures than pure thermal degradation. When gel permeation chromatography was used to determine the molar mass distribution, it was found that solid state reactions occur only in the presence of a catalyst. These reactions change the polymer structure well before the formation of significant amounts of volatile products. The pattern of formation of gaseous and liquid products was studied and found to follow the temperature increase. After the system reached its final temperature, the reaction rate of formation of volatile products decreased rapidly. The product range was typically between C{sub 3} and C{sub 15}. Isobutane and isopentane were the main gaseous products. The liquid product fraction was alkane-rich, as alkenes rapidly undergo bimolecular hydrogen transfer reactions to give alkanes as secondary products.

  2. Openness initiative

    SciTech Connect

    Duncan, S.S.

    1995-12-31

    Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: {open_quotes}Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?{close_quotes} To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need to make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts.

  3. The initiation of free radical peroxidation of low-density lipoproteins by glucose and its metabolite methylglyoxal: a common molecular mechanism of vascular wall injure in atherosclerosis and diabetes.

    PubMed

    Lankin, Vadim; Konovalova, Galina; Tikhaze, Alla; Shumaev, Konstantin; Kumskova, Elena; Viigimaa, Margus

    2014-10-01

    It was found that glucose in the range of concentrations 12.5-100 mM stimulated Cu(2+)-mediated free radical peroxidation of low-density lipoproteins (LDL) from human blood plasma. Considering the kinetic parameters of LDL peroxidation we proposed that intensification of this process may be caused by formation of free radical intermediates of glucose auto-oxidation. Addition of SOD to the medium inhibited LDL oxidation, indicating the formation of superoxide anion-radicals under autoxidation of glucose. Similarly, SOD inhibited free radical peroxidation of liposomes from egg lecithin in the presence of glucose that confirms the generation of superoxide radicals under co-oxidation of unsaturated lipids and glucose. Normalization of glucose level in the blood of patients with type 2 diabetes mellitus during therapy was accompanied by a significant decrease in LDL oxidation in vivo (the decrease in primary and secondary lipoperoxidation products). The formation of superoxide anion-radicals was observed during interaction of aminoacid L-lysine with a product of glucose oxidative metabolism-methylglyoxal, but not with a product of lipoperoxidation malonyldialdehyde. In accordance with the foregoing the administration of sugar-lowering drug metformin, which binds and utilizes methylglyoxal, caused a stronger inhibition of LDL peroxidation in the blood of patients with diabetes mellitus, probably due to decrease in methylglyoxal-dependent generation of superoxide anion-radicals. Based on the results we set out the hypothesis about autocatalytic mechanism of free radical reactions involving natural dicarbonyls and suppose the common molecular mechanism of vascular wall injury in atherosclerosis and diabetes. PMID:24997046

  4. Analysis of atomic thermospheric nitrogen density

    NASA Technical Reports Server (NTRS)

    Engebretson, M. J.

    1985-01-01

    A NASA grant provided support for a research project at Augsbury College, Minneapolis, Minnesota for the analysis of atomic nitrogen density data obtained by the Neutral Atmospheric Composition Spectrometer (NACS) on board the Dynamics Explorer-2 satellite. Initial funding was for an exploratory study of the feasibility of obtaining ambient densities of N from source densities of NO. Funding was continued under the Dynamics Explorer Guest Investigator Program when initial studies indicated probable success in obtaining such ambient densities. The major scientific focus of the later work was to be to characterize the behavior of N densities at high latitudes.

  5. EUROANDRILL Initiative

    NASA Astrophysics Data System (ADS)

    Florindo, Fabio; Steering Committee, Euroandrill

    2010-05-01

    EuroANDRILL is a new initiative to create a European network with the goal to increase future involvement of European countries in the ANDRILL [ANtarctic geological DRILLing] Programme. Antarctica has been heavily glaciated for approximately 34 million years, but its ice sheets have fluctuated considerably and are one of the major driving forces for changes in climate throughout the Cenozoic Era. The spatial scale and temporal pattern of these fluctuations is subject to considerable debate. Understanding the response of large ice masses to climatic forcing is of vital importance because ice volume variations drive global sea level changes and also alter the capacity of ice sheets and sea-ice to act as major heat sinks/insulators. It is particularly important to assess the stability of the cryosphere in the face of rising CO2 levels, as modelling of the climate shift from a warm, vegetated Antarctica to a cold, ice-covered state 34 million years ago suggests a powerful greenhouse gas influence. As Antarctica is the major driver of Earth's climate and sea level, much effort has been expended in deriving models of its behaviour. Some of these models have been successfully validated against modern conditions. EuroANDRILL will provide a coherent, integrated platform for European leadership and involvement in the international ANDRILL programme. The coordination and networking provided by EuroANDRILL will seek to expand participation by European nations, institutions, and individual scientists in the study of the geologic history of the polar regions and their paleoclimatic significance. During the IPY, ANDRILL has been a highly visible and successful programme. This programme seeks to expand on this legacy beyond the IPY and make these contributions sustainable in the European Research Area through networking of research projects and future planning efforts, which establish Europe as a key player in future polar sediment and rock drilling. EuroANDRILL is set up under

  6. Microdrill Initiative - Initial Market Evaluation

    SciTech Connect

    Spears & Associates, Inc

    2003-07-01

    The U.S. Department of Energy (DOE) is launching a major research and development initiative to create a small, fast, inexpensive and environmentally friendly rig for drilling 5000 feet boreholes to investigate potential oil and gas reservoirs. DOE wishes to get input from petroleum industry operators, service companies and equipment suppliers on the operation and application of this coiled-tubing-based drilling unit. To that end, DOE has asked Spears & Associates, Inc. (SAI) to prepare a special state-of-the-market report and assist during a DOE-sponsored project-scoping workshop in Albuquerque near the end of April 2003. The scope of the project is four-fold: (1) Evaluate the history, status and future of demand for very small bore-hole drilling; (2) Measure the market for coiled tubing drilling and describe the state-of-the-art; (3) Identify companies and individuals who should have an interest in micro drilling and invite them to the DOE workshop; and (4) Participate in 3 concurrent workshop sessions, record and evaluate participant comments and report workshop conclusions.

