NF-κB is involved in the LPS-mediated proliferation and apoptosis of MAC-T epithelial cells as part of the subacute ruminal acidosis response in cows.

PubMed

Fan, Wen-Jie; Li, He-Ping; Zhu, He-Shui; Sui, Shi-Ping; Chen, Pei-Ge; Deng, Yue; Sui, Tong-Ming; Wang, Yue-Ying

2016-11-01

To determine the effect of NF-κB on cell proliferation and apoptosis, we investigate the expression of inflammation and apoptosis-related factors in the bovine mammary epithelial cell line, MAC-T. MAC-T cells were cultured in vitro and MTT and LDH assays used to determine the effects of lipopolysaccharide (LPS) on proliferation and cytotoxicity respectively. RT-PCR and western blotting were used to evaluate the effect of LPS and NF-κB inhibition [pyrrolidine dithiocarbamate (PDTC) treatment] on the expression of inflammation and apoptosis-related factors. LPS significantly inhibited MAC-T cell proliferation in a dose- and time-dependent manner. Furthermore, LPS promoted apoptosis while the NF-кB inhibitor PDTC attenuated this effect. After LPS treatment, the NF-кB signaling pathway was activated, and the expression of inflammation and apoptosis-related factors increased. When PDTC blocked NF-кB signaling, the expression of inflammation and apoptosis-related factors were decreased in MAC-T cells. LPS activates the TLR4/NF-κB signaling pathway, inhibits proliferation and promotes apoptosis in MAC-T cells. NF-кB inhibition attenuates MAC-T cell apoptosis and TLR4/NF-κB signaling pathway. NF-кB inhibitor alleviating MAC-T cell apoptosis is presumably modulated by NF-кB.

Characterization of the Murine Myeloid Precursor Cell Line MuMac-E8

PubMed Central

Fricke, Stephan; Riemschneider, Sina; Kohlschmidt, Janine; Hilger, Nadja; Fueldner, Christiane; Knauer, Jens; Sack, Ulrich; Emmrich, Frank; Lehmann, Jörg

2014-01-01

Starting point for the present work was the assumption that the cell line MuMac-E8 represents a murine cell population with stem cell properties. Preliminary studies already pointed to the expression of stem-cell associated markers and a self-regenerative potential of the cells. The cell line MuMac-E8 should be examined for their differential stage within stem cell hierarchy. MuMac-E8 cells were derived from a chimeric mouse model of arthritis. It could be shown that MuMac-E8 cells express mRNA of some genes associated with pluripotent stem cells (Nanog, Nucleostemin), of genes for hematopoietic markers (EPCR, Sca-1, CD11b, CD45), for the mesenchymal marker CD105 and of genes for the neural markers Pax-6 and Ezrin. In methylcellulose and May-Grünwald-Giemsa staining, hematopoietic colonies were obtained but the hematopoietic system of lethally irradiated mice could not be rescued. Osteogenic differentiation was not detectable. Thus, it became evident that MuMac-E8 represents not a stem cell line. However, MuMac-E8 cells expressed several myeloid surface markers (i.e. CD11b, F4/80, CD14, CD64), showed phagocytosis and is capable of producing nitric oxide. Thus, this cell line seems to be arrested an advanced stage of myeloid differentiation. Adherence data measured by impedance-based real-time cell analysis together with cell morphology data suggested that MuMac-E8 represents a new macrophage precursor cell line exhibiting weak adherence. This cell line is suitable as an in-vitro model for testing of macrophage functions. Moreover, it might be also useful for differentiation or reprogramming studies. PMID:25546418

Improvement of Eustachian Tube Function by Tissue-Engineered Regeneration of Mastoid Air Cells

PubMed Central

Kanemaru, Shin-ichi; Umeda, Hiroo; Yamashita, Masaru; Hiraumi, Harukazu; Hirano, Shigeru; Nakamura, Tatsuo; Ito, Juichi

2013-01-01

Objectives/Hypothesis Most cases of chronic otitis media (OMC) are associated with poor development of the mastoid air cells (MACs) and poor Eustachian tube (ET) function. We have previously reported that MAC regeneration can effectively eliminate intractable OMC. In this study, we assessed the ability of regenerated MACs to restore normal gas exchange function and contribute to improved ET function. Study Design Clinical trial with control. Setting General hospitals. Materials and Methods Seventy-six patients with OMC, including cholesteatoma and adhesive otitis media, received tympanoplasty and MAC regeneration therapy. At the first-stage of tympanoplasty, artificial pneumatic bones and/or autologous bone fragments were implanted into the opened mastoid cavity. At the 2nd-stage operation, a nitrous oxide (N2O) gas study was performed in 10 patients to measure middle ear pressure (MEP). For the control group, MEP was measured in five patients with good MAC development during cochlear implantation or facial nerve decompression. ET function was measured twice in each patient, once before the 1st operation and 6 months after the second operation. Results At the 2nd-stage operation, in all cases with regenerated MACs and in the normal control group, MEP changed after administration of N2O. In contrast, no change in MEP was observed in cases with unregenerated MACs. In 70% (n = 37/53) of the regenerated MAC group, ET function was improved, whereas improvement of ET function was observed in only 13% (n = 3/23) of the unregenerated MAC group. Conclusions Tissue-engineered regeneration of MACs improves ET function and gas exchange in the middle ear. Laryngoscope, 2012 Level of Evidence 3b PMID:23086494

MAC/GMC 4.0 User's Manual: Example Problem Manual. Volume 3

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2002-01-01

This document is the third volume in the three volume set of User's Manuals for the Micromechanics Analysis Code with Generalized Method of Cells Version 4.0 (MAC/GMC 4.0). Volume 1 is the Theory Manual, Volume 2 is the Keywords Manual, and this document is the Example Problems Manual. MAC/GMC 4.0 is a composite material and laminate analysis software program developed at the NASA Glenn Research Center. It is based on the generalized method of cells (GMC) micromechanics theory, which provides access to the local stress and strain fields in the composite material. This access grants GMC the ability to accommodate arbitrary local models for inelastic material behavior and various types of damage and failure analysis. MAC/GMC 4.0 has been built around GMC to provide the theory with a user-friendly framework, along with a library of local inelastic, damage, and failure models. Further, application of simulated thermo-mechanical loading, generation of output results, and selection of architectures to represent the composite material, have been automated in MAC/GMC 4.0. Finally, classical lamination theory has been implemented within MAC/GMC 4.0 wherein GMC is used to model the composite material response of each ply. Consequently, the full range of GMC composite material capabilities is available for analysis of arbitrary laminate configurations as well. This volume provides in-depth descriptions of 43 example problems, which were specially designed to highlight many of the most important capabilities of the code. The actual input files associated with each example problem are distributed with the MAC/GMC 4.0 software; thus providing the user with a convenient starting point for their own specialized problems of interest.

Comprehensive Micromechanics-Analysis Code - Version 4.0

NASA Technical Reports Server (NTRS)

Arnold, S. M.; Bednarcyk, B. A.

2005-01-01

Version 4.0 of the Micromechanics Analysis Code With Generalized Method of Cells (MAC/GMC) has been developed as an improved means of computational simulation of advanced composite materials. The previous version of MAC/GMC was described in "Comprehensive Micromechanics-Analysis Code" (LEW-16870), NASA Tech Briefs, Vol. 24, No. 6 (June 2000), page 38. To recapitulate: MAC/GMC is a computer program that predicts the elastic and inelastic thermomechanical responses of continuous and discontinuous composite materials with arbitrary internal microstructures and reinforcement shapes. The predictive capability of MAC/GMC rests on a model known as the generalized method of cells (GMC) - a continuum-based model of micromechanics that provides closed-form expressions for the macroscopic response of a composite material in terms of the properties, sizes, shapes, and responses of the individual constituents or phases that make up the material. Enhancements in version 4.0 include a capability for modeling thermomechanically and electromagnetically coupled ("smart") materials; a more-accurate (high-fidelity) version of the GMC; a capability to simulate discontinuous plies within a laminate; additional constitutive models of materials; expanded yield-surface-analysis capabilities; and expanded failure-analysis and life-prediction capabilities on both the microscopic and macroscopic scales.

Suppression of c-Myc induces apoptosis via an AMPK/mTOR-dependent pathway by 4-O-methyl-ascochlorin in leukemia cells.

PubMed

Shin, Jae-Moon; Jeong, Yun-Jeong; Cho, Hyun-Ji; Magae, Junji; Bae, Young-Seuk; Chang, Young-Chae

2016-05-01

4-O-Methyl-ascochlorin (MAC) is a methylated derivative of the prenyl-phenol antibiotic ascochlorin, which was isolated from an incomplete fungus, Ascochyta viciae. Although the effects of MAC on apoptosis have been reported, the underlying mechanisms remain unknown. Here, we show that MAC promoted apoptotic cell death and downregulated c-Myc expression in K562 human leukemia cells. The effect of MAC on apoptosis was similar to that of 10058-F4 (a c-Myc inhibitor) or c-Myc siRNA, suggesting that the downregulation of c-Myc expression plays a role in the apoptotic effect of MAC. Further investigation showed that MAC downregulated c-Myc by inhibiting protein synthesis. MAC promoted the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its target proteins, including p70S6 K and 4E-BP-1. Treatment of cells with AICAR (an AMPK activator), rapamycin (an mTOR inhibitor), or mTOR siRNA downregulated c-Myc expression and induced apoptosis to a similar extent to that of MAC. These results suggest that the effect of MAC on apoptosis induction in human leukemia cells is mediated by the suppression of c-Myc protein synthesis via an AMPK/mTOR-dependent mechanism.

Deformation, Failure, and Fatigue Life of SiC/Ti-15-3 Laminates Accurately Predicted by MAC/GMC

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2002-01-01

NASA Glenn Research Center's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) (ref.1) has been extended to enable fully coupled macro-micro deformation, failure, and fatigue life predictions for advanced metal matrix, ceramic matrix, and polymer matrix composites. Because of the multiaxial nature of the code's underlying micromechanics model, GMC--which allows the incorporation of complex local inelastic constitutive models--MAC/GMC finds its most important application in metal matrix composites, like the SiC/Ti-15-3 composite examined here. Furthermore, since GMC predicts the microscale fields within each constituent of the composite material, submodels for local effects such as fiber breakage, interfacial debonding, and matrix fatigue damage can and have been built into MAC/GMC. The present application of MAC/GMC highlights the combination of these features, which has enabled the accurate modeling of the deformation, failure, and life of titanium matrix composites.

Magnetic-Activated Cell Sorting for the Fast and Efficient Separation of Human and Rodent Schwann Cells from Mixed Cell Populations.

PubMed

Ravelo, Kristine M; Andersen, Natalia D; Monje, Paula V

2018-01-01

To date, magnetic-activated cell sorting (MACS) remains a powerful method to isolate distinct cell populations based on differential cell surface labeling. Optimized direct and indirect MACS protocols for cell immunolabeling are presented here as methods to divest Schwann cell (SC) cultures of contaminating cells (specifically, fibroblast cells) and isolate SC populations at different stages of differentiation. This chapter describes (1) the preparation of single-cell suspensions from established human and rat SC cultures, (2) the design and application of cell selection strategies using SC-specific (p75 NGFR , O4, and O1) and fibroblast-specific (Thy-1) markers, and (3) the characterization of both the pre- and post-sorting cell populations. A simple protocol for the growth of hybridoma cell cultures as a source of monoclonal antibodies for cell surface immunolabeling of SCs and fibroblasts is provided as a cost-effective alternative for commercially available products. These steps allow for the timely and efficient recovery of purified SC populations without compromising the viability and biological activity of the cells.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Jeremy, E-mail: jeremy.meyer@hcuge.ch; Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Genève; Lacotte, Stéphanie, E-mail: stephanie.lacotte@unige.ch

The objective of the present study was to develop an accurate and reproducible method for liver sinusoidal endothelial cell (LSEC) isolation in mice. Non-parenchymal cells were isolated using a modified two-step collagenase digestion combined with Optiprep density gradient centrifugation. LSEC were further purified using two prevalent methods, short-term selective adherence and CD146+ magnetic-activated cell sorting (MACS), and compared in terms of cell yield, viability and purity to our purification technique using CD11b cell depletion combined with long-term selective adherence. LSEC purification using our technique allowed to obtain 7.07±3.80 million LSEC per liver, while CD146+ MACS and short-term selective adherence yieldedmore » 2.94±1.28 and 0.99±0.66 million LSEC, respectively. Purity of the final cell preparation reached 95.10±2.58% when using our method. In contrast, CD146+ MACS and short-term selective adherence gave purities of 86.75±3.26% and 47.95±9.82%, respectively. Similarly, contamination by non-LSEC was the lowest when purification was performed using our technique, with a proportion of contaminating macrophages of only 1.87±0.77%. Further, isolated cells analysed by scanning electron microscopy presented typical LSEC fenestrations organized in sieve plates, demonstrating that the technique allowed to isolate bona fide LSEC. In conclusion, we described a reliable and reproducible technique for the isolation of high yields of pure LSEC in mice. This protocol provides an efficient method to prepare LSEC for studying their biological functions. - Highlights: • This protocol provides an efficient method to prepare primary mouse LSEC for studying their biological functions. • The liver cell dispersion step was improved by performing a retrograde cannulation of the liver. • The cell yield and the purity obtained were higher than comparative techniques in mice. • Contaminating macrophages were removed by introducing a CD11b- magnetic –activated cell sorting step.« less

Mac-1 (CD11b/CD18) is essential for Fc receptor-mediated neutrophil cytotoxicity and immunologic synapse formation.

PubMed

van Spriel, A B; Leusen, J H; van Egmond, M; Dijkman, H B; Assmann, K J; Mayadas, T N; van de Winkel, J G

2001-04-15

Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1 (complement receptor type 3, CD11b/CD18) has previously been implicated in receptor cooperation with Fc receptors (FcRs). The role of Mac-1 in FcR-mediated lysis of tumor cells was characterized by studying normal human PMNs, Mac-1-deficient mouse PMNs, and mouse PMNs transgenic for human FcR. All PMNs efficiently phagocytosed Ab-coated particles. However, antibody-dependent cellular cytotoxicity (ADCC) was abrogated in Mac-1(-/-) PMNs and in human PMNs blocked with anti-Mac-1 monoclonal Ab (mAb). Mac-1(-/-) PMNs were unable to spread on Ab-opsonized target cells and other Ab-coated surfaces. Confocal laser scanning and electron microscopy revealed a striking difference in immunologic synapse formation between Mac-1(-/-) and wild-type PMNs. Also, respiratory burst activity could be measured outside membrane-enclosed compartments by using Mac-1(-/-) PMNs bound to Ab-coated tumor cells, in contrast to wild-type PMNs. In summary, these data document an absolute requirement of Mac-1 for FcR-mediated PMN cytotoxicity toward tumor targets. Mac-1(-/-) PMNs exhibit defective spreading on Ab-coated targets, impaired formation of immunologic synapses, and absent tumor cytolysis.

Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Recognizes a Novel Ligand, Mac-2-binding Protein, Characteristically Expressed on Human Colorectal Carcinomas*

PubMed Central

Nonaka, Motohiro; Ma, Bruce Yong; Imaeda, Hirotsugu; Kawabe, Keiko; Kawasaki, Nobuko; Hodohara, Keiko; Kawasaki, Nana; Andoh, Akira; Fujiyama, Yoshihide; Kawasaki, Toshisuke

2011-01-01

Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the α1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN ligand expressed on some primary colorectal cancer tissues from certain parts of patients in comparison with CEA from other parts, suggesting that DC-SIGN-binding Mac-2BP bearing tumor-associated Le glycans may become a novel potential colorectal cancer biomarker for some patients instead of CEA. PMID:21515679

Moringa isothiocyanate complexed with α-cyclodextrin: a new perspective in neuroblastoma treatment.

PubMed

Giacoppo, Sabrina; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

2017-07-14

Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as potential chemotherapeutic agents. This study was designed to assess the anti-proliferative activities of a new preparation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin (moringin + α-CD; MAC) on SH-SY5Y human neuroblastoma cells. This new formulation arises in the attempt to overcome the poor solubility and stability of moringin alone in aqueous media. SH-SY5Y cells were cultured and exposed to increasing concentrations of MAC (1.0, 2.5 and 5.0 μg). Cell proliferation was examined by MTT and cell count assays. The cytotoxic activity of the MAC complex was assessed by lactate dehydrogenase (LDH) assay and trypan blue exclusion test. In addition, western blotting analyses for the main apoptosis-related proteins were performed. Treatment of SH-SY5Y cells with the MAC complex reduced cell growth in concentration dependent manner. Specifically, MAC exhibited a potent action in inhibiting the PI3K/Akt/mTOR pathway, whose aberrant activation was found in many types of cancer. MAC was also found to induce the nuclear factor-κB (NF-κB) p65 activation by phosphorylation and its translocation into the nucleus. Moreover, treatment with MAC was able to down-regulate MAPK pathway (results focused on JNK and p38 expression). Finally, MAC was found to trigger apoptotic death pathway (based on expression levels of cleaved-caspase 3, Bax/Bcl-2 balance, p53 and p21). These findings suggest that use of MAC complex may open novel perspectives to improve the poor prognosis of patients with neuroblastoma.

An innovative cascade system for simultaneous separation of multiple cell types.

PubMed

Pierzchalski, Arkadiusz; Mittag, Anja; Bocsi, Jozsef; Tarnok, Attila

2013-01-01

Isolation of different cell types from one sample by fluorescence activated cell sorting is standard but expensive and time consuming. Magnetic separation is more cost effective and faster by but requires substantial effort. An innovative pluriBead-cascade cell isolation system (pluriSelect GmbH, Leipzig, Germany) simultaneously separates two or more different cell types. It is based on antibody-mediated binding of cells to beads of different size and their isolation with sieves of different mesh-size. For the first time, we validated the pluriSelect system for simultaneous separation of CD4+- and CD8+-cells from human EDTA-blood samples. Results were compared with those obtained by magnetic activated cell sorting (MACS; two steps -first isolation of CD4+, then restaining of the residual cell suspension with anti-human CD8+ MACS antibody followed by the second isolation). pluriSelect separation was done in whole blood, MACS separation on density gradient isolated mononuclear cells. Isolated and residual cells were immunophenotyped by 7-color 9-marker panel (CD3; CD16/56; CD4; CD8; CD14; CD19; CD45; HLA-DR) using flow cytometry. Cell count, purity, yield and viability (7-AAD exclusion) were determined. There were no significant differences between both systems regarding purity (MACS (median[range]: 92.4% [91.5-94.9] vs. pluriSelect 95% [94.9-96.8])) of CD4+ cells, however CD8+ isolation showed lower purity by MACS (74.8% [67.6-77.9], pluriSelect 89.9% [89.0-95.7]). Yield was not significantly different for CD4 (MACS 58.5% [54.1-67.5], pluriSelect 67.9% [56.8-69.8]) and for CD8 (MACS 57.2% [41.3-72.0], pluriSelect 67.2% [60.0-78.5]). Viability was slightly higher with MACS for CD4+ (98.4% [97.8-99.0], pluriSelect 94.1% [92.1-95.2]) and for CD8+-cells (98.8% [98.3-99.1], pluriSelect 86.7% [84.2-89.9]). pluriSelect separation was substantially faster than MACS (1h vs. 2.5h) and no pre-enrichment steps were necessary. In conclusion, pluriSelect is a fast, simple and gentle system for efficient simultaneous separation of two and more cell subpopulation directly from whole blood and provides a simple alternative to magnetic separation.

Crystallization and preliminary X-ray crystallographic analysis of MacA from Actinobacillus actinomycetemcomitans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piao, Shunfu; Xu, Yongbin; Ha, Nam-Chul, E-mail: hnc@pusan.ac.kr

2008-05-01

A periplasmic membrane-fusion protein MacA from Actinobacillus actinomycetemcomitans, an essential component of the multidrug efflux pump in Gram-negative bacteria, was crystallized. Periplasmic membrane-fusion proteins (MFPs) are an essential component of the multidrug efflux pump in Gram-negative bacteria. They play a crucial role in bridging the outer membrane porin TolC and two distinct types of inner membrane transporters. The MFP MacA bridges the inner membrane ABC-type multidrug transporter MacB and the outer membrane porin TolC. MacA from the pathogenic bacterium Actinobacillus actinomycetemcomitans was expressed in Escherichia coli B834 (DE3) and the recombinant protein was purified using Ni–NTA affinity, Q anion-exchange andmore » gel-filtration chromatography. The purified MacA protein was crystallized using the vapour-diffusion method. A MAD diffraction data set was collected to a resolution of 3.0 Å at 100 K. The crystal belongs to space group P622, with unit-cell parameters a = b = 109.2, c = 255.4 Å, α = β = 90, γ = 120°, and contains one molecule in the asymmetric unit.« less

Diagnostic usefulness of MUC1 and MUC4 for distinguishing between metastatic adenocarcinoma cells and reactive mesothelial cells in effusion cell blocks.

PubMed

Cho, Jin Seong; Kim, Ga-Eon; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan

2013-01-01

The aim of our study was to determine the diagnostic value of MUC1 and MUC4 for distinguishing between metastatic adenocarcinoma cells (MAC) and reactive mesothelial cells (RMC) in effusion fluids. A total of 237 cell block specimens from pleural and peritoneal effusions, including 196 malignant effusions with MAC and 41 benign effusions with RMC, were stained with antibodies against MUC1 and MUC4. Membranous staining with or without cytoplasmic staining was considered to be positive. MUC1 immunoreactivity was observed in 194 (99.0%) of 196 cases of MAC and in 20 (48.8%) of 41 cases of RMC. MUC4 immunoreactivity was observed in 174 (88.8%) of 196 cases of MAC and in 4 (9.8%) of 41 cases of RMC. For distinguishing MAC from RMC, the MUC1 reactivity was found to be 99.0% sensitive and 51.2% specific with a positive predictive value of 90.7% and a negative predictive value of 91.3%. The sensitivity of MUC4 for MAC was 88.8%, the specificity was 90.2%, the negative predictive value was 62.7%, and the positive predictive value was 97.8%. Our data suggest that MUC4 appears to be a sensitive and specific marker for differentiating between MAC and RMC. Copyright © 2013 S. Karger AG, Basel.

Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes

PubMed Central

Pasquini, Marcelo C.; Logan, Brent R.; Wu, Juan; Devine, Steven M.; Porter, David L.; Maziarz, Richard T.; Warlick, Erica D.; Fernandez, Hugo F.; Alyea, Edwin P.; Hamadani, Mehdi; Bashey, Asad; Giralt, Sergio; Geller, Nancy L.; Leifer, Eric; Le-Rademacher, Jennifer; Mendizabal, Adam M.; Horowitz, Mary M.; Deeg, H. Joachim; Horwitz, Mitchell E.

2017-01-01

Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index ≤ 4 and < 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLA-matched related or unrelated donors. The primary end point was OS 18 months post–random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P < .001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, −0.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC (P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC (P < .01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes. PMID:28380315

Pulsed electromagnetic field affects intrinsic and endoplasmatic reticulum apoptosis induction pathways in MonoMac6 cell line culture.

PubMed

Kaszuba-Zwoinska, J; Chorobik, P; Juszczak, K; Zaraska, W; Thor, P J

2012-10-01

Current studies were aimed to elucidate influence of pulsed electromagnetic field stimulation on cell viability and apoptosis induction pathways. For the experimental model we have chosen monocytic cell line MonoMac6 and several apoptosis inducers with different mechanism of death induction like puromycin, colchicine, cyclophosphamide, minocycline and hydrogen peroxide. MonoMac6 cell line was grown at density 1x10(5) cells/well in 96-well culture plates. To induce cell death cell cultures were treated with different apoptosis inducers like puromycin, colchicine, cyclophosphamide, minocycline, hydrogen peroxide and at the same time with pulsed electromagnetic field 50 Hz, 45±5 mT (PEMF) for 4 hour per each stimulation, three times, in 24 hours intervals. Afterwards, cells were harvested for flow cytometry analysis of cell viability measured by annexin V-APC labeled and propidium iodide staining. Expression of apoptosis related genes was evaluated by semi quantitative reverse transcription (RT)-PCR assay. NuPAGE Novex Western blot analysis was carried out for apoptosis inducing factor (AIF) abundance in cytosolic and nuclear extracts of MonoMac6 cells. Puromycin, colchicine and minocycline activated cells and simultaneously treated with PEMF have shown out diminished percentage of annexinV positive (AnV+) cells comparing to controls without PEMF stimulation. MonaMac6 cells puromycin/colchicyne and PEMF treated were to a higher extent double stained (AnV+,PI+), which means increased late apoptotic as well as necrotic (PI+) cells, than non-stimulated controls. On the other hand, minocycline activated cells prior to PEMF treatment showed diminished amount of apoptotic and necrotic (annexin V, annexin V and propidium iodide, propidium iodide positive staining) cells. The opposite effect of PEMF on the percentage of annexin V positively stained cells has been achieved after treatment of MonoMac6 culture with cyclophoshamide and hydrogen peroxide. PEMF enhanced early phase of apoptosis induced by both apoptosis inducing agents. The analysis of expression of the apoptosis related genes in MonoMac6 cultures treated with puromycin and exposed to PEMF performed in reverse transcription of polymerase chain reaction (PCR) assay has shown changes in mRNA of genes engaged in intrinsic apoptotic pathway and pathway with AIF abundance. The most influenced was expression of gene belonging to pro-apoptotic family of Bcl-2 and AIF agent. Examination of immunoblots developed with anti-AIF antibody showed that cytosol content of AIF protein was diminished after puromycin and PEMF treatment of MonoMac6 cells. The obtained results indicate that PEMF affects induction of apoptosis in MonoMac6 cells stimulated to death with inducing agents to a different extent. Main finding of the current results is that, PEMF stimulation of MonoMac6 cells simultaneously treated with puromycin caused changes in the Bcl-family genes expression as well as in caspase independent pathway of apoptosis inducing factor (AIF).

Fluorescence- and magnetic-activated cell sorting strategies to separate spermatozoa involving plural contributors from biological mixtures for human identification

PubMed Central

Xu, Yan; Xie, Jianhui; Chen, Ronghua; Cao, Yu; Ping, Yuan; Xu, Qingwen; Hu, Wei; Wu, Dan; Gu, Lihua; Zhou, Huaigu; Chen, Xin; Zhao, Ziqin; Zhong, Jiang; Li, Rui

2016-01-01

No effective method has been developed to distinguish sperm cells originating from different men in multi-suspect sexual assault cases. Here we combined MACS and FACS to isolate single donor sperm cells from forensic mixture samples including female vaginal epithelial cells and sperm cells from multiple contributors. Sperms from vaginal swab were isolated by MACS using FITC-conjugated A kinase anchor protein 3 (AKAP3) antibody; target individual sperm cells involving two or three donors were separated by FACS using FITC-labeled blood group A/B antigen antibody. This procedure was further tested in two mock multi-suspect sexual assault samples and one practical casework sample. Our results showed that complete single donor STR profiles could be successfully obtained from sperm/epithelial cell and sperm mixtures from two contributors. For unbalanced sperm/epithelial cells and sperm cells mixtures, sensitivity results revealed that target cells could be detected at as low as 1:32 and 1:8 mixed ratios, respectively. Although highly relies on cell number and blood types or secretor status of the individuals, this procedure would still be useful tools for forensic DNA analysis of multi-suspect sexual assault cases by the combined use of FACS and MACS based on sperm-specific AKAP3 antigen and human blood type antigen. PMID:27857155

Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

EPA Science Inventory

The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

Pleiotrophin, a multifunctional cytokine and growth factor, induces leukocyte responses through the integrin Mac-1.

PubMed

Shen, Di; Podolnikova, Nataly P; Yakubenko, Valentin P; Ardell, Christopher L; Balabiyev, Arnat; Ugarova, Tatiana P; Wang, Xu

2017-11-17

Pleiotrophin (PTN) is a multifunctional, cationic, glycosaminoglycan-binding cytokine and growth factor involved in numerous physiological and pathological processes, including tissue repair and inflammation-related diseases. PTN has been shown to promote leukocyte responses by inducing their migration and expression of inflammatory cytokines. However, the mechanisms through which PTN mediates these responses remain unclear. Here, we identified the integrin Mac-1 (αMβ2, CD11b/CD18) as the receptor mediating macrophage adhesion and migration to PTN. We also found that expression of Mac-1 on the surface of human embryonic kidney (HEK) 293 cells induced their adhesion and migration to PTN. Accordingly, PTN promoted Mac-1-dependent cell spreading and initiated intracellular signaling manifested in phosphorylation of Erk1/2. While binding to PTN, Mac-1 on Mac-1-expressing HEK293 cells appears to cooperate with cell-surface proteoglycans because both anti-Mac-1 function-blocking mAb and heparin were required to block adhesion. Moreover, biolayer interferometry and NMR indicated a direct interaction between the α M I domain, the major ligand-binding region of Mac-1, and PTN. Using peptide libraries, we found that in PTN the α M I domain bound sequences enriched in basic and hydrophobic residues, indicating that PTN conforms to the general principle of ligand-recognition specificity of the α M I domain toward cationic proteins/peptides. Finally, using recombinant PTN-derived fragments, we show that PTN contains two distinct Mac-1-binding sites in each of its constitutive domains. Collectively, these results identify PTN as a ligand for the integrin Mac-1 on the surface of leukocytes and suggest that this interaction may play a role in inflammatory responses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Novel microbial fuel cell design to operate with different wastewaters simultaneously.

PubMed

Mathuriya, Abhilasha Singh

2016-04-01

A novel single cathode chamber and multiple anode chamber microbial fuel cell design (MAC-MFC) was developed by incorporating multiple anode chambers into a single unit and its performance was checked. During 60 days of operation, performance of MAC-MFC was assessed and compared with standard single anode/cathode chamber microbial fuel cell (SC-MFC). The tests showed that MAC-MFC generated stable and higher power outputs compared with SC-MFC and each anode chamber contributed efficiently. Further, MAC-MFCs were incorporated with different wastewaters in different anode chambers and their behavior in MFC performance was observed. MAC-MFC efficiently treated multiple wastewaters simultaneously at low cost and small space, which claims its candidature for future possible scale-up applications. Copyright © 2015. Published by Elsevier B.V.

Citrus-derived oils inhibit Satphylococcus aureus growth and alter its interaction with bovine mammary cells

USDA-ARS?s Scientific Manuscript database

This experiment examined the effects of cold-pressed, terpeneless citrus oil (CDO) on growth of Staphylococcus aureus, which a major cause of contagious bovine mastitis, and invasion of epithelial cells as modeled with bovine mammary cells (MAC-T). The broth dilution method (Muthaiyan et al., 2012)...

High molecular weight kininogen regulates platelet-leukocyte interactions by bridging Mac-1 and glycoprotein Ib.

PubMed

Chavakis, Triantafyllos; Santoso, Sentot; Clemetson, Kenneth J; Sachs, Ulrich J H; Isordia-Salas, Irma; Pixley, Robin A; Nawroth, Peter P; Colman, Robert W; Preissner, Klaus T

2003-11-14

Leukocyte-platelet interaction is important in mediating leukocyte adhesion to a thrombus and leukocyte recruitment to a site of vascular injury. This interaction is mediated at least in part by the beta2-integrin Mac-1 (CD11b/CD18) and its counter-receptor on platelets, glycoprotein Ibalpha (GPIbalpha). High molecular weight kininogen (HK) was previously shown to interact with both GPIbalpha and Mac-1 through its domains 3 and 5, respectively. In this study we investigated the ability of HK to interfere with the leukocyte-platelet interaction. In a purified system, HK binding to GPIbalpha was inhibited by HK domain 3 and the monoclonal antibody (mAb) SZ2, directed against the epitope 269-282 of GPIbalpha, whereas mAb AP1, directed to the region 201-268 of GPIbalpha had no effect. In contrast, mAb AP1 inhibited the Mac-1-GPIbalpha interaction. Binding of GPIbalpha to Mac-1 was enhanced 2-fold by HK. This effect of HK was abrogated in the presence of HK domains 3 or 5 or peptides from the 475-497 region of the carboxyl terminus of domain 5 as well as in the presence of mAb SZ2 but not mAb AP1. Whereas no difference in the affinity of the Mac-1-GPIbalpha interaction was observed in the absence or presence of HK, maximal binding of GPIbalpha to Mac-1 doubled in the presence of HK. Moreover, HK/HKa increased the Mac-1-dependent adhesion of myelomonocytic U937 cells and K562 cells transfected with Mac-1 to immobilized GPIbalpha or to GPIbalpha-transfected Chinese hamster ovary cells. Finally, Mac-1-dependent adhesion of neutrophils to surface-adherent platelets was enhanced by HK. Thus, HK can bridge leukocytes with platelets by interacting via its domain 3 with GPIbalpha and via its domain 5 with Mac-1 thereby augmenting the Mac-1-GPIbalpha interaction. These distinct molecular interactions of HK with leukocytes and platelets contribute to the regulation of the adhesive behavior of vascular cells and provide novel molecular targets for reducing atherothrombotic pathologies.

Xenon neurotoxicity in rat hippocampal slice cultures is similar to isoflurane and sevoflurane.

PubMed

Brosnan, Heather; Bickler, Philip E

2013-08-01

Anesthetic neurotoxicity in the developing brain of rodents and primates has raised concern. Xenon may be a nonneurotoxic alternative to halogenated anesthetics, but its toxicity has only been studied at low concentrations, where neuroprotective effects predominate in animal models. An equipotent comparison of xenon and halogenated anesthetics with respect to neurotoxicity in developing neurons has not been made. Organotypic hippocampal cultures from 7-day-old rats were exposed to 0.75, 1, and 2 minimum alveolar concentrations (MAC) partial pressures (60% xenon at 1.2, 2.67, and 3.67 atm; isoflurane at 1.4, 1.9, and 3.8%; and sevoflurane at 3.4 and 6.8%) for 6 h, at atmospheric pressure or in a pressure chamber. Cell death was assessed 24 h later with fluorojade and fluorescent dye exclusion techniques. Xenon caused death of hippocampal neurons in CA1, CA3, and dentate regions after 1 and 2 MAC exposures, but not at 0.75 MAC. At 1 MAC, xenon increased cell death 40% above baseline (P < 0.01; ANOVA with Dunnett test). Both isoflurane and sevoflurane increased neuron death at 1 but not 2 MAC. At 1 MAC, the increase in cell death compared with controls was 63% with isoflurane and 90% with sevoflurane (both P < 0.001). Pretreatment of cultures with isoflurane (0.75 MAC) reduced neuron death after 1 MAC xenon, isoflurane, and sevoflurane. Xenon causes neuronal cell death in an in vitro model of the developing rodent brain at 1 MAC, as does isoflurane and sevoflurane at similarly potent concentrations. Preconditioning with a subtoxic dose of isoflurane eliminates this toxicity.

Protection of Bovine Mammary Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Cell Damage by Resveratrol.

PubMed

Jin, Xiaolu; Wang, Kai; Liu, Hongyun; Hu, Fuliang; Zhao, Fengqi; Liu, Jianxin

2016-01-01

The mammary epithelial cells (MECs) of high-producing dairy cows are likely to be subject to oxidative stress (OS) due to the intensive cell metabolism. The objectives of this study were to investigate the cytoprotective effects of resveratrol against hydrogen peroxide- (H2O2-) induced OS in cultured bovine MECs (MAC-T). Pretreatment of MAC-T cells with resveratrol could rescue the decrease in cell viability and resulted in lower intracellular reactive oxygen species (ROS) accumulation after H2O2 exposure. Resveratrol helped MAC-T cells to prevent H2O2-induced endoplasmic reticulum stress and mitochondria-related cell apoptosis. Moreover, resveratrol induced mRNA expression of multiple antioxidant defense genes in MAC-T cells under normal/oxidative conditions. Nuclear factor erythroid 2-related factor 2 (Nrf2) was required for the cytoprotective effects on MAC-T cells by resveratrol, as knockdown of Nrf2 significantly abolished resveratrol-induced cytoprotective effects against OS. In addition, by using selective inhibitors, we further confirmed that the induction of Nrf2 by resveratrol was mediated through the prolonged activation of PI3K/Akt and ERK/MAPK pathways but negatively regulated by p38/MAPK pathway. Overall, resveratrol has beneficial effects on bovine MECs redox balance and may be potentially used as a therapeutic medicine against oxidative insult in lactating animals.

Frequency and reactivity of antigen-specific T cells were concurrently measured through the combination of artificial antigen-presenting cell, MACS and ELISPOT.

PubMed

Shen, Chuanlai; Xu, Tao; Wu, You; Li, Xiaoe; Xia, Lingzhi; Wang, Wei; Shahzad, Khawar Ali; Zhang, Lei; Wan, Xin; Qiu, Jie

2017-11-27

Conventional peptide-major histocompatibility complex (pMHC) multimer staining, intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay cannot concurrently determine the frequency and reactivity of antigen-specific T cells (AST) in a single assay. In this report, pMHC multimer, magnetic-activated cell sorting (MACS), and ELISPOT techniques have been integrated into a micro well by coupling pMHC multimers onto cell-sized magnetic beads to characterize AST cell populations in a 96-well microplate which pre-coated with cytokine-capture antibodies. This method, termed AAPC-microplate, allows the enumeration and local cytokine production of AST cells in a single assay without using flow cytometry or fluorescence intensity scanning, thus will be widely applicable. Here, ovalbumin 257-264 -specific CD8 + T cells from OT-1 T cell receptor (TCR) transgenic mice were measured. The methodological accuracy, specificity, reproducibility, and sensitivity in enumerating AST cells compared well with conventional pMHC multimer staining. Furthermore, the AAPC-microplate was applied to detect the frequency and reactivity of Hepatitis B virus (HBV) core antigen 18-27 - and surface antigen 183-191 -specific CD8 + T cells for the patients, and was compared with conventional method. This method without the need of high-end instruments may facilitate the routine analysis of patient-specific cellular immune response pattern to a given antigen in translational studies.

Macro-architectured cellular materials: Properties, characteristic modes, and prediction methods

NASA Astrophysics Data System (ADS)

Ma, Zheng-Dong

2017-12-01

Macro-architectured cellular (MAC) material is defined as a class of engineered materials having configurable cells of relatively large (i.e., visible) size that can be architecturally designed to achieve various desired material properties. Two types of novel MAC materials, negative Poisson's ratio material and biomimetic tendon reinforced material, were introduced in this study. To estimate the effective material properties for structural analyses and to optimally design such materials, a set of suitable homogenization methods was developed that provided an effective means for the multiscale modeling of MAC materials. First, a strain-based homogenization method was developed using an approach that separated the strain field into a homogenized strain field and a strain variation field in the local cellular domain superposed on the homogenized strain field. The principle of virtual displacements for the relationship between the strain variation field and the homogenized strain field was then used to condense the strain variation field onto the homogenized strain field. The new method was then extended to a stress-based homogenization process based on the principle of virtual forces and further applied to address the discrete systems represented by the beam or frame structures of the aforementioned MAC materials. The characteristic modes and the stress recovery process used to predict the stress distribution inside the cellular domain and thus determine the material strengths and failures at the local level are also discussed.

Development and characterization of an injectable cement of nano calcium-deficient hydroxyapatite/multi(amino acid) copolymer/calcium sulfate hemihydrate for bone repair

PubMed Central

Qi, Xiaotong; Li, Hong; Qiao, Bo; Li, Weichao; Hao, Xinyan; Wu, Jun; Su, Bao; Jiang, Dianming

2013-01-01

A novel injectable bone cement was developed by integration of nano calcium-deficient hydroxyapatite/multi(amino acid) copolymer (n-CDHA/MAC) and calcium sulfate hemihydrate (CSH; CaSO4 · 1/2H2O). The structure, setting time, and compressive strength of the cement were investigated. The results showed that the cement with a liquid to powder ratio of 0.8 mL/g exhibited good injectability and appropriate setting time and mechanical properties. In vitro cell studies indicated that MC3T3-E1 cells cultured on the n-CDHA/MAC/CSH composite spread well and showed a good proliferation state. The alkaline phosphatase activity of the MC3T3-E1 cells cultured on the n-CDHA/MAC/CSH composite was significantly higher than that of the cells on pure CSH at 4 and 7 days of culture. The n-CDHA/MAC/CSH cement was implanted into critical size defects of the femoral condyle in rabbits to evaluate its biocompatibility and osteogenesis in vivo. Radiological and histological results indicated that introduction of the n-CDHA/MAC into CSH enhanced new bone formation, and the n-CDHA/MAC/CSH cement exhibited good biocompatibility and degradability. In conclusion, the injectable n-CDHA/MAC/CSH composite cement has a significant clinical advantage over pure CSH cement, and may be a promising bone graft substitute for the treatment of bone defects. PMID:24293996

Preparation of myeloid derived suppressor cells (MDSC) from naive and pancreatic tumor-bearing mice using flow cytometry and automated magnetic activated cell sorting (AutoMACS).

PubMed

Nelson, Nadine; Szekeres, Karoly; Cooper, Denise; Ghansah, Tomar

2012-06-18

MDSC are a heterogeneous population of immature macrophages, dendritic cells and granulocytes that accumulate in lymphoid organs in pathological conditions including parasitic infection, inflammation, traumatic stress, graft-versus-host disease, diabetes and cancer. In mice, MDSC express Mac-1 (CD11b) and Gr-1 (Ly6G and Ly6C) surface antigens. It is important to note that MDSC are well studied in various tumor-bearing hosts where they are significantly expanded and suppress anti-tumor immune responses compared to naïve counterparts. However, depending on the pathological condition, there are different subpopulations of MDSC with distinct mechanisms and targets of suppression. Therefore, effective methods to isolate viable MDSC populations are important in elucidating their different molecular mechanisms of suppression in vitro and in vivo. Recently, the Ghansah group has reported the expansion of MDSC in a murine pancreatic cancer model. Our tumor-bearing MDSC display a loss of homeostasis and increased suppressive function compared to naïve MDSC. MDSC percentages are significantly less in lymphoid compartments of naïve vs. tumor-bearing mice. This is a major caveat, which often hinders accurate comparative analyses of these MDSC. Therefore, enriching Gr-1(+) leukocytes from naïve mice prior to Fluorescence Activated Cell Sorting (FACS) enhances purity, viability and significantly reduces sort time. However, enrichment of Gr-1(+) leukocytes from tumor-bearing mice is optional as these are in abundance for quick FACS sorting. Therefore, in this protocol, we describe a highly efficient method of immunophenotyping MDSC and enriching Gr-1(+) leukocytes from spleens of naïve mice for sorting MDSC in a timely manner. Immunocompetent C57BL/6 mice are inoculated with murine Panc02 cells subcutaneously whereas naïve mice receive 1XPBS. Approximately 30 days post inoculation; spleens are harvested and processed into single-cell suspensions using a cell dissociation sieve. Splenocytes are then Red Blood Cell (RBC) lysed and an aliquot of these leukocytes are stained using fluorochrome-conjugated antibodies against Mac-1 and Gr-1 to immunophenotype MDSC percentages using Flow Cytometry. In a parallel experiment, whole leukocytes from naïve mice are stained with fluorescent-conjugated Gr-1 antibodies, incubated with PE-MicroBeads and positively selected using an automated Magnetic Activated Cell Sorting (autoMACS) Pro Separator. Next, an aliquot of Gr-1(+) leukocytes are stained with Mac-1 antibodies to identify the increase in MDSC percentages using Flow Cytometry. Now, these Gr1(+) enriched leukocytes are ready for FACS sorting of MDSC to be used in comparative analyses (naïve vs. tumor- bearing) in in vivo and in vitro assays.

Pathogen Trojan Horse Delivers Bioactive Host Protein to Alter Maize Anther Cell Behavior in Situ.

PubMed

van der Linde, Karina; Timofejeva, Ljudmilla; Egger, Rachel L; Ilau, Birger; Hammond, Reza; Teng, Chong; Meyers, Blake C; Doehlemann, Gunther; Walbot, Virginia

2018-03-01

Small proteins are crucial signals during development, host defense, and physiology. The highly spatiotemporal restricted functions of signaling proteins remain challenging to study in planta. The several month span required to assess transgene expression, particularly in flowers, combined with the uncertainties from transgene position effects and ubiquitous or overexpression, makes monitoring of spatiotemporally restricted signaling proteins lengthy and difficult. This situation could be rectified with a transient assay in which protein deployment is tightly controlled spatially and temporally in planta to assess protein functions, timing, and cellular targets as well as to facilitate rapid mutagenesis to define functional protein domains. In maize ( Zea mays ), secreted ZmMAC1 (MULTIPLE ARCHESPORIAL CELLS1) was proposed to trigger somatic niche formation during anther development by participating in a ligand-receptor module. Inspired by Homer's Trojan horse myth, we engineered a protein delivery system that exploits the secretory capabilities of the maize smut fungus Ustilago maydis , to allow protein delivery to individual cells in certain cell layers at precise time points. Pathogen-supplied ZmMAC1 cell-autonomously corrected both somatic cell division and differentiation defects in mutant Zm mac1-1 anthers. These results suggest that exploiting host-pathogen interactions may become a generally useful method for targeting host proteins to cell and tissue types to clarify cellular autonomy and to analyze steps in cell responses. © 2018 American Society of Plant Biologists. All rights reserved.

Multicollision attack on CBC-MAC, EMAC, and XCBC-MAC of AES-128 algorithm

NASA Astrophysics Data System (ADS)

Brolin Sihite, Alfonso; Hayat Susanti, Bety

2017-10-01

A Message Authentication Codes (MAC) can be constructed based on a block cipher algorithm. CBC-MAC, EMAC, and XCBC-MAC constructions are some of MAC schemes that used in the hash function. In this paper, we do multicollision attack on CBC-MAC, EMAC, and XCBC-MAC construction which uses AES-128 block cipher algorithm as basic construction. The method of multicollision attack utilizes the concept of existential forgery on CBC-MAC. The results show that the multicollision can be obtained easily in CBC-MAC, EMAC, and XCBC-MAC construction.

Isolation and characterization of human mesenchymal stem cells derived from synovial fluid by magnetic-activated cell sorting (MACS).

PubMed

Jia, Zhaofeng; Liang, Yujie; Xu, Xiao; Li, Xingfu; Liu, Qisong; Ou, Yangkan; Duan, Li; Zhu, Weimin; Lu, Wei; Xiong, Jianyi; Wang, Daping

2018-03-01

Mesenchymal stem cells (MSCs) are the primary source of cells used for cell-based therapy in tissue engineering. MSCs are found in synovial fluid, a source that could be conveniently used for cartilage tissue engineering. However, the purification and characterization of SF-MSCs has been poorly documented in the literature. Here, we outline an easy-to-perform approach for the isolation and culture of MSCs derived from human synovial fluid (hSF-MSCs). We have successfully purified hSF-MSCs using magnetic-activated cell sorting (MACS) using the MSC surface marker, CD90. Purified SF-MSCs demonstrate significant renewal capacity following several passages in culture. Furthermore, we demonstrated that MACS-sorted CD90 + cells could differentiated into osteoblasts, adipocytes, and chondrocytes in vitro. In addition, we show that these cells can generate cartilage tissue in micromass culture as well. This study demonstrates that MACS is a useful tool that can be used for the purification of hSF-MSCs from synovial fluid. The proliferation properties and ability to differentiate into chondrocytes make these hSF-MSCs a promising source of stem cells for applications in cartilage repair. © 2017 International Federation for Cell Biology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang Huayan; Yu Junping; Fu Guo

The interaction between integrin macrophage differentiation antigen associated with complement three receptor function (Mac-1) and intercellular adhesion molecule-1 (ICAM-1), which is controlled tightly by the ligand-binding activity of Mac-1, is central to the regulation of neutrophil adhesion in host defense. Several 'inside-out' signals and extracellular metal ions or antibodies have been found to activate Mac-1, resulting in an increased adhesiveness of Mac-1 to its ligands. However, the molecular basis for Mac-1 activation is not well understood yet. In this work, we have carried out a single-molecule study of Mac-1/ICAM-1 interaction force in living cells by atomic force microscopy (AFM). Ourmore » results showed that the binding probability and adhesion force of Mac-1 with ICAM-1 increased upon Mac-1 activation. Moreover, by comparing the dynamic force spectra of different Mac-1 mutants, we expected that Mac-1 activation is governed by the downward movement of its {alpha}7 helix.« less

Development of an algorithm for production of inactivated arbovirus antigens in cell culture

PubMed Central

Goodman, C.H.; Russell, B.J.; Velez, J.O.; Laven, J.J.; Nicholson, W.L; Bagarozzi, D.A.; Moon, J.L.; Bedi, K.; Johnson, B.W.

2015-01-01

Arboviruses are medically important pathogens that cause human disease ranging from a mild fever to encephalitis. Laboratory diagnosis is essential to differentiate arbovirus infections from other pathogens with similar clinical manifestations. The Arboviral Diseases Branch (ADB) reference laboratory at the CDC Division of Vector-Borne Diseases (DVBD) produces reference antigens used in serological assays such as the virus-specific immunoglobulin M antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Antigen production in cell culture has largely replaced the use of suckling mice; however, the methods are not directly transferable. The development of a cell culture antigen production algorithm for nine arboviruses from the three main arbovirus families, Flaviviridae, Togaviridae, and Bunyaviridae, is described here. Virus cell culture growth and harvest conditions were optimized, inactivation methods were evaluated, and concentration procedures were compared for each virus. Antigen performance was evaluated by the MAC-ELISA at each step of the procedure. The antigen production algorithm is a framework for standardization of methodology and quality control; however, a single antigen production protocol was not applicable to all arboviruses and needed to be optimized for each virus. PMID:25102428

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawamoto, Eiji; Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507; Okamoto, Takayuki, E-mail: okamotot@doc.medic.mie-u.ac.jp

LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding ofmore » PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. - Highlights: • LFA-1 and Mac-1 integrins bind to the anti-coagulant molecule thrombomodulin. • The serine/threonine-rich domain of thrombomodulin is essential to interact with the LFA-1 and Mac-1 integrins on PBMCs. • Integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells.« less

Advanced Method for Isolation of Mouse Hepatocytes, Liver Sinusoidal Endothelial Cells, and Kupffer Cells.

PubMed

Liu, Jia; Huang, Xuan; Werner, Melanie; Broering, Ruth; Yang, Dongliang; Lu, Mengji

2017-01-01

Separation of pure cell populations from the liver is a prerequisite to study the role of hepatic parenchymal and non-parenchymal cells in liver physiology, pathophysiology, and immunology. Traditional methods for hepatic cell separation usually purify only single cell types from liver specimens. Here, we describe an efficient method that can simultaneously purify populations of hepatocytes (HCs), liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs) from a single mouse liver specimen. A liberase-based perfusion technique in combination with a low-speed centrifugation and magnetic-activated cell sorting (MACS) led to the isolation and purification of HCs, KCs, and LSECs with high yields and purity.

Nuclear localization signal targeting to macronucleus and micronucleus in binucleated ciliate Tetrahymena thermophila.

PubMed

Iwamoto, Masaaki; Mori, Chie; Osakada, Hiroko; Koujin, Takako; Hiraoka, Yasushi; Haraguchi, Tokuko

2018-06-08

Ciliated protozoa possess two morphologically and functionally distinct nuclei: a macronucleus (MAC) and a micronucleus (MIC). The MAC is transcriptionally active and functions in all cellular events. The MIC is transcriptionally inactive during cell growth, but functions in meiotic events to produce progeny nuclei. Thus, these two nuclei must be distinguished by the nuclear proteins required for their distinct functions during cellular events such as cell proliferation and meiosis. To understand the mechanism of the nuclear transport specific to either MAC or MIC, we identified specific nuclear localization signals (NLSs) in two MAC- and MIC-specific nuclear proteins, macronuclear histone H1 and micronuclear linker histone-like protein (Mlh1), respectively. By expressing GFP-fused fragments of these proteins in Tetrahymena thermophila cells, two distinct regions in macronuclear histone H1 protein were assigned as independent MAC-specific NLSs and two distinct regions in Mlh1 protein were assigned as independent MIC-specific NLSs. These NLSs contain several essential lysine residues responsible for the MAC- and MIC-specific nuclear transport, but neither contains any consensus sequence with known monopartite or bipartite NLSs in other model organisms. Our findings contribute to understanding how specific nuclear targeting is achieved to perform distinct nuclear functions in binucleated ciliates. © 2018 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Acoustical transmission-line model of the middle-ear cavities and mastoid air cells.

PubMed

Keefe, Douglas H

2015-04-01

An acoustical transmission line model of the middle-ear cavities and mastoid air cell system (MACS) was constructed for the adult human middle ear with normal function. The air-filled cavities comprised the tympanic cavity, aditus, antrum, and MACS. A binary symmetrical airway branching model of the MACS was constructed using an optimization procedure to match the average total volume and surface area of human temporal bones. The acoustical input impedance of the MACS was calculated using a recursive procedure, and used to predict the input impedance of the middle-ear cavities at the location of the tympanic membrane. The model also calculated the ratio of the acoustical pressure in the antrum to the pressure in the middle-ear cavities at the location of the tympanic membrane. The predicted responses were sensitive to the magnitude of the viscothermal losses within the MACS. These predicted input impedance and pressure ratio functions explained the presence of multiple resonances reported in published data, which were not explained by existing MACS models.

Local Debonding and Fiber Breakage in Composite Materials Modeled Accurately

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2001-01-01

A prerequisite for full utilization of composite materials in aerospace components is accurate design and life prediction tools that enable the assessment of component performance and reliability. Such tools assist both structural analysts, who design and optimize structures composed of composite materials, and materials scientists who design and optimize the composite materials themselves. NASA Glenn Research Center's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) software package (http://www.grc.nasa.gov/WWW/LPB/mac) addresses this need for composite design and life prediction tools by providing a widely applicable and accurate approach to modeling composite materials. Furthermore, MAC/GMC serves as a platform for incorporating new local models and capabilities that are under development at NASA, thus enabling these new capabilities to progress rapidly to a stage in which they can be employed by the code's end users.

Immunohistochemical characterisation of the hepatic stem cell niche in feline hepatic lipidosis: a preliminary morphological study.

PubMed

Valtolina, Chiara; Robben, Joris H; Favier, Robert P; Rothuizen, Jan; Grinwis, Guy Cm; Schotanus, Baukje A; Penning, Louis C

2018-05-01

Objectives The aim of this study was to describe the cellular and stromal components of the hepatic progenitor cell niche in feline hepatic lipidosis (FHL). Methods Immunohistochemical staining for the progenitor/bile duct marker (K19), activated Kupffer cells (MAC387), myofibroblasts (alpha-smooth muscle actin [α-SMA]) and the extracellular matrix component laminin were used on seven liver biopsies of cats with FHL and three healthy cats. Double immunofluorescence stainings were performed to investigate co-localisation of different cell types in the hepatic progenitor cell (HPC) niche. Results HPCs, Kupffer cells, myofibroblasts and laminin deposition were observed in the liver samples of FHL, although with variability in the expression and positivity of the different immunostainings between different samples. When compared with the unaffected cats where K19 positivity and minimal α-SMA and laminin positivity were seen mainly in the portal area, in the majority of FHL samples K19 and α-SMA-positive cells and laminin positivity were seen also in the periportal and parenchymatous area. MAC387-positive cells were present throughout the parenchyma. Conclusions and relevance This is a preliminary morphological study to describe the activation and co-localisation of components of the HPC niche in FHL. Although the HPC niche in FHL resembles that described in hepatopathies in dogs and in feline lymphocytic cholangitis, the expression of K19, α-SMA, MAC387 and lamin is more variable in FHL, and a common pattern of activation could not be established. Nevertheless, when HPCs were activated, a spatial association between HPCs and their niche could be demonstrated.

Wound Healing in Mac-1 Deficient Mice

DTIC Science & Technology

2017-05-01

36. Rosenkranz AR, Coxon A, Maurer M, Gurish MF, Austen KF, Friend DS, Galli SJ, Mayadas TN. Impaired mast cell development and innate immunity in Mac...genetically deficient mice. 3 INTRODUCTION Wound healing is a complex yet well-regulated process in which multiple resident cells ...recruited inflammatory cells , and stem cells interact to create an environment that supports the healing process. An optimal inflammatory response is a

Induction of persistent in vivo resistance to Mycobacterium avium infection in BALB/c mice injected with interleukin-18-secreting fibroblasts.

PubMed

Chung, Su W; Choi, Sang H; Kim, Tae S

2004-01-02

Interferon-gamma (IFN-gamma) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) is known to strongly induce IFN-gamma production by T cells and natural killer (NK) cells. To determine whether the paracrine secretion of IL-18 can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transfected to secrete bioactive IL-18 and their effects on MAC infection were investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IL-18. Immunization with IL-18-secreting fibroblasts (3T3/IL-18) during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while rIL-18 reduced the bacterial load at initial 1 week but not by 8 weeks postinfection. Immunization with the 3T3/IL-18 cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than those of rIL-18 immunization. Furthermore, lung cells in mice injected with the 3T3/IL-18 cells showed persistent production of IFN-gamma throughout the 8-week period, suggesting that the 3T3/IL-18 cells induced the resistance to MAC infection via IFN-gamma production. This work suggests that IL-18-secreting fibroblasts may serve as a vehicle for paracrine secretion of IL-18 in immunotherapy of MAC infection.

Micromechanics Analysis Code With Generalized Method of Cells (MAC/GMC): User Guide. Version 3

NASA Technical Reports Server (NTRS)

Arnold, S. M.; Bednarcyk, B. A.; Wilt, T. E.; Trowbridge, D.

1999-01-01

The ability to accurately predict the thermomechanical deformation response of advanced composite materials continues to play an important role in the development of these strategic materials. Analytical models that predict the effective behavior of composites are used not only by engineers performing structural analysis of large-scale composite components but also by material scientists in developing new material systems. For an analytical model to fulfill these two distinct functions it must be based on a micromechanics approach which utilizes physically based deformation and life constitutive models and allows one to generate the average (macro) response of a composite material given the properties of the individual constituents and their geometric arrangement. Here the user guide for the recently developed, computationally efficient and comprehensive micromechanics analysis code, MAC, who's predictive capability rests entirely upon the fully analytical generalized method of cells, GMC, micromechanics model is described. MAC/ GMC is a versatile form of research software that "drives" the double or triply periodic micromechanics constitutive models based upon GMC. MAC/GMC enhances the basic capabilities of GMC by providing a modular framework wherein 1) various thermal, mechanical (stress or strain control) and thermomechanical load histories can be imposed, 2) different integration algorithms may be selected, 3) a variety of material constitutive models (both deformation and life) may be utilized and/or implemented, and 4) a variety of fiber architectures (both unidirectional, laminate and woven) may be easily accessed through their corresponding representative volume elements contained within the supplied library of RVEs or input directly by the user, and 5) graphical post processing of the macro and/or micro field quantities is made available.

Mammalian Synthetic Biology: Time for Big MACs.

PubMed

Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

2016-10-21

The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

PubMed

Takata, Kazuyuki; Kozaki, Tatsuya; Lee, Christopher Zhe Wei; Thion, Morgane Sonia; Otsuka, Masayuki; Lim, Shawn; Utami, Kagistia Hana; Fidan, Kerem; Park, Dong Shin; Malleret, Benoit; Chakarov, Svetoslav; See, Peter; Low, Donovan; Low, Gillian; Garcia-Miralles, Marta; Zeng, Ruizhu; Zhang, Jinqiu; Goh, Chi Ching; Gul, Ahmet; Hubert, Sandra; Lee, Bernett; Chen, Jinmiao; Low, Ivy; Shadan, Nurhidaya Binte; Lum, Josephine; Wei, Tay Seok; Mok, Esther; Kawanishi, Shohei; Kitamura, Yoshihisa; Larbi, Anis; Poidinger, Michael; Renia, Laurent; Ng, Lai Guan; Wolf, Yochai; Jung, Steffen; Önder, Tamer; Newell, Evan; Huber, Tara; Ashihara, Eishi; Garel, Sonia; Pouladi, Mahmoud A; Ginhoux, Florent

2017-07-18

Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of cell types during rat liver development.

PubMed

Fiegel, Henning C; Park, Jonas J h; Lioznov, Michael V; Martin, Andreas; Jaeschke-Melli, Stefan; Kaufmann, Peter M; Fehse, Boris; Zander, Axel R; Kluth, Dietrich

2003-01-01

Hepatic stem cells have been identified in adult liver. Recently, the origin of hepatic progenitors and hepatocytes from bone marrow was demonstrated. Hematopoietic and hepatic stem cells share the markers CD 34, c-kit, and Thy1. Little is known about liver stem cells during liver development. In this study, we investigated the potential stem cell marker Thy1 and hepatocytic marker CK-18 during liver development to identify putative fetal liver stem cell candidates. Livers were harvested from embryonic and fetal day (ED) 16, ED 18, ED 20, and neonatal ED 22 stage rat fetuses from Sprague-Dawley rats. Fetal livers were digested by collagenase-DNAse solution and purified by percoll centrifugation. Magnetic cell sorting (MACS) depletion of fetal liver cells was performed using OX43 and OX44 antibodies. Cells were characterized by immunocytochemistry for Thy1, CK-18, and proliferating cell antigen Ki-67 and double labeling for Thy1 and CK-18. Thy1 expression was found at all stages of liver development before and after MACS in immunocytochemistry. Thy1 positive cells were enriched after MACS only in early developmental stages. An enrichment of CK-18 positive cells was found after MACS at all developmental stages. Cells coexpressing Thy1 and CK-18 were identified by double labeling of fetal liver cell isolates. In conclusion, hepatic progenitor cells (CK-18 positive) in fetal rat liver express Thy1. Other progenitors express only CK-18. This indicates the coexistence of different hepatic cell compartments. Isolation and further characterization of such cells is needed to demonstrate their biologic properties.

Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump

PubMed Central

Llabrés, Salomé; Neuberger, Arthur; Blaza, James N.; Bai, Xiao-chen; Okada, Ui; Murakami, Satoshi; van Veen, Hendrik W.; Zachariae, Ulrich; Scheres, Sjors H.W.; Luisi, Ben F.

2017-01-01

The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that spans the cell envelope and actively extrudes substrates, including macrolide antibiotics and polypeptide virulence factors. These transport processes are energized by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. We present an electron cryo-microscopy structure of the ABC-type tripartite assembly at near-atomic resolution. A hexamer of the periplasmic protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer in the inner membrane, generating a quaternary structure with a central channel for substrate translocation. A gating ring found in MacA is proposed to act as a one-way valve in substrate transport. The MacB structure features an atypical transmembrane domain (TMD) with a closely packed dimer interface and a periplasmic opening that is the likely portal for substrate entry from the periplasm, with subsequent displacement through an allosteric transport mechanism. PMID:28504659

Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

DTIC Science & Technology

2010-10-01

Barry AM, MacKenzie LT, Mikulis DJ, Palmieri D, Bronder JL, Steeg PS, Yoneda T, MacDonald IC, Chambers AF, Rutt BK, Foster PJ: In vivo MRI of cancer...Fransisco, CA). Caspase-3 was immunoprecipitated from cell lysates in the presence of protease inhibitors (Roche complete Mini tablet , EDTA-free and 2

The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa.

PubMed

Middleton, A M; Chadwick, M V; Nicholson, A G; Dewar, A; Groger, R K; Brown, E J; Wilson, R

2000-10-01

Mycobacterium avium complex (MAC) are opportunistic respiratory pathogens that infect non-immunocompromised patients with established lung disease, although they can also cause primary infections. The ability to bind fibronectin is conserved among many mycobacterial species. We have investigated the adherence of a sputum isolate of MAC to the mucosa of organ cultures constructed with human tissue and the contribution of M. avium fibronectin attachment protein (FAP) to the process. MAC adhered to fibrous, but not globular mucus, and to extracellular matrix (ECM) in areas of epithelial damage, but not to intact extruded cells and collagen fibres. Bacteria occasionally adhered to healthy unciliated epithelium and to cells that had degenerated exposing their contents, but never to ciliated cells. The results obtained with different respiratory tissues were similar. Two ATCC strains of MAC gave similar results. There was a significant reduction (P < 0.05) in the number of bacteria adhering to ECM after preincubation of bacteria with fibronectin and after preincubation of the tissue with M. avium FAP in a concentration-dependant manner. The number of bacteria adhering to fibrous mucus was unchanged. Immunogold labelling demonstrated fibronectin in ECM as well as in other areas of epithelial damage, but only ECM bound FAP. A Mycobacterium smegmatis strain had the same pattern of adherence to the mucosa as MAC. When the FAP gene was deleted, the strain demonstrated reduced adherence to ECM, and adherence was restored when the strain was transfected with an M. avium FAP expression construct. We conclude that MAC adheres to ECM in areas of epithelial damage via FAP and to mucus with a fibrous appearance via another adhesin. Epithelial damage exposing ECM and poor mucus clearance will predispose to MAC airway infection.

Tool for Generation of MAC/GMC Representative Unit Cell for CMC/PMC Analysis

NASA Technical Reports Server (NTRS)

Murthy, Pappu L. N.; Pineda, Evan J.

2016-01-01

This document describes a recently developed analysis tool that enhances the resident capabilities of the Micromechanics Analysis Code with the Generalized Method of Cells (MAC/GMC) 4.0. This tool is especially useful in analyzing ceramic matrix composites (CMCs), where higher fidelity with improved accuracy of local response is needed. The tool, however, can be used for analyzing polymer matrix composites (PMCs) as well. MAC/GMC 4.0 is a composite material and laminate analysis software developed at NASA Glenn Research Center. The software package has been built around the concept of the generalized method of cells (GMC). The computer code is developed with a user friendly framework, along with a library of local inelastic, damage, and failure models. Further, application of simulated thermomechanical loading, generation of output results, and selection of architectures to represent the composite material have been automated to increase the user friendliness, as well as to make it more robust in terms of input preparation and code execution. Finally, classical lamination theory has been implemented within the software, wherein GMC is used to model the composite material response of each ply. Thus, the full range of GMC composite material capabilities is available for analysis of arbitrary laminate configurations as well. The primary focus of the current effort is to provide a graphical user interface (GUI) capability that generates a number of different user-defined repeating unit cells (RUCs). In addition, the code has provisions for generation of a MAC/GMC-compatible input text file that can be merged with any MAC/GMC input file tailored to analyze composite materials. Although the primary intention was to address the three different constituents and phases that are usually present in CMCs-namely, fibers, matrix, and interphase-it can be easily modified to address two-phase polymer matrix composite (PMC) materials where an interphase is absent. Currently, the tool capability includes generation of RUCs for square packing, hexagonal packing, and random fiber packing as well as RUCs based on actual composite micrographs. All these options have the fibers modeled as having a circular cross-sectional area. In addition, a simplified version of RUC is provided where the fibers are treated as having a square cross section and are distributed randomly. This RUC facilitates a speedy analysis using the higher fidelity version of GMC known as HFGMC. The first four mentioned options above support uniform subcell discretization. The last one has variable subcell sizes due to the primary intention of keeping the RUC size to a minimum to gain the speed ups using the higher fidelity version of MAC. The code is implemented within the MATLAB (The Mathworks, Inc., Natick, MA) developmental framework; however, a standalone application that does not need a priori MATLAB installation is also created with the aid of the MATLAB compiler.

Complement Membrane Attack and Tumorigenesis: A SYSTEMS BIOLOGY APPROACH.

PubMed

Towner, Laurence D; Wheat, Richard A; Hughes, Timothy R; Morgan, B Paul

2016-07-15

Tumor development driven by inflammation is now an established phenomenon, but the role that complement plays remains uncertain. Recent evidence has suggested that various components of the complement (C) cascade may influence tumor development in disparate ways; however, little attention has been paid to that of the membrane attack complex (MAC). This is despite abundant evidence documenting the effects of this complex on cell behavior, including cell activation, protection from/induction of apoptosis, release of inflammatory cytokines, growth factors, and ECM components and regulators, and the triggering of the NLRP3 inflammasome. Here we present a novel approach to this issue by using global gene expression studies in conjunction with a systems biology analysis. Using network analysis of MAC-responsive expression changes, we demonstrate a cluster of co-regulated genes known to have impact in the extracellular space and on the supporting stroma and with well characterized tumor-promoting roles. Network analysis highlighted the central role for EGF receptor activation in mediating the observed responses to MAC exposure. Overall, the study sheds light on the mechanisms by which sublytic MAC causes tumor cell responses and exposes a gene expression signature that implicates MAC as a driver of tumor progression. These findings have implications for understanding of the roles of complement and the MAC in tumor development and progression, which in turn will inform future therapeutic strategies in cancer. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial).

PubMed

Kröger, Nicolaus; Iacobelli, Simona; Franke, Georg-Nikolaus; Platzbecker, Uwe; Uddin, Ruzena; Hübel, Kai; Scheid, Christof; Weber, Thomas; Robin, Marie; Stelljes, Matthias; Afanasyev, Boris; Heim, Dominik; Deliliers, Giorgio Lambertenghi; Onida, Francesco; Dreger, Peter; Pini, Massimo; Guidi, Stefano; Volin, Liisa; Günther, Andreas; Bethge, Wolfgang; Poiré, Xavier; Kobbe, Guido; van Os, Marleen; Brand, Ronald; de Witte, Theo

2017-07-01

Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.

Binding of CD40L to Mac-1’s I-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis – but does not affect immunity and thrombosis in mice

PubMed Central

Wolf, Dennis; Hohmann, Jan-David; Wiedemann, Ansgar; Bledzka, Kamila; Blankenbach, Hermann; Marchini, Timoteo; Gutte, Katharina; Zeschky, Katharina; Bassler, Nicole; Hoppe, Natalie; Rodriguez, Alexandra Ortiz; Herr, Nadine; Hilgendorf, Ingo; Stachon, Peter; Willecke, Florian; Dürschmied, Daniel; von zur Mühlen, Constantin; Soloviev, Dmitry A.; Zhang, Li; Bode, Christoph; Plow, Edward F.; Libby, Peter; Peter, Karlheinz; Zirlik, Andreas

2012-01-01

Rationale CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and haemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor. Objective Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo. Methods and Results CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high affinity interaction was revealed by surface-plasmon-resonance analysis. We identified the motif EQLKKSKTL, an exposed loop between the α1 helix and the β-sheet B, on Mac-1 as binding site for CD40L. A linear peptide mimicking this sequence, M7, specifically inhibited the interaction of CD40L and Mac-1. cM7, a cyclisized version optimized for in vivo use, decreased peritoneal inflammation and inflammatory cell recruitment in vivo. Finally, LDLr-/- mice treated with intraperitoneal injections of cM7 developed smaller, less inflamed atherosclerotic lesions featuring characteristics of stability. However, cM7 did not interfere with CD40L-CD40 binding in vitro and CD40L-GPIIb/IIIa-mediated thrombus formation in vivo. Conclusions We present the novel finding that CD40L binds to the EQLKKSKTL motif on Mac-1 mediating leukocyte recruitment and atherogenesis. Specific inhibition of CD40L-Mac-1 binding may represent an attractive anti-inflammatory treatment strategy for atherosclerosis and other inflammatory conditions, potentially avoiding the unwanted immunologic and thrombotic effects of global inhibition of CD40L. PMID:21998326

Refined annotation and assembly of the Tetrahymena thermophila genome sequence through EST analysis, comparative genomic hybridization, and targeted gap closure

PubMed Central

Coyne, Robert S; Thiagarajan, Mathangi; Jones, Kristie M; Wortman, Jennifer R; Tallon, Luke J; Haas, Brian J; Cassidy-Hanley, Donna M; Wiley, Emily A; Smith, Joshua J; Collins, Kathleen; Lee, Suzanne R; Couvillion, Mary T; Liu, Yifan; Garg, Jyoti; Pearlman, Ronald E; Hamilton, Eileen P; Orias, Eduardo; Eisen, Jonathan A; Methé, Barbara A

2008-01-01

Background Tetrahymena thermophila, a widely studied model for cellular and molecular biology, is a binucleated single-celled organism with a germline micronucleus (MIC) and somatic macronucleus (MAC). The recent draft MAC genome assembly revealed low sequence repetitiveness, a result of the epigenetic removal of invasive DNA elements found only in the MIC genome. Such low repetitiveness makes complete closure of the MAC genome a feasible goal, which to achieve would require standard closure methods as well as removal of minor MIC contamination of the MAC genome assembly. Highly accurate preliminary annotation of Tetrahymena's coding potential was hindered by the lack of both comparative genomic sequence information from close relatives and significant amounts of cDNA evidence, thus limiting the value of the genomic information and also leaving unanswered certain questions, such as the frequency of alternative splicing. Results We addressed the problem of MIC contamination using comparative genomic hybridization with purified MIC and MAC DNA probes against a whole genome oligonucleotide microarray, allowing the identification of 763 genome scaffolds likely to contain MIC-limited DNA sequences. We also employed standard genome closure methods to essentially finish over 60% of the MAC genome. For the improvement of annotation, we have sequenced and analyzed over 60,000 verified EST reads from a variety of cellular growth and development conditions. Using this EST evidence, a combination of automated and manual reannotation efforts led to updates that affect 16% of the current protein-coding gene models. By comparing EST abundance, many genes showing apparent differential expression between these conditions were identified. Rare instances of alternative splicing and uses of the non-standard amino acid selenocysteine were also identified. Conclusion We report here significant progress in genome closure and reannotation of Tetrahymena thermophila. Our experience to date suggests that complete closure of the MAC genome is attainable. Using the new EST evidence, automated and manual curation has resulted in substantial improvements to the over 24,000 gene models, which will be valuable to researchers studying this model organism as well as for comparative genomics purposes. PMID:19036158

MacCormack's technique-based pressure reconstruction approach for PIV data in compressible flows with shocks

NASA Astrophysics Data System (ADS)

Liu, Shun; Xu, Jinglei; Yu, Kaikai

2017-06-01

This paper proposes an improved approach for extraction of pressure fields from velocity data, such as obtained by particle image velocimetry (PIV), especially for steady compressible flows with strong shocks. The principle of this approach is derived from Navier-Stokes equations, assuming adiabatic condition and neglecting viscosity of flow field boundaries measured by PIV. The computing method is based on MacCormack's technique in computational fluid dynamics. Thus, this approach is called the MacCormack method. Moreover, the MacCormack method is compared with several approaches proposed in previous literature, including the isentropic method, the spatial integration and the Poisson method. The effects of velocity error level and PIV spatial resolution on these approaches are also quantified by using artificial velocity data containing shock waves. The results demonstrate that the MacCormack method has higher reconstruction accuracy than other approaches, and its advantages become more remarkable with shock strengthening. Furthermore, the performance of the MacCormack method is also validated by using synthetic PIV images with an oblique shock wave, confirming the feasibility and advantage of this approach in real PIV experiments. This work is highly significant for the studies on aerospace engineering, especially the outer flow fields of supersonic aircraft and the internal flow fields of ramjets.

Fibrin(ogen) is internalized and degraded by activated human monocytoid cells via Mac-1 (CD11b/CD18): a nonplasmin fibrinolytic pathway.

PubMed

Simon, D I; Ezratty, A M; Francis, S A; Rennke, H; Loscalzo, J

1993-10-15

Fibrin(ogen) (FGN) is important for hemostasis and wound healing and is cleared from sites of injury primarily by the plasminogen activator system. However, there is emerging evidence in plasminogen activator-deficient transgenic mice that nonplasmin pathways may be important in fibrin(ogen)olysis, as well. Given the proximity of FGN and monocytes within the occlusive thrombus at sites of vascular injury, we considered the possibility that monocytes may play an ancillary role in the degradation and clearance of fibrin. We found that monocytes possess an alternative fibrinolytic pathway that uses the integrin Mac-1, which directly binds and internalizes FGN, resulting in its lysosomal degradation. At 4 degrees C, FGN binds to U937 monocytoid cells in a specific and saturable manner with a kd of 1.8 mumol/L. Binding requires adenosine diphosphate stimulation and is calcium-dependent. At 37 degrees C, FGN and fibrin monomer (FM) are internalized and degraded at rates of 0.37 +/- 0.13 and 0.55 +/- 0.03 microgram/10(6) cells/h by U937 cells, 1.38 +/- 0.02 and 1.20 +/- 0.30 microgram/10(6) cells/h by THP-1 cells, and 2.10 +/- 0.20 and 2.52 +/- 0.18 micrograms/10(6) cells/h by human peripheral blood mononuclear cells, respectively. The serine protease inhibitors, PPACK and aprotinin, and the specific elastase inhibitor, AAPVCK, do not significantly inhibit degradation. However, degradation is inhibited by chloroquine, suggesting that a lysosomal pathway is involved. Factor X, a competitive ligand with FGN for the Mac-1 receptor, also blocks degradation, as does a monoclonal antibody to the alpha-subunit of Mac-1. Autoradiography of radioiodinated, internalized FGN shows that FGN proteolysis by the pathway produces a unique degradation pattern distinct from that observed with plasmin. In a fibrin clot lysis assay, Mac-1-mediated fibrinolysis contributed significantly to total fibrinolysis. In summary, FGN is internalized and degraded by activated human monocytoid cells via Mac-1 in the absence of plasmin, thereby providing an alternative fibrinolytic pathway. Thus, in addition to the function of cell adhesion, integrins may also act as receptors that mediate the internalization and degradation of bound ligands.

An energy-stable method for solving the incompressible Navier-Stokes equations with non-slip boundary condition

NASA Astrophysics Data System (ADS)

Lee, Byungjoon; Min, Chohong

2018-05-01

We introduce a stable method for solving the incompressible Navier-Stokes equations with variable density and viscosity. Our method is stable in the sense that it does not increase the total energy of dynamics that is the sum of kinetic energy and potential energy. Instead of velocity, a new state variable is taken so that the kinetic energy is formulated by the L2 norm of the new variable. Navier-Stokes equations are rephrased with respect to the new variable, and a stable time discretization for the rephrased equations is presented. Taking into consideration the incompressibility in the Marker-And-Cell (MAC) grid, we present a modified Lax-Friedrich method that is L2 stable. Utilizing the discrete integration-by-parts in MAC grid and the modified Lax-Friedrich method, the time discretization is fully discretized. An explicit CFL condition for the stability of the full discretization is given and mathematically proved.

De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications.

PubMed

Katona, Robert L

2015-02-01

Mammalian artificial chromosomes (MACs) are non-integrating, autonomously replicating natural chromosome-based vectors that may carry a vast amount of genetic material, which in turn enable potentially prolonged, safe, and regulated therapeutic transgene expression and render MACs as attractive genetic vectors for "gene replacement" or for controlling differentiation pathways in target cells. Satellite-DNA-based artificial chromosomes (SATACs) can be made by induced de novo chromosome formation in cells of different mammalian and plant species. These artificially generated accessory chromosomes are composed of predictable DNA sequences, and they contain defined genetic information. SATACs have already passed a number of obstacles crucial to their further development as gene therapy vectors, including large-scale purification, transfer of purified artificial chromosomes into different cells and embryos, generation of transgenic animals and germline transmission with purified SATACs, and the tissue-specific expression of a therapeutic gene from an artificial chromosome in the milk of transgenic animals. SATACs could be used in cell therapy protocols. For these methods, the most versatile target cell would be one that was pluripotent and self-renewing to address multiple disease target cell types, thus making multilineage stem cells, such as adult derived early progenitor cells and embryonic stem cells, as attractive universal host cells.

Mycobacterium avium subspecies paratuberculosis isolates from sheep and goats show reduced persistence in bovine macrophages than cattle, bison, deer and wild boar strains regardless of genotype.

PubMed

Abendaño, Naiara; Sevilla, Iker A; Prieto, José Miguel; Garrido, Joseba M; Juste, Ramon A; Alonso-Hearn, Marta

2013-05-03

Assessment of the virulence of isolates of Mycobacterium avium subsp. paratuberculosis (Map) exhibiting distinct genotypes and isolated from different hosts may help to clarify the degree to which clinical manifestations of the disease in cattle can be attributed to bacterial or to host factors. The objective of this study was to test the ability of 10 isolates of Map representing distinct genotypes and isolated from domestic (cattle, sheep, and goat), and wildlife animal species (fallow deer, deer, wild boar, and bison) to enter and grow in bovine macrophages. The isolates were previously typed using IS1311 PCR followed by restriction endonuclease analysis into types C, S or B. Intracellular growth of the isolates in a bovine macrophage-like cell line (BoMac) and in primary bovine monocyte-derived macrophages (MDM) was evaluated by quantification of CFU numbers in the initial inoculum and inside of the host cells at 2h and 7 d p.i. using an automatic liquid culture system (Bactec MGIT 960). Individual data illustrated that growth was less variable in BoMac than in MDM cells. All the isolates from goat and sheep hosts persisted within BoMac cells in lower CFU numbers than the other tested isolates after 7 days of infection regardless of genotype. In addition, BoMac cells exhibited differential inflammatory, apoptotic and destructive responses when infected with a bovine or an ovine isolate; which correlated with the differential survival of these strains within BoMac cells. Our results indicated that the survival of the tested Map isolates within bovine macrophages is associated with the specific host from which the isolates were initially isolated. Copyright © 2013 Elsevier B.V. All rights reserved.

Dendritic cells and macrophages in the kidney: a spectrum of good and evil

PubMed Central

Rogers, NM; Ferenbach, DA; Isenberg, JS; Thomson, AW; Hughes, J

2015-01-01

Renal dendritic cells (DC) and macrophages (Mac) represent a constitutive, extensive and contiguous network of innate immune cells that provide sentinel and immune intelligence function. They induce and regulate inflammatory responses to freely-filtered antigenic material and protect the kidney from infection. Tissue–resident or infiltrating DC and Mac are key to the initiation and propagation of renal disease, as well as essential contributors to subsequent tissue regeneration regardless of its etiology and pathogenesis. Their identification, functional and phenotypic distinction, interplay and relationship with effector and regulatory adaptive immune cells is complex and incompletely understood. This review discusses both the common and distinct characteristics of these cells, as well as recent key advances in the field that have identified renal-specific functions of DC and Mac that enable these important, phagocytic, antigen-presenting, cells to mediate or mitigate intrinsic kidney disease. We also identify priority areas for further investigation and prospects for translational and therapeutic application of acquired knowledge. PMID:25266210

Antibiotic Resistance Mediated by the MacB ABC Transporter Family: A Structural and Functional Perspective.

PubMed

Greene, Nicholas P; Kaplan, Elise; Crow, Allister; Koronakis, Vassilis

2018-01-01

The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria. Here, we review recent structural and functional data on MacB and its homologs. MacB has a fold that is distinct from other structurally characterized ABC transporters and uses a unique molecular mechanism termed mechanotransmission. Unlike other bacterial ABC transporters, MacB does not transport substrates across the inner membrane in which it is based, but instead couples cytoplasmic ATP hydrolysis with transmembrane conformational changes that are used to perform work in the extra-cytoplasmic space. In the MacAB-TolC tripartite pump, mechanotransmission drives efflux of antibiotics and export of a protein toxin from the periplasmic space via the TolC exit duct. Homologous tripartite systems from pathogenic bacteria similarly export protein-like signaling molecules, virulence factors and siderophores. In addition, many MacB-like ABC transporters do not form tripartite pumps, but instead operate in diverse cellular processes including antibiotic sensing, cell division and lipoprotein trafficking.

Microcystic adnexal carcinoma with sebaceous differentiation: Three cases.

PubMed

Fernandez-Flores, Angel; Llamas-Velasco, Mar; Saus, Carles; Patel, Anisha; Rutten, Arno

2018-04-01

Microcystic adnexal carcinoma (MAC) is a low-grade malignant tumor of the skin. Histologically, this tumor shows a biphasic pattern, with cords and nests of basaloid cells, as well as keratin horn cysts. This biphasic histological appearance has been interpreted by some authors as a sign of double eccrine and folliculosebaceous-apocrine differentiation, whereas some other authors defend a solely eccrine differentiation. In this context, sebaceous differentiation in MAC would support the first option. However, there are only 3 cases of MAC with sebaceous differentiation in the literature, and all of them were reported before adipophilin was available, which in the appropriate context (eg, testing clear cells for sebaceous vs eccrine differentiation) is very useful. In this study, we present 3 cases of MAC with focal sebaceous differentiation confirmed by immunoexpression of adipophilin in the sebaceous foci. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Framework for Performing Multiscale Stochastic Progressive Failure Analysis of Composite Structures

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2006-01-01

A framework is presented that enables coupled multiscale analysis of composite structures. The recently developed, free, Finite Element Analysis - Micromechanics Analysis Code (FEAMAC) software couples the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) with ABAQUS to perform micromechanics based FEA such that the nonlinear composite material response at each integration point is modeled at each increment by MAC/GMC. As a result, the stochastic nature of fiber breakage in composites can be simulated through incorporation of an appropriate damage and failure model that operates within MAC/GMC on the level of the fiber. Results are presented for the progressive failure analysis of a titanium matrix composite tensile specimen that illustrate the power and utility of the framework and address the techniques needed to model the statistical nature of the problem properly. In particular, it is shown that incorporating fiber strength randomness on multiple scales improves the quality of the simulation by enabling failure at locations other than those associated with structural level stress risers.

A Framework for Performing Multiscale Stochastic Progressive Failure Analysis of Composite Structures

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2007-01-01

A framework is presented that enables coupled multiscale analysis of composite structures. The recently developed, free, Finite Element Analysis-Micromechanics Analysis Code (FEAMAC) software couples the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) with ABAQUS to perform micromechanics based FEA such that the nonlinear composite material response at each integration point is modeled at each increment by MAC/GMC. As a result, the stochastic nature of fiber breakage in composites can be simulated through incorporation of an appropriate damage and failure model that operates within MAC/GMC on the level of the fiber. Results are presented for the progressive failure analysis of a titanium matrix composite tensile specimen that illustrate the power and utility of the framework and address the techniques needed to model the statistical nature of the problem properly. In particular, it is shown that incorporating fiber strength randomness on multiple scales improves the quality of the simulation by enabling failure at locations other than those associated with structural level stress risers.

MAC/GMC Code Enhanced for Coupled Electromagnetothermoelastic Analysis of Smart Composites

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.; Aboudi, Jacob

2002-01-01

Intelligent materials are those that exhibit coupling between their electromagnetic response and their thermomechanical response. This coupling allows smart materials to react mechanically (e.g., an induced displacement) to applied electrical or magnetic fields (for instance). These materials find many important applications in sensors, actuators, and transducers. Recently interest has arisen in the development of smart composites that are formed via the combination of two or more phases, one or more of which is a smart material. To design with and utilize smart composites, designers need theories that predict the coupled smart behavior of these materials from the electromagnetothermoelastic properties of the individual phases. The micromechanics model known as the generalized method of cells (GMC) has recently been extended to provide this important capability. This coupled electromagnetothermoelastic theory has recently been incorporated within NASA Glenn Research Center's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC). This software package is user friendly and has many additional features that render it useful as a design and analysis tool for composite materials in general, and with its new capabilities, for smart composites as well.

Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

PubMed Central

Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

2013-01-01

Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

PubMed

Lu, Chenggang; Fuller, Margaret T

2015-12-01

Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.

Synthesis, spectroscopic, physicochemical and structural characterization of tetrandrine-based macrocycles functionalized with acridine and anthracene groups: DNA binding and anti-proliferative activity.

PubMed

Calvillo-Páez, Viviana; Sotelo-Mundo, Rogerio R; Leyva-Peralta, Mario; Gálvez-Ruiz, Juan Carlos; Corona-Martínez, David; Moreno-Corral, Ramón; Escobar-Picos, Raymundo; Höpfl, Herbert; Juárez-Sánchez, Octavio; Lara, Karen Ochoa

2018-04-25

In this work, we report on the synthesis of two new mono-alkylated tetrandrine derivatives with acridine and anthracene units, MAcT and MAnT. The compounds were fully characterized by physicochemical techniques and single-crystal X-ray diffraction analysis. In addition, both derivatives were studied as nucleotide receptors and double-stranded DNA binders in aqueous phosphate buffer at pH = 7.2 using UV-vis and fluorescence spectroscopy. According to the molecular recognition studies, MAcT and MAnT exhibit high affinity (K ∼ 10 5  M -1 ) and selectivity for ds-DNA, presumably in an intercalation mode. Finally, the anti-proliferative effects of the tetrandrine derivatives on different cancer cell lines were explored, revealing promising activities. Particularly, the mono-anthracene tetrandrine derivative MAnT showed an IC 50 of 2.74 μg/mL on the HeLa cervical cancer cell line, representing a value 3.3 times smaller than that obtained for unsubstituted tetrandrine. Examination of the cytotoxic effects on the HeLa cell line by inverted microscopy suggests that the cell death mechanism consists basically in apoptosis. The molecular modelling of three ds-DNA-MAcT complexes, suggested that the macrocycles may use an intercalation binding mode towards DNA. MAcT is predicted to bind into the major groove of the ds-DNA providing non-covalent interactions such as electrostatic, van der Waals and hydrophobic interactions that lead to selectivity. Overall experimental data supports the mode of action of MAnT and MAcT as cytotoxic compounds against cancer cell lines via a DNA interaction mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

Improved immunomagnetic enrichment of CD34(+) cells from umbilical cord blood using the CliniMACS cell separation system.