  7. Gluon density in nuclei

    SciTech Connect

    Ayala, A.L.; Ducati, M.B.G.; Levin, E.M.

    1996-10-01

    In this talk we present our detailed study (theory and numbers) on the shadowing corrections to the gluon structure functions for nuclei. Starting from rather controversial information on the nucleon structure function which is originated by the recent HERA data, we develop the Glauber approach for the gluon density in a nucleus based on Mueller formula and estimate the value of the shadowing corrections in this case. Then we calculate the first corrections to the Glauber approach and show that these corrections are big. Based on this practical observation we suggest the new evolution equation which takes into account the shadowing corrections and solve it. We hope to convince you that the new evolution equation gives a good theoretical tool to treat the shadowing corrections for the gluons density in a nucleus and, therefore, it is able to provide the theoretically reliable initial conditions for the time evolution of the nucleus-nucleus cascade. The initial conditions should be fixed both theoretically and phenomenologically before to attack such complicated problems as the mixture of hard and soft processes in nucleus-nucleus interactions at high energy or the theoretically reliable approach to hadron or/and parton cascades for high energy nucleus-nucleus interaction. 35 refs., 24 figs., 1 tab.

  8. Breast Density Analysis Using an Automatic Density Segmentation Algorithm.

    PubMed

    Oliver, Arnau; Tortajada, Meritxell; Lladó, Xavier; Freixenet, Jordi; Ganau, Sergi; Tortajada, Lidia; Vilagran, Mariona; Sentís, Melcior; Martí, Robert

    2015-10-01

    Breast density is a strong risk factor for breast cancer. In this paper, we present an automated approach for breast density segmentation in mammographic images based on a supervised pixel-based classification and using textural and morphological features. The objective of the paper is not only to show the feasibility of an automatic algorithm for breast density segmentation but also to prove its potential application to the study of breast density evolution in longitudinal studies. The database used here contains three complete screening examinations, acquired 2 years apart, of 130 different patients. The approach was validated by comparing manual expert annotations with automatically obtained estimations. Transversal analysis of the breast density analysis of craniocaudal (CC) and mediolateral oblique (MLO) views of both breasts acquired in the same study showed a correlation coefficient of ρ = 0.96 between the mammographic density percentage for left and right breasts, whereas a comparison of both mammographic views showed a correlation of ρ = 0.95. A longitudinal study of breast density confirmed the trend that dense tissue percentage decreases over time, although we noticed that the decrease in the ratio depends on the initial amount of breast density. PMID:25720749

  9. The dynamics of variable-density turbulence

    SciTech Connect

    Sandoval, D.L.

    1995-11-01

    The dynamics of variable-density turbulent fluids are studied by direct numerical simulation. The flow is incompressible so that acoustic waves are decoupled from the problem, and implying that density is not a thermodynamic variable. Changes in density occur due to molecular mixing. The velocity field, is in general, divergent. A pseudo-spectral numerical technique is used to solve the equations of motion. Three-dimensional simulations are performed using a grid size of 128{sup 3} grid points. Two types of problems are studied: (1) the decay of isotropic, variable-density turbulence, and (2) buoyancy-generated turbulence in a fluid with large density fluctuations. In the case of isotropic, variable-density turbulence, the overall statistical decay behavior, for the cases studied, is relatively unaffected by the presence of density variations when the initial density and velocity fields are statistically independent. The results for this case are in quantitative agreement with previous numerical and laboratory results. In this case, the initial density field has a bimodal probability density function (pdf) which evolves in time towards a Gaussian distribution. The pdf of the density field is symmetric about its mean value throughout its evolution. If the initial velocity and density fields are statistically dependent, however, the decay process is significantly affected by the density fluctuations. For the case of buoyancy-generated turbulence, variable-density departures from the Boussinesq approximation are studied. The results of the buoyancy-generated turbulence are compared with variable-density model predictions. Both a one-point (engineering) model and a two-point (spectral) model are tested against the numerical data. Some deficiencies in these variable-density models are discussed and modifications are suggested.

  10. Significance of microvascular density (MVD) in cervical cancer recurrence.

    PubMed

    Cantu De León, D; Lopez-Graniel, C; Frias Mendivil, M; Chanona Vilchis, G; Gomez, C; De La Garza Salazar, J

    2003-01-01

    The purpose of this retrospective study of 118 patients with squamous cell cervical cancer from January 1990 to December 1993 was to evaluate angiogenesis as predictive factor of recurrence in cervical cancer stages II-III treated with standard radiotherapy. Microvessel density (MVD) was evaluated and correlated with other prognostic factors. MVD was greater than 20 in 67.8% of patients with recurrence (P = 0.002) in comparison to 39% of patients without. Disease-free survival was shorter in stage IIA and MVD >20 (P = 0.0193) as well as for stage IIB (P < 0.05 ), but not for IIIB (P = 0.1613 ). Global survival was significantly shorter when MVD was >20 (P = 0.0316). For stage IIA and MVD >20 survival was shorter (P = 0.0008) for stage IIB (P < 0.05) but not for IIIB (P = 0.14). Patients younger than 40 years and MVD >20 had poorer disease-free interval and survival (P = 0.0029). MVD in patients with squamous cell cervical cancer stage II and age younger than 40 may play a role in predicting recurrence and survival. PMID:14675324