PubMed

Blake, Joseph M; Nicoud, Ian B; Weber, Daniel; Voorhies, Howard; Guthrie, Katherine A; Heimfeld, Shelly; Delaney, Colleen

2012-08-01

CD34(+) enrichment from cord blood units (CBU) is used increasingly in clinical applications involving ex vivo expansion. The CliniMACS instrument from Miltenyi Biotec is a current good manufacturing practice (cGMP) immunomagnetic selection system primarily designed for processing larger numbers of cells: a standard tubing set (TS) can process a maximum of 60 billion cells, while the larger capacity tubing set (LS) will handle 120 billion cells. In comparison, most CBU contain only 1-2 billion cells, raising a question regarding the optimal tubing set for CBU CD34(+) enrichment. We compared CD34(+) cell recovery and overall viability after CliniMACS processing of fresh CBU with either TS or LS. Forty-six freshly collected CBU (≤ 36 h) were processed for CD34(+) enrichment; 22 consecutive units were selected using TS and a subsequent 24 processed with LS. Cell counts and immunophenotyping were performed pre- and post-selection to assess total nucleated cells (TNC), viability and CD34(+) cell content. Two-sample t-tests of mean CD34(+) recovery and viability revealed significant differences in favor of LS (CD34(+) recovery, LS = 56%, TS = 45%, P = 0.003; viability, LS = 74%, TS = 59%, P = 0.011). Stepwise linear regression, considering pre-processing unit age, viability, TNC and CD34(+) purity, demonstrated statistically significant correlations only with the tubing set used and age of unit. For CD34(+) enrichment from fresh CBU, LS provided higher post-selection viability and more efficient recovery. In this case, a lower maximum TNC specification of TS was not predictive of better performance. The same may hold for smaller scale enrichment of other cell types with the CliniMACS instrument.

Th17 cytokine differentiation and loss of plasticity after SOCS1 inactivation in a cutaneous T-cell lymphoma.

PubMed

Ehrentraut, Stefan; Schneider, Björn; Nagel, Stefan; Pommerenke, Claudia; Quentmeier, Hilmar; Geffers, Robert; Feist, Maren; Kaufmann, Maren; Meyer, Corinna; Kadin, Marshall E; Drexler, Hans G; MacLeod, Roderick A F

2016-06-07

We propose that deregulated T-helper-cell (Th) signaling underlies evolving Th17 cytokine expression seen during progression of cutaneous T-cell lymphoma (CTCL). Accordingly, we developed a lymphoma progression model comprising cell lines established at indolent (MAC-1) and aggressive (MAC-2A) CTCL stages. We discovered activating JAK3 (V722I) mutations present at indolent disease, reinforced in aggressive disease by novel compound heterozygous SOCS1 (G78R/D105N) JAK-binding domain inactivating mutations. Though isogenic, indolent and aggressive-stage cell lines had diverged phenotypically, the latter expressing multiple Th17 related cytokines, the former a narrower profile. Importantly, indolent stage cells remained poised for Th17 cytokine expression, readily inducible by treatment with IL-2 - a cytokine which mitigates Th17 differentiation in mice. In indolent stage cells JAK3 expression was boosted by IL-2 treatment. Th17 conversion of MAC-1 cells by IL-2 was blocked by pharmacological inhibition of JAK3 or STAT5, implicating IL2RG - JAK3 - STAT5 signaling in plasticity responses. Like IL-2 treatment, SOCS1 knockdown drove indolent stage cells to mimic key aggressive stage properties, notably IL17F upregulation. Co-immunoprecipitation experiments showed that SOCS1 mutations abolished JAK3 binding, revealing a key role for SOCS1 in regulating JAK3/STAT5 signaling. Collectively, our results show how JAK/STAT pathway mutations contribute to disease progression in CTCL cells by potentiating inflammatory cytokine signaling, widening the potential therapeutic target range for this intractable entity. MAC-1/2A cells also provide a candidate human Th17 laboratory model for identifying potentally actionable CTCL markers or targets and testing their druggability in vitro.

Accuracy Test of the OPLS-AA Force Field for Calculating Free Energies of Mixing and Comparison with PAC-MAC

PubMed Central

2017-01-01

We have calculated the excess free energy of mixing of 1053 binary mixtures with the OPLS-AA force field using two different methods: thermodynamic integration (TI) of molecular dynamics simulations and the Pair Configuration to Molecular Activity Coefficient (PAC-MAC) method. PAC-MAC is a force field based quasi-chemical method for predicting miscibility properties of various binary mixtures. The TI calculations yield a root mean squared error (RMSE) compared to experimental data of 0.132 kBT (0.37 kJ/mol). PAC-MAC shows a RMSE of 0.151 kBT with a calculation speed being potentially 1.0 × 104 times greater than TI. OPLS-AA force field parameters are optimized using PAC-MAC based on vapor–liquid equilibrium data, instead of enthalpies of vaporization or densities. The RMSE of PAC-MAC is reduced to 0.099 kBT by optimizing 50 force field parameters. The resulting OPLS-PM force field has a comparable accuracy as the OPLS-AA force field in the calculation of mixing free energies using TI. PMID:28418655

Annexin V-MACS in infertile couples as method for separation of sperm without DNA fragmentation.

PubMed

Troya, Jhon; Zorrilla, Ingrid

2015-05-01

To determine the effect of using MACS technology on clinical pregnancy, as a method for separation of damaged sperm in infertile patients. 136 infertile men having normal semen parameters in accordance with WHO 2010 criterion, undergoing ICSI cycle were enrolled during the course of the study. The patients were prospectively randomized and enrolled after oocyte retrieval and were assigned to the ICSI group, PICSI group or MACS group. Embryo development and clinical pregnancy were assessed. In 17 randomized MACS patients, sperm DNA fragmentation was tested in the presumptive apoptotic and no apoptotic spermatozoa fractions. Similar results were obtained between groups for the following parameters: fertilization rates of 78.97% (95% confidence interval [CI]:74.37-83.57), 70.15 %(95% CI:63.98-76.33) and 80.28%(95% CI:73.74-86.81) for ICSI, PICSI and MACS group, respectively; Number of Day-3 embryos was 5.04 (95% CI:4.09-5.98), 5.17(95% CI:4.24-6.10) and 5.59(95% CI:4.31-6.87) for ICSI, PICSI and MACS group, respectively; number of freezing embryos in blastocyst stage was 0.78 (95% CI:0.25- 1.31), 0.70(95% CI:0.27-1.14) and 1 (95% CI:0.37-1.6) for ICSI, PICSI and MACS group, respectively. However, clinical pregnancy rates of 58.1% for MACS group versus 40.4% and 27.3% for PICSI and ICSI group, respectively, were showed statistical difference (P=0.019). DNA fragmentation index for the two sperm MACS fraction showed statistical differences (P=0.000), MACS reduced the D.F.I of the sperm sample. The use of MACS technology improves the clinical pregnancy on infertile couples and can be applied as a method for sperm separation, discriminating sperm with high DNA fragmentation.

Isolated Cerebellar Spindle Cell Pseudotumor Caused by Mycobacterium Avium-Intracellulare Complex in a Patient without AIDS.

PubMed

Lim, Ming-Sheng; Bermingham, Niamh; O'Broin, Cathal; Khalil, Ayman; Keohane, Catherine; Lim, Chris

2016-06-01

Spindle cell pseudotumors are formed by histiocytes in response to infection by Mycobacterium avium-intracellulare complex (MAC) and are rare in patients without AIDS. A 66-year-old man presented with neck pain, ataxia, and a history of sarcoidosis. A cerebellar lesion was identified on magnetic resonance imaging and surgically excised. Histopathology revealed this to be a spindle cell pseudotumor and MAC was isolated by bacterial culture of cerebrospinal fluid. Hematology revealed cluster of differentiation 4 lymphocytopenia but human immunodeficiency virus serology was negative. The patient was commenced on antimicrobial treatment that included a macrolide and remained well at 1 year follow-up. This rare presentation of isolated intracranial MAC was treated with surgical excision and antimicrobials with a good outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

[Circannual rhythms of bone marrow cell composition in animals during aging: the role of pineal factors].

PubMed

Labunets', I F

2007-01-01

It was investigated the influence of pineal gland's peptides (epithalamin, epithalon) and indols (melatonin) on the aging changes of circannual rhythms of stromal cells-precurcors (CFC-F), granulocyte-macrophage cells-precurcors (CFC-GM), CD4+, Mac-1+ and CD19+-cells amount in bone marrow of mice CBA. In old animals the rhythmical disturbances of the indices were characterized by loss of fluctuations (Mac 1+-cells), increase of CD4+-cells amplitude, displacement of seasonal acrophase (CFC-F), inversion of rhythm (CFC-GM), desynchronization. In old mice after epithalamin injections the season differences between the amount of Mac-1+-cells restored, CD4+-cells amplitude diminished, the amount of CFC-GM increased in spring and CFC-F diminished in autumn. The influence of epithalon on CFC-F and CFG-GM rhythm was in a smaller dose. The rhythms of some indices in old animals showed a pattern observed in adults. After melatonin injections to adult mice in winter the amount of CD4+-cells increased; the ratio CFC-GM and CFC-F changed because of increase of stromal fibroblasts. In old mice the indices were without changes.

Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

PubMed

Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S Munir; Fenizia, Claudio; Lifson, Jeffrey D; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David; Franchini, Genoveffa

2013-02-01

The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)β(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

Antibiotic Resistance Mediated by the MacB ABC Transporter Family: A Structural and Functional Perspective

PubMed Central

Greene, Nicholas P.; Kaplan, Elise; Crow, Allister; Koronakis, Vassilis

2018-01-01

The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria. Here, we review recent structural and functional data on MacB and its homologs. MacB has a fold that is distinct from other structurally characterized ABC transporters and uses a unique molecular mechanism termed mechanotransmission. Unlike other bacterial ABC transporters, MacB does not transport substrates across the inner membrane in which it is based, but instead couples cytoplasmic ATP hydrolysis with transmembrane conformational changes that are used to perform work in the extra-cytoplasmic space. In the MacAB-TolC tripartite pump, mechanotransmission drives efflux of antibiotics and export of a protein toxin from the periplasmic space via the TolC exit duct. Homologous tripartite systems from pathogenic bacteria similarly export protein-like signaling molecules, virulence factors and siderophores. In addition, many MacB-like ABC transporters do not form tripartite pumps, but instead operate in diverse cellular processes including antibiotic sensing, cell division and lipoprotein trafficking. PMID:29892271

Hepatocyte-specific PPARA expression exclusively promotes agonist-induced cell proliferation without influence from nonparenchymal cells

PubMed Central

Brocker, Chad N.; Yue, Jiang; Kim, Donghwan; Qu, Aijuan; Bonzo, Jessica A.

2017-01-01

Peroxisome proliferator-activated receptor-α (PPARA) is a nuclear transcription factor and key mediator of systemic lipid metabolism. Prolonged activation in rodents causes hepatocyte proliferation and hepatocellular carcinoma. Little is known about the contribution of nonparenchymal cells (NPCs) to PPARA-mediated cell proliferation. NPC contribution to PPARA agonist-induced hepatomegaly was assessed in hepatocyte (Ppara△Hep)- and macrophage (Ppara△Mac)-specific Ppara null mice. Mice were treated with the agonist Wy-14643 for 14 days, and response of conditional null mice was compared with conventional knockout mice (Ppara−/−). Wy-14643 treatment caused weight loss and severe hepatomegaly in wild-type and Ppara△Mac mice, and histological analysis revealed characteristic hepatocyte swelling; Ppara△Hep and Ppara−/− mice were protected from these effects. Ppara△Mac serum chemistries, as well as aspartate aminotransferase and alanine aminotransferase levels, matched wild-type mice. Agonist-treated Ppara△Hep mice had elevated serum cholesterol, phospholipids, and triglycerides when compared with Ppara−/− mice, indicating a possible role for extrahepatic PPARA in regulating circulating lipid levels. BrdU labeling confirmed increased cell proliferation only in wild-type and Ppara△Mac mice. Macrophage PPARA disruption did not impact agonist-induced upregulation of lipid metabolism, cell proliferation, or DNA damage and repair-related gene expression, whereas gene expression was repressed in Ppara△Hep mice. Interestingly, downregulation of inflammatory cytokines IL-15 and IL-18 was dependent on macrophage PPARA. Cell type-specific regulation of target genes was confirmed in primary hepatocytes and Kupffer cells. These studies conclusively show that cell proliferation is mediated exclusively by PPARA activation in hepatocytes and that Kupffer cell PPARA has an important role in mediating the anti-inflammatory effects of PPARA agonists. PMID:28082284

Sero-Diagnosis of Mycobacterium avium Complex Lung Disease Using Serum Immunoglobulin A Antibody against Glycopeptidolipid Antigen in Taiwan

PubMed Central

Wang, Jann-Tay; Jou, Ruwen; Wang, Jann-Yuan; Kobayashi, Kazuo; Lai, Hsin-Chih; Yu, Chong-Jen; Lee, Li-Na; Luh, Kwen-Tay

2013-01-01

Background Lung disease (LD) due to non-tuberculous mycobacteria is an important clinical concern. Mycobacterium avium complex (MAC) is one of the most common causative agents but the diagnosis of MAC-LD remains challenging. Detection of serum IgA antibody against MAC glycopeptidolipid (GPL) has recently been shown to improve the diagnosis of MAC-LD, but has yet to be validated worldwide. Methods This prospective study was conducted in a tertiary referral center in northern Taiwan and enrolled patients with MAC-LD, MAC contamination, other lung diseases, and control subjects. Serum immunoglobulin A (IgA) antibody against MAC-GPL was detected in the participants and its specificity and sensitivity was assessed. Results There were 56 patients with MAC-LD, 11 with MAC contamination, 13 M. kansasii-LD, 26 LD due to rapidly-growing mycobacteria (RGM), 48 pulmonary tuberculosis, and 42 household contacts of patients with TB. Patients with MAC-LD were older and 32% of them had an underlying co-morbidity. By logistic regression, serum MAC-GPL IgA level was an independent predictor of MAC-LD among the study subjects and those with culture-positive specimens for MAC. By the receiver operating characteristic curve, serum MAC-GPL IgA had a good power to discriminate MAC-LD from MAC contamination. Under the optimal cut-off value of 0.73 U/mL, its sensitivity and specificity were 60% and 91%, respectively. Among MAC-LD patients, presence of co-morbidity was associated with MAC-GPL <0.73 U/ml in logistic regression analysis. Conclusions Measurement of serum anti-MAC-GPL IgA level is useful for the diagnosis of MAC-LD. However, its implement in clinical practice for immuno-compromised hosts needs careful consideration. PMID:24260398

Magnetic cell sorting purification of differentiated embryonic stem cells stably expressing truncated human CD4 as surface marker.

PubMed

David, Robert; Groebner, Michael; Franz, Wolfgang-Michael

2005-04-01

Embryonic stem (ES) cells offer great potential in regenerative medicine and tissue engineering. Clinical applications are still hampered by the lack of protocols for gentle, high-yield isolation of specific cell types for transplantation expressing no immunogenic markers. We describe labeling of stably transfected ES cells expressing a human CD4 molecule lacking its intracellular domain (DeltaCD4) under control of the phosphoglycerate kinase promoter for magnetic cell sorting (MACS). To track the labeled ES cells, we fused DeltaCD4 to an intracellular enhanced green fluorescent protein domain (DeltaCD4EGFP). We showed functionality of the membrane-bound fluorescent fusion protein and its suitability for MACS leading to purities greater than 97%. Likewise, expression of DeltaCD4 yielded up to 98.5% positive cells independently of their differentiation state. Purities were not limited by the initial percentage of DeltaCD4(+) cells, ranging from 0.6%-16%. The viability of MACS-selected cells was demonstrated by reaggregation and de novo formation of embryoid bodies developing all three germ layers. Thus, expression of DeltaCD4 in differentiated ES cells may enable rapid, high-yield purification of a desired cell type for tissue engineering and transplantation studies.

Novel platform for minimizing cell loss on separation process: Droplet-based magnetically activated cell separator

NASA Astrophysics Data System (ADS)

Kim, Youngho; Hong, Su; Lee, Sang Ho; Lee, Kangsun; Yun, Seok; Kang, Yuri; Paek, Kyeong-Kap; Ju, Byeong-Kwon; Kim, Byungkyu

2007-07-01

To reduce the problem of cell loss due to adhesion, one of the basic phenomena in microchannel, we proposed the droplet-based magnetically activated cell separator (DMACS). Based on the platform of the DMACS—which consists of permanent magnets, a coverslip with a circle-shaped boundary, and an injection tube—we could collect magnetically (CD45)-labeled (positive) cells with high purity and minimize cell loss due to adhesion. To compare separation efficiency between the MACS and the DMACS, the total number of cells before and after separation with both the separators was counted by flow cytometry. We could find that the number (3241/59940) of cells lost in the DMACS is much less than that (22360/59940) in the MACS while the efficiency of cell separation in the DMACS (96.07%) is almost the same as that in the MACS (96.72%). Practically, with fluorescent images, it was visually confirmed that the statistical data are reliable. From the viability test by using Hoechst 33 342, it was also demonstrated that there was no cell damage on a gas-liquid interface. Conclusively, DMACS will be a powerful tool to separate rare cells and applicable as a separator, key component of lab-on-a-chip.

A sestrin-dependent Erk/Jnk/p38 MAPK activation complex inhibits immunity during ageing

PubMed Central

Lanna, Alessio; Gomes, Daniel C O; Muller-Durovic, Bojana; McDonnell, Thomas; Escors, David; Gilroy, Derek W; Lee, Jun Hee; Karin, Michael; Akbar, Arne N

2016-01-01

Mitogen activated protein kinases (MAPKs) including Erk, Jnk and p38 regulate diverse cellular functions, and are thought to be controlled by independent upstream activation cascades. Here we show that the sestrins bind to and co-ordinate simultaneous Erk, Jnk and p38 MAPK activation in T lymphocytes within a new immune-inhibitory complex (sestrin-MAPK Activation Complex; sMAC). Whereas sestrin ablation resulted in broad reconstitution of immune function in stressed T cells, inhibition of individual MAPKs only allowed partial functional recovery. T cells from old humans and mice were more likely to form the sMAC, and disruption of this complex restored antigen-specific functional responses in these cells. Correspondingly, sestrin deficiency or simultaneous inhibition of all three MAPKs enhanced vaccine responsiveness in old mice. Thus, disruption of sMAC provides a foundation for rejuvenating immunity during ageing. PMID:28114291

A comparative study of upwind and MacCormack schemes for CAA benchmark problems

NASA Technical Reports Server (NTRS)

Viswanathan, K.; Sankar, L. N.

1995-01-01

In this study, upwind schemes and MacCormack schemes are evaluated as to their suitability for aeroacoustic applications. The governing equations are cast in a curvilinear coordinate system and discretized using finite volume concepts. A flux splitting procedure is used for the upwind schemes, where the signals crossing the cell faces are grouped into two categories: signals that bring information from outside into the cell, and signals that leave the cell. These signals may be computed in several ways, with the desired spatial and temporal accuracy achieved by choosing appropriate interpolating polynomials. The classical MacCormack schemes employed here are fourth order accurate in time and space. Results for categories 1, 4, and 6 of the workshop's benchmark problems are presented. Comparisons are also made with the exact solutions, where available. The main conclusions of this study are finally presented.

RNA-transfection of γ/δ T cells with a chimeric antigen receptor or an α/β T-cell receptor: a safer alternative to genetically engineered α/β T cells for the immunotherapy of melanoma.

PubMed

Harrer, Dennis C; Simon, Bianca; Fujii, Shin-Ichiro; Shimizu, Kanako; Uslu, Ugur; Schuler, Gerold; Gerer, Kerstin F; Hoyer, Stefanie; Dörrie, Jan; Schaft, Niels

2017-08-17

Adoptive T-cell therapy relying on conventional T cells transduced with T-cell receptors (TCRs) or chimeric antigen receptors (CARs) has caused substantial tumor regression in several clinical trials. However, genetically engineered T cells have been associated with serious side-effects due to off-target toxicities and massive cytokine release. To obviate these concerns, we established a protocol adaptable to GMP to expand and transiently transfect γ/δ T cells with mRNA. PBMC from healthy donors were stimulated using zoledronic-acid or OKT3 to expand γ/δ T cells and bulk T cells, respectively. Additionally, CD8 + T cells and γ/δ T cells were MACS-isolated from PBMC and expanded with OKT3. Next, these four populations were electroporated with RNA encoding a gp100/HLA-A2-specific TCR or a CAR specific for MCSP. Thereafter, receptor expression, antigen-specific cytokine secretion, specific cytotoxicity, and killing of the endogenous γ/δ T cell-target Daudi were analyzed. Using zoledronic-acid in average 6 million of γ/δ T cells with a purity of 85% were generated from one million PBMC. MACS-isolation and OKT3-mediated expansion of γ/δ T cells yielded approximately ten times less cells. OKT3-expanded and CD8 + MACS-isolated conventional T cells behaved correspondingly similar. All employed T cells were efficiently transfected with the TCR or the CAR. Upon respective stimulation, γ/δ T cells produced IFNγ and TNF, but little IL-2 and the zoledronic-acid expanded T cells exceeded MACS-γ/δ T cells in antigen-specific cytokine secretion. While the cytokine production of γ/δ T cells was in general lower than that of conventional T cells, specific cytotoxicity against melanoma cell lines was similar. In contrast to OKT3-expanded and MACS-CD8 + T cells, mock-electroporated γ/δ T cells also lysed tumor cells reflecting the γ/δ T cell-intrinsic anti-tumor activity. After transfection, γ/δ T cells were still able to kill MHC-deficient Daudi cells. We present a protocol adaptable to GMP for the expansion of γ/δ T cells and their subsequent RNA-transfection with tumor-specific TCRs or CARs. Given the transient receptor expression, the reduced cytokine release, and the equivalent cytotoxicity, these γ/δ T cells may represent a safer complementation to genetically engineered conventional T cells in the immunotherapy of melanoma (Exper Dermatol 26: 157, 2017, J Investig Dermatol 136: A173, 2016).

Three-dimensional low Reynolds number flows with a free surface

NASA Technical Reports Server (NTRS)

Degani, D.; Gutfinger, C.

1977-01-01

The two-dimensional leveling problem (Degani, Gutfinger, 1976) is extended to three dimensions in the case where the flow Re number is very low and attention is paid to the free surface boundary condition with surface tension effects included. The no-slip boundary condition on the wall is observed. The numerical solution falls back on the Marker and Cell (MAC) method (Harlow and Welch, 1965) with the computation region divided into a finite number of stationary rectangular cells (or boxes in the 3-D case) and fluid flow traverses the cells (or boxes).

Two-stage microfluidic chip for selective isolation of circulating tumor cells (CTCs).

PubMed

Hyun, Kyung-A; Lee, Tae Yoon; Lee, Su Hyun; Jung, Hyo-Il

2015-05-15

Over the past few decades, circulating tumor cells (CTCs) have been studied as a means of overcoming cancer. However, the rarity and heterogeneity of CTCs have been the most significant hurdles in CTC research. Many techniques for CTC isolation have been developed and can be classified into positive enrichment (i.e., specifically isolating target cells using cell size, surface protein expression, and so on) and negative enrichment (i.e., specifically eluting non-target cells). Positive enrichment methods lead to high purity, but could be biased by their selection criteria, while the negative enrichment methods have relatively low purity, but can isolate heterogeneous CTCs. To compensate for the known disadvantages of the positive and negative enrichments, in this study we introduced a two-stage microfluidic chip. The first stage involves a microfluidic magnetic activated cell sorting (μ-MACS) chip to elute white blood cells (WBCs). The second stage involves a geometrically activated surface interaction (GASI) chip for the selective isolation of CTCs. We observed up to 763-fold enrichment in cancer cells spiked into 5 mL of blood sample using the μ-MACS chip at 400 μL/min flow rate. Cancer cells were successfully separated with separation efficiencies ranging from 10.19% to 22.91% based on their EpCAM or HER2 surface protein expression using the GASI chip at a 100 μL/min flow rate. Our two-stage microfluidic chips not only isolated CTCs from blood cells, but also classified heterogeneous CTCs based on their characteristics. Therefore, our chips can contribute to research on CTC heterogeneity of CTCs, and, by extension, personalized cancer treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

The Leishmania donovani histidine acid ecto-phosphatase LdMAcP: insight into its structure and function.

PubMed

Papadaki, Amalia; Politou, Anastasia S; Smirlis, Despina; Kotini, Maria P; Kourou, Konstadina; Papamarcaki, Thomais; Boleti, Haralabia

2015-05-01

Acid ecto-phosphatase activity has been implicated in Leishmania donovani promastigote virulence. In the present study, we report data contributing to the molecular/structural and functional characterization of the L. donovani LdMAcP (L. donovani membrane acid phosphatase), member of the histidine acid phosphatase (HAcP) family. LdMAcP is membrane-anchored and shares high sequence identity with the major secreted L. donovani acid phosphatases (LdSAcPs). Sequence comparison of the LdMAcP orthologues in Leishmania sp. revealed strain polymorphism and species specificity for the L. donovani complex, responsible for visceral leishmaniasis (Khala azar), proposing thus a potential value of LdMAcP as an epidemiological or diagnostic tool. The extracellular orientation of the LdMAcP catalytic domain was confirmed in L. donovani promastigotes, wild-type (wt) and transgenic overexpressing a recombinant LdMAcP-mRFP1 (monomeric RFP1) chimera, as well as in transiently transfected mammalian cells expressing rLdMAcP-His. For the first time it is demonstrated in the present study that LdMAcP confers tartrate resistant acid ecto-phosphatase activity in live L. donovani promastigotes. The latter confirmed the long sought molecular identity of at least one enzyme contributing to this activity. Interestingly, the L. donovani rLdMAcP-mRFP1 promastigotes generated in this study, showed significantly higher infectivity and virulence indexes than control parasites in the infection of J774 mouse macrophages highlighting thereby a role for LdMAcP in the parasite's virulence.

Functional characterization of the copper transcription factor AfMac1 from Aspergillus fumigatus.

PubMed

Park, Yong-Sung; Kim, Tae-Hyoung; Yun, Cheol-Won

2017-07-03

Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 ( A spergillus f umigatus Mac1 homolog) and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA-binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae , and AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1 resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1 failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of A. fumigatus failed to grow in copper-limited media, and its growth was restored by introducing ctrC We found that AfMac1 specifically bound to the promoter region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was identified from the promoter region of ctrC , and the addition of mutant ctrC lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus Furthermore, deletion of Afmac1 significantly reduced strain virulence and activated conidial killing activity by neutrophils and macrophages. Taken together, these results suggest that AfMac1 is a copper transcription factor that regulates cellular copper homeostasis in A. fumigatus . © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Bifunctional role of ephrin A1-Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells.

PubMed

Kang, Minkyung; Jeong, Wooyoung; Bae, Hyocheol; Lim, Whasun; Bazer, Fuller W; Song, Gwonhwa

2018-03-01

Structural and functional development of the mammary gland is constant in the mammary gland life cycle. Eph receptors and their ligands, ephrins, control events through cell-to-cell interactions during embryonic development, and adult tissue homeostasis; however, little information on participation of ephrin A1, a representative ligand of the Eph receptor, in the development and function of normal mammary glands is known. In this study, we demonstrated functional effects of the ephrin A1-Eph system and mechanisms of its action on bovine mammary epithelial (MAC-T) cells. The in vitro cultured MAC-T cells expressed the ephrin A1 ligand and EphA1, A2, A4, A7, and A8 among the eight members of the Eph A family. Our results revealed that ephrin A1 induced MAC-T cell cycle progression and stimulated cell proliferation with abundant expression of nucleic PCNA and cyclin D1 proteins. Additionally, ephrin A1 induced activation of intracellular signaling molecules involved in PI3 K/AKT and MAPK signaling, and the proliferation-stimulating effect of ephrin A1 was mediated by activation of these pathways. Furthermore, ephrin A1 influenced expression and activation of various ER stress-related proteins and protected MAC-T cells from stress-induced cell death. Finally, ephrin A1 alleviated LPS-induced cell death through down-regulation of inflammatory cytokines. In conclusion, the results of this study suggest that the Eph A-ephrin A1 system is a positive factor in the increase and maintenance of epithelial cells in mammary glands of cows; the signaling system contributes to development, remodeling, and functionality of normal mammary glands and could overcome mastitis in cows and other mammals. © 2017 Wiley Periodicals, Inc.

Progressive Failure Analysis of Composite Stiffened Panels

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Yarrington, Phillip W.; Collier, Craig S.; Arnold, Steven M.

2006-01-01

A new progressive failure analysis capability for stiffened composite panels has been developed based on the combination of the HyperSizer stiffened panel design/analysis/optimization software with the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC). MAC/GMC discretizes a composite material s microstructure into a number of subvolumes and solves for the stress and strain state in each while providing the homogenized composite properties as well. As a result, local failure criteria may be employed to predict local subvolume failure and the effects of these local failures on the overall composite response. When combined with HyperSizer, MAC/GMC is employed to represent the ply level composite material response within the laminates that constitute a stiffened panel. The effects of local subvolume failures can then be tracked as loading on the stiffened panel progresses. Sample progressive failure results are presented at both the composite laminate and the composite stiffened panel levels. Deformation and failure model predictions are compared with experimental data from the World Wide Failure Exercise for AS4/3501-6 graphite/epoxy laminates.

Effects of Subscale Size and Shape on Global Energy Dissipation in a Multiscale Model of a Fiber-Reinforced Composite Exhibiting Post-Peak Strain Softening Using Abaqus and FEAMAC

NASA Technical Reports Server (NTRS)

Pineda, Evan, J.; Bednarcyk, Brett, A.; Arnold, Steven, M.

2012-01-01

A mesh objective crack band model is implemented in the generalized method of cells (GMC) micromechanics model to predict failure of a composite repeating unit cell (RUC). The micromechanics calculations are achieved using the MAC/GMC core engine within the ImMAC suite of micromechanics codes, developed at the NASA Glenn Research Center. The microscale RUC is linked to a macroscale Abaqus/Standard finite element model using the FEAMAC multiscale framework (included in the ImMAC suite). The effects of the relationship between the characteristic length of the finite element and the size of the microscale RUC on the total energy dissipation of the multiscale model are investigated. A simple 2-D composite square subjected to uniaxial tension is used to demonstrate the effects of scaling the dimensions of the RUC such that the length of the sides of the RUC are equal to the characteristic length of the finite element. These results are compared to simulations where the size of the RUC is fixed, independent of the element size. Simulations are carried out for a variety of mesh densities and element shapes, including square and triangular. Results indicate that a consistent size and shape must be used to yield preserve energy dissipation across the scales.

Lipid vesicle-mediated affinity chromatography using magnetic activated cell sorting (LIMACS): a novel method to analyze protein-lipid interaction.

PubMed

Bieberich, Erhard

2011-04-26

The analysis of lipid protein interaction is difficult because lipids are embedded in cell membranes and therefore, inaccessible to most purification procedures. As an alternative, lipids can be coated on flat surfaces as used for lipid ELISA and Plasmon resonance spectroscopy. However, surface coating lipids do not form microdomain structures, which may be important for the lipid binding properties. Further, these methods do not allow for the purification of larger amounts of proteins binding to their target lipids. To overcome these limitations of testing lipid protein interaction and to purify lipid binding proteins we developed a novel method termed lipid vesicle-mediated affinity chromatography using magnetic-activated cell sorting (LIMACS). In this method, lipid vesicles are prepared with the target lipid and phosphatidylserine as the anchor lipid for Annexin V MACS. Phosphatidylserine is a ubiquitous cell membrane phospholipid that shows high affinity to the protein Annexin V. Using magnetic beads conjugated to Annexin V the phosphatidylserine-containing lipid vesicles will bind to the magnetic beads. When the lipid vesicles are incubated with a cell lysate the protein binding to the target lipid will also be bound to the beads and can be co-purified using MACS. This method can also be used to test if recombinant proteins reconstitute a protein complex binding to the target lipid. We have used this method to show the interaction of atypical PKC (aPKC) with the sphingolipid ceramide and to co-purify prostate apoptosis response 4 (PAR-4), a protein binding to ceramide-associated aPKC. We have also used this method for the reconstitution of a ceramide-associated complex of recombinant aPKC with the cell polarity-related proteins Par6 and Cdc42. Since lipid vesicles can be prepared with a variety of sphingo- or phospholipids, LIMACS offers a versatile test for lipid-protein interaction in a lipid environment that resembles closely that of the cell membrane. Additional lipid protein complexes can be identified using proteomics analysis of lipid binding protein co-purified with the lipid vesicles.

[Regulatory T cells inhibit proliferation of mouse lymphoma cell line EL4 in vitro].

PubMed

Zhang, Chen; Kong, Yan; Guo, Jun; Ying, Zhi-Tao; Yuan, Zhi-Hong; Zhang, Yun-Tao; Zheng, Wen; Song, Yu-Qin; Li, Ping-Ping; Zhu, Jun

2010-10-01

This study was aimed to investigate the effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cells and its mechanism in vitro. C57BL/6 mouse Treg cells were isolated by magnetic cell sorting (MACS). The purity of Treg cells and their expression of Foxp3 were identified by flow cytometry (FCM) and PT-PCR respectively. The suppression of Treg cells on EL4 cells was detected by 3H-TdR method. At the same time, enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokine TGF-β1 and IL-10. The results showed that CD4+CD25+ T cells could be successfully isolated by MACS with the purity reaching 94.52% and the expression of Foxp3 reaching 84.72%. After sorting, the expression of Foxp3 mRNA could be detected by RT-PCR. 3H-TdR assay confirmed that regulatory T cells could suppress the proliferation of EL4 cells with or without antigen presenting cells (APC) or dendritic cells (DC), APC or DC might effectively enhance the suppression. In addition, DC alone also suppressed the proliferation. TGF-β1 and IL-10 could be detected in the supernatant by ELISA. It is concluded that the Treg cells can obviously suppress the proliferation of T cell lymphoma cells in vitro, APC or DC can enhance this suppressive effect, while the DC alone also can suppress the proliferation of EL4 cells, the TGF-β1 and IL-10 cytokine pathway may be one of the mechanisms of suppression.

Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

PubMed Central

Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

2016-01-01

Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

Micromechanics Analysis Code (MAC) User Guide: Version 1.0

NASA Technical Reports Server (NTRS)

Wilt, T. E.; Arnold, S. M.

1994-01-01

The ability to accurately predict the thermomechanical deformation response of advanced composite materials continues to play an important role in the development of these strategic materials. Analytical models that predict the effective behavior of composites are used not only by engineers performing structural analysis of large-scale composite components but also by material scientists in developing new material systems. For an analytical model to fulfill these two distinct functions it must be based on a micromechanics approach which utilizes physically based deformation and life constitutive models and allows one to generate the average (macro) response of a composite material given the properties of the individual constituents and their geometric arrangement. Here the user guide for the recently developed, computationally efficient and comprehensive micromechanics analysis code, MAC, who's predictive capability rests entirely upon the fully analytical generalized method of cells, GMC, micromechanics model is described. MAC is a versatile form of research software that 'drives' the double or triple ply periodic micromechanics constitutive models based upon GMC. MAC enhances the basic capabilities of GMC by providing a modular framework wherein (1) various thermal, mechanical (stress or strain control), and thermomechanical load histories can be imposed; (2) different integration algorithms may be selected; (3) a variety of constituent constitutive models may be utilized and/or implemented; and (4) a variety of fiber architectures may be easily accessed through their corresponding representative volume elements.

Micromechanics Analysis Code (MAC). User Guide: Version 2.0

NASA Technical Reports Server (NTRS)

Wilt, T. E.; Arnold, S. M.

1996-01-01

The ability to accurately predict the thermomechanical deformation response of advanced composite materials continues to play an important role in the development of these strategic materials. Analytical models that predict the effective behavior of composites are used not only by engineers performing structural analysis of large-scale composite components but also by material scientists in developing new material systems. For an analytical model to fulfill these two distinct functions it must be based on a micromechanics approach which utilizes physically based deformation and life constitutive models and allows one to generate the average (macro) response of a composite material given the properties of the individual constituents and their geometric arrangement. Here the user guide for the recently developed, computationally efficient and comprehensive micromechanics analysis code's (MAC) who's predictive capability rests entirely upon the fully analytical generalized method of cells (GMC), micromechanics model is described. MAC is a versatile form of research software that 'drives' the double or triply periodic micromechanics constitutive models based upon GMC. MAC enhances the basic capabilities of GMC by providing a modular framework wherein (1) various thermal, mechanical (stress or strain control) and thermomechanical load histories can be imposed, (2) different integration algorithms may be selected, (3) a variety of constituent constitutive models may be utilized and/or implemented, and (4) a variety of fiber and laminate architectures may be easily accessed through their corresponding representative volume elements.

Utilization of the Generalized Method of Cells to Analyze the Deformation Response of Laminated Ceramic Matrix Composites

NASA Technical Reports Server (NTRS)

Goldberg, Robert K.

2012-01-01

In order to practically utilize ceramic matrix composites in aircraft engine components, robust analysis tools are required that can simulate the material response in a computationally efficient manner. The MAC/GMC software developed at NASA Glenn Research Center, based on the Generalized Method of Cells micromechanics method, has the potential to meet this need. Utilizing MAC/GMC, the effective stiffness properties, proportional limit stress and ultimate strength can be predicted based on the properties and response of the individual constituents. In this paper, the effective stiffness and strength properties for a representative laminated ceramic matrix composite with a large diameter fiber are predicted for a variety of fiber orientation angles and laminate orientations. As part of the analytical study, methods to determine the in-situ stiffness and strength properties of the constituents required to appropriately simulate the effective composite response are developed. The stiffness properties of the representative composite have been adequately predicted for all of the fiber orientations and laminate configurations examined in this study. The proportional limit stresses and strains and ultimate stresses and strains were predicted with varying levels of accuracy, depending on the laminate orientation. However, for the cases where the predictions did not have the desired level of accuracy, the specific issues related to the micromechanics theory were identified which could lead to difficulties that were encountered that could be addressed in future work.

In Situ complement activation and T-cell immunity in leprosy spectrum: An immunohistological study on leprosy lesional skin.

PubMed

Bahia El Idrissi, Nawal; Iyer, Anand M; Ramaglia, Valeria; Rosa, Patricia S; Soares, Cleverson T; Baas, Frank; Das, Pranab K

2017-01-01

Mycobacterium leprae (M. leprae) infection causes nerve damage and the condition worsens often during and long after treatment. Clearance of bacterial antigens including lipoarabinomannan (LAM) during and after treatment in leprosy patients is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves by in situ generation of the membrane attack complex (MAC). Investigating the role of complement activation in skin lesions of leprosy patients might provide insight into the dynamics of in situ immune reactivity and the destructive pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy patients, whether M. leprae antigen LAM deposition correlates with the deposition of complement activation products MAC and C3d on nerves and cells in the surrounding tissue. Skin biopsies of paucibacillary (n = 7), multibacillary leprosy patients (n = 7), and patients with erythema nodosum leprosum (ENL) (n = 6) or reversal reaction (RR) (n = 4) and controls (n = 5) were analyzed. The percentage of C3d, MAC and LAM deposition was significantly higher in the skin biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p = <0.001 and p = <0.001 respectively), with a significant association between LAM and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001 and r = 0.8585, p<0.0001 respectively). In skin lesions of multibacillary patients, MAC deposition was found on axons and co-localizing with LAM. In skin lesions of paucibacillary patients, we found C3d positive T-cells in and surrounding granulomas, but hardly any MAC deposition. In addition, MAC immunoreactivity was increased in both ENL and RR skin lesions compared to non-reactional leprosy patients (p = <0.01 and p = <0.01 respectively). The present findings demonstrate that complement is deposited in skin lesions of leprosy patients, suggesting that inflammation driven by complement activation might contribute to nerve damage in the lesions of these patients. This should be regarded as an important factor in M. leprae nerve damage pathology.

[Methodical problems of monitoring of fine particulate matters in atmospheric air of residential areas].

PubMed

Karelin, A O; Lomtev, A Yu; Mozzhukhina, N A; Yeremin, G B; Nikonov, V A

Inhalation of fine particulate matters (PM and PM ) poses a threat for the health of population. Purpose of the study the analysis of the monitoring of fine particulate matters in the atmospheric air of Saint-Petersburg and identification of the main problems of the monitoring. Research methods methods of scientific hypothetical deductive cognition, sanitary-statistical methods, general logical methods and approaches of researches: analysis, synthesis, abstracting, generalization, induction. Results. The article represents the analysis of the monitoring of fine particulate matters in the atmospheric air of Saint- Petersburg. Only 11 in automatic monitoring stations out of 22 there is carried out the control of fine particulate matters: in 7 - PM and PM, and in 4 - PM The average year concentrations were below MAC in all the stations. The maximum concentrations achieved 3 MAC, but the repeatance of cases of exceedence of concentrations more than MAC was very rare. On the average of the city concentrations of PM were decreased from 0,8 MAC in 2006 and 1,1 MAC in 2007 to 0,5 MAC in 2013-14. The executed analysis revealed main problems of the monitoring of fine particulate matters in the Russian Federation. They include the absence of the usage 1of the officially approved methods of controlling of PM and PM in the atmospheric air until March 1, 2016, lack of the modern equipment for measurement of fine particulate matters. Conclusions. Therefore, the state of the monitoring of fine particulate matters in the atmospheric air in the Russian Federation fails to be satisfactory. It is necessary to improve system of the monitoring, create modern Russian appliances, methods and means for measurement of fine particulate matters concentrations in the atmospheric air.

Comparative study of MacCormack and TVD MacCormack schemes for three-dimensional separation at wing/body junctions in supersonic flows

NASA Technical Reports Server (NTRS)

Lakshmanan, Balakrishnan; Tiwari, Surendra N.

1992-01-01

A robust, discontinuity-resolving TVD MacCormack scheme containing no dependent parameters requiring adjustment is presently used to investigate the 3D separation of wing/body junction flows at supersonic speeds. Many production codes employing MacCormack schemes can be adapted to use this method. A numerical simulation of laminar supersonic junction flow is found to yield improved separation location predictions, as well as the axial velocity profiles in the separated flow region.

Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia.

PubMed

Cherepanoff, Svetlana; Killingsworth, Murray C; Zhu, Meidong; Nolan, Timothy; Hunyor, Alex P; Young, Stephanie H; Hageman, Gregory S; Gillies, Mark C

2012-11-01

To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented.

Retinal Crystals in Type 2 Idiopathic Macular Telangiectasia

PubMed Central

Sallo, Ferenc B; Leung, Irene; Chung, Mina; Wolf-Schnurrbusch, Ute EK; Dubra, Alfredo; Williams, David R; Clemons, Traci; Pauleikhoff, Daniel; Bird, Alan C; Peto, Tunde

2012-01-01

Purpose To characterize the phenotype and investigate the associations of intraretinal crystalline deposits in a large cohort of Type 2 Idiopathic Macular Telangiectasia (MacTel) Design Case-control study Participants Patients with and without retinal crystals from the Macular Telangiectasia Project, an international multi-centre prospective study of Type 2 MacTel. Methods Grading of stereoscopic 30° colour fundus (CF), confocal blue light reflectance (CBR), red-free (RF) and infrared (IR) images was performed according to the MacTel Natural History Study protocol and staged using the classification system devised by Gass & Blodi. SD-OCT and adaptive optics imaging were used for a finer analysis of the phenotype. Associations between crystals and other characteristics of the disease as well as potential risk factors were investigated. Main outcome measures Presence of crystals, fundus signs of MacTel, clinical characteristics, presence of potential risk factors of MacTel. Results Out of 443 probands enrolled in the MacTel study, 203 (46%) had crystalline deposits present; 60% of the cases were bilateral at baseline. Eyes with crystals had a mean letter score of 70.7 (SD=15.9) while those without crystals had a mean of 66.5 letters (SD=15.5, p<0.001). Crystals were present at all stages of the disease and showed high reflectivity within a wide wavelength range. They were located at the anterior surface of the nerve fibre layer, arranged along the nerve fibres, within an annular area centred on the fovea. Significant associations of crystalline deposits were found with a loss of retinal transparency, MPOD loss, fluorescein leakage, retinal thickness and a break in the IS/OS junction line. Associations with environmental risk factors were not found. Conclusions Intraretinal crystals are a frequent phenomenon associated with type 2 MacTel, they may appear at all stages and may aid in the early diagnosis of the disease. Their morphology further implicates Müller cells in the pathogenesis of the disease. Insight into their physical and chemical properties may provide clues to the metabolic pathways involved in the pathogenesis of the disease. PMID:21839520

Increasing lanthanide luminescence by use of the RETEL effect.

PubMed

Leif, Robert C; Vallarino, Lidia M; Becker, Margie C; Yang, Sean

2006-08-01

Luminescent lanthanide complexes produce emissions with the narrowest-known width at half maximum; however, their significant use in cytometry required an increase in luminescence intensity. The companion review, Leif et al., Cytometry 2006;69A:767-778, described a new technique for the enhancement of lanthanide luminescence, the Resonance Energy Transfer Enhanced Luminescence (RETEL) effect, which increases luminescence and is compatible with standard slide microscopy. The luminescence of the europium ion macrocyclic complex, EuMac, was increased by employing the RETEL effect. After adding the nonluminescent gadolinium ion complex of the thenoyltrifluoroacetonate (TTFA) ligand or the sodium salt of TTFA in ethanol solution, the EuMac-labeled sample was allowed to dry. Both a conventional arc lamp and a time-gated UV LED served as light sources for microscopic imaging. The emission intensity was measured with a CCD camera. Multiple time-gated images were summed with special software to permit analysis and effective presentation of the final image. With the RETEL effect, the luminescence of the EuMac-streptavidin conjugate increased at least six-fold upon drying. Nuclei of apoptotic cells were stained with DAPI and tailed with 5BrdUrd to which a EuMac-anti-5BrdU conjugate was subsequently attached. Time-gated images showed the long-lived EuMac luminescence but did not show the short-lived DAPI fluorescence. Imaging of DNA-synthesizing cells with an arc lamp showed that both S phase and apoptotic cells were labeled, and that their labeling patterns were different. The images of the luminescent EuMac and fluorescent DAPI were combined to produce a color image on a white background. This combination of simple chemistry, instrumentation, and presentation should make possible the inexpensive use of the lanthanide macrocycles, Quantum Dyes, as molecular diagnostics for cytological and histopathological microscopic imaging. (c) 2006 International Society for Analytical Cytology.

Control of viremia and maintenance of intestinal CD4(+) memory T cells in SHIV(162P3) infected macaques after pathogenic SIV(MAC251) challenge.

PubMed

Pahar, Bapi; Lackner, Andrew A; Piatak, Michael; Lifson, Jeffrey D; Wang, Xiaolei; Das, Arpita; Ling, Binhua; Montefiori, David C; Veazey, Ronald S

2009-05-10

Recent HIV vaccine failures have prompted calls for more preclinical vaccine testing in non-human primates. However, similar to HIV infection of humans, developing a vaccine that protects macaques from infection following pathogenic SIV(MAC251) challenge has proven difficult, and current vaccine candidates at best, only reduce viral loads after infection. Here we demonstrate that prior infection with a chimeric simian-human immunodeficiency virus (SHIV) containing an HIV envelope gene confers protection against intravenous infection with the heterologous, highly pathogenic SIV(MAC251) in rhesus macaques. Although definitive immune correlates of protection were not identified, preservation and/or restoration of intestinal CD4(+) memory T cells were associated with protection from challenge and control of viremia. These results suggest that protection against pathogenic lentiviral infection or disease progression is indeed possible, and may correlate with preservation of mucosal CD4(+) T cells.

Embedded biofilm, a new biofilm model based on the embedded growth of bacteria.

PubMed

Jung, Yong-Gyun; Choi, Jungil; Kim, Soo-Kyoung; Lee, Joon-Hee; Kwon, Sunghoon

2015-01-01

A variety of systems have been developed to study biofilm formation. However, most systems are based on the surface-attached growth of microbes under shear stress. In this study, we designed a microfluidic channel device, called a microfluidic agarose channel (MAC), and found that microbial cells in the MAC system formed an embedded cell aggregative structure (ECAS). ECASs were generated from the embedded growth of bacterial cells in an agarose matrix and better mimicked the clinical environment of biofilms formed within mucus or host tissue under shear-free conditions. ECASs were developed with the production of extracellular polymeric substances (EPS), the most important feature of biofilms, and eventually burst to release planktonic cells, which resembles the full developmental cycle of biofilms. Chemical and genetic effects have also confirmed that ECASs are a type of biofilm. Unlike the conventional biofilms formed in the flow cell model system, this embedded-type biofilm completes the developmental cycle in only 9 to 12 h and can easily be observed with ordinary microscopes. We suggest that ECASs are a type of biofilm and that the MAC is a system for observing biofilm formation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Development of in-house serological methods for diagnosis and surveillance of chikungunya

PubMed Central

Galo, Saira Saborío; González, Karla; Téllez, Yolanda; García, Nadezna; Pérez, Leonel; Gresh, Lionel; Harris, Eva; Balmaseda, Ángel

2017-01-01

Objective To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. Methods Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014–2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention’s IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. Results All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MAC-ELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%–95.9%. Conclusion Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease. PMID:28902269

Inverse metal-assisted chemical etching produces smooth high aspect ratio InP nanostructures.

PubMed

Kim, Seung Hyun; Mohseni, Parsian K; Song, Yi; Ishihara, Tatsumi; Li, Xiuling

2015-01-14

Creating high aspect ratio (AR) nanostructures by top-down fabrication without surface damage remains challenging for III-V semiconductors. Here, we demonstrate uniform, array-based InP nanostructures with lateral dimensions as small as sub-20 nm and AR > 35 using inverse metal-assisted chemical etching (I-MacEtch) in hydrogen peroxide (H2O2) and sulfuric acid (H2SO4), a purely solution-based yet anisotropic etching method. The mechanism of I-MacEtch, in contrast to regular MacEtch, is explored through surface characterization. Unique to I-MacEtch, the sidewall etching profile is remarkably smooth, independent of metal pattern edge roughness. The capability of this simple method to create various InP nanostructures, including high AR fins, can potentially enable the aggressive scaling of InP based transistors and optoelectronic devices with better performance and at lower cost than conventional etching methods.

Photocopy of drawing (original drawing of Fire and Guard House ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing (original drawing of Fire and Guard House with Communication Center in possession of MacDill Air Force Base, Civil Engineering, Tampa, Florida; 1940 architectural drawings by Construction Division, Office of the Quartermaster General) CELL BLOCK DETAILS - MacDill Air Force Base, Fire & Guard House, 2709 Florida Keys Avenue, Tampa, Hillsborough County, FL

Staging of Macular Telangiectasia: Power-Doppler Optical Coherence Tomography and Macular Pigment Optical Density

PubMed Central

Chin, Eric K.; Kim, Dae Yu; Hunter, Allan A.; Pilli, Suman; Wilson, Machelle; Zawadzki, Robert J.; Werner, John S.; Park, Susanna S.

2013-01-01

Purpose. Two methods were used to study the stages of macular telangiectasia (MacTel): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids. Methods. Among 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT. Results. Stage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea. Conclusions. PD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel. PMID:23716628

Investigation of Attitudinal Differences among Individuals of Different Employment Status

DTIC Science & Technology

2010-10-28

be included in order to statistically control for common method variance (see Podsakoff , MacKenzie, Lee, & Podsakoff , 2003). Results Hypotheses 1...social identity theory. Social Psychology Quarterly, 58, 255-269. Podsakoff , P. M., MacKenzie, S. B., Lee, J., & Podsakoff , N. P. (2003). Common method

A Novel Method Linking Antigen Presentation by Human Monocyte-Derived Macrophages to CD8+ T Cell Polyfunctionality

PubMed Central

Short, Kirsty R.; Grant, Emma J.; Vissers, Marloes; Reading, Patrick C.; Diavatopoulos, Dimitri A.; Kedzierska, Katherine

2013-01-01

To understand the interactions between innate and adaptive immunity, and specifically how virally infected macrophages impact T cell function, novel assays examining the ability of macrophages to present antigen to CD8+ T cells are needed. In the present study, we have developed a robust in vitro assay to measure how antigen presentation by human monocyte-derived macrophages (MDMs) affects the functional capacity of autologous CD8+ T cells. The assay is based on the polyfunctional characteristics of antigen-specific CD8+ T cells, and is thus called a Mac-CD8 Polyfunctionality Assay. Following purification of monocytes and their maturation to MDMs, MDMs were pulsed with an antigenic peptide to be presented to CD8+ T cells. Peptide-pulsed MDMs were then incubated with antigen-specific CD8+ T cells in order to assess the efficacy of antigen presentation to T cells. CD8+ T cell polyfunctionality was assessed by staining with mAbs to IFN-γ, TNF-α, and CD107a in a multi-color intracellular cytokine staining assay. To highlight the utility of the Mac-CD8 Polyfunctionality Assay, we assessed the effects of influenza infection on the ability of human macrophages to present antigen to CD8+ T cells. We found that influenza infection of human MDMs can alter the effector efficacy of MDMs to activate more CD8+ T cells with cytotoxic capacity. This has important implications for understanding how the virus-infected macrophages affect adaptive immunity at the site of infection. PMID:24312096

RNA sequencing analysis reveals quiescent microglia isolation methods from postnatal mouse brains and limitations of BV2 cells.

PubMed

He, Yingbo; Yao, Xiang; Taylor, Natalie; Bai, Yuchen; Lovenberg, Timothy; Bhattacharya, Anindya

2018-05-22

Microglia play key roles in neuron-glia interaction, neuroinflammation, neural repair, and neurotoxicity. Currently, various microglial in vitro models including primary microglia derived from distinct isolation methods and immortalized microglial cell lines are extensively used. However, the diversity of these existing models raises difficulty in parallel comparison across studies since microglia are sensitive to environmental changes, and thus, different models are likely to show widely varied responses to the same stimuli. To better understand the involvement of microglia in pathophysiological situations, it is critical to establish a reliable microglial model system. With postnatal mouse brains, we isolated microglia using three general methods including shaking, mild trypsinization, and CD11b magnetic-associated cell sorting (MACS) and applied RNA sequencing to compare transcriptomes of the isolated cells. Additionally, we generated a genome-wide dataset by RNA sequencing of immortalized BV2 microglial cell line to compare with primary microglia. Furthermore, based on the outcomes of transcriptional analysis, we compared cellular functions between primary microglia and BV2 cells including immune responses to LPS by quantitative RT-PCR and Luminex Multiplex Assay, TGFβ signaling probed by Western blot, and direct migration by chemotaxis assay. We found that although the yield and purity of microglia were comparable among the three isolation methods, mild trypsinization drove microglia in a relatively active state, evidenced by high amount of amoeboid microglia, enhanced expression of microglial activation genes, and suppression of microglial quiescent genes. In contrast, CD11b MACS was the most reliable and consistent method, and microglia isolated by this method maintained a relatively resting state. Transcriptional and functional analyses revealed that as compared to primary microglia, BV2 cells remain most of the immune functions such as responses to LPS but showed limited TGFβ signaling and chemotaxis upon chemoattractant C5a. Collectively, we determined the optimal isolation methods for quiescent microglia and characterized the limitations of BV2 cells as an alternative of primary microglia. Considering transcriptional and functional differences, caution should be taken when extrapolating data from various microglial models. In addition, our RNA sequencing database serves as a valuable resource to provide novel insights for appropriate application of microglia as in vitro models.

Stochastic-Strength-Based Damage Simulation Tool for Ceramic Matrix and Polymer Matrix Composite Structures

NASA Technical Reports Server (NTRS)

Nemeth, Noel N.; Bednarcyk, Brett A.; Pineda, Evan J.; Walton, Owen J.; Arnold, Steven M.

2016-01-01

Stochastic-based, discrete-event progressive damage simulations of ceramic-matrix composite and polymer matrix composite material structures have been enabled through the development of a unique multiscale modeling tool. This effort involves coupling three independently developed software programs: (1) the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC), (2) the Ceramics Analysis and Reliability Evaluation of Structures Life Prediction Program (CARES/ Life), and (3) the Abaqus finite element analysis (FEA) program. MAC/GMC contributes multiscale modeling capabilities and micromechanics relations to determine stresses and deformations at the microscale of the composite material repeating unit cell (RUC). CARES/Life contributes statistical multiaxial failure criteria that can be applied to the individual brittle-material constituents of the RUC. Abaqus is used at the global scale to model the overall composite structure. An Abaqus user-defined material (UMAT) interface, referred to here as "FEAMAC/CARES," was developed that enables MAC/GMC and CARES/Life to operate seamlessly with the Abaqus FEA code. For each FEAMAC/CARES simulation trial, the stochastic nature of brittle material strength results in random, discrete damage events, which incrementally progress and lead to ultimate structural failure. This report describes the FEAMAC/CARES methodology and discusses examples that illustrate the performance of the tool. A comprehensive example problem, simulating the progressive damage of laminated ceramic matrix composites under various off-axis loading conditions and including a double notched tensile specimen geometry, is described in a separate report.

Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Retrospective Study of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

PubMed

Beaussant, Yvan; Daguindau, Etienne; Pugin, Aurore; Mohty, Mohamad; Avet-Loiseau, Hervé; Roos-Weil, Damien; Michallet, Mauricette; Chevalier, Patrice; Raus, Nicole; El-Cheikh, Jean; Tabrizi, Reza; Huyn, Anne; Buzyn, Agnès; Socié, Gérard; Vincent, Laure; Guilhot, François; Yakoub-Agha, Ibrahim; Lenain, Pascal; François, Sylvie; Beckerich, Florence; Lioure, Bruno; Bulabois, Claude-Eric; Deconinck, Eric

2015-08-01

Because the indication of allograft (allogeneic stem cell transplantation [alloSCT]) for multiple myeloma (MM) has widened in recent years, thanks to the development of reduced-intensity conditionings (RIC), it is still unclear if myeloablative conditioning (MAC) remains appropriate. This study compares retrospectively outcomes of patients undergoing either RIC or MAC regimens for MM. Based on the SFGM-TC registry, we included 446 MM patients receiving alloSCT between 1999 and 2009 for whom a minimal data set was available. Median follow-up for the entire cohort was 33.6 months (range, 0 to 164.5). RIC and MAC populations were different regarding age (53.5 versus 47.1 years, respectively), number of prior autologous (auto)SCTs (93.2% versus 79.6% had at least 2 autoSCTs), and stem cell source (90.2% versus 61.2% received peripheral blood). For RIC and MAC populations the nonrelapse mortality at 2 years was 24.6% and 22.4%, respectively, progression-free survival 35.5% and 51.1%, and overall survival 59.5% and 66.7% (not significant). These outcomes were not affected by conditioning intensity either on univariate or multivariate analysis. Despite some limitations in the study design, these results indicate that MAC should remain a valuable option in alloSCT for MM, especially for young and less-treated patient with no comorbidity. The constant progress in induction treatments of MM and supportive care after alloSCT could improve these results in the near future. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A multilevel trait-based approach to the ecological performance of Microcystis aeruginosa complex from headwaters to the ocean.

PubMed

Kruk, Carla; Segura, Angel M; Nogueira, Lucía; Alcántara, Ignacio; Calliari, Danilo; Martínez de la Escalera, Gabriela; Carballo, Carmela; Cabrera, Carolina; Sarthou, Florencia; Scavone, Paola; Piccini, Claudia

2017-12-01

The Microcystis aeruginosa complex (MAC) clusters cosmopolitan and conspicuous harmful bloom-forming cyanobacteria able to produce cyanotoxins. It is hypothesized that low temperatures and brackish salinities are the main barriers to MAC proliferation. Here, patterns at multiple levels of organization irrespective of taxonomic identity (i.e. a trait-based approach) were analyzed. MAC responses from the intracellular (e.g. respiratory activity) to the ecosystem level (e.g. blooms) were evaluated in wide environmental gradients. Experimental results on buoyancy and respiratory activity in response to increased salinity (0-35) and a literature review of maximum growth rates under different temperatures and salinities were combined with field sampling from headwaters (800km upstream) to the marine end of the Rio de la Plata estuary (Uruguay-South America). Salinity and temperature were the major variables affecting MAC responses. Experimentally, freshwater MAC cells remained active for 24h in brackish waters (salinity=15) while colonies increased their flotation velocity. At the population level, maximum growth rate decreased with salinity and presented a unimodal exponential response with temperature, showing an optimum at 27.5°C and a rapid decrease thereafter. At the community and ecosystem levels, MAC occurred from fresh to marine waters (salinity 30) with a sustained relative increase of large mucilaginous colonies biovolume with respect to individual cells. Similarly, total biomass and, specific and morphological richness decreased with salinity while blooms were only detected in freshwater both at high (33°C) and low (11°C) temperatures. In brackish waters, large mucilaginous colonies presented advantages under osmotic restrictive conditions. These traits values have also been associated with higher toxicity potential. This suggest salinity or low temperatures would not represent effective barriers for the survival and transport of potentially toxic MAC under likely near future scenarios of increasing human impacts (i.e. eutrophication, dam construction and climate change). Copyright © 2017 Elsevier B.V. All rights reserved.

Development of in-house serological methods for diagnosis and surveillance of chikungunya.

PubMed

Galo, Saira Saborío; González, Karla; Téllez, Yolanda; García, Nadezna; Pérez, Leonel; Gresh, Lionel; Harris, Eva; Balmaseda, Ángel

2017-08-21

To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014-2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention's IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MAC-ELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%-95.9%. Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease.

Effects of solid-medium type on routine identification of bacterial isolates by use of matrix-assisted laser desorption ionization-time of flight mass spectrometry.

PubMed

Anderson, Neil W; Buchan, Blake W; Riebe, Katherine M; Parsons, Lauren N; Gnacinski, Stacy; Ledeboer, Nathan A

2012-03-01

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a rapid method for the identification of bacteria. Factors that may alter protein profiles, including growth conditions and presence of exogenous substances, could hinder identification. Bacterial isolates identified by conventional methods were grown on various media and identified using the MALDI Biotyper (Bruker Daltonics, Billerica, MA) using a direct smear method and an acid extraction method. Specimens included 23 Pseudomonas isolates grown on blood agar, Pseudocel (CET), and MacConkey agar (MAC); 20 Staphylococcus isolates grown on blood agar, colistin-nalidixic acid agar (CNA), and mannitol salt agar (MSA); and 25 enteric isolates grown on blood agar, xylose lysine deoxycholate agar (XLD), Hektoen enteric agar (HE), salmonella-shigella agar (SS), and MAC. For Pseudomonas spp., the identification rate to genus using the direct method was 83% from blood, 78% from MAC, and 94% from CET. For Staphylococcus isolates, the identification rate to genus using the direct method was 95% from blood, 75% from CNA, and 95% from MSA. For enteric isolates, the identification rate to genus using the direct method was 100% from blood, 100% from MAC, 100% from XLD, 92% from HE, and 87% from SS. Extraction enhanced identification rates. The direct method of MALDI-TOF analysis of bacteria from selective and differential media yields identifications of varied confidence. Notably, Staphylococci spp. from CNA exhibit low identification rates. Extraction enhances identification rates and is recommended for colonies from this medium.

Micromechanics-Based Structural Analysis (FEAMAC) and Multiscale Visualization within Abaqus/CAE Environment

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Bednarcyk, Brett A.; Hussain, Aquila; Katiyar, Vivek

2010-01-01

A unified framework is presented that enables coupled multiscale analysis of composite structures and associated graphical pre- and postprocessing within the Abaqus/CAE environment. The recently developed, free, Finite Element Analysis--Micromechanics Analysis Code (FEAMAC) software couples NASA's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) with Abaqus/Standard and Abaqus/Explicit to perform micromechanics based FEA such that the nonlinear composite material response at each integration point is modeled at each increment by MAC/GMC. The Graphical User Interfaces (FEAMAC-Pre and FEAMAC-Post), developed through collaboration between SIMULIA Erie and the NASA Glenn Research Center, enable users to employ a new FEAMAC module within Abaqus/CAE that provides access to the composite microscale. FEA IAC-Pre is used to define and store constituent material properties, set-up and store composite repeating unit cells, and assign composite materials as sections with all data being stored within the CAE database. Likewise FEAMAC-Post enables multiscale field quantity visualization (contour plots, X-Y plots), with point and click access to the microscale i.e., fiber and matrix fields).

An immunohistochemical study of the inflammatory infiltrate associated with nasal carcinoma in dogs and cats.

PubMed

Vanherberghen, M; Day, M J; Delvaux, F; Gabriel, A; Clercx, C; Peeters, D

2009-07-01

The aims of this study were to characterize the inflammatory infiltrate associated with nasal carcinoma in dogs and cats and to determine whether this differed between the two species or with different types of carcinoma. Sections from fixed tissue biopsy samples of intranasal carcinoma from 31 dogs and six cats were labelled immunohistochemically to detect expression of the T-lymphocyte marker CD3, class II molecules of the major histocompatibility complex (MHC II), the myelomonocytic antigen MAC387 and immunoglobulin (Ig) G, IgA and IgM within the cytoplasm of plasma cells. All canine carcinomas were heavily infiltrated by MAC387(+) neutrophils, with smaller numbers of MAC387(+) macrophages. T cells were particularly prominent in the infiltrate associated with transitional carcinoma, and in such tumours were frequently mixed with MHC II(+) cells having macrophage or dendritic cell morphology. IgG(+) and IgA(+) plasma cells were detected at the peripheral margins of all types of canine carcinoma. In contrast, feline intranasal carcinoma was invariably associated with a marked infiltration of CD3(+) T cells. The feline tumour infiltrates contained sparse neutrophils and macrophages and few IgG(+) and IgA(+) plasma cells. These findings suggest that qualitatively different immune responses are induced in response to specific types of canine intranasal carcinoma, and that the canine and feline immune response to these neoplasms is also distinct.

Induction of passive Heymann nephritis in complement component 6-deficient PVG rats.

PubMed

Spicer, S Timothy; Tran, Giang T; Killingsworth, Murray C; Carter, Nicole; Power, David A; Paizis, Kathy; Boyd, Rochelle; Hodgkinson, Suzanne J; Hall, Bruce M

2007-07-01

Passive Heymann nephritis (PHN), a model of human membranous nephritis, is induced in susceptible rat strains by injection of heterologous antisera to rat renal tubular Ag extract. PHN is currently considered the archetypal complement-dependent form of nephritis, with the proteinuria resulting from sublytic glomerular epithelial cell injury induced by the complement membrane attack complex (MAC) of C5b-9. This study examined whether C6 and MAC are essential to the development of proteinuria in PHN by comparing the effect of injection of anti-Fx1A antisera into PVG rats deficient in C6 (PVG/C6(-)) and normal PVG rats (PVG/c). PVG/c and PVG/C6(-) rats developed similar levels of proteinuria at 3, 7, 14, and 28 days following injection of antisera. Isolated whole glomeruli showed similar deposition of rat Ig and C3 staining in PVG/c and PVG/C6(-) rats. C9 deposition was abundant in PVG/c but was not detected in PVG/C6(-) glomeruli, indicating C5b-9/MAC had not formed in PVG/C6(-) rats. There was also no difference in the glomerular cellular infiltrate of T cells and macrophages nor the size of glomerular basement membrane deposits measured on electron micrographs. To examine whether T cells effect injury, rats were depleted of CD8+ T cells which did not affect proteinuria in the early heterologous phase but prevented the increase in proteinuria associated with the later autologous phase. These studies showed proteinuria in PHN occurs without MAC and that other mechanisms, such as immune complex size, early complement components, CD4+ and CD8+ T cells, disrupt glomerular integrity and lead to proteinuria.

Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease.

PubMed

Wallace, Richard J; Iakhiaeva, Elena; Williams, Myra D; Brown-Elliott, Barbara A; Vasireddy, Sruthi; Vasireddy, Ravikiran; Lande, Leah; Peterson, Donald D; Sawicki, Janet; Kwait, Rebecca; Tichenor, Wellington S; Turenne, Christine; Falkinham, Joseph O

2013-06-01

Recent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates of Mycobacterium avium could be matched by DNA fingerprinting. To determine if this is true for Mycobacterium intracellulare, household water sources for 36 patients with Mycobacterium avium complex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M. intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%) household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specific M. avium and M. intracellulare probes), and 3 (7%) were M. avium; none were M. intracellulare. In comparison, M. avium was recovered from 141 water/biofilm samples. These results indicate that M. intracellulare lung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such as M. intracellulare and M. chimaera). This is the first report of M. chimaera recovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC.

Abacavir and didanosine induce the interaction between human leukocytes and endothelial cells through Mac-1 upregulation.

PubMed

De Pablo, Carmen; Orden, Samuel; Apostolova, Nadezda; Blanquer, Amando; Esplugues, Juan V; Alvarez, Angeles

2010-06-01

Abacavir and didanosine are nucleoside reverse transcriptase inhibitors (NRTI) widely used in therapy for HIV-infection but which have been linked to cardiovascular complications. The objective of this study was to analyze the effects of clinically relevant doses of abacavir and didanosine on human leukocyte-endothelium interactions and to compare them with those of other NRTIs. The interactions between human leukocytes - specifically peripheral blood polymorphonuclear (PMN) or mononuclear (PBMC) cells - and human umbilical vein endothelial cells were evaluated in a flow chamber system that reproduces conditions in vivo. The expression of adhesion molecules was analyzed by flow cytometry. Abacavir induced a dose-dependent increase in PMN and PBMC rolling and adhesion. This was reproduced by didanosine but not by lamivudine or zidovudine. Both abacavir and didanosine increased Mac-1 expression in neutrophils and monocytes, but produced no effects on either lymphocytes or the expression of endothelial adhesion molecules. The PMN/PBMC rolling and adhesion induced by abacavir or didanosine did not occur when antibodies against Mac-1 or its ligand ICAM-1 were blocked. Abacavir induces significant human leukocyte accumulation through the activation of Mac-1, which in turn interacts with its endothelial ligand ICAM-1. The fact that didanosine exhibits similar effects and that lamivudine and zidovudine do not points to a relationship between the chemical structure of NRTIs and the induction of leukocyte/endothelial cell interactions. This mechanism may be especially relevant to the progression of the vascular damage associated with atherosclerosis and myocardial infarction in abacavir and didanosine-treated patients.

Versatile control of metal-assisted chemical etching for vertical silicon microwire arrays and their photovoltaic applications

PubMed Central

Um, Han-Don; Kim, Namwoo; Lee, Kangmin; Hwang, Inchan; Hoon Seo, Ji; Yu, Young J.; Duane, Peter; Wober, Munib; Seo, Kwanyong

2015-01-01

A systematic study was conducted into the use of metal-assisted chemical etching (MacEtch) to fabricate vertical Si microwire arrays, with several models being studied for the efficient redox reaction of reactants with silicon through a metal catalyst by varying such parameters as the thickness and morphology of the metal film. By optimizing the MacEtch conditions, high-quality vertical Si microwires were successfully fabricated with lengths of up to 23.2 μm, which, when applied in a solar cell, achieved a conversion efficiency of up to 13.0%. These solar cells also exhibited an open-circuit voltage of 547.7 mV, a short-circuit current density of 33.2 mA/cm2, and a fill factor of 71.3% by virtue of the enhanced light absorption and effective carrier collection provided by the Si microwires. The use of MacEtch to fabricate high-quality Si microwires therefore presents a unique opportunity to develop cost-effective and highly efficient solar cells. PMID:26060095

Cyanobacteria and Cyanotoxins Occurrence and Removal from Five High-Risk Conventional Treatment Drinking Water Plants.

PubMed

Szlag, David C; Sinclair, James L; Southwell, Benjamin; Westrick, Judy A

2015-06-12

An environmental protection agency EPA expert workshop prioritized three cyanotoxins, microcystins, anatoxin-a, and cylindrospermopsin (MAC), as being important in freshwaters of the United States. This study evaluated the prevalence of potentially toxin producing cyanobacteria cell numbers relative to the presence and quantity of the MAC toxins in the context of this framework. Total and potential toxin producing cyanobacteria cell counts were conducted on weekly raw and finished water samples from utilities located in five US states. An Enzyme-Linked Immunosorbant Assay (ELISA) was used to screen the raw and finished water samples for microcystins. High-pressure liquid chromatography with a photodiode array detector (HPLC/PDA) verified microcystin concentrations and quantified anatoxin-a and cylindrospermopsin concentrations. Four of the five utilities experienced cyanobacterial blooms in their raw water. Raw water samples from three utilities showed detectable levels of microcystins and a fourth utility had detectable levels of both microcystin and cylindrospermopsin. No utilities had detectable concentrations of anatoxin-a. These conventional plants effectively removed the cyanobacterial cells and all finished water samples showed MAC levels below the detection limit by ELISA and HPLC/PDA.

Clinical efficacy of anti-glycopeptidolipid-core IgA test for diagnosing Mycobacterium avium complex infection in lung.

PubMed

Numata, Takanori; Araya, Jun; Yoshii, Yutaka; Shimizu, Kenichiro; Hara, Hiromichi; Nakayama, Katsutoshi; Kuwano, Kazuyoshi

2015-11-01

It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test. We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029). The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases. © 2015 Asian Pacific Society of Respirology.

An observational study on patient admission in the anaesthesia gas monitor and minimum alveolar concentration monitoring: A deficiency with huge impact

PubMed Central

Karim, Habib Md Reazaul; Narayan, Anilkumar; Yunus, Md; Kumar, Sanjay; Prakash, Avinash; Sahoo, Sarasa Kumar

2017-01-01

Background and Aims: Minimum alveolar concentration (MAC) monitoring is an integral part of modern-day anaesthesia. Both MAC and MAC-awake are age dependant, and age of the patient needs to be entered in the monitor. This study was aimed to assess the practice of patient birth year entry in the anaesthesia monitor and its impact on MAC monitoring. Methods: Sixty volatile anaesthetic-based general anaesthetics (GAs) were observed silently in two tertiary care teaching hospitals with regard to ‘birth year’ entry in the patient monitor. The impact on MAC for non-entry of age was assessed. The observed MAC reading and the MAC corrected for age (MACage) of the patients were noted. Paired t-test was used to compare the differences in observed MAC and MACage values. P <0.05 was significant. Results: Sixty GAs of patients aged between 10 and 68 years were observed; 96.67% anaesthetics were conducted without entering ‘birth year’. Thirty-four patients (mean age 35.14 ± 15.38 years) were further assessed for impact of non-entry of age. The observed MAC was similar to MACage in patients aged 40 ± 5 years (36–45 years group). Nearly 79.41% of the observed MACs were incorrect; 55.88% patients were potentially underdosed whereas 23.53% were overdosed. Conclusion: Omitting patient age entry in the monitor results in erroneous MAC values, exposing patients <40 years to underdosing and older patients to overdose. PMID:28794529

A New Local Failure Model with Application to the Longitudinal Tensile Behavior of Continuously Reinforced Titanium Composites

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2000-01-01

A new model for local fiber failures in composite materials loaded longitudinally is presented. In developing the model, the goal was to account for the effects of fiber breakage on the global response of a composite in a relatively simple and efficient manner. Towards this end, the model includes the important feature of local stress unloading, even as global loading of the composite continues. The model has been incorporated into NASA Glenn's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) and was employed to simulate the longitudinal tensile deformation and failure behavior of several silicon carbide fiber/titanium matrix (SiC/Ti) composites. The model is shown to be quite realistic and capable of accurate predictions for various temperatures, fiber volume fractions, and fiber diameters. Further- more, the new model compares favorably to Curtin's (1993) effective fiber breakage model, which has also been incorporated into MAC/GMC.

Quality testing of an innovative cascade separation system for multiple cell separation

NASA Astrophysics Data System (ADS)

Pierzchalski, Arkadiusz; Moszczynska, Aleksandra; Albrecht, Bernd; Heinrich, Jan-Michael; Tarnok, Attila

2012-03-01

Isolation of different cell types from mixed samples in one separation step by FACS is feasible but expensive and slow. It is cheaper and faster but still challenging by magnetic separation. An innovative bead-based cascade-system (pluriSelect GmbH, Leipzig, Germany) relies on simultaneous physical separation of different cell types. It is based on antibody-mediated binding of cells to beads of different size and isolation with sieves of different mesh-size. We validated pluriSelect system for single parameter (CD3) and simultaneous separation of CD3 and CD15 cells from EDTA blood-samples. Results were compared with those obtained by MACS (Miltenyi-Biotech) magnetic separation (CD3 separation). pluriSelect separation was done in whole blood, MACS on Ficoll gradient isolated leukocytes, according to the manufacturer's protocols. Isolated and residual cells were immunophenotyped (7-color 8-antibody panel (CD3; CD16/56; CD4; CD8; CD14; CD19; CD45; HLADR) on a CyFlowML flow cytometer (Partec GmbH). Cell count (Coulter), purity, yield and viability (7-AAD exclusion) were determined. There were no significant differences between both systems regarding purity (92-98%), yield (50-60%) and viability (92-98%) of isolated cells. PluriSelect separation was slightly faster than MACS (1.15 h versus 1.5h). Moreover, no preenrichment steps were necessary. In conclusion, pluriSelect is a fast, simple and gentle system for efficient simultaneous separation of two cell subpopulation directly from whole blood and can provide a simple alternative to FACS. The isolated cells can be used for further research applications.

A Hybrid Path-Oriented Code Assignment CDMA-Based MAC Protocol for Underwater Acoustic Sensor Networks

PubMed Central

Chen, Huifang; Fan, Guangyu; Xie, Lei; Cui, Jun-Hong

2013-01-01

Due to the characteristics of underwater acoustic channel, media access control (MAC) protocols designed for underwater acoustic sensor networks (UWASNs) are quite different from those for terrestrial wireless sensor networks. Moreover, in a sink-oriented network with event information generation in a sensor field and message forwarding to the sink hop-by-hop, the sensors near the sink have to transmit more packets than those far from the sink, and then a funneling effect occurs, which leads to packet congestion, collisions and losses, especially in UWASNs with long propagation delays. An improved CDMA-based MAC protocol, named path-oriented code assignment (POCA) CDMA MAC (POCA-CDMA-MAC), is proposed for UWASNs in this paper. In the proposed MAC protocol, both the round-robin method and CDMA technology are adopted to make the sink receive packets from multiple paths simultaneously. Since the number of paths for information gathering is much less than that of nodes, the length of the spreading code used in the POCA-CDMA-MAC protocol is shorter greatly than that used in the CDMA-based protocols with transmitter-oriented code assignment (TOCA) or receiver-oriented code assignment (ROCA). Simulation results show that the proposed POCA-CDMA-MAC protocol achieves a higher network throughput and a lower end-to-end delay compared to other CDMA-based MAC protocols. PMID:24193100

A hybrid path-oriented code assignment CDMA-based MAC protocol for underwater acoustic sensor networks.

PubMed

Chen, Huifang; Fan, Guangyu; Xie, Lei; Cui, Jun-Hong

2013-11-04

Due to the characteristics of underwater acoustic channel, media access control (MAC) protocols designed for underwater acoustic sensor networks (UWASNs) are quite different from those for terrestrial wireless sensor networks. Moreover, in a sink-oriented network with event information generation in a sensor field and message forwarding to the sink hop-by-hop, the sensors near the sink have to transmit more packets than those far from the sink, and then a funneling effect occurs, which leads to packet congestion, collisions and losses, especially in UWASNs with long propagation delays. An improved CDMA-based MAC protocol, named path-oriented code assignment (POCA) CDMA MAC (POCA-CDMA-MAC), is proposed for UWASNs in this paper. In the proposed MAC protocol, both the round-robin method and CDMA technology are adopted to make the sink receive packets from multiple paths simultaneously. Since the number of paths for information gathering is much less than that of nodes, the length of the spreading code used in the POCA-CDMA-MAC protocol is shorter greatly than that used in the CDMA-based protocols with transmitter-oriented code assignment (TOCA) or receiver-oriented code assignment (ROCA). Simulation results show that the proposed POCA-CDMA-MAC protocol achieves a higher network throughput and a lower end-to-end delay compared to other CDMA-based MAC protocols.

Comparative analysis of cytokeratin 15, TDAG51, cytokeratin 20 and androgen receptor in sclerosing adnexal neoplasms and variants of basal cell carcinoma.

PubMed

Evangelista, Mara Therese P; North, Jeffrey P

2015-11-01

Desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (BCC) and microcystic adnexal carcinoma (MAC) are sclerosing adnexal neoplasms with overlapping histopathologic features. We compared cytokeratin 15, (CK15), T-cell death-associated gene 51 (TDAG51), cytokeratin 20 (CK20) and androgen receptor (AR) in differentiating these tumors and assessed their expression in BCC subtypes. Fifteen DTE, 15 infundibulocystic BCC, 18 micronodular BCC, 18 morpheaform BCC and 6 MAC were assessed for CK15, TDAG51, CK20 and AR expression. Quantitative CK15 staining was higher in DTE compared with BCC (p < 0.0001) and MAC (p = 0.02). Quantitative TDAG51 staining was higher in DTE than BCC (p < 0.0001). The CK20+AR- immunophenotype was 100% sensitive and specific in diagnosing DTE. The CK20-AR+ immunophenotype was 95.24% specific and 83.33% sensitive for BCC. The CK20-AR- immunophenotype was 83.33% sensitive and 90.91% specific for MAC. CK15, CK20 and AR were positive in 87, 53 and 67% of infundibulocystic BCC cases, respectively. Combination of CK20 and AR best differentiated these sclerosing adnexal neoplasms. Greater positivity for CK15 and TDAG51 generally favors benign lesions. Infundibulocystic BCC has higher CK20 and lower AR immunopositivity than other BCC variants and a high degree of CK15 and TDAG51 positivity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

NF-κB and enhancer-binding CREB protein scaffolded by CREB-binding protein (CBP)/p300 proteins regulate CD59 protein expression to protect cells from complement attack.

PubMed

Du, Yiqun; Teng, Xiaoyan; Wang, Na; Zhang, Xin; Chen, Jianfeng; Ding, Peipei; Qiao, Qian; Wang, Qingkai; Zhang, Long; Yang, Chaoqun; Yang, Zhangmin; Chu, Yiwei; Du, Xiang; Zhou, Xuhui; Hu, Weiguo

2014-01-31

The complement system can be activated spontaneously for immune surveillance or induced to clear invading pathogens, in which the membrane attack complex (MAC, C5b-9) plays a critical role. CD59 is the sole membrane complement regulatory protein (mCRP) that restricts MAC assembly. CD59, therefore, protects innocent host cells from attacks by the complement system, and host cells require the constitutive and inducible expression of CD59 to protect themselves from deleterious destruction by complement. However, the mechanisms that underlie CD59 regulation remain largely unknown. In this study we demonstrate that the widely expressed transcription factor Sp1 may regulate the constitutive expression of CD59, whereas CREB-binding protein (CBP)/p300 bridge NF-κB and CREB, which surprisingly functions as an enhancer-binding protein to induce the up-regulation of CD59 during in lipopolysaccharide (LPS)-triggered complement activation, thus conferring host defense against further MAC-mediated destruction. Moreover, individual treatment with LPS, TNF-α, and the complement activation products (sublytic MAC (SC5b-9) and C5a) could increase the expression of CD59 mainly by activating NF-κB and CREB signaling pathways. Together, our findings identify a novel gene regulation mechanism involving CBP/p300, NF-κB, and CREB; this mechanism suggests potential drug targets for controlling various complement-related human diseases.

Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

PubMed Central

Shetty, Dinesh; Kim, Yong Joon; Shim, Hyunsuk; Snyder, James P.

2015-01-01

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria. PMID:25547726

An Expert System Model of Organizational Climate and Performance

DTIC Science & Technology

1988-01-01

In 0. Meister, Behavioral analysis and measurement methods, New York: Wiley. Farace , R.V., and MacDonald, D. (1974). New directions in the study of...efficiency and resource use (EFFICIENCY). (Berlo in Farace and MacDonald, 1974) Commitment Communications Groups with greater commitment to goals...my work are correct and accurate (Muchlnsky, 1977; Klauss, 1977). ANSWERS.AVAIL S- 2. It’s easy to get answers in my organization ( Farace and MacDonald

Increased ICAM-1 Expression in Transformed Human Oral Epithelial Cells: Molecular Mechanism and Functional Role in Peripheral Blood Mononuclear Cell Adhesion and Lymphokine-Activated-Killer Cell Cytotoxicity

PubMed Central

Huang, George T.-J.; Zhang, Xinli; Park, No-Hee

2012-01-01

The intercellular adhesion molecule-1 (ICAM-1, CD54) serves as a counter-receptor for the β2-integrins, LFA-1 and Mac-1, which are expressed on leukocytes. Although expression of ICAM-1 on tumor cells has a role in tumor progression and development, information on ICAM-1 expression and its role in oral cancer has not been established. Normal human oral keratinocytes (NHOK), human papilloma virus (HPV)-immortalized human oral keratinocyte lines (HOK-16B, HOK-18A, and HOK-18C), and six human oral neoplastic cell lines (HOK-16B-BaP-T1, SCC-4, SCC-9, HEp-2, Tu-177 and 1483) were used to study ICAM-1 expression and its functional role in vitro. Our results demonstrated that NHOK express negligible levels of ICAM-1, whereas immortalized human oral keratinocytes and cancer cells express significantly higher levels of ICAM-1, except for HOK-16B-BaP-T1 and HEp-2. Altered mRNA half-lives did not fully account for the increased accumulation of ICAM-1 mRNA. Adhesion of peripheral blood mononuclear cells (PBMC) to epithelial cells correlated with cell surface ICAM-1 expression levels. This adhesion was inhibited by antibodies specific for either ICAM-1 or LFA-1/Mac-1, suggesting a role for these molecules in adhesion. In contrast, lymphokine-activated-killer (LAK) cell cytotoxic killing of epithelial cells did not correlate with ICAM-1 levels or with adhesion. Nonetheless, within each cell line, blocking of ICAM-1 or LFA-1/Mac-1 reduced LAK cells killing, suggesting that ICAM-1 is involved in mediating this killing. PMID:10938387

A critical evaluation of magnetic activated carbon's potential for the remediation of sediment impacted by polycyclic aromatic hydrocarbons.

PubMed

Han, Zhantao; Sani, Badruddeen; Akkanen, Jarkko; Abel, Sebastian; Nybom, Inna; Karapanagioti, Hrissi K; Werner, David

2015-04-09

Addition of activated carbon (AC) or biochar (BC) to sediment to reduce the chemical and biological availability of organic contaminants is a promising in-situ remediation technology. But concerns about leaving the adsorbed pollutants in place motivate research into sorbent recovery methods. This study explores the use of magnetic sorbents. A coal-based magnetic activated carbon (MAC) was identified as the strongest of four AC and BC derived magnetic sorbents for polycyclic aromatic hydrocarbons (PAHs) remediation. An 8.1% MAC amendment (w/w, equal to 5% AC content) was found to be as effective as 5% (w/w) pristine AC in reducing aqueous PAHs within three months by 98%. MAC recovery from sediment after three months was 77%, and incomplete MAC recovery had both, positive and negative effects. A slight rebound of aqueous PAH concentrations was observed following the MAC recovery, but aqueous PAH concentrations then dropped again after six months, likely due to the presence of the 23% unrecovered MAC. On the other hand, the 77% recovery of the 8.1% MAC dose was insufficient to reduce ecotoxic effects of fine grained AC or MAC amendment on the egestion rate, growth and reproduction of the AC sensitive species Lumbriculus variegatus. Copyright © 2014 Elsevier B.V. All rights reserved.

Awake Craniotomy Anesthesia: A Comparison of the Monitored Anesthesia Care and Asleep-Awake-Asleep Techniques.

PubMed

Eseonu, Chikezie I; ReFaey, Karim; Garcia, Oscar; John, Amballur; Quiñones-Hinojosa, Alfredo; Tripathi, Punita

2017-08-01

Commonly used sedation techniques for an awake craniotomy include monitored anesthesia care (MAC), using an unprotected airway, and the asleep-awake-asleep (AAA) technique, using a partially or totally protected airway. We present a comparative analysis of the MAC and AAA techniques, evaluating anesthetic management, perioperative outcomes, and complications in a consecutive series of patients undergoing the removal of an eloquent brain lesion. Eighty-one patients underwent awake craniotomy for an intracranial lesion over a 9-year period performed by a single-surgeon and a team of anesthesiologists. Fifty patients were treated using the MAC technique, and 31 were treated using the AAA technique. A retrospective analysis evaluated anesthetic management, intraoperative complications, postoperative outcomes, pain management, and complications. The MAC and AAA groups had similar preoperative patient and tumor characteristics. Mean operative time was shorter in the MAC group (283.5 minutes vs. 313.3 minutes; P = 0.038). Hypertension was the most common intraoperative complication seen (8% in the MAC group vs. 9.7% in the AAA group; P = 0.794). Intraoperative seizure occurred at a rate of 4% in the MAC group and 3.2% in the AAA group (P = 0.858). Awake cases were converted to general anesthesia in no patients in the MAC group and in 1 patient (3.2%) in the AAA group (P = 0.201). No cases were aborted in either group. The mean hospital length of stay was 3.98 days in the MAC group and 3.84 days in the AAA group (P = 0.833). Both the MAC and AAA sedation techniques provide an efficacious and safe method for managing awake craniotomy cases and produce similar perioperative outcomes, with the MAC technique associated with shorter operative time. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation.

PubMed

Kállay, Krisztián; Kassa, Csaba; Réti, Marienn; Karászi, Éva; Sinkó, János; Goda, Vera; Stréhn, Anita; Csordás, Katalin; Horváth, Orsolya; Szederjesi, Attila; Tasnády, Szabolcs; Hardi, Apor; Kriván, Gergely

2018-04-01

Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

Bioequivalence comparison of a new freezing bag (CryoMACS(®)) with the Cryocyte(®) freezing bag for cryogenic storage of human hematopoietic progenitor cells.

PubMed

Sputtek, Andreas; Lioznov, Michael; Kröger, Nikolaus; Rowe, Arthur W

2011-04-01

We investigated two different plastic freezing bags, namely the most recently U.S. Food and Drug Administration (FDA)-approved CryoMACS(®) freezing bag (200-074-402) from Miltenyi Biotec and the familiar Cryocyte(®) freezing bag (R4R9955) from (Baxter Healthcare, Deerfield, IL, United States) for the cryogenic storage of human hematopoietic progenitor cells (HPC). The study material consisted of 12 frozen HPC pairs (= 24 transplant units) that were no longer needed for autologous treatment of patients. After thawing, one unit of a pair was transferred into the Miltenyi (M) bag; the other unit remained in the original Baxter (B) bag. After refreezing both units, all units were stored again under cryogenic conditions either partially immersed in liquid nitrogen (n = 22) or in the vapor phase over liquid nitrogen, n = 2, <-170°) before thawing. The correlation coefficients (r) between the results obtained from the two bag types were high for white blood cells (WBC) content (r = 0.98), mononuclear cells (MNC) (r = 0.97), lymphocytes (r = 0.98), monocytes (r = 0.96), membrane integrity (r = 0.93), concentration of 'free' hemoglobin (r = 0.97) and hemolysis rate (r = 0.95). With regard to clonogenicity, there were no significant differences (Student's paired t-test) for the three parameters investigated [i.e. total number of colonies, including the numbers of burst-forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) colonies, respectively). The CryoMACS freezing bag 200-074-402 is bioequivalent to the Cryocyte freezing container R4R9955. An advantageous feature of the CryoMACS is that its double-sterile wrapping provides additional safety regarding potential cross-contamination during cryogenic storage.

Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs.

PubMed

Ko, J C; Lange, D N; Mandsager, R E; Payton, M E; Bowen, C; Kamata, A; Kuo, W C

2000-10-01

To evaluate the effects of butorphanol and carprofen, alone and in combination, on the minimal alveolar concentration (MAC) of isoflurane in dogs. Randomized complete-block crossover study. 6 healthy adult dogs. Minimal alveolar concentration of isoflurane was determined following administration of carprofen alone, butorphanol alone, carprofen and butorphanol, and neither drug (control). Anesthesia was induced with isoflurane in oxygen, and MAC was determined by use of a tail clamp method. Three hours prior to induction of anesthesia, dogs were fed a small amount of canned food without any drugs (control) or with carprofen (2.2 mg/kg of body weight [1 mg/lb]). Following initial determination of MAC, butorphanol (0.4 mg/kg [0.18 mg/lb], i.v.) was administered, and MAC was determined again. Heart rate, respiratory rate, indirect arterial blood pressure, endtidal partial pressure of CO2, and saturation of hemoglobin with oxygen were recorded at the time MAC was determined. Mean +/- SD MAC of isoflurane following administration of butorphanol alone (1.03 +/- 0.22%) or carprofen and butorphanol (0.90 +/- 0.21%) were significantly less than the control MAC (1.28 +/- 0.14%), but MAC after administration of carprofen alone (1.20 +/- 0.13%) was not significantly different from the control value. The effects of carprofen and butorphanol on the MAC of isoflurane were additive. There were not any significant differences among treatments in regard to cardiorespiratory data. Results suggest that administration of butorphanol alone or in combination with carprofen significantly reduces the MAC of isoflurane in dogs; however, the effects of butorphanol and carprofen are additive, not synergistic.

Integrin-directed modulation of macrophage responses to biomaterials.

PubMed

Zaveri, Toral D; Lewis, Jamal S; Dolgova, Natalia V; Clare-Salzler, Michael J; Keselowsky, Benjamin G

2014-04-01

Macrophages are the primary mediator of chronic inflammatory responses to implanted biomaterials, in cases when the material is either in particulate or bulk form. Chronic inflammation limits the performance and functional life of numerous implanted medical devices, and modulating macrophage interactions with biomaterials to mitigate this response would be beneficial. The integrin family of cell surface receptors mediates cell adhesion through binding to adhesive proteins nonspecifically adsorbed onto biomaterial surfaces. In this work, the roles of integrin Mac-1 (αMβ2) and RGD-binding integrins were investigated using model systems for both particulate and bulk biomaterials. Specifically, the macrophage functions of phagocytosis and inflammatory cytokine secretion in response to a model particulate material, polystyrene microparticles were investigated. Opsonizing proteins modulated microparticle uptake, and integrin Mac-1 and RGD-binding integrins were found to control microparticle uptake in an opsonin-dependent manner. The presence of adsorbed endotoxin did not affect microparticle uptake levels, but was required for the production of inflammatory cytokines in response to microparticles. Furthermore, it was demonstrated that integrin Mac-1 and RGD-binding integrins influence the in vivo foreign body response to a bulk biomaterial, subcutaneously implanted polyethylene terephthalate. A thinner foreign body capsule was formed when integrin Mac-1 was absent (~30% thinner) or when RGD-binding integrins were blocked by controlled release of a blocking peptide (~45% thinner). These findings indicate integrin Mac-1 and RGD-binding integrins are involved and may serve as therapeutic targets to mitigate macrophage inflammatory responses to both particulate and bulk biomaterials. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identity of the segment of human complement C8 recognized by complement regulatory protein CD59.

PubMed

Lockert, D H; Kaufman, K M; Chang, C P; Hüsler, T; Sodetz, J M; Sims, P J

1995-08-25

CD59 antigen is a membrane glycoprotein that inhibits the activity of the C5b-9 membrane attack complex (MAC), thereby protecting human cells from lysis by human complement. The inhibitory function of CD59 derives from its capacity to interact with both the C8 and C9 components of MAC, preventing assembly of membrane-inserted C9 polymer. MAC-inhibitory activity of CD59 is species-selective and is most effective when both C8 and C9 derive from human or other primate plasma. Rabbit C8 and C9, which can substitute for human C8 and C9 in MAC, mediate virtually unrestricted lysis of human cells expressing CD59. In order to identify the segment of human C8 that is recognized by CD59, recombinant peptides containing human or rabbit C8 sequence were expressed in Escherichia coli and purified. CD59 was found to specifically bind to a peptide corresponding to residues 334-385 of the human C8 alpha-subunit, and to require a disulfide bond between Cys345 and Cys369. No specific binding was observed to the corresponding sequence from rabbit C8 alpha (residues 334-386). To obtain functional evidence that this segment of human C8 alpha is selectively recognized by CD59, recombinant C8 proteins were prepared by co-transfecting COS-7 cells with human/rabbit chimeras of the C8 alpha cDNA, and cDNAs encoding the C8 beta and C8 gamma chains. Hemolytic activity of MAC formed with chimeric C8 was analyzed using target cells reconstituted with CD59. These experiments confirmed that CD59 recognizes a conformationally sensitive epitope that is within a segment of human C8 alpha internal to residues 320-415. Our data also suggest that optimal interaction of CD59 with this segment of human C8 alpha is influenced by N-terminal flanking sequence in C8 alpha and by human C8 beta, but is unaffected by C8 gamma.

Heterogeneous organocatalysis at work: functionalization of hollow periodic mesoporous organosilica spheres with MacMillan catalyst.

PubMed

Shi, Jiao Yi; Wang, Chang An; Li, Zhi Jun; Wang, Qiong; Zhang, Yuan; Wang, Wei

2011-05-23

We report a new method for the synthesis of hollow-structured phenylene-bridged periodic mesoporous organosilica (PMO) spheres with a uniform particle size of 100-200 nm using α-Fe(2)O(3) as a hard template. Based on this method, the hollow-structured phenylene PMO could be easily functionalized with MacMillan catalyst (H-PhPMO-Mac) by a co-condensation process and a "click chemistry" post-modification. The synthesized H-PhPMO-Mac catalyst has been found to exhibit high catalytic activity (98% yield, 81% enantiomeric excess (ee) for endo and 81% ee for exo) in asymmetric Diels-Alder reactions with water as solvent. The catalyst could be reused for at least seven runs without a significant loss of catalytic activity. Our results have also indicated that hollow-structured PMO spheres exhibit higher catalytic efficiency than solid (non-hollow) PMO spheres, and that catalysts prepared by the co-condensation process and "click chemistry" post-modification exhibit higher catalytic efficiency than those prepared by a grafting method. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sparsey™: event recognition via deep hierarchical sparse distributed codes

PubMed Central

Rinkus, Gerard J.

2014-01-01

The visual cortex's hierarchical, multi-level organization is captured in many biologically inspired computational vision models, the general idea being that progressively larger scale (spatially/temporally) and more complex visual features are represented in progressively higher areas. However, most earlier models use localist representations (codes) in each representational field (which we equate with the cortical macrocolumn, “mac”), at each level. In localism, each represented feature/concept/event (hereinafter “item”) is coded by a single unit. The model we describe, Sparsey, is hierarchical as well but crucially, it uses sparse distributed coding (SDC) in every mac in all levels. In SDC, each represented item is coded by a small subset of the mac's units. The SDCs of different items can overlap and the size of overlap between items can be used to represent their similarity. The difference between localism and SDC is crucial because SDC allows the two essential operations of associative memory, storing a new item and retrieving the best-matching stored item, to be done in fixed time for the life of the model. Since the model's core algorithm, which does both storage and retrieval (inference), makes a single pass over all macs on each time step, the overall model's storage/retrieval operation is also fixed-time, a criterion we consider essential for scalability to the huge (“Big Data”) problems. A 2010 paper described a nonhierarchical version of this model in the context of purely spatial pattern processing. Here, we elaborate a fully hierarchical model (arbitrary numbers of levels and macs per level), describing novel model principles like progressive critical periods, dynamic modulation of principal cells' activation functions based on a mac-level familiarity measure, representation of multiple simultaneously active hypotheses, a novel method of time warp invariant recognition, and we report results showing learning/recognition of spatiotemporal patterns. PMID:25566046

Low-temperature MIR to submillimeter mass absorption coefficient of interstellar dust analogues. II. Mg and Fe-rich amorphous silicates

NASA Astrophysics Data System (ADS)

Demyk, K.; Meny, C.; Leroux, H.; Depecker, C.; Brubach, J.-B.; Roy, P.; Nayral, C.; Ojo, W.-S.; Delpech, F.

2017-10-01

Context. To model the cold dust emission observed in the diffuse interstellar medium, in dense molecular clouds or in cold clumps that could eventually form new stars, it is mandatory to know the physical and spectroscopic properties of this dust and to understand its emission. Aims: This work is a continuation of previous studies aiming at providing astronomers with spectroscopic data of realistic cosmic dust analogues for the interpretation of observations. The aim of the present work is to extend the range of studied analogues to iron-rich silicate dust analogues. Methods: Ferromagnesium amorphous silicate dust analogues were produced by a sol-gel method with a mean composition close to Mg1-xFexSiO3 with x = 0.1, 0.2, 0.3, 0.4. Part of each sample was annealed at 500 °C for two hours in a reducing atmosphere to modify the oxidation state of iron. We have measured the mass absorption coefficient (MAC) of these eight ferromagnesium amorphous silicate dust analogues in the spectral domain 30-1000 μm for grain temperature in the range 10-300 K and at room temperature in the 5-40 μm range. Results: The MAC of ferromagnesium samples behaves in the same way as the MAC of pure Mg-rich amorphous silicate samples. In the 30-300 K range, the MAC increases with increasing grain temperature whereas in the range 10-30 K, we do not see any change of the MAC. The MAC cannot be described by a single power law in λ- β. The MAC of the samples does not show any clear trend with the iron content. However the annealing process has, on average, an effect on the MAC that we explain by the evolution of the structure of the samples induced by the processing. The MAC of all the samples is much higher than the MAC calculated by dust models. Conclusions: The complex behavior of the MAC of amorphous silicates with wavelength and temperature is observed whatever the exact silicate composition (Mg vs. Fe amount). It is a universal characteristic of amorphous materials, and therefore of amorphous cosmic silicates, that should be taken into account in astronomical modeling. The enhanced MAC of the measured samples compared to the MAC calculated for cosmic dust model implies that dust masses are overestimated by the models. The tabulated mass absorption coefficients are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/606/A50

Efficient removal of amoxicillin and paracetamol from aqueous solutions using magnetic activated carbon.

PubMed

Saucier, Caroline; Karthickeyan, P; Ranjithkumar, V; Lima, Eder C; Dos Reis, Glaydson S; de Brum, Irineu A S

2017-02-01

Activated carbon (AC)/CoFe 2 O 4 nanocomposites, MAC-1 and MAC-2, were prepared by a simple pyrolytic method using a mixture of iron(III)/cobalt(II) benzoates and iron(III)/cobalt(II) oxalates, respectively, and were used as efficient adsorbents for the removal of amoxicillin (AMX) and paracetamol (PCT) of aqueous effluents. The synthesized nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and transmission electron microscopy (TEM). The sizes of cobalt ferrite nanoparticles formed from benzoates of iron(III)/cobalt(II) and oxalates of iron(III)/cobalt(II) precursors were in the ranges of 5-80 and 6-27 nm, respectively. The saturation magnetization (M s ), remanence (M r ) and coercivity (H c ) of the MAC-2 nanocomposites were found to be 3.07 emu g -1 , 1.36 emu g -1 and 762.49 Oe; for MAC-1, they were 0.2989 emu g -1 , 0.0466 emu g -1 and 456.82 Oe. The adsorption kinetics and isotherm studies were investigated, and the results showed that the as-prepared nanocomposites MAC-1 and MAC-2 could be utilized as an efficient, magnetically separable adsorbent for environmental cleanup. The maximum sorption capacities obtained were 280.9 and 444.2 mg g -1 of AMX for MAC-1 and MAC-2, respectively, and 215.1 and 399.9 mg g -1 of PCT using MAC-1 and MAC-2, respectively. Both adsorbents were successfully used for simulated hospital effluents, removing at least 93.00 and 96.77% for MAC-1 and MAC-2, respectively, of a mixture of nine pharmaceuticals with high concentrations of sugars, organic components and saline concentrations.

Cyanobacteria and Cyanotoxins Occurrence and Removal from Five High-Risk Conventional Treatment Drinking Water Plants

PubMed Central

Szlag, David C.; Sinclair, James L.; Southwell, Benjamin; Westrick, Judy A.

2015-01-01

An environmental protection agency EPA expert workshop prioritized three cyanotoxins, microcystins, anatoxin-a, and cylindrospermopsin (MAC), as being important in freshwaters of the United States. This study evaluated the prevalence of potentially toxin producing cyanobacteria cell numbers relative to the presence and quantity of the MAC toxins in the context of this framework. Total and potential toxin producing cyanobacteria cell counts were conducted on weekly raw and finished water samples from utilities located in five US states. An Enzyme-Linked Immunosorbant Assay (ELISA) was used to screen the raw and finished water samples for microcystins. High-pressure liquid chromatography with a photodiode array detector (HPLC/PDA) verified microcystin concentrations and quantified anatoxin-a and cylindrospermopsin concentrations. Four of the five utilities experienced cyanobacterial blooms in their raw water. Raw water samples from three utilities showed detectable levels of microcystins and a fourth utility had detectable levels of both microcystin and cylindrospermopsin. No utilities had detectable concentrations of anatoxin-a. These conventional plants effectively removed the cyanobacterial cells and all finished water samples showed MAC levels below the detection limit by ELISA and HPLC/PDA. PMID:26075379

Channel MAC Protocol for Opportunistic Communication in Ad Hoc Wireless Networks

NASA Astrophysics Data System (ADS)

Ashraf, Manzur; Jayasuriya, Aruna; Perreau, Sylvie

2008-12-01

Despite significant research effort, the performance of distributed medium access control methods has failed to meet theoretical expectations. This paper proposes a protocol named "Channel MAC" performing a fully distributed medium access control based on opportunistic communication principles. In this protocol, nodes access the channel when the channel quality increases beyond a threshold, while neighbouring nodes are deemed to be silent. Once a node starts transmitting, it will keep transmitting until the channel becomes "bad." We derive an analytical throughput limit for Channel MAC in a shared multiple access environment. Furthermore, three performance metrics of Channel MAC—throughput, fairness, and delay—are analysed in single hop and multihop scenarios using NS2 simulations. The simulation results show throughput performance improvement of up to 130% with Channel MAC over IEEE 802.11. We also show that the severe resource starvation problem (unfairness) of IEEE 802.11 in some network scenarios is reduced by the Channel MAC mechanism.

Gene expression profiling of immunomagnetically separated cells directly from stabilized whole blood for multicenter clinical trials

PubMed Central

2014-01-01

Background Clinically useful biomarkers for patient stratification and monitoring of disease progression and drug response are in big demand in drug development and for addressing potential safety concerns. Many diseases influence the frequency and phenotype of cells found in the peripheral blood and the transcriptome of blood cells. Changes in cell type composition influence whole blood gene expression analysis results and thus the discovery of true transcript level changes remains a challenge. We propose a robust and reproducible procedure, which includes whole transcriptome gene expression profiling of major subsets of immune cell cells directly sorted from whole blood. Methods Target cells were enriched using magnetic microbeads and an autoMACS® Pro Separator (Miltenyi Biotec). Flow cytometric analysis for purity was performed before and after magnetic cell sorting. Total RNA was hybridized on HGU133 Plus 2.0 expression microarrays (Affymetrix, USA). CEL files signal intensity values were condensed using RMA and a custom CDF file (EntrezGene-based). Results Positive selection by use of MACS® Technology coupled to transcriptomics was assessed for eight different peripheral blood cell types, CD14+ monocytes, CD3+, CD4+, or CD8+ T cells, CD15+ granulocytes, CD19+ B cells, CD56+ NK cells, and CD45+ pan leukocytes. RNA quality from enriched cells was above a RIN of eight. GeneChip analysis confirmed cell type specific transcriptome profiles. Storing whole blood collected in an EDTA Vacutainer® tube at 4°C followed by MACS does not activate sorted cells. Gene expression analysis supports cell enrichment measurements by MACS. Conclusions The proposed workflow generates reproducible cell-type specific transcriptome data which can be translated to clinical settings and used to identify clinically relevant gene expression biomarkers from whole blood samples. This procedure enables the integration of transcriptomics of relevant immune cell subsets sorted directly from whole blood in clinical trial protocols. PMID:25984272

Streptococcal inhibitor of complement (SIC) inhibits the membrane attack complex by preventing uptake of C567 onto cell membranes

PubMed Central

Fernie-King, Barbara A; Seilly, David J; Willers, Christine; Würzner, Reinhard; Davies, Alexandra; Lachmann, Peter J

2001-01-01

Streptococcal inhibitor of complement (SIC) was first described in 1996 as a putative inhibitor of the membrane attack complex of complement (MAC). SIC is a 31 000 MW protein secreted in large quantities by the virulent Streptococcus pyogenes strains M1 and M57, and is encoded by a gene which is extremely variable. In order to study further the interactions of SIC with the MAC, we have made a recombinant form of SIC (rSIC) in Escherichia coli and purified native M1 SIC which was used to raise a polyclonal antibody. SIC prevented reactive lysis of guinea pig erythrocytes by the MAC at a stage prior to C5b67 complexes binding to cell membranes, presumably by blocking the transiently expressed membrane insertion site on C7. The ability of SIC and clusterin (another putative fluid phase complement inhibitor) to inhibit complement lysis was compared, and found to be equally efficient. In parallel, by enzyme-linked immunosorbent assay both SIC and rSIC bound strongly to C5b67 and C5b678 complexes and to a lesser extent C5b-9, but only weakly to individual complement components. The implications of these data for virulence of SIC-positive streptococci are discussed, in light of the fact that Gram-positive organisms are already protected against complement lysis by the presence of their peptidoglycan cell walls. We speculate that MAC inhibition may not be the sole function of SIC. PMID:11454069

EFFECTS OF TRAMADOL ON THE MINIMUM ANESTHETIC CONCENTRATION OF ISOFLURANE IN WHITE-EYED PARAKEETS (PSITTACARA LEUCOPHTHALMUS).

PubMed

Escobar, André; da Rocha, Rozana Wendler; Midon, Monica; de Almeida, Ricardo Miyasaka; Filho, Darcio Zangirolami; Werther, Karin

2017-06-01

The aim of this study was to determine the minimum anesthetic concentration (MAC) of isoflurane, and to investigate if tramadol changes the isoflurane MAC in white-eyed parakeets (Psittacara leucophthalmus). Ten adult birds weighing 157 ± 9 g were anesthetized with isoflurane in oxygen under mechanical ventilation. Isoflurane concentration for the first bird was adjusted to 2.2%, and after 15 min an electrical stimulus was applied in the thigh area to observe the response (movement or nonmovement). Isoflurane concentration for the subsequent bird was increased by 10% if the previous bird moved, or decreased by 10% if the previous bird did not move. This procedure was performed serially until at least four sequential crossover events were detected. A crossover event was defined as a sequence of two birds with different responses (positive or negative) to the electrical stimulus. Isoflurane MAC was calculated as the mean isoflurane concentration value at the crossover events. After 1 wk, the same birds were reanesthetized with isoflurane and MAC was determined at 15 and 30 min after intramuscular administration of 10 mg/kg of tramadol using the same method. A paired t-test (P < 0.05%) was used to detect significant differences for MAC between treatments. Isoflurane MAC in this population of white-eyed parakeets was 2.47 ± 0.09%. Isoflurane MAC values 15 and 30 min after tramadol administration were indistinguishable from each other (pooled value was 2.50 ± 0.18%); they were also indistinguishable from isoflurane MAC without tramadol. The isoflurane MAC value in white-eyed parakeets is higher than reported for other bird species. Tramadol (10 mg/kg, i.m.) does not change isoflurane MAC in these birds.

Effects of Methadone on the Minimum Anesthetic Concentration of Isoflurane, and Its Effects on Heart Rate, Blood Pressure and Ventilation during Isoflurane Anesthesia in Hens (Gallus gallus domesticus)

PubMed Central

Pypendop, Bruno Henri; Zangirolami Filho, Darcio; Sousa, Samuel Santos; Valadão, Carlos Augusto Araújo

2016-01-01

The aim of this study was to measure the temporal effects of intramuscular methadone administration on the minimum anesthetic concentration (MAC) of isoflurane in hens, and to evaluate the effects of the isoflurane-methadone combination on heart rate and rhythm, blood pressure and ventilation. Thirteen healthy adult hens weighing 1.7 ± 0.2 kg were used. The MAC of isoflurane was determined in each individual using the bracketing method. Subsequently, the reduction in isoflurane MAC produced by methadone (3 or 6 mg kg-1, IM) was determined by the up-and-down method. Stimulation was applied at 15 and 30 minutes, and at 45 minutes if the bird had not moved at 30 minutes. Isoflurane MAC reduction was calculated at each time point using logistic regression. After a washout period, birds were anesthetized with isoflurane and methadone, 6 mg kg-1 IM was administered. Heart rate and rhythm, respiratory rate, blood gas values and invasive blood pressure were measured at 1.0 and 0.7 isoflurane MAC, and during 45 minutes after administration of methadone once birds were anesthetized with 0.7 isoflurane MAC. Fifteen minutes after administration of 3 mg kg-1 of methadone, isoflurane MAC was reduced by 2 (-9 to 13)% [logistic regression estimate (95% Wald confidence interval)]. Administration of 6 mg kg-1 of methadone decreased isoflurane MAC by 29 (11 to 46)%, 27 (-3 to 56)% and 10 (-8 to 28)% after 15, 30 and 45 minutes, respectively. Methadone (6 mg kg-1) induced atrioventricular block in three animals and ventricular premature contractions in two. Methadone caused an increase in arterial blood pressure and arterial partial pressure of carbon dioxide, while heart rate and pH decreased. Methadone, 6 mg kg-1 IM significantly reduced isoflurane MAC by 30% in hens 15 minutes after administration. At this dose, methadone caused mild respiratory acidosis and increase in systemic blood pressure. PMID:27018890

Vascular nanomedicine: Site specific delivery of elastin stabilizing therapeutics to damaged arteries

NASA Astrophysics Data System (ADS)

Sinha, Aditi

Elastin, a structural protein in the extra-cellular matrix, plays a critical role in the normal functioning of blood vessels. Apart from performing its primary function of providing resilience to arteries, it also plays major role in regulating cell-cell and cell-matrix interactions, response to injury, and morphogenesis. Medial arterial calcification (MAC) and abdominal aortic aneurysm (AAA) are two diseases where the structural and functional integrity of elastin is severely compromised. Although the clinical presentation of MAC and AAA differ, they have one common underlying causative mechanism---pathological degradation of elastin. Hence prevention of elastin degradation in the early stages of MAC and AAA can mitigate, partially if not wholly, the fatal consequences of both the diseases. The work presented here is motivated by the overwhelming statistics of people afflicted by elastin associated cardiovascular diseases and the unavailability of cure for the same. Overall goal of our research is to understand role of elastin degradation in cardiovascular diseases and to develop a targeted vascular drug delivery system that is minimally invasive, biodegradable, and non-toxic, that prevents elastin from degradation. Our hope is that such treatment will also help regenerate elastin, thereby providing a multi-fold treatment option for elasto-degenerative vascular diseases. For this purpose, we have first confirmed the combined role of degraded elastin and hyperglycemia in the pathogenesis of MAC. We have shown that in the absence of degraded elastin and TGF-beta1 (abundantly present in diabetic arteries) vascular smooth muscle cells maintain their homeostatic state, regardless of environmental glucose concentrations. However simultaneous exposure to glucose, elastin peptides and TGF-beta1 causes the pathological transgenesis of vascular cells to osteoblast-like cells. We show that plant derived polyphenols bind to vascular elastin with great affinity resulting in improved resistance to elastolytic digestion. We further show that the same polyphenols interact with monomeric tropoelastin released by the vascular cells and dramatically increasing their self-assembly in-vitro. In addition, we demonstrate the elastogenic ability of these polyphenols in aiding the crosslinking of tropoelastin released by aneurysmal cells converting it into mature elastin. Finally, we developed a nanoparticle system functionalized with elastin antibody on the surface that, upon systemic delivery, can recognize and bind to sites of damaged elastin in the aorta. We are able to show that this nanoparticle system works in representative animal models for MAC and AAA. These nanoparticles demonstrated spatial and functional specificity for degraded elastin. In conclusion, our work is focused on understanding the role of elastin degradation in vascular calcification and aortic aneurysms. We tested approaches to halt elastin degradation and to regenerate elastin in arteries so that homeostasis can be achieved.

Effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration of sevoflurane in dogs.

PubMed

Yamashita, Kazuto; Okano, Yoshihiko; Yamashita, Maiko; Umar, Mohammed A; Kushiro, Tokiko; Muir, William W

2008-01-01

Sparing effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration (MAC) of sevoflurane were determined in 6 dogs. Anesthesia was induced and maintained with sevoflurane in oxygen, and MAC was determined by use of a tail clamp method. The dogs were administered a subcutaneous injection of carprofen (4 mg/kg) or meloxicam (0.2 mg/kg), or no medication (control) one hour prior to induction of anesthesia. Following the initial determination of MAC, butorphanol (0.3 mg/kg) was administered intramuscularly, and MAC was determined again. The sevoflurane MACs for carprofen alone (2.10 +/- 0.26%) and meloxicam alone (2.06 +/- 0.20%) were significantly less than the control (2.39 +/- 0.26%). The sevoflurane MACs for the combination of carprofen with butorphanol (1.78 +/- 0.20%) and meloxicam with butorphanol (1.66 +/- 0.29%) were also significantly less than the control value after the administration of butorphanol (2.12 +/- 0.28%). The sevoflurane sparing effects of the combinations of carprofen with butorphanol and meloxicam with butorphanol were additive.

Maximal Aortic Valve Cusp Separation and Severity of Aortic Stenosis

PubMed Central

Dilu, VP; George, Raju

2017-01-01

Introduction An integrated approach that incorporates two dimensional, M mode and Doppler echocardiographic evaluation has become the standard means for accurate quantification of severity of valvular aortic stenosis. Maximal separation of the aortic valve cusps during systole has been shown to correlate well with the severity of aortic stenosis measured by other echocardiographic parameters. Aim To study the correlation between Maximal Aortic valve Cusp Separation (MACS) and severity of aortic valve stenosis and to find cut-off values of MACS for detecting severe and mild aortic stenosis. Materials and Methods In the present prospective observational study, we have compared the accuracy of MACS distance and the aortic valve area calculated by continuity equation in 59 patients with varying degrees of aortic valve stenosis. Aortic leaflet separation in M mode was identified as the distance between the inner edges of the tips of these structures at mid systole in the parasternal long axis view. Cuspal separation was also measured in 2D echocardiography from the parasternal long axis view and the average of the two values was taken as the MACS. Patients were grouped into mild, moderate and severe aortic stenosis based on the aortic valve area calculated by continuity equation. The resultant data regarding maximal leaflet separation on cross-sectional echocardiogram was then subjected to linear regression analysis in regard to correlation with the peak transvalvular aortic gradient as well as the calculated aortic valve area. A cut-off value for each group was derived using ROC curve. Results There was a strong correlation between MACS and aortic valve area measured by continuity equation and the peak and mean transvalvular aortic gradients. Mean MACS was 6.89 mm in severe aortic stenosis, 9.97 mm in moderate aortic stenosis and 12.36 mm in mild aortic stenosis. MACS below 8.25 mm reliably predicted severe aortic stenosis, with high sensitivity, specificity and positive predictive value. MACS above 11.25 mm practically ruled out significant aortic stenosis. Conclusion Measurement of MACS is a simple echocardio-graphic method to assess the severity of valvular aortic stenosis, with high sensitivity and specificity. MACS can be extremely useful in two clinical situations as a simple screening tool for assessment of stenosis severity and also helps in decision making non invasively when there is discordance between the other echocardiographic parameters of severity of aortic stenosis. PMID:28764221

Plasmacytoid Dendritic Cell Infection and Sensing Capacity during Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infection

PubMed Central

Jochems, Simon P.; Jacquelin, Beatrice; Chauveau, Lise; Huot, Nicolas; Petitjean, Gaël; Lepelley, Alice; Liovat, Anne-Sophie; Ploquin, Mickaël J.; Cartwright, Emily K.; Bosinger, Steven E.; Silvestri, Guido; Barré-Sinoussi, Françoise; Lebon, Pierre; Schwartz, Olivier

2015-01-01

ABSTRACT Human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques (MAC) lead to chronic inflammation and AIDS. Natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM), are protected against SIV-induced chronic inflammation and AIDS. Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC and human pDC. Despite this, AGM pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both AGM and SM pDC were found to be, in contrast to MAC pDC, predominantly negative for CCR5. Despite such limited CD4 and CCR5 expression, lymphoid tissue pDC were infected to a degree similar to that seen with CD4+ T cells in both MAC and AGM. Altogether, our finding of efficient pDC infection by SIV in vivo identifies pDC as a potential viral reservoir in lymphoid tissues. We discovered low expression of CD4 on AGM pDC, which did not preclude efficient sensing of host-adapted viruses. Therefore, pDC infection and efficient sensing are not prerequisites for chronic inflammation. The high level of pDC infection by SIVagm suggests that if CCR5 paucity on immune cells is important for nonpathogenesis of natural hosts, it is possibly not due to its role as a coreceptor. IMPORTANCE The ability of certain key immune cell subsets to resist infection might contribute to the asymptomatic nature of simian immunodeficiency virus (SIV) infection in its natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM). This relative resistance to infection has been correlated with reduced expression of CD4 and/or CCR5. We show that plasmacytoid dendritic cells (pDC) of natural hosts display reduced CD4 and/or CCR5 expression, unlike macaque pDC. Surprisingly, this did not protect AGM pDC, as infection levels were similar to those found in MAC pDC. Furthermore, we show that AGM pDC did not consistently produce type I interferon (IFN-I) upon heterologous SIVmac/HIV type 1 (HIV-1) encounter, while they sensed autologous SIVagm isolates. Pseudotyping SIVmac/HIV-1 overcame this deficiency, suggesting that reduced uptake of heterologous viral strains underlays this lack of sensing. The distinct IFN-I responses depending on host species and HIV/SIV isolates reveal the host/virus species specificity of pDC sensing. PMID:25903334

High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse.

PubMed

Machaczka, Maciej; Johansson, Jan-Erik; Remberger, Mats; Hallböök, Helene; Lazarevic, Vladimir Lj; Wahlin, Björn Engelbrekt; Omar, Hamdy; Wahlin, Anders; Juliusson, Gunnar; Kimby, Eva; Hägglund, Hans

2013-12-01

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.

Real-time imaging of Toxoplasma-infected human monocytes under fluidic shear stress reveals rapid translocation of intracellular parasites across endothelial barriers

PubMed Central

Ueno, Norikiyo; Harker, Katherine S.; Clarke, Elizabeth V.; McWhorter, Frances Y.; Liu, Wendy F.; Tenner, Andrea J.; Lodoen, Melissa B.

2014-01-01

Summary Peripheral blood monocytes are actively infected by Toxoplasma gondii and can function as “Trojan horses” for parasite spread in the bloodstream. Using dynamic live-cell imaging, we visualized the transendothelial migration (TEM) of T. gondii-infected primary human monocytes during the initial minutes following contact with human endothelium. On average, infected and uninfected monocytes required only 9.8 and 4.1 minutes, respectively, to complete TEM. Infection increased monocyte crawling distances and velocities on endothelium, but overall TEM frequencies were comparable between infected and uninfected cells. In the vasculature, monocytes adhere to endothelium under the conditions of shear stress found in rapidly flowing blood. Remarkably, the addition of fluidic shear stress increased the TEM frequency of infected monocytes 4.5-fold compared to static conditions (to 45.2% from 10.3%). Infection led to a modest increase in expression of the high affinity conformation of the monocyte integrin Mac-1, and Mac-1 accumulated near endothelial junctions during TEM. Blocking Mac-1 inhibited the crawling and TEM of infected monocytes to a greater degree than uninfected monocytes, and blocking the Mac-1 ligand, ICAM-1, dramatically reduced crawling and TEM for both populations. These findings contribute to a greater understanding of parasite dissemination from the vasculature into tissues. PMID:24245749

[Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

PubMed

Xu, Si-Miao; Yang, Yang; Zhou, Mi; Zhao, Xue-Jiao; Qin, Yu; Zhang, Pei-Ling; Yuan, Rui-Feng; Zhou, Jian-Feng; Fang, Yong

2013-10-01

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

Matrix-assisted cocrystallization (MAC) simultaneous production and formulation of pharmaceutical cocrystals by hot-melt extrusion.

PubMed

Boksa, Kevin; Otte, Andrew; Pinal, Rodolfo

2014-09-01

A novel method for the simultaneous production and formulation of pharmaceutical cocrystals, matrix-assisted cocrystallization (MAC), is presented. Hot-melt extrusion (HME) is used to create cocrystals by coprocessing the drug and coformer in the presence of a matrix material. Carbamazepine (CBZ), nicotinamide (NCT), and Soluplus were used as a model drug, coformer, and matrix, respectively. The MAC product containing 80:20 (w/w) cocrystal:matrix was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. A partial least squares (PLS) regression model was developed for quantifying the efficiency of cocrystal formation. The MAC product was estimated to be 78% (w/w) cocrystal (theoretical 80%), with approximately 0.3% mixture of free (unreacted) CBZ and NCT, and 21.6% Soluplus (theoretical 20%) with the PLS model. A physical mixture (PM) of a reference cocrystal (RCC), prepared by precipitation from solution, and Soluplus resulted in faster dissolution relative to the pure RCC. However, the MAC product with the exact same composition resulted in considerably faster dissolution and higher maximum concentration (∼five-fold) than those of the PM. The MAC product consists of high-quality cocrystals embedded in a matrix. The processing aspect of MAC plays a major role on the faster dissolution observed. The MAC approach offers a scalable process, suitable for the continuous manufacturing and formulation of pharmaceutical cocrystals. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid: single biomarker re-derivation and external validation in three cohorts

PubMed Central

Body, Richard; Sperrin, Matthew; Lewis, Philip S; Burrows, Gillian; Carley, Simon; McDowell, Garry; Buchan, Iain; Greaves, Kim; Mackway-Jones, Kevin

2017-01-01

Background The original Manchester Acute Coronary Syndromes model (MACS) ‘rules in’ and ‘rules out’ acute coronary syndromes (ACS) using high sensitivity cardiac troponin T (hs-cTnT) and heart-type fatty acid binding protein (H-FABP) measured at admission. The latter is not always available. We aimed to refine and validate MACS as Troponin-only Manchester Acute Coronary Syndromes (T-MACS), cutting down the biomarkers to just hs-cTnT. Methods We present secondary analyses from four prospective diagnostic cohort studies including patients presenting to the ED with suspected ACS. Data were collected and hs-cTnT measured on arrival. The primary outcome was ACS, defined as prevalent acute myocardial infarction (AMI) or incident death, AMI or coronary revascularisation within 30 days. T-MACS was built in one cohort (derivation set) and validated in three external cohorts (validation set). Results At the ‘rule out’ threshold, in the derivation set (n=703), T-MACS had 99.3% (95% CI 97.3% to 99.9%) negative predictive value (NPV) and 98.7% (95.3%–99.8%) sensitivity for ACS, ‘ruling out’ 37.7% patients (specificity 47.6%, positive predictive value (PPV) 34.0%). In the validation set (n=1459), T-MACS had 99.3% (98.3%–99.8%) NPV and 98.1% (95.2%–99.5%) sensitivity, ‘ruling out’ 40.4% (n=590) patients (specificity 47.0%, PPV 23.9%). T-MACS would ‘rule in’ 10.1% and 4.7% patients in the respective sets, of which 100.0% and 91.3% had ACS. C-statistics for the original and refined rules were similar (T-MACS 0.91 vs MACS 0.90 on validation). Conclusions T-MACS could ‘rule out’ ACS in 40% of patients, while ‘ruling in’ 5% at highest risk using a single hs-cTnT measurement on arrival. As a clinical decision aid, T-MACS could therefore help to conserve healthcare resources. PMID:27565197

A New Local Debonding Model with Application to the Transverse Tensile and Creep Behavior of Continuously Reinforced Titanium Composites

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M.

2000-01-01

A new, widely applicable model for local interfacial debonding in composite materials is presented. Unlike its direct predecessors, the new model allows debonding to progress via unloading of interfacial stresses even as global loading of the composite continues. Previous debonding models employed for analysis of titanium matrix composites are surpassed by the accuracy, simplicity, and efficiency demonstrated by the new model. The new model was designed to operate seamlessly within NASA Glenn's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC), which was employed to simulate the time- and rate-dependent (viscoplastic) transverse tensile and creep behavior of SiC/Ti composites. MAC/GMC's ability to simulate the transverse behavior of titanium matrix composites has been significantly improved by the new debonding model. Further, results indicate the need for a more accurate constitutive representation of the titanium matrix behavior in order to enable predictions of the composite transverse response, without resorting to recalibration of the debonding model parameters.

Assessing the effectiveness of low-pressure ultraviolet light for inactivating Mycobacterium avium complex (MAC) micro-organisms

EPA Science Inventory

Aims: To assess low-pressure ultraviolet light (LP-UV) inactivation kinetics of Mycobacterium avium complex (MAC) strains in a water matrix using collimated beam apparatus. Methods and Results: Strains of M. avium (n = 3) and Mycobacterium intracellulare (n = 2) were exposed t...

A retrospective study comparing histopathological and immunopathological features of nasal planum dermatitis in 20 dogs with discoid lupus erythematosus or leishmaniosis.

PubMed

De Lucia, Michela; Mezzalira, Giorgia; Bardagí, Mar; Fondevila, Dolors M; Fabbri, Elisabetta; Fondati, Alessandra

2017-04-01

In areas endemic for leishmaniosis, discoid lupus erythematosus (DLE) and canine leishmaniosis (CanL) are the most common differential diagnoses for nasal planum erosive-ulcerative dermatitis in dogs. To compare histopathological and immunopathological features of canine nasal planum erosive-ulcerative dermatitis with depigmentation due to DLE or CanL. Nasal planum biopsies from dogs with nasal planum loss of architecture, depigmentation, swelling, erosions or ulcerations due to DLE (n = 14) or CanL (n = 6). Sections of paraffin-embedded samples, stained with haematoxylin and eosin were reviewed. Samples were examined using antibodies targeting T cells (CD3), B cells (CD20), macrophages (Mac387) and class II major histocompatibility complex (MHC II). Histopathological and immunophenotypical findings were compared between DLE and CanL cases. Lichenoid and interface dermatitis were observed in both DLE and CanL cases. A nodular-to-diffuse, superficial and/or deep dermatitis with macrophages, lymphocytes and plasma cells was present only in CanL samples. CD20-positive cells predominated over CD3- and Mac387-positive cells in the two conditions. The percentage of dermal Mac387-positive cells was higher in CanL compared to DLE samples and the difference was statistically significant (P = 0.025). In this study, similar histopathological and immunopathological findings were observed in dogs with nasal planum lesions due to DLE or CanL. Therefore, in areas endemic for leishmaniosis, the presence of the parasite should be investigated in canine nasal planum dermatitis showing clinical and histopathological features suggestive of DLE. © 2017 ESVD and ACVD.

[Allogeneic hematopoietic stem cell transplantation using myeloablative conditioning including total body irradiation for pediatric acute lymphoblastic leukemia: a single-center retrospective analysis].

PubMed

Honda, Mamoru; Arakawa, Yuki; Kawakami, Ryota; Itabashi, Toshikazu; Yanagi, Masato; Sasaki, Koji; Watanabe, Kentaro; Isobe, Kiyotaka; Mori, Makiko; Hanada, Ryoji; Koh, Katsuyoshi

2018-01-01

This study aimed to investigate the clinical outcomes of hematopoietic stem cell transplantation (HSCT) with total body irradiation-based myeloablative conditioning (TBI-MAC) in pediatric patients with acute lymphoblastic leukemia (ALL). We retrospectively examined patients with ALL who underwent HSCT with TBI-MAC from January 2000 to August 2016 at our institute. We enrolled 67 patients with a median follow-up period of 8 years. The 5-year event-free survival (EFS) and overall survival (OS) were 51.2% and 59.6%, respectively. At the first complete remission, HSCT exhibited significantly superior EFS and OS in our patients than that in patients with other diseases. We encountered 57.9% of patients with at least one late complication. Major late complications were short stature (26.3%) and hypogonadism (18.4%). While late complications were observed in several recipients of HSCT, late complication-related deaths occurred in three patients. The TBI-MAC regimen led to favorable clinical outcomes in pediatric patients with ALL who underwent HSCT. Thus, proper evaluation and management of late complications are mandatory.

Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease.

PubMed

Bachanova, V; Marks, D I; Zhang, M-J; Wang, H; de Lima, M; Aljurf, M D; Arellano, M; Artz, A S; Bacher, U; Cahn, J-Y; Chen, Y-B; Copelan, E A; Drobyski, W R; Gale, R P; Greer, J P; Gupta, V; Hale, G A; Kebriaei, P; Lazarus, H M; Lewis, I D; Lewis, V A; Liesveld, J L; Litzow, M R; Loren, A W; Miller, A M; Norkin, M; Oran, B; Pidala, J; Rowe, J M; Savani, B N; Saber, W; Vij, R; Waller, E K; Wiernik, P H; Weisdorf, D J

2014-03-01

The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.

Intranasally delivered small interfering RNA-mediated suppression of scavenger receptor Mac-1 attenuates microglial phenotype switching and working memory impairment following hypoxia.

PubMed

Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B

2018-05-05

Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene. Here, we implicate Mac-1 scavenger receptor in microglial phenotype switching, neurodegeneration in prefrontal cortex, hippocampus and working memory impairment. RNA mediated silencing of Mac-1 in both in vitro and in vivo model showed significant impact of it on hypoxia induced altered expression of Mac-1 endogenous ligand, signaling cascade proteins, transcription factors and NADPH oxidase pathway. Efficient degradation of Mac-1 mRNA suppressed expression of M1 phenotypic markers, inflammatory chemokines, and cytokines, but on the other hand, it upregulated M2 phenotypic markers and anti-inflammatory cytokines. Neuronal viability and synaptic plasticity markers were also modulated significantly by this strategy. Behavioral study revealed significant downregulation in the number of working memory errors at a time-dependent manner after silencing the Mac-1 gene during continuous hypoxic exposure. The novel findings of this study for the very first time, unmasked the role of Mac-1 receptor in neurodegenerative disease progression under hypoxic condition and at the same time indicated the potential therapeutic value of this non-invasive siRNA delivery approach for treating working memory loss. Copyright © 2018 Elsevier Ltd. All rights reserved.

Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

PubMed

Westerterp, Marit; Murphy, Andrew J; Wang, Mi; Pagler, Tamara A; Vengrenyuk, Yuliya; Kappus, Mojdeh S; Gorman, Darren J; Nagareddy, Prabhakara R; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S; Welch, Carrie; Fisher, Edward A; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R

2013-05-24

Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling

PubMed Central

Shynlova, Oksana; Nedd-Roderique, Tamara; Li, Yunqing; Dorogin, Anna; Nguyen, Tina; Lye, Stephen J

2013-01-01

Leucocyte infiltration in the decidua (maternal–foetal interface) before, during and after term (TL) and preterm labour (PTL) was studied in mouse. We also investigated the mechanism of peripheral leucocyte recruitment into decidua by analysing the tissue cytokine profiles. Decidual tissues were collected during late gestation, TL and post-partum (PP). PTL was initiated on gestational day 15 by intrauterine injection of Lipopolysaccharide (LPS, 125 μg) or progesterone signalling antagonism by RU486. Animals were killed during PTL or PP. Decidua basalis was analysed using FACS and immunohistochemistry. Markers of myeloid cell differentiation (Gr1, Ly6G, Neu7/4, F4/80) were assessed to define tissue monocytes (M), neutrophils (N) and macrophages (Macs). Flow cytometry revealed a significant (P < 0.05) increase in decidual Macs prior to TL; M and N numbers increased during TL and further increased during PP, which correlated with immunohistochemistry data. Massive influx of N, but not Macs and M, was detected by FACS during LPS-PTL (P < 0.05) but not RU486-PTL. Highest levels of N infiltration into the decidua occurred PP in both LPS and RU486 groups. Decidual infiltration during TL and RU486-PTL was accompanied by an increase in pro-inflammatory cytokines (IL1b and IL6) and CCL2 chemokine; LPS-PTL showed increases in multiple cytokines. PP period following TL and PTL was associated with further up-regulation of multiple cytokines/chemokines (P < 0.05). Our data suggest a programme of myeloid cells involvement in parturition with the pre-partum influx of Macs into the decidua contributing to the progression of labour, whereas the later influx of M and N contribute to PP decidual involution. PMID:23379349

Isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina L.).

PubMed

Saaby, Lasse; Jäger, Anna Katharina; Moesby, Lise; Hansen, Erik Wind; Christensen, Søren Brøgger

2011-02-01

A previously published systematic review and a metaanalysis have concluded that the consumption of standardized rose hip powder (Rosa canina L.) can reduce pain in osteoarthritis patients. Synovial inflammation has been suggested to play an important role in the pathogenesis of osteoarthritis and mainly to involve infiltration of the synovial membrane by macrophages. Therefore, the immunomodulatory effect of standardized rose hip powder of Rosa canina L. was investigated and active principles isolated using the Mono Mac 6 cell line as a model for human macrophages. Treatment of Mono Mac 6 cells with the residue of a crude dichloromethane extract of rose hip powder significantly and concentration dependently inhibited the lipopolysaccharide induced interleukin-6 release. Through bioassay-guided fractionation the immunomodulatory effect of the dichloromethane extract was correlated to a mixture of three triterpene acids; oleanolic acid, betulinic acid and ursolic acid (IC(50) 21 ± 6 µm). Further studies revealed that only oleanolic acid and ursolic acid, but not betulinic acid, could inhibit the lipopolysaccharide induced interleukin-6 release from Mono Mac 6 cells when tested separately. Combination of either oleanolic acid or ursolic acid with betulinic acid enhanced the immunomodulatory effect of the two triterpene acids. Copyright © 2010 John Wiley & Sons, Ltd.

Computational Fluid Dynamics Modeling of a Supersonic Nozzle and Integration into a Variable Cycle Engine Model

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Friedlander, David; Kopasakis, George

2015-01-01

This paper covers the development of an integrated nonlinear dynamic simulation for a variable cycle turbofan engine and nozzle that can be integrated with an overall vehicle Aero-Propulso-Servo-Elastic (APSE) model. A previously developed variable cycle turbofan engine model is used for this study and is enhanced here to include variable guide vanes allowing for operation across the supersonic flight regime. The primary focus of this study is to improve the fidelity of the model's thrust response by replacing the simple choked flow equation convergent-divergent nozzle model with a MacCormack method based quasi-1D model. The dynamic response of the nozzle model using the MacCormack method is verified by comparing it against a model of the nozzle using the conservation element/solution element method. A methodology is also presented for the integration of the MacCormack nozzle model with the variable cycle engine.

Computational Fluid Dynamics Modeling of a Supersonic Nozzle and Integration into a Variable Cycle Engine Model

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Friedlander, David; Kopasakis, George

2014-01-01

This paper covers the development of an integrated nonlinear dynamic simulation for a variable cycle turbofan engine and nozzle that can be integrated with an overall vehicle Aero-Propulso-Servo-Elastic (APSE) model. A previously developed variable cycle turbofan engine model is used for this study and is enhanced here to include variable guide vanes allowing for operation across the supersonic flight regime. The primary focus of this study is to improve the fidelity of the model's thrust response by replacing the simple choked flow equation convergent-divergent nozzle model with a MacCormack method based quasi-1D model. The dynamic response of the nozzle model using the MacCormack method is verified by comparing it against a model of the nozzle using the conservation element/solution element method. A methodology is also presented for the integration of the MacCormack nozzle model with the variable cycle engine.

Integration of active and passive cool roof system for attic temperature reduction

NASA Astrophysics Data System (ADS)

Yew, Ming Chian; Yew, Ming Kun; Saw, Lip Huat; Durairaj, Rajkumar

2017-04-01

The aim of this project is to study the capability of cool roof system in the reduction of heat transmission through metal roof into an attic. The cool roof system is designed in active and passive methods to reduce the thermal loads imposed to a building. Two main features are introduced to this cool roof system, which is thermal insulation coating (TIC) and moving air cavity (MAC) that served as active and passive manner, respectively. For MAC, two designs are introduced. Normal MAC is fabricated by six aluminium tubes whereby each aluminium tube is made up by sticking up of five aluminium cans. While improved MAC is also made by six aluminium tubes whereby each aluminium tube is custom made from steel rods and aluminium foils. MAC provides ventilation and heat reflection under the metal roof before the heat transfer into attic. It also coupled with three solar powered fans to increase heat flow inside the channel. The cool roof that incorporated TIC, MAC with solar powered fans and opened attic inlet showed a significant improvement with a reduction of up to 14 °C in the attic temperature compared to conventional roof system.

Musculoskeletal injuries sustained in modern army combatives.

PubMed

Possley, Daniel R; Johnson, Anthony E

2012-01-01

Participation in martial arts has grown over the past 15 years with an estimated 8 million participants. In 2004, the Chief of Staff of the Army directed that all Initial Military Training soldiers receive Modern Army Combatives (MAC) training. The mechanical differences between the various martial arts styles incorporated into mixed martial arts/MAC pose challenges to the medical professional. We report the incidence of musculoskeletal injuries by Level 1 and 2 trained active duty soldiers participating in MAC over a 3-year period. From June 1, 2005 to January 1, 2009, the Orthopaedic Surgery service treated and tracked all injuries in MAC. Data was analyzed using the Chi(2) method of analysis. (p < 0.05). 155 of 1,025 soldiers presenting with MAC injuries reported inability to perform their military occupation specialty duties. The knee was most frequently injured followed by shoulder. Surgical intervention was warranted 24% of the time. Participants in MAC reported injuries severe enough to impact occupational duties at 15.5%. Surgical intervention was warranted only 24% of the time. The knee and shoulder are the most frequently injured body parts. Labral repair was the most frequent surgical procedure.

Design and FPGA implementation for MAC layer of Ethernet PON

NASA Astrophysics Data System (ADS)

Zhu, Zengxi; Lin, Rujian; Chen, Jian; Ye, Jiajun; Chen, Xinqiao

2004-04-01

Ethernet passive optical network (EPON), which represents the convergence of low-cost, high-bandwidth and supporting multiple services, appears to be one of the best candidates for the next-generation access network. The work of standardizing EPON as a solution for access network is still underway in the IEEE802.3ah Ethernet in the first mile (EFM) task force. The final release is expected in 2004. Up to now, there has been no standard application specific integrated circuit (ASIC) chip available which fulfills the functions of media access control (MAC) layer of EPON. The MAC layer in EPON system has many functions, such as point-to-point emulation (P2PE), Ethernet MAC functionality, multi-point control protocol (MPCP), network operation, administration and maintenance (OAM) and link security. To implement those functions mentioned above, an embedded real-time operating system (RTOS) and a flexible programmable logic device (PLD) with an embedded processor are used. The software and hardware functions in MAC layer are realized through programming embedded microprocessor and field programmable gate array(FPGA). Finally, some experimental results are given in this paper. The method stated here can provide a valuable reference for developing EPON MAC layer ASIC.

Reliable Acquisition of RAM Dumps from Intel-Based Apple Mac Computers over FireWire

NASA Astrophysics Data System (ADS)

Gladyshev, Pavel; Almansoori, Afrah

RAM content acquisition is an important step in live forensic analysis of computer systems. FireWire offers an attractive way to acquire RAM content of Apple Mac computers equipped with a FireWire connection. However, the existing techniques for doing so require substantial knowledge of the target computer configuration and cannot be used reliably on a previously unknown computer in a crime scene. This paper proposes a novel method for acquiring RAM content of Apple Mac computers over FireWire, which automatically discovers necessary information about the target computer and can be used in the crime scene setting. As an application of the developed method, the techniques for recovery of AOL Instant Messenger (AIM) conversation fragments from RAM dumps are also discussed in this paper.

Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease

PubMed Central

Matsumura, Yoko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Yasui, Satsuki; Mochida, Naoko; Nakano, Ryuichi; Kasahara, Kei; Tomoda, Koichi; Yano, Hisakazu; Kayano, Shin-ichi

2017-01-01

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection. PMID:28827842

Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease.

PubMed

Matsumura, Yoko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Yasui, Satsuki; Mochida, Naoko; Nakano, Ryuichi; Kasahara, Kei; Tomoda, Koichi; Yano, Hisakazu; Kayano, Shin-Ichi; Ito, Toshihiro

2017-01-01

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection.

Sitting position does not alter minimum alveolar concentration for desflurane.

PubMed

Lin, Chun-Ming; Wu, Chieh-Tsai; Lee, Shih-Tseng; Lui, Tai-Ngar; Huang, Chia-Chun; Li, Allen Hon-Lun; Doufas, Anthony G

2007-07-01

Hypotension is a common complication of the sitting position during anesthesia, and is often counteracted by decreasing anesthetic depth, thereby exposing patients to the risk of being inadequately anesthetized. Baroreceptor unloading and the consequent sympathoexcitation, as during head up tilt, decreases pain threshold and arouses the central nervous system (CNS), whereas hypotension exerts a direct CNS depressant effect. We estimated the minimal alveolar concentration (MAC) of desflurane for immobility in patients undergoing surgery in the sitting position, in comparison to MAC desflurane for patients having a similar type of surgery in the supine position. The Dixon up-and-down method was used to evaluate the MAC for desflurane in patients undergoing cervical spine laminoplasty (n = 24) or discectomy (n = 24) in the sitting and supine positions, respectively. Logistic regression with co-variate adjustment was employed to examine if the two positions (sitting and supine) have different or share the same concentration vs response relationship for immobility. Monte Carlo simulation was used to calculate 95% confidence intervals (CI) for the MAC in each position, and to estimate the difference in MAC (delta MAC) between the sitting and supine positions. Modeling both sitting [6.54% (6.50-6.66, 95% CI)] and supine [6.70 (6.55-6.81)] patients as having different MAC concentrations did not significantly improve our simplified model, which treats the two patient groups as one [6.61 (6.52-6.70), delta -2 log likelihood = 2.735, P = 0.098]. Mean delta MAC (95% CI) was -0.14 (-0.30, 0.03). The sitting position does not change desflurane anesthetic requirements for immobility.

The periplasmic membrane proximal domain of MacA acts as a switch in stimulation of ATP hydrolysis by MacB transporter.

PubMed

Modali, Sita D; Zgurskaya, Helen I

2011-08-01

Escherichia coli MacAB-TolC is a tripartite macrolide efflux transporter driven by hydrolysis of ATP. In this complex, MacA is the periplasmic membrane fusion protein that stimulates the activity of MacB transporter and establishes the link with the outer membrane channel TolC. The molecular mechanism by which MacA stimulates MacB remains unknown. Here, we report that the periplasmic membrane proximal domain of MacA plays a critical role in functional MacA-MacB interactions and stimulation of MacB ATPase activity. Binding of MacA to MacB stabilizes the ATP-bound conformation of MacB, whereas interactions with both MacB and TolC affect the conformation of MacA. A single G353A substitution in the C-terminus of MacA inactivates MacAB-TolC function by changing the conformation of the membrane proximal domain of MacA and disrupting the proper assembly of the MacA-MacB complex. We propose that MacA acts in transport by promoting MacB transition into the closed ATP-bound conformation and in this respect, is similar to the periplasmic solute-binding proteins. © 2011 Blackwell Publishing Ltd.

The periplasmic membrane proximal domain of MacA acts as a switch in stimulation of ATP hydrolysis by MacB transporter

PubMed Central

Modali, Sita D.; Zgurskaya, Helen I.

2011-01-01

Escherichia coli MacAB-TolC is a tri-partite macrolide efflux transporter driven by hydrolysis of ATP. In this complex, MacA is the periplasmic membrane fusion protein that stimulates the activity of MacB transporter and establishes the link with the outer membrane channel TolC. The molecular mechanism by which MacA stimulates MacB remains unknown. Here, we report that the periplasmic membrane proximal domain of MacA plays a critical role in functional MacA-MacB interactions and stimulation of MacB ATPase activity. Binding of MacA to MacB stabilizes the ATP-bound conformation of MacB, whereas interactions with both MacB and TolC affect the conformation of MacA. A single G353A substitution in the C-terminus of MacA inactivates MacAB-TolC function by changing the conformation of the membrane proximal domain of MacA and disrupting the proper assembly of the MacA-MacB complex. We propose that MacA acts in transport by promoting MacB transition into the closed ATP-bound conformation and in this respect, is similar to the periplasmic solute-binding proteins. PMID:21696464

Estimation of the mass absorption cross-section of the black and brown carbon aerosols during GoPoEx 2014

NASA Astrophysics Data System (ADS)

Cho, C.; Kim, S. W.; Lee, M.; Gustafsson, O.; Fang, W.

2017-12-01

Black carbon (BC) is a major contributor to the atmospheric heating by absorbing the solar radiation. According to recent studies, the solar absorption of brown carbon (BrC) is not negligible and even comparable to that of BC at visible to UV wavelengths, but most optical instruments that quantify light absorption are unable to distinguish each other. Thus, light absorption properties of BC or BrC usually have been studied through modeling researches by using mass absorption cross-section (MAC). Although MAC has a large spatial and temporal variability, most modeling studies have used a specific value of BC MAC and even the absorption by BrC is seldom considered in most chemical and climate models. The generalization of modeling research can lead to serious errors of radiative forcing by BC and BrC. In this study, MAC of BC and BrC are separately determined and the contribution of BC and BrC on aerosol light absorption are estimated from co-located simultaneous in-situ measurements, COSMOS, CLAP and Sunset EC/OC analyzer, at Gosan climate observatory, Korea during Gosan Pollution Experiment in January 2014 (GoPoEx 2014). At 565 nm, MAC of BC is found to be about 6.4±1.5 m2 g-1 from COSMOS and Sunset EC/OC analyzer measurements. This value is similar to those from previous studies in China (Cui et al., STE, 2016), but lower than those observed to be ranged 10-18 m2 g-1 in America or Europe (Lack et al., PNAS, 2012). Aerosol absorption coefficient (AAC) and BC mass concentration from COSMOS, meanwhile, are approximately 15-20% lower than those of CLAP. This difference can be attributable to the contribution of BrC. The MAC of BrC was calculated using the absorption coefficient of BrC and by the following three methods: (1) the difference of mass concentration from Aethalometer and COSMOS applied new BC MAC of this study, (2) The mass concentration of water-soluble organic carbon, (3) a method using the mass concentration of organic carbon suggested by Chung et al. (ACP, 2012). The MAC of BrC values obtained from the three methods ranged from 1.0 m2 g-1 to 1.5 m2 g-1 at 565 nm which is slightly higher than those from previous studies (Srinivas et al., AE, 2016). The contribution of BC to AAC is estimated to be about 85-90%, while BrC accounts for about 10-15% of total AAC, having increases about 1% of BrC contribution when the BrC MAC value increases 10%.

Efficient Numerical Methods for Nonlinear-Facilitated Transport and Exchange in a Blood-Tissue Exchange Unit

PubMed Central

Poulain, Christophe A.; Finlayson, Bruce A.; Bassingthwaighte, James B.

2010-01-01

The analysis of experimental data obtained by the multiple-indicator method requires complex mathematical models for which capillary blood-tissue exchange (BTEX) units are the building blocks. This study presents a new, nonlinear, two-region, axially distributed, single capillary, BTEX model. A facilitated transporter model is used to describe mass transfer between plasma and intracellular spaces. To provide fast and accurate solutions, numerical techniques suited to nonlinear convection-dominated problems are implemented. These techniques are the random choice method, an explicit Euler-Lagrange scheme, and the MacCormack method with and without flux correction. The accuracy of the numerical techniques is demonstrated, and their efficiencies are compared. The random choice, Euler-Lagrange and plain MacCormack method are the best numerical techniques for BTEX modeling. However, the random choice and Euler-Lagrange methods are preferred over the MacCormack method because they allow for the derivation of a heuristic criterion that makes the numerical methods stable without degrading their efficiency. Numerical solutions are also used to illustrate some nonlinear behaviors of the model and to show how the new BTEX model can be used to estimate parameters from experimental data. PMID:9146808

Assessment of yeast Saccharomyces cerevisiae component binding to Mycobacterium avium subspecies paratuberculosis using bovine epithelial cells.

PubMed

Li, Ziwei; You, Qiumei; Ossa, Faisury; Mead, Philip; Quinton, Margaret; Karrow, Niel A

2016-03-01

Since yeast Saccharomyces cerevisiae and its components are being used for the prevention and treatment of enteric diseases in different species, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium spp. paratuberculosis (MAP). This study aimed to identify potential yeast derivatives that may be used to help prevent MAP infection. The adherence of mCherry-labeled MAP to bovine mammary epithelial cell line (MAC-T cells) and bovine primary epithelial cells (BECs) co-cultured with yeast cell wall components (CWCs) from four different yeast strains (A, B, C and D) and two forms of dead yeast from strain A was investigated. The CWCs from all four yeast strains and the other two forms of dead yeast from strain A reduced MAP adhesion to MAC-T cells and BECs in a concentration-dependent manner after 6-h of exposure, with the dead yeast having the greatest effect. The following in vitro binding studies suggest that dead yeast and its' CWCs may be useful for reducing risk of MAP infection.

Inter-Relationships of Functional Status in Cerebral Palsy: Analyzing Gross Motor Function, Manual Ability, and Communication Function Classification Systems in Children

ERIC Educational Resources Information Center

Hidecker, Mary Jo Cooley; Ho, Nhan Thi; Dodge, Nancy; Hurvitz, Edward A.; Slaughter, Jaime; Workinger, Marilyn Seif; Kent, Ray D.; Rosenbaum, Peter; Lenski, Madeleine; Messaros, Bridget M.; Vanderbeek, Suzette B.; Deroos, Steven; Paneth, Nigel

2012-01-01

Aim: To investigate the relationships among the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) in children with cerebral palsy (CP). Method: Using questionnaires describing each scale, mothers reported GMFCS, MACS, and CFCS levels in 222…

A VLSI implementation of DCT using pass transistor technology

NASA Technical Reports Server (NTRS)

Kamath, S.; Lynn, Douglas; Whitaker, Sterling

1992-01-01

A VLSI design for performing the Discrete Cosine Transform (DCT) operation on image blocks of size 16 x 16 in a real time fashion operating at 34 MHz (worst case) is presented. The process used was Hewlett-Packard's CMOS26--A 3 metal CMOS process with a minimum feature size of 0.75 micron. The design is based on Multiply-Accumulate (MAC) cells which make use of a modified Booth recoding algorithm for performing multiplication. The design of these cells is straight forward, and the layouts are regular with no complex routing. Two versions of these MAC cells were designed and their layouts completed. Both versions were simulated using SPICE to estimate their performance. One version is slightly faster at the cost of larger silicon area and higher power consumption. An improvement in speed of almost 20 percent is achieved after several iterations of simulation and re-sizing.

Design of the frame structure for a multiservice interactive system using ATM-PON

NASA Astrophysics Data System (ADS)

Nam, Jae-Hyun; Jang, Jongwook; Lee, Jung-Tae

1998-10-01

The MAC (Medium Access Control) protocol controls B-NT1s' (Optical Network Unit) access to the shared capacity on the PON, this protocol is very important if TDMA (Time Division Multiple Access) multiplexing is used on the upstream. To control the upstream traffic some kind of access protocol has to be implemented. There are roughly two different approaches to use request cells: in a collision free way or such that collisions in a request slot are allowed. It is the objective of this paper to describe a MAC-protocol structure that supports both approaches and hybrids of it. In our paper we grantee the QoS (Quality of Service) of each B-NT1 through LOC, LOV, LOA field that are the length field of the transmitted cell at each B-NT1. Each B-NT1 transmits its status of request on request cell.

Method of calculating gas dynamics and heat transfer in single stage refrigeration units

NASA Technical Reports Server (NTRS)

Zhitomirskiy, I. S.; Popolskiy, A. B.

1974-01-01

A generalized mathematical model of gas-dynamic and heat transfer processes in single-stage regenerative installations operating in Stirling, MacMahon, Gifford-MacMahon, and pulsating tube cycles is proposed. A numerical method os solving initial equations on a digital computer is given. This makes it possible to calculate the change in the thermodynamic parameters in the working cycle in different machine components, as well as the dependence of cold productivity on the temperature level in the steady regime.

Simulated single molecule microscopy with SMeagol.

PubMed

Lindén, Martin; Ćurić, Vladimir; Boucharin, Alexis; Fange, David; Elf, Johan

2016-08-01

SMeagol is a software tool to simulate highly realistic microscopy data based on spatial systems biology models, in order to facilitate development, validation and optimization of advanced analysis methods for live cell single molecule microscopy data. SMeagol runs on Matlab R2014 and later, and uses compiled binaries in C for reaction-diffusion simulations. Documentation, source code and binaries for Mac OS, Windows and Ubuntu Linux can be downloaded from http://smeagol.sourceforge.net johan.elf@icm.uu.se Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Comparison of equi-minimum alveolar concentration of sevoflurane and isoflurane on bispectral index values during both wash in and wash out phases: A prospective randomised study

PubMed Central

Gupta, Madhu; Shri, Iti; Sakia, Prashant; Govil, Deepika

2015-01-01

Background and Aims: At equal minimum alveolar concentration (MAC), volatile agents may produce different bispectral index (BIS) values especially at low BIS levels when the effect is volatile agent specific. The present study was performed to compare the BIS values produced by sevoflurane and isoflurane at equal MAC and thereby assessing which is a better hypnotic agent. Methods: Sixty American Society of Anaesthesiologists I and II patients undergoing elective mastoidectomy were divided into groups receiving either isoflurane or sevoflurane, and at equi-MAC. BIS value was measured during both wash in and wash out phase, keeping other parameters same. Statistical analysis was performed using the Friedman two-way analysis and Mann-Whitney U-test. A P < 0.05 was considered significant. Results: BIS value was significantly lower with sevoflurane at all MAC values as compared to isoflurane, except in the beginning and at MAC awake. However, both the drugs proved to be cardiostable. Conclusion: At equi-MAC sevoflurane produces lower BIS values during wash in as well as wash out phase as compared to isoflurane, reflecting probably an agent specific effect and a deficiency in BIS algorithm for certain agents and their interplay. PMID:25788739

Why not make a PC cluster of your own? 5. AppleSeed: A Parallel Macintosh Cluster for Scientific Computing

NASA Astrophysics Data System (ADS)

Decyk, Viktor K.; Dauger, Dean E.

We have constructed a parallel cluster consisting of Apple Macintosh G4 computers running both Classic Mac OS as well as the Unix-based Mac OS X, and have achieved very good performance on numerically intensive, parallel plasma particle-in-cell simulations. Unlike other Unix-based clusters, no special expertise in operating systems is required to build and run the cluster. This enables us to move parallel computing from the realm of experts to the mainstream of computing.

Automation of cellular therapy product manufacturing: results of a split validation comparing CD34 selection of peripheral blood stem cell apheresis product with a semi-manual vs. an automatic procedure.

PubMed

Hümmer, Christiane; Poppe, Carolin; Bunos, Milica; Stock, Belinda; Wingenfeld, Eva; Huppert, Volker; Stuth, Juliane; Reck, Kristina; Essl, Mike; Seifried, Erhard; Bonig, Halvard

2016-03-16

Automation of cell therapy manufacturing promises higher productivity of cell factories, more economical use of highly-trained (and costly) manufacturing staff, facilitation of processes requiring manufacturing steps at inconvenient hours, improved consistency of processing steps and other benefits. One of the most broadly disseminated engineered cell therapy products is immunomagnetically selected CD34+ hematopoietic "stem" cells (HSCs). As the clinical GMP-compliant automat CliniMACS Prodigy is being programmed to perform ever more complex sequential manufacturing steps, we developed a CD34+ selection module for comparison with the standard semi-automatic CD34 "normal scale" selection process on CliniMACS Plus, applicable for 600 × 10(6) target cells out of 60 × 10(9) total cells. Three split-validation processings with healthy donor G-CSF-mobilized apheresis products were performed; feasibility, time consumption and product quality were assessed. All processes proceeded uneventfully. Prodigy runs took about 1 h longer than CliniMACS Plus runs, albeit with markedly less hands-on operator time and therefore also suitable for less experienced operators. Recovery of target cells was the same for both technologies. Although impurities, specifically T- and B-cells, were 5 ± 1.6-fold and 4 ± 0.4-fold higher in the Prodigy products (p = ns and p = 0.013 for T and B cell depletion, respectively), T cell contents per kg of a virtual recipient receiving 4 × 10(6) CD34+ cells/kg was below 10 × 10(3)/kg even in the worst Prodigy product and thus more than fivefold below the specification of CD34+ selected mismatched-donor stem cell products. The products' theoretical clinical usability is thus confirmed. This split validation exercise of a relatively short and simple process exemplifies the potential of automatic cell manufacturing. Automation will further gain in attractiveness when applied to more complex processes, requiring frequent interventions or handling at unfavourable working hours, such as re-targeting of T-cells.

Using the manual ability classification system in young adults with cerebral palsy and normal intelligence.

PubMed

van Meeteren, Jetty; Nieuwenhuijsen, Channah; de Grund, Arthur; Stam, Henk J; Roebroeck, Marij E

2010-01-01

The study aimed to establish whether the manual ability classification system (MACS), a valid classification system for manual ability in children with cerebral palsy (CP), is applicable in young adults with CP and normal intelligence. The participants (n = 83) were young adults with CP and normal intelligence and had a mean age of 19.9 years. In this study, inter observer reliability of the MACS was determined. We investigated relationships between the MACS level and patient characteristics (such as the gross motor function classification system (GMFCS) level, limb distribution of the spastic paresis and educational level) and with functional activities of the upper extremity (assessed with the Melbourne assessment, the Abilhand questionnaire and the domain self-care of the functional independence measure (FIM)). Furthermore, with a linear regression analysis it was determined whether the MACS is a significant determinant of activity limitations and participation restrictions. The reliability was good (intraclass correlation coefficient 0.83). The Spearman correlation coefficients with GMFCS level, limb distribution of the spastic paresis and educational level were 0.53, 0.46, and 0.26, respectively. MACS level correlated moderately with outcome measures of functional activities (correlations ranging from -0.38 to -0.55). MACS level is, in addition to the GMFCS level, an important determinant for limitations in activities and restrictions in participation. We conclude that the MACS is a feasible method to classify manual ability in young adults with CP and normal intelligence with a good manual ability.

Myasthenia gravis: the role of complement at the neuromuscular junction.

PubMed

Howard, James F

2018-01-01

Generalized myasthenia gravis (gMG) is a rare autoimmune disorder characterized by skeletal muscle weakness caused by disrupted neurotransmission at the neuromuscular junction (NMJ). Approximately 74-88% of patients with gMG have acetylcholine receptor (AChR) autoantibodies. Complement plays an important role in innate and antibody-mediated immunity, and activation and amplification of complement results in the formation of membrane attack complexes (MACs), lipophilic proteins that damage cell membranes. The role of complement in gMG has been demonstrated in animal models and patients. Studies in animals lacking specific complement proteins have confirmed that MAC formation is required to induce experimental autoimmune MG (EAMG) and NMJ damage. Complement inhibition in EAMG models can prevent disease induction and reverse its progression. Patients with anti-AChR + MG have autoantibodies and MACs present at NMJs. Damaged NMJs are associated with more severe disease, fewer AChRs, and MACs in synaptic debris. Current MG therapies do not target complement directly. Eculizumab is a humanized monoclonal antibody that inhibits cleavage of complement protein C5, preventing MAC formation. Eculizumab treatment improved symptoms compared with placebo in a phase II study in patients with refractory gMG. Direct complement inhibition could preserve NMJ physiology and muscle function in patients with anti-AChR + gMG. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

PubMed

Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

2013-11-01

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE. Copyright © 2013 by the American College of Rheumatology.

In Vitro Assays for Mouse Müller Cell Phenotyping Through microRNA Profiling in the Damaged Retina.

PubMed

Reyes-Aguirre, Luis I; Quintero, Heberto; Estrada-Leyva, Brenda; Lamas, Mónica

2018-01-01

microRNA profiling has identified cell-specific expression patterns that could represent molecular signatures triggering the acquisition of a specific phenotype; in other words, of cellular identity and its associated function. Several groups have hypothesized that retinal cell phenotyping could be achieved through the determination of the global pattern of miRNA expression across specific cell types in the adult retina. This is especially relevant for Müller glia in the context of retinal damage, as these cells undergo dramatic changes of gene expression in response to injury, that render them susceptible to acquire a progenitor-like phenotype and be a source of new neurons.We describe a method that combines an experimental protocol for excitotoxic-induced retinal damage through N-methyl-D-aspartate subretinal injection with magnetic-activated cell sorting (MACS) of Müller cells and RNA isolation for microRNA profiling. Comparison of microRNA patterns of expression should allow Müller cell phenotyping under different experimental conditions.

[Autologous regulatory T cells can suppress the proliferation of lymphoma cell line in vitro].

PubMed

Ying, Zhi-Tao; Guo, Jun; Ren, Jun; Kong, Yan; Yuan, Zhi-Hong; Liu, Xi-Juan; Zhang, Chen; Zheng, Wen; Song, Yu-Qin; Zhang, Yun-Tao; Zhu, Jun

2009-06-01

This study was aimed to investigate the suppressive effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cell line and to explore its mechanism. C57BL/6 Mouse Treg cells were isolated by MACS (magnetic cell sorting). The purity and the expression of Foxp3 were detected by flow cytometry. The suppressive effect of sorted Treg cells on EL4 cells was detected by MTT assay. The secretion of TGF-beta1 and IL-10 was examined by enzyme-linked immunosorbent assay (ELISA). The results showed that CD4(+)CD25(+) T cells could be successfully isolated by MACS with the purity reaching 91.6% and the expression level of Foxp3 was 78.9%. The ratio of viable cells was more than 95%. Regulatory T cells could suppress the proliferation of EL4 cells effectively in the presence of antigen presenting cells (APCs). And the suppressive effect was most significant at 1:1 ratio. In addition, the suppression still existed without APCs. TGF-beta1 and IL-10 could not be detected by ELISA. It is concluded that the Treg cells can suppress T lymphoma cell in vitro. The suppressive effect of Treg cells works in dose-dependent manner, but not in cytokine-dependent manner. The mechanism of this suppression may take effect through cell-cell contact.

Optimization of Human NK Cell Manufacturing: Fully Automated Separation, Improved Ex Vivo Expansion Using IL-21 with Autologous Feeder Cells, and Generation of Anti-CD123-CAR-Expressing Effector Cells.

PubMed

Klöß, Stephan; Oberschmidt, Olaf; Morgan, Michael; Dahlke, Julia; Arseniev, Lubomir; Huppert, Volker; Granzin, Markus; Gardlowski, Tanja; Matthies, Nadine; Soltenborn, Stephanie; Schambach, Axel; Koehl, Ulrike

2017-10-01

The administration of ex vivo expanded natural killer (NK) cells as potential antitumor effector cells appears to be suitable for effector cell-based immunotherapies in high-risk cancer patients. However, good manufacturing practice (GMP)-compliant manufacturing of clinical-grade NK cells at sufficiently high numbers represents a great challenge. Therefore, previous expansion protocols for those effector cells were improved and optimized by using newly developed culture medium, interleukin (IL)-21, and autologous feeder cells (FCs). Separation of primary human NK cells (CD56 + CD3 - ) was carried out with the CliniMACS Prodigy ® in a single process, starting with approximately 1.2 × 10 9 leukocytes collected by small-scale lymphapheresis or from buffy coats. Enriched NK cells were adjusted to starting cell concentrations within approximately 1 × 10 6 effector cells/mL and cultured in comparative expansion experiments for 14 days with IL-2 (1,000 IU/mL) in different GMP-compliant media (X-VIVO ™ 10, CellGro ® , TexMACS ™ , and NK MACS ® ). After medium optimization, beneficial effects for functionality and phenotype were investigated at the beginning of cell expansion with irradiated (25 Gy) autologous FCs at a ratio of 20:1 (feeder: NK) in the presence or absence of IL-21 (100 ng/mL). Additionally, expanded NK cells were gene modified to express chimeric antigen receptors (CARs) against CD123, a common marker for acute myeloid leukemia (AML). Cytotoxicity, degranulation, and cytokine release of transduced NK cells were determined against KG1a cells in flow cytometric analysis and fluorescent imaging. The Prodigy manufacturing process revealed high target cell viabilities (median 95.4%), adequate NK cell recovery (median 60.4%), and purity of 95.4% in regard to CD56 + CD3 - target cells. The process in its early phase of development led to a median T-cell depletion of log 3.5 after CD3 depletion and log 3.6 after the whole process, including CD3 depletion and CD56 enrichment steps. Manually performed experiments to test different culture media demonstrated significantly higher NK cell expansion rates and an approximately equal distribution of CD56 dim CD16 pos and CD56 bright CD16 dim&neg NK subsets on day 14 with cells cultivated in NK MACS ® media. Moreover, effector cell expansion in manually performed experiments with NK MACS ® containing IL-2 and irradiated autologous FCs and IL-21, both added at the initiation of the culture, induced an 85-fold NK cell expansion. Compared to freshly isolated NK cells, expanded NK cells expressed significantly higher levels of NKp30, NKp44, NKG2D, TRAIL, FasL, CD69, and CD137, and showed comparable cell viabilities and killing/degranulation activities against tumor and leukemic cell lines in vitro. NK cells used for CAR transduction showed the highest anti-CD123 CAR expression on day 3 after gene modification. These anti-CD123 CAR-engineered NK cells demonstrated improved cytotoxicity against the CD123 pos AML cell line KG1a and primary AML blasts. In addition, CAR NK cells showed higher degranulation and enhanced secretion of tumor necrosis factor alpha, interferon gamma, and granzyme A and B. In fluorescence imaging, specific interactions that initiated apoptotic processes in the AML target cells were detected between CAR NK cells and KG1a. After the fully automated NK cell separation process on Prodigy, a new NK cell expansion protocol was generated that resulted in high numbers of NK cells with potent antitumor activity, which could be modified efficiently by novel third-generation, alpha-retroviral SIN vector constructs. Next steps are the integration of the manual expansion procedure in the fully integrated platform for a standardized GMP-compliant overall process in this closed system that also may include gene modification of NK cells to optimize target-specific antitumor activity.

Stromal Mesenchyme Cell Genes in Prostate Cancer Development: Epigenetic Markers for Cancer and Potential Targets for Therapy

DTIC Science & Technology

2006-12-01

magnetic beads (MACS) Our CD phenotyping result showed a layer of stromal cells beneath the bladder urothelium that was positive for CD13 whereas the...bladder, CD13 stains a subpopulation of stromal cells (black arrow) in the lamina propria as shown on the right. The partially denuded urothelium is

Maintenance of “stem cell” features of cartilage cell sub-populations during in vitro propagation

PubMed Central

2013-01-01

Background The discovery of mesenchymal stem cells (MSCs) or MSC-like cells in cartilage tissue does not tie in well with the established view that MSCs derive from a perivascular niche. The presence of MSCs may raise concerns about specificity and application safety, particularly in terms of the regulatory site. The aim of the present study was to investigate the benefits or possible risks of the MSC-like properties of cells isolated from cartilage in the context of autologous chondrocyte implantation. Methods Chondrocytic cells were isolated from cartilage or intervertebral disc tissue. Flow cytometry was used to analyze the expression of cell surface antigens. MSC-like cells were either enriched or depleted by means of magnetic cell sorting (MACS) involving the monoclonal antibodies W5C5/SUSD2 and W8B2/MSCA-1. We addressed the issues of prolonged expansion of such cells as well as the influence of culture medium as a trigger for selecting a single cell type. Established protocols were used to study in vitro differentiation. In addition to histological and biochemical assessment, the acquired phenotypes were also evaluated on the mRNA transcript level. Results In the studied cells, we found strongly analogous expression of antigens typically expressed on MSCs, including CD49e, CD73, CD90, CD105, CD140b and CD166. The expression of W5C5 and W8B2 antigens in cartilage cell sub-populations did not correlate with multi-potency. We demonstrated that a chondroid precursor, but not a bona fide multipotent mesenchymal, cell type can be obtained under established in vitro culture conditions. The culture media used for expansion influenced the cell phenotype. Conclusions The risk of adverse adipose or osseous differentiation is not posed by expanded chondrocyte cultures, even after enrichment of putative MSC-like cell populations by MACS. It is possible that this limited “stemness” in chondrocytes, expanded for use in ACI, may instead be beneficial as it allows re-differentiation under appropriate conditions despite prolonged times in culture. PMID:23363653

Technician Marshall MacCready installs solar cells on the Helios Prototype

NASA Technical Reports Server (NTRS)

2000-01-01

Technician Marshall MacCready carefully lays a panel of solar cells into place on a wing section of the Helios Prototype flying wing at AeroVironment's Design Development Center in Simi Valley, California. The bi-facial cells, manufactured by SunPower, Inc., of Sunnyvale, California, are among 64,000 solar cells which have been installed on the solar-powered aircraft to provide electricity to its 14 motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights above 50,000 feet altitude 2003 with the aid of a regenerative fuel cell-based energy storage system now being developed.

Macrophage cell lines derived from major histocompatibility complex II-negative mice

NASA Technical Reports Server (NTRS)

Beharka, A. A.; Armstrong, J. W.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1998-01-01

Two bone-marrow-derived macrophage cell lines, C2D and C2Dt, were isolated from major histocompatibility class II negative knock-out mice. The C2D cell line was stabilized by continuous culture in colony-stimulating factor-1 and the C2Dt cell line was transformed with SV40 virus large T antigen. These cells exhibited phenotypic properties of macrophages including morphology and expression of Mac 1 and Mac 2 cell surface molecules. These cells also had comparable growth to the bone-marrow-derived macrophage cell line B6MP102. These new cell lines were not spontaneously cytotoxic and were only capable of modest killing of F5b tumor cells when stimulated with LPS and interferon-gamma, but not when stimulated with LPS alone or with staphylococcal exotoxin. C2D and C2Dt cells phagocytosed labeled Staphylococcus aureus similarly to B6MP102 cells but less well than C2D peritoneal macrophages. These cell lines secreted interleukin-6, but not tumor necrosis factor or nitric oxide in response to LPS or staphlococcal enterotoxins A or B C2D(t) cells were tumorigenic in C2D and C57BL/6J mice but C2D cells were not. These data suggest that macrophage cell lines can be established from bone marrow cells of major histocompatibility complex II-negative mice.

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4[S

PubMed Central

Lukic, Ana; Ji, Jie; Idborg, Helena; Samuelsson, Bengt; Palmberg, Lena

2016-01-01

Leukotrienes (LTs) play major roles in lung immune responses, and LTD4 is the most potent agonist for cysteinyl LT1, leading to bronchoconstriction and tissue remodeling. Here, we studied LT crosstalk between myeloid cells and pulmonary epithelial cells. Monocytic cells (Mono Mac 6 cell line, primary dendritic cells) and eosinophils produced primarily LTC4. In coincubations of these myeloid cells and epithelial cells, LTD4 became a prominent product. LTC4 released from the myeloid cells was further transformed by the epithelial cells in a transcellular manner. Formation of LTD4 was rapid when catalyzed by γ-glutamyl transpeptidase (GGT)1 in the A549 epithelial lung cancer cell line, but considerably slower when catalyzed by GGT5 in primary bronchial epithelial cells. When A549 cells were cultured in the presence of IL-1β, GGT1 expression increased about 2-fold. Also exosomes from A549 cells contained GGT1 and augmented LTD4 formation. Serine-borate complex (SBC), an inhibitor of GGT, inhibited conversion of LTC4 to LTD4. Unexpectedly, SBC also upregulated translocation of 5-lipoxygenase (LO) to the nucleus in Mono Mac 6 cells, and 5-LO activity. Our results demonstrate an active role for epithelial cells in biosynthesis of LTD4, which may be of particular relevance in the lung. PMID:27436590

C-MAC compared with direct laryngoscopy for intubation in patients with cervical spine immobilization: A manikin trial.

PubMed

Smereka, Jacek; Ladny, Jerzy R; Naylor, Amanda; Ruetzler, Kurt; Szarpak, Lukasz

2017-08-01

The aim of this study was to compare C-MAC videolaryngoscopy with direct laryngoscopy for intubation in simulated cervical spine immobilization conditions. The study was designed as a prospective randomized crossover manikin trial. 70 paramedics with <5years of medical experience participated in the study. The paramedics attempted to intubate manikins in 3 airway scenarios: normal airway without cervical immobilization (Scenario A); manual inline cervical immobilization (Scenario B); cervical immobilization using cervical extraction collar (Scenario C). Scenario A: Nearly all participants performed successful intubations with both MAC and C-MAC on the first attempt (95.7% MAC vs. 100% C-MAC), with similar intubation times (16.5s MAC vs. 18s C-MAC). Scenario B: The results with C-MAC were significantly better than those with MAC (p<0.05) for the time of intubation (23 s MAC vs. 19 s C-MAC), success of the first intubation attempt (88.6% MAC vs. 100% C-MAC), Cormack-Lehane grade, POGO score, severity of dental compression, device difficulty score, and preferred airway device. Scenario C: The results with C-MAC were significantly better than those with MAC (p<0.05) for all the analysed variables: success of the first attempt (51.4% MAC vs. 100% C-MAC), overall success rate, intubation time (27 s MAC vs. 20.5 s C-MAC), Cormack-Lehane grade, POGO score, dental compression, device difficulty score and the preferred airway device. The C-MAC videolaryngoscope is an excellent alternative to the MAC laryngoscope for intubating manikins with cervical spine immobilization. Copyright © 2017 Elsevier Inc. All rights reserved.

[Pulmonary Mycobacterium Avium-Complex (MAC) Disease Differentially Diagnosed from Metastasis of Testicular Cancer : A Case Report].

PubMed

Mori, Kohei; Teranishi, Jyn-Ichi; Yoneyama, Shuko; Ishida, Hiroaki; Hattori, Yusuke; Yumura, Yasushi; Miyoshi, Yasuhide; Kondo, Keiichi; Uemura, Hiroji; Noguchi, Kazumi

2017-01-01

A 45 year-old-man was admitted to our hospital because of discomfort in his left scrotum. He had a left testicular tumor. We performed high orchiectomy and pathological findings revealed testicular cancer. He was treated with bleomycin, etoposide and cisplatin. Computed tomography showed a new mass in the left lung after 3 cycles of the chemotherapy. Because of its rapid growth, the tumor was thought to be a metastasis lesion of testicular cancer or pulmonary infection. Transbronchial lung biopsy showed an invasion of multinucleated giant cells and granuloma. The culture and polymerase chain reaction of the bronchial sputum were positive for myobacterium avium-complex (MAC). From these findings, the left lung tumor was diagnosed as pulmonary MAC disease. He received partial resection of the left lung and the lesion was diagnosed as granuloma. There was no recurrence of testicular cancer or pulmonary disease after the surgery.

Recent advancements of wide-angle polarization analysis with 3He neutron spin filters

NASA Astrophysics Data System (ADS)

Chen, W. C.; Gentile, T. R.; Ye, Q.; Kirchhoff, A.; Watson, S. M.; Rodriguez-Rivera, J. A.; Qiu, Y.; Broholm, C.

2016-09-01

Wide-angle polarization analysis with polarized 3He based neutron spin filters (NSFs) has recently been employed on the Multi-Axis Crystal Spectrometer (MACS) at the National Institute of Standards and Technology Center for Neutron Research (NCNR). Over the past several years, the apparatus has undergone many upgrades to address the fundamental requirements for wide angle polarization analysis using spin exchange optical pumping based 3He NSFs. In this paper, we report substantial improvements in the on-beam-line performance of the apparatus and progress toward routine user capability. We discuss new standard samples used for 3He NSF characterization and the flipping ratio measurement on MACS. We further discuss the management of stray magnetic fields produced by operation of superconducting magnets on the MACS instrument, which can significantly reduce the 3He polarization relaxation time. Finally, we present the results of recent development of horseshoe-shaped wide angle cells.

Characterization of a novel variant of Mycobacterium chimaera.

PubMed

van Ingen, J; Hoefsloot, W; Buijtels, P C A M; Tortoli, E; Supply, P; Dekhuijzen, P N R; Boeree, M J; van Soolingen, D

2012-09-01

In this study, nonchromogenic mycobacteria were isolated from pulmonary samples of three patients in the Netherlands. All isolates had identical, unique 16S rRNA gene and 16S-23S ITS sequences, which were closely related to those of Mycobacterium chimaera and Mycobacterium marseillense. The biochemical features of the isolates differed slightly from those of M. chimaera, suggesting that the isolates may represent a possible separate species within the Mycobacterium avium complex (MAC). However, the cell-wall mycolic acid pattern, analysed by HPLC, and the partial sequences of the hsp65 and rpoB genes were identical to those of M. chimaera. We concluded that the isolates represent a novel variant of M. chimaera. The results of this analysis have led us to question the currently used methods of species definition for members of the genus Mycobacterium, which are based largely on 16S rRNA or rpoB gene sequencing. Definitions based on a single genetic target are likely to be insufficient. Genetic divergence, especially in the MAC, yields strains that cannot be confidently assigned to a specific species based on the analysis of a single genetic target.

Loperamide Restricts Intracellular Growth of Mycobacterium tuberculosis in Lung Macrophages.

PubMed

Juárez, Esmeralda; Carranza, Claudia; Sánchez, Guadalupe; González, Mitzi; Chávez, Jaime; Sarabia, Carmen; Torres, Martha; Sada, Eduardo

2016-12-01

New approaches for improving tuberculosis (TB) control using adjunct host-directed cellular and repurposed drug therapies are needed. Autophagy plays a crucial role in the response to TB, and a variety of autophagy-inducing drugs that are currently available for various medical conditions may serve as an adjunct treatment in pulmonary TB. Here, we evaluated the potential of loperamide, carbamazepine, valproic acid, verapamil, and rapamycin to enhance the antimicrobial immune response to Mycobacterium tuberculosis (Mtb). Human monocyte-derived macrophages (MDMs) and murine alveolar cells (MACs) were infected with Mtb and treated with loperamide, carbamazepine, valproic acid, verapamil, and rapamycin in vitro. Balb/c mice were intraperitoneally administered loperamide, valproic acid, and verapamil, and MACs were infected in vitro with Mtb. The induction of autophagy, the containment of Mtb within autophagosomes and the intracellular Mtb burden were determined. Autophagy was induced by all of the drugs in human and mouse macrophages, and loperamide significantly increased the colocalization of microtubule-associated protein 1 light chain 3 with Mtb in MDMs. Carbamazepine, loperamide, and valproic acid induced microtubule-associated protein 1 light chain 3 and autophagy related 16- like protein 1 gene expression in MDMs and in MACs. Loperamide also induced a reduction in TNF-α production. Loperamide and verapamil induced autophagy, which was associated with a significant reduction in the intracellular growth of Mtb in MACs and alveolar macrophages. The intraperitoneal administration of loperamide and valproic acid induced autophagy in freshly isolated MACs. The antimycobacterial activity in MACs was higher after loperamide treatment and was associated with the degradation of p62. In conclusion, loperamide shows potential as an adjunctive therapy for the treatment of TB.

Membrane attack complex of complement is not essential for immune mediated demyelination in experimental autoimmune neuritis.

PubMed

Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Killingsworth, Murray; Nomura, Masaru; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

2010-12-15

Antibody deposition and complement activation, especially membrane attack complex (MAC) formation are considered central for immune mediated demyelination. To examine the role of MAC in immune mediated demyelination, we studied experimental allergic neuritis (EAN) in Lewis rats deficient in complement component 6 (C6) that cannot form MAC. A C6 deficient Lewis (Lewis/C6-) strain of rats was bred by backcrossing the defective C6 gene, from PVG/C6- rats, onto the Lewis background. Lewis/C6- rats had the same C6 gene deletion as PVG/C6- rats and their sera did not support immune mediated haemolysis unless C6 was added. Active EAN was induced in Lewis and Lewis/C6- rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), and Lewis/C6- rats had delayed clinical EAN compared to the Lewis rats. Peripheral nerve demyelination in Lewis/C6- was also delayed but was similar in extent at the peak of disease. Compared to Lewis, Lewis/C6- nerves had no MAC deposition, reduced macrophage infiltrate and IL-17A, but similar T cell infiltrate and Th1 cytokine mRNA expression. ICAM-1 and P-selectin mRNA expression and immunostaining on vascular endothelium were delayed in Lewis C6- compared to Lewis rats' nerves. This study found that MAC was not required for immune mediated demyelination; but that MAC enhanced early symptoms and early demyelination in EAN, either by direct lysis or by sub-lytic induction of vascular endothelial expression of ICAM-1 and P-selectin. Copyright © 2010 Elsevier B.V. All rights reserved.

Rheology of Membrane-Attached Minimal Actin Cortices.

PubMed

Nöding, Helen; Schön, Markus; Reinermann, Corinna; Dörrer, Nils; Kürschner, Aileen; Geil, Burkhard; Mey, Ingo; Heussinger, Claus; Janshoff, Andreas; Steinem, Claudia

2018-04-26

The actin cortex is a thin cross-linked network attached to the plasma membrane, which is responsible for the cell's shape during migration, division, and growth. In a reductionist approach, we created a minimal actin cortex (MAC) attached to a lipid membrane to correlate the filamentous actin architecture with its viscoelastic properties. The system is composed of a supported 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine bilayer doped with the receptor lipid phosphatidylinositol(4,5)-bisphosphate (PtdIns(4,5)P 2 ) to which a constitutively active mutant of ezrin, which is a direct membrane-cytoskeleton linker, is bound. The formation of the MAC on the supported lipid bilayer is analyzed as a function of increasing PtdIns(4,5)P 2 /ezrin pinning points, revealing an increase in the intersections between actin filaments, that is, the node density of the MAC. Bead tracking microrheology on the membrane-attached actin network provides information about its viscoelastic properties. The results show that ezrin serves as a dynamic cross-linker for the actin cortex attached to the lipid bilayer and that the stiffness of the network is influenced by the pinning point density, relating the plateau storage modulus G 0 to the node density of the MAC.

A novel leukocyte adhesion deficiency caused by expressed but nonfunctional β2 integrins Mac-1 and LFA-1

PubMed Central

Hogg, Nancy; Stewart, Mairi P.; Scarth, Sarah L.; Newton, Rebecca; Shaw, Jacqueline M.; Law, S.K. Alex; Klein, Nigel

1999-01-01

In the leukocyte adhesion deficiency (LAD)-1 syndrome, there is diminished expression of β2(CD18) integrins. This is caused by lesions in the β2-subunit gene and gives rise to recurrent bacterial infections, impaired pus formation, and poor wound healing. We describe a patient with clinical features compatible with a moderately severe phenotype of LAD-1 but who expresses the β2 integrins lymphocyte function– associated molecule (LFA)-1 and Mac-1 at 40%–60% of normal levels. This level of expression should be adequate for normal integrin function, but both the patient's Mac-1 on neutrophils and LFA-1 on T cells failed to bind ligands such as fibrinogen and intercellular adhesion molecule (ICAM)-1, respectively, or to display a β2-integrin activation epitope after adhesion-inducing stimuli. Unexpectedly, divalent cation treatment induced the patient's T cells to bind to ICAM-2 and ICAM-3. Sequencing of the patient's two CD18 alleles revealed the mutations S138P and G273R. Both mutations are in the β2-subunit conserved domain, with S138P a putative divalent cation coordinating residue in the metal ion–dependent adhesion site (MIDAS) motif. After K562 cell transfection with α subunits, the mutated S138P β subunit was coexpressed but did not support function, whereas the G273R mutant was not expressed. In summary, the patient described here exhibits failure of the β2 integrins to function despite adequate levels of cell-surface expression. PMID:9884339

Depletion of UBC9 Causes Nuclear Defects during the Vegetative and Sexual Life Cycles in Tetrahymena thermophila.

PubMed

Yang, Qianyi; Nasir, Amjad M; Coyne, Robert S; Forney, James D

2015-12-01

Ubc9p is the sole E2-conjugating enzyme for SUMOylation, and its proper function is required for regulating key nuclear events such as transcription, DNA repair, and mitosis. In Tetrahymena thermophila, the genome is separated into a diploid germ line micronucleus (MIC) that divides by mitosis and a polyploid somatic macronucleus (MAC) that divides amitotically. This unusual nuclear organization provides novel opportunities for the study of SUMOylation and Ubc9p function. We identified the UBC9 gene and demonstrated that its complete deletion from both MIC and MAC genomes is lethal. Rescue of the lethal phenotype with a GFP-UBC9 fusion gene driven by a metallothionein promoter generated a cell line with CdCl2-dependent expression of green fluorescent protein (GFP)-Ubc9p. Depletion of Ubc9p in vegetative cells resulted in the loss of MICs, but MACs continued to divide. In contrast, expression of catalytically inactive Ubc9p resulted in the accumulation of multiple MICs. Critical roles for Ubc9p were also identified during the sexual life cycle of Tetrahymena. Cell lines that were depleted for Ubc9p did not form mating pairs and therefore could not complete any of the subsequent stages of conjugation, including meiosis and macronuclear development. Mating between cells expressing catalytically inactive Ubc9p resulted in arrest during macronuclear development, consistent with our observation that Ubc9p accumulates in the developing macronucleus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Ability of paramedics to perform endotracheal intubation during continuous chest compressions: a randomized cadaver study comparing Pentax AWS and Macintosh laryngoscopes.

PubMed

Truszewski, Zenon; Czyzewski, Lukasz; Smereka, Jacek; Krajewski, Paweł; Fudalej, Marcin; Madziala, Marcin; Szarpak, Lukasz

2016-09-01

The aim of the trial was to compare the time parameters for intubation with the use of the Macintosh (MAC) laryngoscope and Pentax AWS-S100 videolaryngoscope (AWS; Pentax Corporation, Tokyo, Japan) with and without chest compression (CC) by paramedics during simulated cardiopulmonary resuscitation in a cadaver model. This was a randomized crossover cadaver trial. Thirty-five paramedics with no experience in videolaryngoscopy participated in the study. They performed intubation in two emergency scenarios: scenario A, normal airway without CC; scenario B, normal airway with continuous CC. The median time to first ventilation with the use of the AWS and the MAC was similar in scenario A: 25 (IQR, 22-27) seconds vs. 24 (IQR, 22.5-26) seconds (P=.072). A statistically significant difference in TTFV between AWS and MAC was noticed in scenario B (P=.011). In scenario A, the first endotracheal intubation (ETI) attempt success rate was achieved in 97.1% with AWS compared with 94.3% with MAC (P=.43). In scenario B, the success rate after the first ETI attempt with the use of the different intubation methods varied and amounted to 88.6% vs. 77.1% for AWS and MAC, respectively (P=.002). The Pentax AWS offered a superior glottic view as compared with the MAC laryngoscope, which was associated with a higher intubation rate and a shorter intubation time during an uninterrupted CC scenario. However, in the scenario without CC, the results for AWS and MAC were comparable. Copyright © 2016 Elsevier Inc. All rights reserved.

Development, Implementation and Application of Micromechanical Analysis Tools for Advanced High Temperature Composites

NASA Technical Reports Server (NTRS)

2005-01-01

This document contains the final report to the NASA Glenn Research Center (GRC) for the research project entitled Development, Implementation, and Application of Micromechanical Analysis Tools for Advanced High-Temperature Composites. The research supporting this initiative has been conducted by Dr. Brett A. Bednarcyk, a Senior Scientist at OM in Brookpark, Ohio from the period of August 1998 to March 2005. Most of the work summarized herein involved development, implementation, and application of enhancements and new capabilities for NASA GRC's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) software package. When the project began, this software was at a low TRL (3-4) and at release version 2.0. Due to this project, the TRL of MAC/GMC has been raised to 7 and two new versions (3.0 and 4.0) have been released. The most important accomplishments with respect to MAC/GMC are: (1) A multi-scale framework has been built around the software, enabling coupled design and analysis from the global structure scale down to the micro fiber-matrix scale; (2) The software has been expanded to analyze smart materials; (3) State-of-the-art micromechanics theories have been implemented and validated within the code; (4) The damage, failure, and lifing capabilities of the code have been expanded from a very limited state to a vast degree of functionality and utility; and (5) The user flexibility of the code has been significantly enhanced. MAC/GMC is now the premier code for design and analysis of advanced composite and smart materials. It is a candidate for the 2005 NASA Software of the Year Award. The work completed over the course of the project is summarized below on a year by year basis. All publications resulting from the project are listed at the end of this report.

Nanoscale silver-assisted wet etching of crystalline silicon for anti-reflection surface textures.

PubMed

Li, Rui; Wang, Shuling; Chuwongin, Santhad; Zhou, Weidong

2013-01-01

We report here an electro-less metal-assisted chemical etching (MacEtch) process as light management surface-texturing technique for single crystalline Si photovoltaics. Random Silver nanostructures were formed on top of the Si surface based on the thin film evaporation and annealing process. Significant reflection reduction was obtained from the fabricated Si sample, with approximately 2% reflection over a wide spectra range (300 to 1050 nm). The work demonstrates the potential of MacEtch process for anti-reflection surface texture fabrication of large area, high efficiency, and low cost thin film solar cell.

Fabrication of ultra-high aspect ratio (>160:1) silicon nanostructures by using Au metal assisted chemical etching

NASA Astrophysics Data System (ADS)

Li, Hailiang; Ye, Tianchun; Shi, Lina; Xie, Changqing

2017-12-01

We present a facile and effective approach for fabricating high aspect ratio, dense and vertical silicon nanopillar arrays, using a combination of metal etching following electron-beam lithography and Au metal assisted chemical etching (MacEtch). Ti/Au nanostructures used as catalysts in MacEtch are formed by single layer resist-based electron-beam exposure followed by ion beam etching. The effects of MacEtch process parameters, including half period, etching time, the concentrations of H2O2 and HF, etching temperature and drying method are systematically investigated. Especially, we demonstrate an enhancement of etching quality by employing cold MacEtch process, and an enhancement in preventing the collapse of high aspect ratio nanostructures by employing low surface tension rinse liquid and natural evaporation in the drying stage. Using an optimized MacEtch process, vertical silicon nanopillar arrays with a period of 250 nm and aspect ratio up to 160:1 are realized. Our results should be instructive for exploring the achievable aspect ratio limit in silicon nanostructures and may find potential applications in photovoltaic devices, thermoelectric devices and x-ray diffractive optics.

Interleukin-1 or tumor necrosis factor-alpha augmented the cytotoxic effect of mycobacteria on human fibroblasts: application to evaluation of pathogenesis of clinical isolates of Mycobacterium tuberculosis and M. avium complex.

PubMed

Takii, T; Abe, C; Tamura, A; Ramayah, S; Belisle, J T; Brennan, P J; Onozaki, K

2001-03-01

Mycobacteria-induced in vitro events reflecting human tuberculosis can contribute to the evaluation of the pathogenesis of Mycobacterium tuberculosis (MTB). In this study, we propose such an in vitro method based on live mycobacteria-induced cytotoxicity to human cell lines. When human lung-derived normal fibroblast cell line MRC-5 was infected with various strains of mycobacteria (M. tuberculosis H(37)Rv and H(37) Ra, Mycobacterium avium 427S and 2151SmO, and Mycobacterium bovis BCG Pasteur and Tokyo), the fibroblasts were killed by mycobacteria according to the degree of virulence. Other human originated macrophage (U-937, THP-1), myeloid (HL-60), and epithelial carcinoma (A549) cell lines exhibited a similar cytotoxic response to virulent mycobacteria. MRC-5 was most susceptible to virulent mycobacteria among various human cell lines examined. The cytotoxicity was enhanced by the proinflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-alpha), which in the absence of mycobacteria stimulate the growth of normal human fibroblasts. This in vitro evaluation system was applied to clinical isolates of drug-sensitive MTB (DS-MTB), drug-resistant MTB (DR-MTB) including multidrug-resistant (MDR-MTB), and M. avium complex (MAC). MTB strains (n = 24) exhibited strong cytotoxic activity, but MAC strains (n = 5) had only weak activity. Furthermore, there was no significant difference in cytotoxicity between DS-MTB (n = 11) and DR-MTB (n = 13). Collectively, these results suggest that this new in vitro system is useful for evaluating the pathogenesis of mycobacteria and that there was no difference in the pathogenesis between drug-susceptible and drug-resistant clinical isolates.

Hematopoietic Stem-Cell Transplantation for Advanced Systemic Mastocytosis

PubMed Central

Ustun, Celalettin; Reiter, Andreas; Scott, Bart L.; Nakamura, Ryotaro; Damaj, Gandhi; Kreil, Sebastian; Shanley, Ryan; Hogan, William J.; Perales, Miguel-Angel; Shore, Tsiporah; Baurmann, Herrad; Stuart, Robert; Gruhn, Bernd; Doubek, Michael; Hsu, Jack W.; Tholouli, Eleni; Gromke, Tanja; Godley, Lucy A.; Pagano, Livio; Gilman, Andrew; Wagner, Eva Maria; Shwayder, Tor; Bornhäuser, Martin; Papadopoulos, Esperanza B.; Böhm, Alexandra; Vercellotti, Gregory; Van Lint, Maria Teresa; Schmid, Christoph; Rabitsch, Werner; Pullarkat, Vinod; Legrand, Faezeh; Yakoub-agha, Ibrahim; Saber, Wael; Barrett, John; Hermine, Olivier; Hagglund, Hans; Sperr, Wolfgang R.; Popat, Uday; Alyea, Edwin P.; Devine, Steven; Deeg, H. Joachim; Weisdorf, Daniel; Akin, Cem; Valent, Peter

2014-01-01

Purpose Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown. Patients and Methods In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non–mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC). Results Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response. Conclusion AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial. PMID:25154823

Role of ATP binding and hydrolysis in assembly of MacAB-TolC macrolide transporter

PubMed Central

Lu, Shuo; Zgurskaya, Helen I.

2012-01-01

Summary MacB is a founding member of the Macrolide Exporter family of transporters belonging to the ATP-Binding Cassette superfamily. These proteins are broadly represented in genomes of both gram-positive and gram-negative bacteria and are implicated in virulence and protection against antibiotics and peptide toxins. MacB transporter functions together with MacA, a periplasmic membrane fusion protein, which stimulates MacB ATPase. In gram-negative bacteria, MacA is believed to couple ATP hydrolysis to transport of substrates across the outer membrane through a TolC-like channel. In this study, we report a real-time analysis of concurrent ATP hydrolysis and assembly of MacAB-TolC complex. MacB binds nucleotides with a low millimolar affinity and fast on- and off-rates. In contrast, MacA-MacB complex is formed with a nanomolar affinity, which further increases in the presence of ATP. Our results strongly suggest that association between MacA and MacB is stimulated by ATP binding to MacB but remains unchanged during ATP hydrolysis cycle. We also found that the large periplasmic loop of MacB plays the major role in coupling reactions separated in two different membranes. This loop is required for MacA-dependent stimulation of MacB ATPase and at the same time, contributes to recruitment of TolC into a trans-envelope complex. PMID:23057817

AeroVironment Technician Marshall MacCready carefully lays a panel of solar cells into place on a wi

NASA Technical Reports Server (NTRS)

2000-01-01

Technician Marshall MacCready carefully lays a panel of solar cells into place on a wing section of the Helios Prototype flying wing at AeroVironment's Design Development Center in Simi Valley, California. More than 1,800 panels containing some 64,000 bi-facial cells, fabricated by SunPower, Inc., of Sunnyvale, California, have been installed on the solar-powered aircraft to provide electricity to its 14 motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights above 50,000 feet altitude 2003 with the aid of a regenerative fuel cell-based energy storage system now being developed.

Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

PubMed

Malkevitch, Nina V; Patterson, L Jean; Aldrich, M Kristine; Wu, Yichen; Venzon, David; Florese, Ruth H; Kalyanaraman, V S; Pal, Ranajit; Lee, Eun Mi; Zhao, Jun; Cristillo, Anthony; Robert-Guroff, Marjorie

2006-09-15

Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting <50 SIV RNA copies. Decreased viremia compared to naïve controls was observed in the other three. The SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4 counts < or =200, unlike the protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained <50 SIV RNA copies; SIV RNA emerged in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular immunity coincided with viremia suppression. Overall, cellular immunity induced by vaccination and/or low-level, inapparent viremia post-first SIV(mac251) challenge, was associated with durable protection against re-challenge.

Damage-Free Smooth-Sidewall InGaAs Nanopillar Array by Metal-Assisted Chemical Etching.

PubMed

Kong, Lingyu; Song, Yi; Kim, Jeong Dong; Yu, Lan; Wasserman, Daniel; Chim, Wai Kin; Chiam, Sing Yang; Li, Xiuling

2017-10-24

Producing densely packed high aspect ratio In 0.53 Ga 0.47 As nanostructures without surface damage is critical for beyond Si-CMOS nanoelectronic and optoelectronic devices. However, conventional dry etching methods are known to produce irreversible damage to III-V compound semiconductors because of the inherent high-energy ion-driven process. In this work, we demonstrate the realization of ordered, uniform, array-based In 0.53 Ga 0.47 As pillars with diameters as small as 200 nm using the damage-free metal-assisted chemical etching (MacEtch) technology combined with the post-MacEtch digital etching smoothing. The etching mechanism of In x Ga 1-x As is explored through the characterization of pillar morphology and porosity as a function of etching condition and indium composition. The etching behavior of In 0.53 Ga 0.47 As, in contrast to higher bandgap semiconductors (e.g., Si or GaAs), can be interpreted by a Schottky barrier height model that dictates the etching mechanism constantly in the mass transport limited regime because of the low barrier height. A broader impact of this work relates to the complete elimination of surface roughness or porosity related defects, which can be prevalent byproducts of MacEtch, by post-MacEtch digital etching. Side-by-side comparison of the midgap interface state density and flat-band capacitance hysteresis of both the unprocessed planar and MacEtched pillar In 0.53 Ga 0.47 As metal-oxide-semiconductor capacitors further confirms that the surface of the resultant pillars is as smooth and defect-free as before etching. MacEtch combined with digital etching offers a simple, room-temperature, and low-cost method for the formation of high-quality In 0.53 Ga 0.47 As nanostructures that will potentially enable large-volume production of In 0.53 Ga 0.47 As-based devices including three-dimensional transistors and high-efficiency infrared photodetectors.

New Methods for Representing and Interacting with Qualitative Geographic Information

DTIC Science & Technology

2012-10-31

Penn State University Report on Component 3: SensePlace2 Evaluation Anthony C. Robinson, Scott Pezanowski, Alexander Savelyev , and Alan M...NUMBER 6. AUTHOR(S) Alexander Savelyev , Scott Pezanowski, Anthony C. Robinson, and Alan M. MacEachren 5d. PROJECT NUMBER 5e. TASK NUMBER 5f...2012. SensePlace2 Interface Mini-Guide Alan M. MacEachren, Alexander Savelyev , and Scott Pezanowski GeoVISTA Center, Pennsylvania State University

A Low-Cost and Energy-Efficient Multiprocessor System-on-Chip for UWB MAC Layer

NASA Astrophysics Data System (ADS)

Xiao, Hao; Isshiki, Tsuyoshi; Khan, Arif Ullah; Li, Dongju; Kunieda, Hiroaki; Nakase, Yuko; Kimura, Sadahiro

Ultra-wideband (UWB) technology has attracted much attention recently due to its high data rate and low emission power. Its media access control (MAC) protocol, WiMedia MAC, promises a lot of facilities for high-speed and high-quality wireless communication. However, these benefits in turn involve a large amount of computational load, which challenges the traditional uniprocessor architecture based implementation method to provide the required performance. However, the constrained cost and power budget, on the other hand, makes using commercial multiprocessor solutions unrealistic. In this paper, a low-cost and energy-efficient multiprocessor system-on-chip (MPSoC), which tackles at once the aspects of system design, software migration and hardware architecture, is presented for the implementation of UWB MAC layer. Experimental results show that the proposed MPSoC, based on four simple RISC processors and shared-memory infrastructure, achieves up to 45% performance improvement and 65% power saving, but takes 15% less area than the uniprocessor implementation.

Bioavailability of Bergamot (Citrus bergamia) Flavanones and Biological Activity of Their Circulating Metabolites in Human Pro-Angiogenic Cells

PubMed Central

Spigoni, Valentina; Fantuzzi, Federica; Tassotti, Michele; Brighenti, Furio; Bonadonna, Riccardo C.; Dei Cas, Alessandra

2017-01-01

Myeloid angiogenic cells (MACs) play a key role in endothelial repairing processes and functionality but their activity may be impaired by the lipotoxic effects of some molecules like stearic acid (SA). Among the dietary components potentially able to modulate endothelial function in vivo, (poly)phenolic compounds represent serious candidates. Here, we apply a comprehensive multidisciplinary approach to shed light on the prospects of Bergamot (Citrus bergamia), a citrus fruit rich in flavanones and other phenolic compounds, in the framework of lipotoxicity-induced MACs impairment. The flavanone profile of bergamot juice was characterized and 16 compounds were identified, with a new 3-hydroxy-3-methylglutaryl (HMG) flavanone, isosakuranetin-7-O-neohesperidoside-6″-O-HMG, described for the first time. Then, a pilot bioavailability study was conducted in healthy volunteers to assess the circulating flavanone metabolites in plasma and urine after consumption of bergamot juice. Up to 12 flavanone phase II conjugates (sulfates and glucuronides of hesperetin, naringenin and eriodyctiol) were detected and quantified. Finally, the effect of some of the metabolites identified in vivo, namely hesperetin-7-O-glucuronide, hesperetin-3′-O-glucuronide, naringenin-7-O-glucuronide and naringenin-4′-O-glucuronide, was tested, at physiological concentrations, on gene expression of inflammatory markers and apoptosis in MACs exposed to SA. Under these conditions, naringenin-4′-O-glucuronide and hesperetin-7-O-glucuronide were able to modulate inflammation, while no flavanone glucuronide was effective in curbing stearate-induced lipoapoptosis. These results demonstrate that some flavanone metabolites, derived from the in vivo transformation of bergamot juice phenolics in humans, may mitigate stearate-induced inflammation in MACs. PMID:29211032

Bioavailability of Bergamot (Citrus bergamia) Flavanones and Biological Activity of Their Circulating Metabolites in Human Pro-Angiogenic Cells.

PubMed

Spigoni, Valentina; Mena, Pedro; Fantuzzi, Federica; Tassotti, Michele; Brighenti, Furio; Bonadonna, Riccardo C; Del Rio, Daniele; Dei Cas, Alessandra

2017-12-06

Myeloid angiogenic cells (MACs) play a key role in endothelial repairing processes and functionality but their activity may be impaired by the lipotoxic effects of some molecules like stearic acid (SA). Among the dietary components potentially able to modulate endothelial function in vivo, (poly)phenolic compounds represent serious candidates. Here, we apply a comprehensive multidisciplinary approach to shed light on the prospects of Bergamot ( Citrus bergamia ), a citrus fruit rich in flavanones and other phenolic compounds, in the framework of lipotoxicity-induced MACs impairment. The flavanone profile of bergamot juice was characterized and 16 compounds were identified, with a new 3-hydroxy-3-methylglutaryl (HMG) flavanone, isosakuranetin-7- O -neohesperidoside-6″- O -HMG, described for the first time. Then, a pilot bioavailability study was conducted in healthy volunteers to assess the circulating flavanone metabolites in plasma and urine after consumption of bergamot juice. Up to 12 flavanone phase II conjugates (sulfates and glucuronides of hesperetin, naringenin and eriodyctiol) were detected and quantified. Finally, the effect of some of the metabolites identified in vivo, namely hesperetin-7- O -glucuronide, hesperetin-3'- O -glucuronide, naringenin-7- O -glucuronide and naringenin-4'- O -glucuronide, was tested, at physiological concentrations, on gene expression of inflammatory markers and apoptosis in MACs exposed to SA. Under these conditions, naringenin-4'- O -glucuronide and hesperetin-7- O -glucuronide were able to modulate inflammation, while no flavanone glucuronide was effective in curbing stearate-induced lipoapoptosis. These results demonstrate that some flavanone metabolites, derived from the in vivo transformation of bergamot juice phenolics in humans, may mitigate stearate-induced inflammation in MACs.

Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation.

PubMed

Woollard, Kevin J; Suhartoyo, Andreas; Harris, Emma E; Eisenhardt, Steffen U; Jackson, Shaun P; Peter, Karlheinz; Dart, Anthony M; Hickey, Michael J; Chin-Dusting, Jaye P F

2008-11-07

Plasma soluble P-selectin (sP-selectin) levels are increased in pathologies associated with atherosclerosis, including peripheral arterial occlusive disease (PAOD). However, the role of sP-selectin in regulating leukocyte-endothelial adhesion is unclear. The aim of this study was to assess the ability of exogenous and endogenous sP-selectin to induce leukocyte responses that promote their adhesion to various forms of endothelium. In flow chamber assays, sP-selectin dose-dependently increased neutrophil adhesion to resting human iliac artery endothelial cells. Similarly, sP-selectin induced neutrophil adhesion to the endothelial surface of murine aortae and human radial venous segments in ex vivo flow chamber experiments. Using intravital microscopy to examine postcapillary venules in the mouse cremaster muscle, in vivo administration of sP-selectin was also found to significantly increase leukocyte rolling and adhesion in unstimulated postcapillary venules. Using a Mac-1-specific antibody and P-selectin knockout mouse, it was demonstrated that this finding was dependent on a contribution of Mac-1 to leukocyte rolling and endothelial P-selectin expression. This was confirmed in an ex vivo perfusion model using viable mouse aorta and human radial vessels. In contrast, with tumor necrosis factor-alpha-activated endothelial cells and intact endothelium, where neutrophil adhesion was already elevated, sP-selectin failed to further increase adhesion. Plasma samples from PAOD patients containing pathologically elevated concentrations of sP-selectin also increased neutrophil adhesion to the endothelium in a sP-selectin-dependent manner, as demonstrated by immunodepletion of sP-selectin. These studies demonstrate that raised plasma sP-selectin may influence the early progression of vascular disease by promoting leukocyte adhesion to the endothelium in PAOD, through Mac-1-mediated rolling and dependent on endothelial P-selectin expression.

Magnetic-activated cell sorting for sperm preparation reduces spermatozoa with apoptotic markers and improves the acrosome reaction in couples with unexplained infertility.

PubMed

Lee, Tsung-Hsien; Liu, Chung-Hsien; Shih, Yang-Tse; Tsao, Hui-Mei; Huang, Chun-Chia; Chen, Hsiu-Hui; Lee, Maw-Sheng

2010-04-01

Couples with unexplained infertility (UI) tend to have low fertilization rates with current IVF procedures. Here, we attempted to identify spermatozoa with apoptotic markers in couples with UI and unsuccessful intrauterine insemination (IUI) and we investigated the efficiency and benefit of magnetic-activated cell sorting (MACS) for sperm preparation in such patients. Sixty couples with UI and two IUI failures were recruited. The sperm were prepared by conventional density gradient centrifugation (DGC) and divided into two aliquots. One aliquot was used as a control and the other was further processed by MACS (D + M). Apoptotic markers were identified using fluorescence-labeled dye and flow cytometry, including externalization of phosphatidylserine (EPS), disrupted mitochondrial membrane potential (MMP) and DNA fragmentation. The fertilization potential of prepared spermatozoa was analyzed by basic semen analysis, computer-aided sperm analysis and the induced acrosome reaction test (IART). After DGC, spermatozoa showed 18.6% EPS, 28.3% disrupted MMP and 13.5% DNA fragmentation. Numbers of spermatozoa with apoptotic markers were significantly reduced by D + M, versus DGC alone (P < 0.001). Although the motility of spermatozoa was slightly decreased after MACS, most sperm motion characteristics were not impaired. Interestingly, the IART significantly improved after D + M, versus DGC alone, especially for the couples with a normal hemizona assay (P < 0.001). The spermatozoa prepared by D + M showed a reduced level of apoptotic markers. Improvement in the IART suggests a high fertilization potential of the processed spermatozoa. The identification of apoptotic markers and use of MACS may be helpful in directing the management plan for patients with UI and multiple IUI failures.

Hydrodynamic shear shows distinct roles for LFA-1 and Mac-1 in neutrophil adhesion to intercellular adhesion molecule-1.

PubMed

Neelamegham, S; Taylor, A D; Burns, A R; Smith, C W; Simon, S I

1998-09-01

The binding of neutrophil beta2 integrin to intercellular adhesion molecule-1 (ICAM-1) expressed on the inflamed endothelium is critical for neutrophil arrest at sites of tissue inflammation. To quantify the strength and kinetics of this interaction, we measured the adhesion between chemotactically stimulated neutrophils and ICAM-1-transfected mouse cells (E3-ICAM) in suspension in a cone-plate viscometer at shear rates typical of venular blood flow (100 s-1 to 500 s-1). The kinetics of aggregation were fit with a mathematical model based on two-body collision theory. This enabled estimation of adhesion efficiency, defined as the probability with which collisions between cells resulted in firm adhesion. The efficiency of beta2-integrin-dependent adhesion was highest ( approximately 0.2) at 100 s-1 and it decreased to approximately zero at 400 s-1. Both LFA-1 and Mac-1 contributed equally to adhesion efficiency over the initial 30 seconds of stimulation, but adhesion was entirely Mac-1-dependent by 120 seconds. Two hydrodynamic parameters were observed to influence integrin-dependent adhesion efficiency: the level of shear stress and the intercellular contact duration. Below a critical shear stress (<2 dyn/cm2), contact duration predominantly limited adhesion efficiency. The estimated minimum contact duration for beta2-integrin binding was approximately 6.5 ms. Above the critical shear stress (>2 dyn/cm2), the efficiency of neutrophil adhesion to E3-ICAM was limited by both the contact duration and the tensile stress. We conclude that at low shear, neutrophil adhesion is modulated independently through either LFA-1 or Mac-1, which initially contribute with equal efficiency, but differ over the duration of chemotactic stimulation. Copyright 1998 by The American Society of Hematology.

Design and performance evaluation of a distributed OFDMA-based MAC protocol for MANETs.

PubMed

Park, Jaesung; Chung, Jiyoung; Lee, Hyungyu; Lee, Jung-Ryun

2014-01-01

In this paper, we propose a distributed MAC protocol for OFDMA-based wireless mobile ad hoc multihop networks, in which the resource reservation and data transmission procedures are operated in a distributed manner. A frame format is designed considering the characteristics of OFDMA that each node can transmit or receive data to or from multiple nodes simultaneously. Under this frame structure, we propose a distributed resource management method including network state estimation and resource reservation processes. We categorize five types of logical errors according to their root causes and show that two of the logical errors are inevitable while three of them are avoided under the proposed distributed MAC protocol. In addition, we provide a systematic method to determine the advertisement period of each node by presenting a clear relation between the accuracy of estimated network states and the signaling overhead. We evaluate the performance of the proposed protocol in respect of the reservation success rate and the success rate of data transmission. Since our method focuses on avoiding logical errors, it could be easily placed on top of the other resource allocation methods focusing on the physical layer issues of the resource management problem and interworked with them.

Characterization of inflammatory cell infiltration in feline allergic skin disease.

PubMed

Taglinger, K; Day, M J; Foster, A P

2007-11-01

Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.

Timing of Bone Marrow Cell Delivery Has Minimal Effects on Cell Viability and Cardiac Recovery Following Myocardial Infarction

PubMed Central

Swijnenburg, Rutger-Jan; Govaert, Johannes A.; van der Bogt, Koen E.A.; Pearl, Jeremy I.; Huang, Mei; Stein, William; Hoyt, Grant; Vogel, Hannes; Contag, Christopher H.; Robbins, Robert C.; Wu, Joseph C.

2011-01-01

Background Despite ongoing clinical trials, the optimal time for delivery of bone marrow mononuclear cells (BMCs) following myocardial infarction (MI) is unclear. We compared the viability and effects of transplanted BMCs on cardiac function in the acute and sub-acute inflammatory phases of MI. Methods and Results The time-course of acute inflammatory cell infiltration was quantified by FACS analysis of enzymatically digested hearts of FVB mice (n=12) following LAD ligation. Mac-1+Gr-1high neutrophil infiltration peaked at day 4. BMCs were harvested from transgenic FVB mice expressing firefly luciferase (Fluc) and green fluorescent protein (GFP). Afterwards, 2.5×106 BMCs were injected into the left ventricle of wild-type FVB mice either immediately (Acute BMC) or 7 days (Sub-acute BMC) after MI, or after a sham procedure (n=8 per group). In vivo bioluminescence imaging (BLI) showed an early signal increase in both BMC groups at day 7, followed by a non-significant trend (P=0.203) towards improved BMC survival in the Sub-acute BMC group that persisted until the BLI signal reached background levels after 42 days. Compared to controls (MI + saline injection), echocardiography showed a significant preservation of fractional shortening at 4 weeks (Acute BMC vs saline; P<0.01) and 6 weeks (both BMC groups vs saline; P<0.05), but no significant differences between the two BMC groups. FACS analysis of BMC injected hearts at day 7 revealed that GFP+ BMCs expressed hematopoietic (CD45, Mac-1, Gr-1), minimal progenitor (Sca-1, c-kit), and no endothelial (CD133, Flk-1) or cardiac (Trop-T) cell markers. Conclusion Timing of BMC delivery has minimal effects on intramyocardial retention and preservation of cardiac function. In general, there is poor long-term engraftment and BMCs tend to adopt inflammatory cell phenotypes. PMID:19920031

EC00-0283-4

NASA Image and Video Library

2000-09-18

Technician Marshall MacCready carefully lays a panel of solar cells into place on a wing section of the Helios Prototype flying wing at AeroVironment's Design Development Center in Simi Valley, California. The bi-facial cells, manufactured by SunPower, Inc., of Sunnyvale, California, are among 64,000 solar cells which have been installed on the solar-powered aircraft to provide electricity to its 14 motors and operating systems.

Pollution Emissions, Environmental Policy, and Marginal Abatement Costs.

PubMed

He, Ling-Yun; Ou, Jia-Jia

2017-12-05

Pollution emissions impose serious social negative externalities, especially in terms of public health. To reduce pollution emissions cost-effectively, the marginal abatement costs (MACs) of pollution emissions must be determined. Since the industrial sectors are the essential pillars of China's economic growth, as well as leading energy consumers and sulfur dioxide (SO₂) emitters, estimating MACs of SO₂ emissions at the industrial level can provide valuable information for all abatement efforts. This paper tries to address the critical and essential issue in pollution abatement: How do we determine the MACs of pollution emissions in China? This paper first quantifies the SO₂ emission contribution of different industrial sectors in the Chinese economy by an Input-Output method and then estimates MACs of SO₂ for industrial sectors at the national level, provincial level, and sectoral level by the shadow price theory. Our results show that six sectors (e.g., the Mining and Washing of Coal sector) should be covered in the Chinese pollution emission trading system. We have also found that the lowest SO₂ shadow price is 2000 Yuan/ton at the national level, and that shadow prices should be set differently at the provincial level. Our empirical study has several important policy implications, e.g., the estimated MACs may be used as a pricing benchmark through emission allowance allocation. In this paper, the MACs of industrial sectors are calculated from the national, provincial and sectoral levels; therefore, we provide an efficient framework to track the complex relationship between sectors and provinces.

Evaluation of GenoType NTM-DR Assay for Identification of Mycobacterium chimaera.

PubMed

Mok, Simone; Rogers, Thomas R; Fitzgibbon, Margaret

2017-06-01

Identification of species within the Mycobacterium avium complex (MAC) is difficult, and most current diagnostic laboratory tests cannot distinguish between species included in the complex. Differentiation of species within the MAC is important, as Mycobacterium chimaera has recently emerged as a major cause of invasive cardiovascular infections following open heart surgery. A new commercial diagnostic assay, GenoType NTM-DR ver. 1.0, is intended to differentiate between three species within the MAC, namely, Mycobacterium avium , Mycobacterium intracellulare , and Mycobacterium chimaera In this study, we investigated an archival collection of 173 MAC isolates using 16S rRNA and 16S-23S internal transcribed spacer (ITS) gene sequencing, and GenoType NTM-DR was evaluated for identifying M. chimaera and other species belonging to the MAC. Species identification of 157/173 (91%) isolates with the GenoType NTM-DR assay was in agreement with 16S rRNA and 16S-23S ITS gene sequencing results. Misidentification occurred with 16 isolates which belonged to four species included in the MAC that are rarely encountered in clinical specimens. Despite some limitations of this assay, GenoType NTM-DR had 100% specificity for identifying M. chimaera This novel assay will enable diagnostic laboratories to differentiate species belonging to the Mycobacterium avium complex and to accurately identify M. chimaera It can produce rapid results and is also more cost efficient than gene sequencing methods. Copyright © 2017 American Society for Microbiology.

C-reactive protein specifically binds to Fcgamma receptor type I on a macrophage-like cell line.

PubMed

Tron, Kyrylo; Manolov, Dimitar E; Röcker, Carlheinz; Kächele, Martin; Torzewski, Jan; Nienhaus, G Ulrich

2008-05-01

C-reactive protein (CRP) is a prototype acute-phase protein that may be intimately involved in human disease. Its cellular receptors are still under debate; the main candidates are FcR for immunoglobulin G, as CRP was shown to bind specifically to FcgammaRI and FcgammaRIIa. Using ultrasensitive confocal live-cell imaging, we have studied CRP binding to FcgammaR naturally expressed in the plasma membranes of cells from a human leukemia cell line (Mono Mac 6). These macrophage-like cells express high levels of FcgammaRI and FcgammaRII. They were shown to bind fluorescently labeled CRP with micromolar affinity, KD = (6.6 +/- 1.5) microM. CRP binding could be inhibited by pre-incubation with human but not mouse IgG and was thus FcgammaR-specific. Blocking of FcgammaRI by an FcgammaRI-specific antibody abolished CRP binding essentially completely, whereas application of antibodies against FcgammaRII did not have a noticeable effect. In fluorescence images of Mono Mac 6 cells, the intensity patterns of bound CRP were correlated with those of FcgammaRI, but not FcgammaRII. These results provide clear evidence of specific interactions between CRP and FcgammaR (predominantly FcgammaRI) naturally expressed on macrophage-like cells.

Effects of Chinese Propolis in Protecting Bovine Mammary Epithelial Cells against Mastitis Pathogens-Induced Cell Damage.

PubMed

Wang, Kai; Jin, Xiao-Lu; Shen, Xiao-Ge; Sun, Li-Ping; Wu, Li-Ming; Wei, Jiang-Qin; Marcucci, Maria Cristina; Hu, Fu-Liang; Liu, Jian-Xin

2016-01-01

Chinese propolis (CP), an important hive product, can alleviate inflammatory responses. However, little is known regarding the potential of propolis treatment for mastitis control. To investigate the anti-inflammatory effects of CP on bovine mammary epithelial cells (MAC-T), we used a range of pathogens to induce cellular inflammatory damage. Cell viability was determined and expressions of inflammatory/antioxidant genes were measured. Using a cell-based reporter assay system, we evaluated CP and its primary constituents on the NF-κB and Nrf2-ARE transcription activation. MAC-T cells treated with bacterial endotoxin (lipopolysaccharide, LPS), heat-inactivated Escherichia coli, and Staphylococcus aureus exhibited significant decreases in cell viability while TNF-α and lipoteichoic acid (LTA) did not. Pretreatment with CP prevented losses in cell viability associated with the addition of killed bacteria or bacterial endotoxins. There were also corresponding decreases in expressions of proinflammatory IL-6 and TNF-α mRNA. Compared with the mastitis challenged cells, enhanced expressions of antioxidant genes HO-1, Txnrd-1, and GCLM were observed in CP-treated cells. CP and its polyphenolic active components (primarily caffeic acid phenethyl ester and quercetin) had strong inhibitive effects against NF-κB activation and increased the transcriptional activity of Nrf2-ARE. These findings suggest that propolis may be valuable in the control of bovine mastitis.

Effects of Chinese Propolis in Protecting Bovine Mammary Epithelial Cells against Mastitis Pathogens-Induced Cell Damage

PubMed Central

Jin, Xiao-Lu; Shen, Xiao-Ge; Sun, Li-Ping; Wu, Li-Ming; Wei, Jiang-Qin; Marcucci, Maria Cristina; Hu, Fu-Liang; Liu, Jian-Xin

2016-01-01

Chinese propolis (CP), an important hive product, can alleviate inflammatory responses. However, little is known regarding the potential of propolis treatment for mastitis control. To investigate the anti-inflammatory effects of CP on bovine mammary epithelial cells (MAC-T), we used a range of pathogens to induce cellular inflammatory damage. Cell viability was determined and expressions of inflammatory/antioxidant genes were measured. Using a cell-based reporter assay system, we evaluated CP and its primary constituents on the NF-κB and Nrf2-ARE transcription activation. MAC-T cells treated with bacterial endotoxin (lipopolysaccharide, LPS), heat-inactivated Escherichia coli, and Staphylococcus aureus exhibited significant decreases in cell viability while TNF-α and lipoteichoic acid (LTA) did not. Pretreatment with CP prevented losses in cell viability associated with the addition of killed bacteria or bacterial endotoxins. There were also corresponding decreases in expressions of proinflammatory IL-6 and TNF-α mRNA. Compared with the mastitis challenged cells, enhanced expressions of antioxidant genes HO-1, Txnrd-1, and GCLM were observed in CP-treated cells. CP and its polyphenolic active components (primarily caffeic acid phenethyl ester and quercetin) had strong inhibitive effects against NF-κB activation and increased the transcriptional activity of Nrf2-ARE. These findings suggest that propolis may be valuable in the control of bovine mastitis. PMID:27433029

Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications

PubMed Central

LAPTEVA, NATALIA; DURETT, APRIL G.; SUN, JIALI; ROLLINS, LISA A.; HUYE, LESLIE L.; FANG, JIAN; DANDEKAR, VARADA; MEI, ZHUYONG; JACKSON, KIMBERLEY; VERA, JUAN; ANDO, JUN; NGO, MINHTRAN C.; COUSTAN-SMITH, ELAINE; CAMPANA, DARIO; SZMANIA, SUSANN; GARG, TARUN; MORENO-BOST, AMBERLY; VANRHEE, FRITS; GEE, ADRIAN P.; ROONEY, CLIONA M.

2016-01-01

Background aims Interest in natural killer (NK) cell-based immunotherapy has resurged since new protocols for the purification and expansion of large numbers of clinical-grade cells have become available. Methods We have successfully adapted a previously described NK expansion method that uses K562 cells expressing interleukin (IL)-15 and 4-1 BB Ligand (BBL) (K562-mb15-41BBL) to grow NK cells in novel gas-permeable static cell culture flasks (G-Rex). Results Using this system we produced up to 19 × 109 functional NK cells from unseparated apheresis products, starting with 15 × 107 CD3− CD56+ NK cells, within 8–10 days of culture. The G-Rex yielded a higher fold expansion of NK cells than conventional gas-permeable bags and required no cell manipulation or feeding during the culture period. We also showed that K562-mb15-41BBL cells up-regulated surface HLA class I antigen expression upon stimulation with the supernatants from NK cultures and stimulated alloreactive CD8+ T cells within the NK cultures. However, these CD3+ T cells could be removed successfully using the CliniMACS system. We describe our optimized NK cell cryopreservation method and show that the NK cells are viable and functional even after 12 months of cryopreservation. Conclusions We have successfully developed a static culture protocol for large-scale expansion of NK cells in the gas permeable G-Rex system under good manufacturing practice (GMP) conditions. This strategy is currently being used to produce NK cells for cancer immunotherapy. PMID:22900959

The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation

PubMed Central

Volmering, Stephanie; Block, Helena; Boras, Mark; Lowell, Clifford A.; Zarbock, Alexander

2016-01-01

SUMMARY Neutrophils are recruited from the blood to sites of sterile inflammation, where they are involved in wound healing but can also cause tissue damage. During sterile inflammation, necrotic cells release pro-inflammatory molecules including formylated peptides. However, the signaling pathway triggered by formylated peptides to integrin activation and leukocyte recruitment is unknown. By using spinning-disk confocal intravital microscopy, we examined the molecular mechanisms of leukocyte recruitment to sites of focal hepatic necrosis in vivo. We demonstrated that the Bruton’s tyrosine kinase (Btk) was required for multiple Mac-1 activation events involved in neutrophil recruitment and functions during sterile inflammation triggered by fMLF. The Src family kinase Hck, Wiskott-Aldrich-syndrome protein, and phospholipase Cγ2 were also involved in this pathway required for fMLF-triggered Mac-1 activation and neutrophil recruitment. Thus, we have identified a neutrophil Btk signalosome that is involved in a signaling pathway triggered by formylated peptides leading to the selective activation of Mac-1 and neutrophil recruitment during sterile inflammation. PMID:26777396

[Regulating effect of pineal gland peptides on development of T-lymphocytes in CBA aging mice: role of microenvironment of immune system organs and neuroendocrine factors].

PubMed

Labunets, I F; Butenko, G M; Khavinson, V Kh; Magdich, L V; Dragunova, V A; Pishel', I N; Azarskova, M V

2003-01-01

Studies were undertaken on the development of T-lymphocytes in adult and old CBA mice and its changes at aging after injections of pineal gland peptides. It was shown that in old mice the disturbances of T-cells differentiation are registered in bone marrow, thymus, spleen and characterized by the changes of lymphocyte markers expression, migration and proliferation of cells. In old mice FTS titer, melatonin and testosterone levels decreased, the balance of noradrenalin and serotonin in hypothalamus and the cell composition of microenvironment immune systems organs impaired. After chronic (18 mo) administration of the pineal gland preparation epithalamin the amount of stromal cells-precursors, CD4+ and Mac-1(+)-cells in old bone marrow increased, improved the migration of T-cell precursors from bone marrow to thymus and their proliferative potential. The proportion of CD3+, CD4+CD8-, CD4-CD8+, Mac-1(+)-cells in old thymus increased, while that of CD44(+)-cells decreased. The proportion of CD4-CD8(+)-cells in spleen increased. The most number of indices and their balance showed a pattern of adult mice. In old mice after epithalamin the balance of amines in hypothalamus improved, concentration of melatonin in pineal gland, testosterone and FTS titer in blood increased. Epithalon has also the possibility to increase of thymic endocrine function.

HOXB2, an adverse prognostic indicator for stage I lung adenocarcinomas, promotes invasion by transcriptional regulation of metastasis-related genes in HOP-62 non-small cell lung cancer cells.

PubMed

Inamura, Kentaro; Togashi, Yuki; Ninomiya, Hironori; Shimoji, Takashi; Noda, Tetsuo; Ishikawa, Yuichi

2008-01-01

Previously, using microarray and real-time RT-PCR analysis, we established that HOXB2 is an adverse prognostic indicator for Stage I lung adenocarcinomas. HOXB2 is one of the homeobox master development-controlling genes regulating morphogenesis and cell differentiation. The molecular functions of HOXB2 were analyzed with a small interfering RNA (siRNA) approach in HOP-62 human non-small cell lung cancer (NSCLC) cells featuring high HOXB2 expression. Matrigel invasion assays and microarray gene expression analysis were compared between the HOXB2-siRNA cells and the control cells. The Matrigel invasion assays showed attenuation of HOXB2 expression by siRNA to result in a significant decrease of invasiveness compared to the control cells (p = 0.0013, paired t-test). On microarray gene expression analysis, up-regulation of many metastasis-related genes and others correlating with HOXB2 expression was observed in the control case. With attenuation of HOXB2 expression, downregulation was noted for laminins alpha 4 and 5, involved in enriched signaling, and for Mac-2BP (Mac-2 binding protein) and integrin beta 4 amongst the genes having an enriched glycoprotein ontology. HOXB2 promotes invasion of lung cancer cells through the regulation of metastasis-related genes.

Calculation of the temporal gravity variation from spatially variable water storage change in soils and aquifers

NASA Astrophysics Data System (ADS)

Leirião, Sílvia; He, Xin; Christiansen, Lars; Andersen, Ole B.; Bauer-Gottwein, Peter

2009-02-01

SummaryTotal water storage change in the subsurface is a key component of the global, regional and local water balances. It is partly responsible for temporal variations of the earth's gravity field in the micro-Gal (1 μGal = 10 -8 m s -2) range. Measurements of temporal gravity variations can thus be used to determine the water storage change in the hydrological system. A numerical method for the calculation of temporal gravity changes from the output of hydrological models is developed. Gravity changes due to incremental prismatic mass storage in the hydrological model cells are determined to give an accurate 3D gravity effect. The method is implemented in MATLAB and can be used jointly with any hydrological simulation tool. The method is composed of three components: the prism formula, the MacMillan formula and the point-mass approximation. With increasing normalized distance between the storage prism and the measurement location the algorithm switches first from the prism equation to the MacMillan formula and finally to the simple point-mass approximation. The method was used to calculate the gravity signal produced by an aquifer pump test. Results are in excellent agreement with the direct numerical integration of the Theis well solution and the semi-analytical results presented in [Damiata, B.N., and Lee, T.-C., 2006. Simulated gravitational response to hydraulic testing of unconfined aquifers. Journal of Hydrology 318, 348-359]. However, the presented method can be used to forward calculate hydrology-induced temporal variations in gravity from any hydrological model, provided earth curvature effects can be neglected. The method allows for the routine assimilation of ground-based gravity data into hydrological models.

UW VLSI chip tester

NASA Astrophysics Data System (ADS)

McKenzie, Neil

1989-12-01

We present a design for a low-cost, functional VLSI chip tester. It is based on the Apple MacIntosh II personal computer. It tests chips that have up to 128 pins. All pin drivers of the tester are bidirectional; each pin is programmed independently as an input or an output. The tester can test both static and dynamic chips. Rudimentary speed testing is provided. Chips are tested by executing C programs written by the user. A software library is provided for program development. Tests run under both the Mac Operating System and A/UX. The design is implemented using Xilinx Logic Cell Arrays. Price/performance tradeoffs are discussed.

Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study

PubMed Central

van Halsema, Clare L.; Chihota, Violet N.; Gey van Pittius, Nicolaas C.; Fielding, Katherine L.; Lewis, James J.; van Helden, Paul D.; Churchyard, Gavin J.; Grant, Alison D.

2015-01-01

Background. The clinical relevance of nontuberculous mycobacteria (NTM), detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. Methods. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively. Results. Of 232 individuals included (228 (98%) male, median age 44 years), M. gordonae (60 individuals), M. kansasii (50), and M. avium complex (MAC: 38) were the commonest species. Of 38 MAC isolates, only 2 (5.3%) were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77%) among those tested. No differences were found in probability of death or medical separation by NTM species. Conclusions. M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment. PMID:26180817

A Convenient and Efficient Method to Enrich and Maintain Highly Proliferative Human Fetal Liver Stem Cells

PubMed Central

Guo, Xuan; Wang, Shu; Dou, Ya-ling; Guo, Xiang-fei; Chen, Zhao-li; Wang, Xin-wei; Shen, Zhi-qiang; Qiu, Zhi-gang

2015-01-01

Abstract Pluripotent human hepatic stem cells have broad research and clinical applications, which are, however, restricted by both limited resources and technical difficulties with respect to isolation of stem cells from the adult or fetal liver. In this study, we developed a convenient and efficient method involving a two-step in situ collagenase perfusion, gravity sedimentation, and Percoll density gradient centrifugation to enrich and maintain highly proliferative human fetal liver stem cells (hFLSCs). Using this method, the isolated hFLSCs entered into the exponential growth phase within 10 days and maintained sufficient proliferative activity to permit subculture for at least 20 passages without differentiation. Immunocytochemistry, immunofluorescence, and flow cytometry results showed that these cells expressed stem cell markers, such as c-kit, CD44, epithelial cell adhesion molecule (EpCAM), oval cell marker-6 (OV-6), epithelial marker cytokeratin 18 (CK18), biliary ductal marker CK19, and alpha-fetoprotein (AFP). Gene expression analysis showed that these cells had stable mRNA expression of c-Kit, EpCAM, neural cell adhesion molecule (NCAM), CK19, CK18, AFP, and claudin 3 (CLDN-3) throughout each passage while maintaining low levels of ALB, but with complete absence of cytochrome P450 3A4 (C3A4), phosphoenolpyruvate carboxykinase (PEPCK), telomeric repeat binding factor (TRF), and connexin 26 (CX26) expression. When grown in appropriate medium, these isolated liver stem cells could differentiate into hepatocytes, cholangiocytes, osteoblasts, adipocytes, or endothelial cells. Thus, we have demonstrated a more economical and efficient method to isolate hFLSCs than magnetic-activated cell sorting (MACS). This novel approach may provide an excellent tool to isolate highly proliferative hFLSCs for tissue engineering and regenerative therapies. PMID:25556695

A Convenient and Efficient Method to Enrich and Maintain Highly Proliferative Human Fetal Liver Stem Cells.

PubMed

Guo, Xuan; Wang, Shu; Dou, Ya-ling; Guo, Xiang-fei; Chen, Zhao-li; Wang, Xin-wei; Shen, Zhi-qiang; Qiu, Zhi-gang; Jin, Min; Li, Jun-wen

2015-06-01

Pluripotent human hepatic stem cells have broad research and clinical applications, which are, however, restricted by both limited resources and technical difficulties with respect to isolation of stem cells from the adult or fetal liver. In this study, we developed a convenient and efficient method involving a two-step in situ collagenase perfusion, gravity sedimentation, and Percoll density gradient centrifugation to enrich and maintain highly proliferative human fetal liver stem cells (hFLSCs). Using this method, the isolated hFLSCs entered into the exponential growth phase within 10 days and maintained sufficient proliferative activity to permit subculture for at least 20 passages without differentiation. Immunocytochemistry, immunofluorescence, and flow cytometry results showed that these cells expressed stem cell markers, such as c-kit, CD44, epithelial cell adhesion molecule (EpCAM), oval cell marker-6 (OV-6), epithelial marker cytokeratin 18 (CK18), biliary ductal marker CK19, and alpha-fetoprotein (AFP). Gene expression analysis showed that these cells had stable mRNA expression of c-Kit, EpCAM, neural cell adhesion molecule (NCAM), CK19, CK18, AFP, and claudin 3 (CLDN-3) throughout each passage while maintaining low levels of ALB, but with complete absence of cytochrome P450 3A4 (C3A4), phosphoenolpyruvate carboxykinase (PEPCK), telomeric repeat binding factor (TRF), and connexin 26 (CX26) expression. When grown in appropriate medium, these isolated liver stem cells could differentiate into hepatocytes, cholangiocytes, osteoblasts, adipocytes, or endothelial cells. Thus, we have demonstrated a more economical and efficient method to isolate hFLSCs than magnetic-activated cell sorting (MACS). This novel approach may provide an excellent tool to isolate highly proliferative hFLSCs for tissue engineering and regenerative therapies.

High-throughput, low-loss, low-cost, and label-free cell separation using electrophysiology-activated cell enrichment.

PubMed

Faraghat, Shabnam A; Hoettges, Kai F; Steinbach, Max K; van der Veen, Daan R; Brackenbury, William J; Henslee, Erin A; Labeed, Fatima H; Hughes, Michael P

2017-05-02

Currently, cell separation occurs almost exclusively by density gradient methods and by fluorescence- and magnetic-activated cell sorting (FACS/MACS). These variously suffer from lack of specificity, high cell loss, use of labels, and high capital/operating cost. We present a dielectrophoresis (DEP)-based cell-separation method, using 3D electrodes on a low-cost disposable chip; one cell type is allowed to pass through the chip whereas the other is retained and subsequently recovered. The method advances usability and throughput of DEP separation by orders of magnitude in throughput, efficiency, purity, recovery (cells arriving in the correct output fraction), cell losses (those which are unaccounted for at the end of the separation), and cost. The system was evaluated using three example separations: live and dead yeast; human cancer cells/red blood cells; and rodent fibroblasts/red blood cells. A single-pass protocol can enrich cells with cell recovery of up to 91.3% at over 300,000 cells per second with >3% cell loss. A two-pass protocol can process 300,000,000 cells in under 30 min, with cell recovery of up to 96.4% and cell losses below 5%, an effective processing rate >160,000 cells per second. A three-step protocol is shown to be effective for removal of 99.1% of RBCs spiked with 1% cancer cells while maintaining a processing rate of ∼170,000 cells per second. Furthermore, the self-contained and low-cost nature of the separator device means that it has potential application in low-contamination applications such as cell therapies, where good manufacturing practice compatibility is of paramount importance.

Real-Time Three-Dimensional Cell Segmentation in Large-Scale Microscopy Data of Developing Embryos.

PubMed

Stegmaier, Johannes; Amat, Fernando; Lemon, William C; McDole, Katie; Wan, Yinan; Teodoro, George; Mikut, Ralf; Keller, Philipp J

2016-01-25

We present the Real-time Accurate Cell-shape Extractor (RACE), a high-throughput image analysis framework for automated three-dimensional cell segmentation in large-scale images. RACE is 55-330 times faster and 2-5 times more accurate than state-of-the-art methods. We demonstrate the generality of RACE by extracting cell-shape information from entire Drosophila, zebrafish, and mouse embryos imaged with confocal and light-sheet microscopes. Using RACE, we automatically reconstructed cellular-resolution tissue anisotropy maps across developing Drosophila embryos and quantified differences in cell-shape dynamics in wild-type and mutant embryos. We furthermore integrated RACE with our framework for automated cell lineaging and performed joint segmentation and cell tracking in entire Drosophila embryos. RACE processed these terabyte-sized datasets on a single computer within 1.4 days. RACE is easy to use, as it requires adjustment of only three parameters, takes full advantage of state-of-the-art multi-core processors and graphics cards, and is available as open-source software for Windows, Linux, and Mac OS. Copyright © 2016 Elsevier Inc. All rights reserved.

Value of a quality assessment program in optimizing cryopreservation of peripheral blood mononuclear cells in a multicenter study.

PubMed

Aziz, Najib; Margolick, Joseph B; Detels, Roger; Rinaldo, Charles R; Phair, John; Jamieson, Beth D; Butch, Anthony W

2013-04-01

Cryopreservation of peripheral blood mononuclear cells (PBMC) allows assays of cellular function and phenotype to be performed in batches at a later time on PBMC at a central laboratory to minimize assay variability. The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of the natural and treated history of human immunodeficiency virus (HIV) infection that stores cryopreserved PBMC from participants two times a year at four study sites. In order to ensure consistent recovery of viable PBMC after cryopreservation, a quality assessment program was implemented and conducted in the MACS over a 6-year period. Every 4 months, recently cryopreserved PBMC from HIV-1-infected and HIV-1-uninfected participants at each MACS site were thawed and evaluated. The median recoveries of viable PBMC for HIV-1-infected and -uninfected participants were 80% and 83%, respectively. Thawed PBMC from both HIV-1-infected and -uninfected participants mounted a strong proliferative response to phytohemagglutinin, with median stimulation indices of 84 and 120, respectively. Expression of the lymphocyte surface markers CD3, CD4, and CD8 by thawed PBMC was virtually identical to what was observed on cells measured in real time using whole blood from the same participants. Furthermore, despite overall excellent performance of the four participating laboratories, problems were identified that intermittently compromised the quality of cryopreserved PBMC, which could be corrected and monitored for improvement over time. Ongoing quality assessment helps laboratories improve protocols and performance on a real-time basis to ensure optimal cryopreservation of PBMC for future studies.

Low-Power Embedded DSP Core for Communication Systems

NASA Astrophysics Data System (ADS)

Tsao, Ya-Lan; Chen, Wei-Hao; Tan, Ming Hsuan; Lin, Maw-Ching; Jou, Shyh-Jye

2003-12-01

This paper proposes a parameterized digital signal processor (DSP) core for an embedded digital signal processing system designed to achieve demodulation/synchronization with better performance and flexibility. The features of this DSP core include parameterized data path, dual MAC unit, subword MAC, and optional function-specific blocks for accelerating communication system modulation operations. This DSP core also has a low-power structure, which includes the gray-code addressing mode, pipeline sharing, and advanced hardware looping. Users can select the parameters and special functional blocks based on the character of their applications and then generating a DSP core. The DSP core has been implemented via a cell-based design method using a synthesizable Verilog code with TSMC 0.35[InlineEquation not available: see fulltext.]m SPQM and 0.25[InlineEquation not available: see fulltext.]m 1P5M library. The equivalent gate count of the core area without memory is approximately 50 k. Moreover, the maximum operating frequency of a[InlineEquation not available: see fulltext.] version is 100 MHz (0.35[InlineEquation not available: see fulltext.]m) and 140 MHz (0.25[InlineEquation not available: see fulltext.]m).

Energy-efficient boarder node medium access control protocol for wireless sensor networks.

PubMed

Razaque, Abdul; Elleithy, Khaled M

2014-03-12

This paper introduces the design, implementation, and performance analysis of the scalable and mobility-aware hybrid protocol named boarder node medium access control (BN-MAC) for wireless sensor networks (WSNs), which leverages the characteristics of scheduled and contention-based MAC protocols. Like contention-based MAC protocols, BN-MAC achieves high channel utilization, network adaptability under heavy traffic and mobility, and low latency and overhead. Like schedule-based MAC protocols, BN-MAC reduces idle listening time, emissions, and collision handling at low cost at one-hop neighbor nodes and achieves high channel utilization under heavy network loads. BN-MAC is particularly designed for region-wise WSNs. Each region is controlled by a boarder node (BN), which is of paramount importance. The BN coordinates with the remaining nodes within and beyond the region. Unlike other hybrid MAC protocols, BN-MAC incorporates three promising models that further reduce the energy consumption, idle listening time, overhearing, and congestion to improve the throughput and reduce the latency. One of the models used with BN-MAC is automatic active and sleep (AAS), which reduces the ideal listening time. When nodes finish their monitoring process, AAS lets them automatically go into the sleep state to avoid the idle listening state. Another model used in BN-MAC is the intelligent decision-making (IDM) model, which helps the nodes sense the nature of the environment. Based on the nature of the environment, the nodes decide whether to use the active or passive mode. This decision power of the nodes further reduces energy consumption because the nodes turn off the radio of the transceiver in the passive mode. The third model is the least-distance smart neighboring search (LDSNS), which determines the shortest efficient path to the one-hop neighbor and also provides cross-layering support to handle the mobility of the nodes. The BN-MAC also incorporates a semi-synchronous feature with a low duty cycle, which is advantageous for reducing the latency and energy consumption for several WSN application areas to improve the throughput. BN-MAC uses a unique window slot size to enhance the contention resolution issue for improved throughput. BN-MAC also prefers to communicate within a one-hop destination using Anycast, which maintains load balancing to maintain network reliability. BN-MAC is introduced with the goal of supporting four major application areas: monitoring and behavioral areas, controlling natural disasters, human-centric applications, and tracking mobility and static home automation devices from remote places. These application areas require a congestion-free mobility-supported MAC protocol to guarantee reliable data delivery. BN-MAC was evaluated using network simulator-2 (ns2) and compared with other hybrid MAC protocols, such as Zebra medium access control (Z-MAC), advertisement-based MAC (A-MAC), Speck-MAC, adaptive duty cycle SMAC (ADC-SMAC), and low-power real-time medium access control (LPR-MAC). The simulation results indicate that BN-MAC is a robust and energy-efficient protocol that outperforms other hybrid MAC protocols in the context of quality of service (QoS) parameters, such as energy consumption, latency, throughput, channel access time, successful delivery rate, coverage efficiency, and average duty cycle.

Energy-Efficient Boarder Node Medium Access Control Protocol for Wireless Sensor Networks

PubMed Central

Razaque, Abdul; Elleithy, Khaled M.

2014-01-01

This paper introduces the design, implementation, and performance analysis of the scalable and mobility-aware hybrid protocol named boarder node medium access control (BN-MAC) for wireless sensor networks (WSNs), which leverages the characteristics of scheduled and contention-based MAC protocols. Like contention-based MAC protocols, BN-MAC achieves high channel utilization, network adaptability under heavy traffic and mobility, and low latency and overhead. Like schedule-based MAC protocols, BN-MAC reduces idle listening time, emissions, and collision handling at low cost at one-hop neighbor nodes and achieves high channel utilization under heavy network loads. BN-MAC is particularly designed for region-wise WSNs. Each region is controlled by a boarder node (BN), which is of paramount importance. The BN coordinates with the remaining nodes within and beyond the region. Unlike other hybrid MAC protocols, BN-MAC incorporates three promising models that further reduce the energy consumption, idle listening time, overhearing, and congestion to improve the throughput and reduce the latency. One of the models used with BN-MAC is automatic active and sleep (AAS), which reduces the ideal listening time. When nodes finish their monitoring process, AAS lets them automatically go into the sleep state to avoid the idle listening state. Another model used in BN-MAC is the intelligent decision-making (IDM) model, which helps the nodes sense the nature of the environment. Based on the nature of the environment, the nodes decide whether to use the active or passive mode. This decision power of the nodes further reduces energy consumption because the nodes turn off the radio of the transceiver in the passive mode. The third model is the least-distance smart neighboring search (LDSNS), which determines the shortest efficient path to the one-hop neighbor and also provides cross-layering support to handle the mobility of the nodes. The BN-MAC also incorporates a semi-synchronous feature with a low duty cycle, which is advantageous for reducing the latency and energy consumption for several WSN application areas to improve the throughput. BN-MAC uses a unique window slot size to enhance the contention resolution issue for improved throughput. BN-MAC also prefers to communicate within a one-hop destination using Anycast, which maintains load balancing to maintain network reliability. BN-MAC is introduced with the goal of supporting four major application areas: monitoring and behavioral areas, controlling natural disasters, human-centric applications, and tracking mobility and static home automation devices from remote places. These application areas require a congestion-free mobility-supported MAC protocol to guarantee reliable data delivery. BN-MAC was evaluated using network simulator-2 (ns2) and compared with other hybrid MAC protocols, such as Zebra medium access control (Z-MAC), advertisement-based MAC (A-MAC), Speck-MAC, adaptive duty cycle SMAC (ADC-SMAC), and low-power real-time medium access control (LPR-MAC). The simulation results indicate that BN-MAC is a robust and energy-efficient protocol that outperforms other hybrid MAC protocols in the context of quality of service (QoS) parameters, such as energy consumption, latency, throughput, channel access time, successful delivery rate, coverage efficiency, and average duty cycle. PMID:24625737

Pollution Emissions, Environmental Policy, and Marginal Abatement Costs

PubMed Central

He, Ling-Yun; Ou, Jia-Jia

2017-01-01

Pollution emissions impose serious social negative externalities, especially in terms of public health. To reduce pollution emissions cost-effectively, the marginal abatement costs (MACs) of pollution emissions must be determined. Since the industrial sectors are the essential pillars of China’s economic growth, as well as leading energy consumers and sulfur dioxide (SO2) emitters, estimating MACs of SO2 emissions at the industrial level can provide valuable information for all abatement efforts. This paper tries to address the critical and essential issue in pollution abatement: How do we determine the MACs of pollution emissions in China? This paper first quantifies the SO2 emission contribution of different industrial sectors in the Chinese economy by an Input-Output method and then estimates MACs of SO2 for industrial sectors at the national level, provincial level, and sectoral level by the shadow price theory. Our results show that six sectors (e.g., the Mining and Washing of Coal sector) should be covered in the Chinese pollution emission trading system. We have also found that the lowest SO2 shadow price is 2000 Yuan/ton at the national level, and that shadow prices should be set differently at the provincial level. Our empirical study has several important policy implications, e.g., the estimated MACs may be used as a pricing benchmark through emission allowance allocation. In this paper, the MACs of industrial sectors are calculated from the national, provincial and sectoral levels; therefore, we provide an efficient framework to track the complex relationship between sectors and provinces. PMID:29206170

Clinical grade isolation of regulatory T cells from G-CSF mobilized peripheral blood improves with initial depletion of monocytes

PubMed Central

Patel, Pritesh; Mahmud, Dolores; Park, Youngmin; Yoshinaga, Kazumi; Mahmud, Nadim; Rondelli, Damiano

2015-01-01

Clinical isolation of circulating CD4+CD25+ regulatory T cells (Tregs) from peripheral blood mononuclear cells is usually performed by CD4+ cell negative selection followed by CD25+ cell positive selection. Although G-CSF mobilized peripheral blood (G-PBSC) contains a high number of Tregs, a high number of monocytes in G-PBSC limits Treg isolation. Using a small scale device (MidiMACS, Miltenyi) we initially demonstrated that an initial depletion of monocytes would be necessary to obtaina separation of CD4+CD25+FoxP3+CD127- cells from G-PBSC (G-Tregs) with a consistent purity >70% and inhibitory activity of T cell alloreactivity in-vitro. We then validated the same approach in a clinical scale setting by separating G-Tregs with clinically available antibodies to perform a CD8+CD19+CD14+ cell depletion followed by CD25+ cell selection (2-step process) or by adding an initial CD14+ cell depletion (3-step process) using a CliniMACS column. The 3-step approach resulted in a better purity (81±12% vs. 35±33%) and yield (66% vs. 39%). Clinically isolated G-Tregs were also FoxP3+CD127dim and functionally suppressive in-vitro. Our findings suggest that a better and more consistent purity of Tregs can be achieved from G-PBSC by an initial single depletion of monocytes prior to selection of CD4+CD25+ cells. PMID:27069755

Streamlined method for parallel identification of single domain antibodies to membrane receptors on whole cells

PubMed Central

Rossotti, Martín; Tabares, Sofía; Alfaya, Lucía; Leizagoyen, Carmen; Moron, Gabriel; González-Sapienza, Gualberto

2015-01-01

BACKGROUND Owing to their minimal size, high production yield, versatility and robustness, the recombinant variable domain (nanobody) of camelid single chain antibodies are valued affinity reagents for research, diagnostic, and therapeutic applications. While their preparation against purified antigens is straightforward, the generation of nanobodies to difficult targets such as multi-pass or complex membrane cell receptors remains challenging. Here we devised a platform for high throughput identification of nanobodies to cell receptor based on the use of a biotin handle. METHODS Using a biotin-acceptor peptide tag, the in vivo biotinylation of nanobodies in 96 well culture blocks was optimized allowing their parallel analysis by flow cytometry and ELISA, and their direct used for pull-down/MS target identification. RESULTS The potential of this strategy was demonstrated by the selection and characterization of panels of nanobodies to Mac-1 (CD11b/CD18), MHC II and the mouse Ly-5 leukocyte common antigen (CD45) receptors, from a VHH library obtained from a llama immunized with mouse bone marrow derived dendritic cells. By on and off switching of the addition of biotin, the method also allowed the epitope binning of the selected Nbs directly on cells. CONCLUSIONS This strategy streamline the selection of potent nanobodies to complex antigens, and the selected nanobodies constitute ready-to-use biotinylated reagents. GENERAL SIGNIFICANCE This method will accelerate the discovery of nanobodies to cell membrane receptors which comprise the largest group of drug and analytical targets. PMID:25819371

Prognostic Comparison Between Mucinous and Nonmucinous Adenocarcinoma in Colorectal Cancer

PubMed Central

Park, Jong Seob; Huh, Jung Wook; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong; Chun, Ho-Kyung

2015-01-01

Abstract Mucinous adenocarcinoma (MAC) is a histological subtype of colorectal cancer. The oncologic behavior of MAC differs from nonmucinous adenocarcinoma (non-MAC). Our aim in this study was to characterize patients with colorectal MAC through evaluation of a large, institutional-based cohort with long-term follow-up. A total of 6475 patients with stages I to III colorectal cancer who underwent radical surgery were enrolled from January 2000 to December 2010. Prognostic comparison between MAC (n = 274, 4.2%) and non-MAC was performed. The median follow-up period was 48.0 months. Patients with MAC were younger than those without MAC (P = 0.012) and had larger tumor size (P < 0.001), higher preoperative carcinoembryonic antigen (P < 0.001), higher pathologic T stage (P < 0.001), more right-sided colon cancer (49.3%, P < 0.001), and more frequent high-frequency microsatellite instability (10.2%, P < 0.001). Five-year disease-free survival (DFS) was 76.5% in the MAC group and 83.2% in the non-MAC group (P = 0.008), and 5-year overall survival was 81.4% versus 87.4%, respectively (P = 0.005). Mucinous histology (MAC vs non-MAC) in the entire cohort was not an independent prognostic factor of DFS but had a statistical tendency (P = 0.071). In subgroup analysis of colon cancer without rectal cancer, mucinous histology was an independent prognostic factor (P = 0.026). MAC was found at more advanced stage, located mainly at the right side and was an independent factor of survival in colon cancer. Because of the unique biological behavior of MAC, patients with MAC require special consideration during follow-up. PMID:25881840

Functional implications of an intermeshing cogwheel-like interaction between TolC and MacA in the action of macrolide-specific efflux pump MacAB-TolC.

PubMed

Xu, Yongbin; Song, Saemee; Moeller, Arne; Kim, Nahee; Piao, Shunfu; Sim, Se-Hoon; Kang, Mooseok; Yu, Wookyung; Cho, Hyun-Soo; Chang, Iksoo; Lee, Kangseok; Ha, Nam-Chul

2011-04-15

Macrolide-specific efflux pump MacAB-TolC has been identified in diverse gram-negative bacteria including Escherichia coli. The inner membrane transporter MacB requires the outer membrane factor TolC and the periplasmic adaptor protein MacA to form a functional tripartite complex. In this study, we used a chimeric protein containing the tip region of the TolC α-barrel to investigate the role of the TolC α-barrel tip region with regard to its interaction with MacA. The chimeric protein formed a stable complex with MacA, and the complex formation was abolished by substitution at the functionally essential residues located at the MacA α-helical tip region. Electron microscopic study delineated that this complex was made by tip-to-tip interaction between the tip regions of the α-barrels of TolC and MacA, which correlated well with the TolC and MacA complex calculated by molecular dynamics. Taken together, our results demonstrate that the MacA hexamer interacts with TolC in a tip-to-tip manner, and implies the manner by which MacA induces opening of the TolC channel.

Functional Implications of an Intermeshing Cogwheel-like Interaction between TolC and MacA in the Action of Macrolide-specific Efflux Pump MacAB-TolC*

PubMed Central

Xu, Yongbin; Song, Saemee; Moeller, Arne; Kim, Nahee; Piao, Shunfu; Sim, Se-Hoon; Kang, Mooseok; Yu, Wookyung; Cho, Hyun-Soo; Chang, Iksoo; Lee, Kangseok; Ha, Nam-Chul

2011-01-01

Macrolide-specific efflux pump MacAB-TolC has been identified in diverse Gram-negative bacteria including Escherichia coli. The inner membrane transporter MacB requires the outer membrane factor TolC and the periplasmic adaptor protein MacA to form a functional tripartite complex. In this study, we used a chimeric protein containing the tip region of the TolC α-barrel to investigate the role of the TolC α-barrel tip region with regard to its interaction with MacA. The chimeric protein formed a stable complex with MacA, and the complex formation was abolished by substitution at the functionally essential residues located at the MacA α-helical tip region. Electron microscopic study delineated that this complex was made by tip-to-tip interaction between the tip regions of the α-barrels of TolC and MacA, which correlated well with the TolC and MacA complex calculated by molecular dynamics. Taken together, our results demonstrate that the MacA hexamer interacts with TolC in a tip-to-tip manner, and implies the manner by which MacA induces opening of the TolC channel. PMID:21325274

The MacGyver effect: alive and well in health services research?

PubMed Central

2011-01-01

Background In a manner similar to the television action hero MacGyver, health services researchers need to respond to the pressure of unpredictable demands and constrained time frames. The results are often both innovative and functional, with the creation of outputs that could not have been anticipated in the initial planning and design of the research. Discussion In the conduct of health services research many challenges to robust research processes are generated as a result of the interface between academic research, health policy and implementation agendas. Within a complex and rapidly evolving environment the task of the health services researcher is, therefore, to juggle sometimes contradictory pressures to produce valid results. Summary This paper identifies the MacGyver-type dilemmas which arise in health services research, wherein innovation may be called for, to maintain the intended scientific method and rigour. These 'MacGyver drivers' are framed as opposing issues from the perspective of both academic and public policy communities. The ideas expressed in this paper are illustrated by four examples from research projects positioned at the interface between public policy strategy and academia. PMID:21929826

Right hemisphere damage: Communication processing in adults evaluated by the Brazilian Protocole MEC – Bateria MAC

PubMed Central

Fonseca, Rochele Paz; Fachel, Jandyra Maria Guimarães; Chaves, Márcia Lorena Fagundes; Liedtke, Francéia Veiga; Parente, Maria Alice de Mattos Pimenta

2007-01-01

Right-brain-damaged individuals may present discursive, pragmatic, lexical-semantic and/or prosodic disorders. Objective To verify the effect of right hemisphere damage on communication processing evaluated by the Brazilian version of the Protocole Montréal d’Évaluation de la Communication (Montreal Communication Evaluation Battery) – Bateria Montreal de Avaliação da Comunicação, Bateria MAC, in Portuguese. Methods A clinical group of 29 right-brain-damaged participants and a control group of 58 non-brain-damaged adults formed the sample. A questionnaire on sociocultural and health aspects, together with the Brazilian MAC Battery was administered. Results Significant differences between the clinical and control groups were observed in the following MAC Battery tasks: conversational discourse, unconstrained, semantic and orthographic verbal fluency, linguistic prosody repetition, emotional prosody comprehension, repetition and production. Moreover, the clinical group was less homogeneous than the control group. Conclusions A right-brain-damage effect was identified directly, on three communication processes: discursive, lexical-semantic and prosodic processes, and indirectly, on pragmatic process. PMID:29213400

[Mechanical testing of implant properties of thoracoscopic implantation of ventral spinal stabilizing systems. Comparative study with the ISO/DIS 12189-2 corpectomy model and an improved synthetic model].

PubMed

Grupp, T M; Beisse, R; Potulski, M; Marnay, T; Beger, J; Blömer, W

2002-04-01

A new modular anterior fixation system MACS TL (modular anterior construct system for the thoracic and lumbar spine) has been developed for use in thoracoscopic spondylodesis. This system demonstrates high angular stability and meets the surgical requirements for an endoscopic approach. The objective of the current study was fatigue testing of the MACS TL implant system using a corpectomy model according to ISO/DIS 12189-2 and a synthetic model recently developed by Kotani et al. [6]. The MACS TL system demonstrated good mechanical properties with a high stiffness compared to the published data reviewed. The importance of dynamic testing in a corpectomy model has been demonstrated by comparing the MACS TL plate system with an early prototype, which has not yet been clinically evaluated. The corpectomy model according to Kotani et al. offers an interesting alternative to the ISO/DIS 12189-2 test method for asymmetrically designed and antero-laterally positioned spinal implants due to the unconstrained ball joint.

Numerical simulation of heat transfer in power law fluid flow through a stenosed artery

NASA Astrophysics Data System (ADS)

Talib, Amira Husni; Abdullah, Ilyani

2017-11-01

A numerical study of heat transfer in a power law fluid is investigated in this paper. The blood flow is treated as power law fluid with a presence of cosine shaped stenosis. This study reveals the effect of stenosis on the heat transfer and velocity of blood flowing in the constricted artery. The governing and energy equations are formulated in a cylindrical coordinate system. Hence, the set of equations and boundary conditions are solved numerically by Marker and Cell (MAC) method. The graphical result shows the profile of blood temperature is increased while the blood velocity is decreased at the critical height of stenosis.

FEAMAC/CARES Stochastic-Strength-Based Damage Simulation Tool for Ceramic Matrix Composites

NASA Technical Reports Server (NTRS)

Nemeth, Noel; Bednarcyk, Brett; Pineda, Evan; Arnold, Steven; Mital, Subodh; Murthy, Pappu; Bhatt, Ramakrishna

2016-01-01

Reported here is a coupling of two NASA developed codes: CARES (Ceramics Analysis and Reliability Evaluation of Structures) with the MAC/GMC (Micromechanics Analysis Code/ Generalized Method of Cells) composite material analysis code. The resulting code is called FEAMAC/CARES and is constructed as an Abaqus finite element analysis UMAT (user defined material). Here we describe the FEAMAC/CARES code and an example problem (taken from the open literature) of a laminated CMC in off-axis loading is shown. FEAMAC/CARES performs stochastic-strength-based damage simulation response of a CMC under multiaxial loading using elastic stiffness reduction of the failed elements.

Stochastic-Strength-Based Damage Simulation Tool for Ceramic Matrix Composite

NASA Technical Reports Server (NTRS)

Nemeth, Noel; Bednarcyk, Brett; Pineda, Evan; Arnold, Steven; Mital, Subodh; Murthy, Pappu

2015-01-01

Reported here is a coupling of two NASA developed codes: CARES (Ceramics Analysis and Reliability Evaluation of Structures) with the MAC/GMC (Micromechanics Analysis Code/ Generalized Method of Cells) composite material analysis code. The resulting code is called FEAMAC/CARES and is constructed as an Abaqus finite element analysis UMAT (user defined material). Here we describe the FEAMAC/CARES code and an example problem (taken from the open literature) of a laminated CMC in off-axis loading is shown. FEAMAC/CARES performs stochastic-strength-based damage simulation response of a CMC under multiaxial loading using elastic stiffness reduction of the failed elements.

Development and Application of a Tool for Optimizing Composite Matrix Viscoplastic Material Parameters

NASA Technical Reports Server (NTRS)

Murthy, Pappu L. N.; Naghipour Ghezeljeh, Paria; Bednarcyk, Brett A.

2018-01-01

This document describes a recently developed analysis tool that enhances the resident capabilities of the Micromechanics Analysis Code with the Generalized Method of Cells (MAC/GMC) and its application. MAC/GMC is a composite material and laminate analysis software package developed at NASA Glenn Research Center. The primary focus of the current effort is to provide a graphical user interface (GUI) capability that helps users optimize highly nonlinear viscoplastic constitutive law parameters by fitting experimentally observed/measured stress-strain responses under various thermo-mechanical conditions for braided composites. The tool has been developed utilizing the MATrix LABoratory (MATLAB) (The Mathworks, Inc., Natick, MA) programming language. Illustrative examples shown are for a specific braided composite system wherein the matrix viscoplastic behavior is represented by a constitutive law described by seven parameters. The tool is general enough to fit any number of experimentally observed stress-strain responses of the material. The number of parameters to be optimized, as well as the importance given to each stress-strain response, are user choice. Three different optimization algorithms are included: (1) Optimization based on gradient method, (2) Genetic algorithm (GA) based optimization and (3) Particle Swarm Optimization (PSO). The user can mix and match the three algorithms. For example, one can start optimization with either 2 or 3 and then use the optimized solution to further fine tune with approach 1. The secondary focus of this paper is to demonstrate the application of this tool to optimize/calibrate parameters for a nonlinear viscoplastic matrix to predict stress-strain curves (for constituent and composite levels) at different rates, temperatures and/or loading conditions utilizing the Generalized Method of Cells. After preliminary validation of the tool through comparison with experimental results, a detailed virtual parametric study is presented wherein the combined effects of temperature and loading rate on the predicted response of a braided composite is investigated.

Hydroxyapatite and Calcified Elastin Induce Osteoblast-like Differentiation in Rat Aortic Smooth Muscle Cells

PubMed Central

Lei, Yang; Sinha, Aditi; Nosoudi, Nasim; Grover, Ankit; Vyavahare, Naren

2014-01-01

Vascular calcification can be categorized into two different types. Intimal calcification related to atherosclerosis and elastin-specific medial arterial calcification (MAC). Osteoblast-like differentiation of vascular smooth muscle cells (VSMCs) has been shown in both types; however, how this relates to initiation of vascular calcification is unclear. We hypothesize that the initial deposition of hydroxyapatite-like mineral in MAC occurs on degraded elastin first and that causes osteogenic transformation of VSMCs. To test this, rat aortic smooth muscle cells (RASMCs) were cultured on hydroxyapatite crystals and calcified aortic elastin. Using RT-PCR and specific protein assays, we demonstrate that RASMCs lose their smooth muscle lineage markers like alpha smooth muscle actin (SMA) and myosin heavy chain (MHC) and undergo chondrogenic/osteogenic transformation. This is indicated by an increase in the expression of typical chondrogenic proteins such as aggrecan, collagen type II alpha 1(Col2a1) and bone proteins such as runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, when calcified conditions are removed, cells return to their original phenotype. Our data supports the hypothesis that elastin degradation and calcification precedes VSMCs' osteoblast-like differentiation. PMID:24447384

Leishmaniosis and generalized demodicosis in three dogs: a clinicopathological and immunohistochemical study.

PubMed

Mozos, E; Pérez, J; Day, M J; Lucena, R; Ginel, P J

1999-04-01

This paper describes the clinicopathological and immunohistochemical aspects of the skin lesions in three dogs with leishmaniosis and generalized demodicosis. Diffuse alopecia, crusts, folliculitis and furunculosis, as commonly seen in generalized demodicosis, were prominent in all the dogs. MicroIscopically, there was a diffuse and perifollicular superficial and deep granulomatous dermatitis and, in two dogs, both Copyright Demodex canis mites and Leishmania spp. amastigotes were observed in the same lesions. Numerous Mac387(+)macrophages were observed in the inflammatory infiltrates, but macrophages loaded with amastigotes were Mac387(-). In all cases, immunoreactive CD3 lymphocytes were sparse, both in the granulomatous and perifollicular infiltrates. There were numerous IgG+, IgG4(+)-secreting plasma cells in areas of folliculitis and furunculosis and fewer IgG2(+), IgG3(+), IgA+and IgM+-secreting plasma cells in the inflammatory infiltrate. In all cases, MHC Class II was expressed by the majority of dermal macrophages and dendritic cells, as well as by lymphocytes and fibroblasts. The paucity of CD3(+)lymphocytes, usually abundant in D. canis lesions, points to leishmania-induced cell-mediated immunosuppression as a predisposing factor for generalized demodicosis. 1999 W.B. Saunders and Company Ltd.

Global Phosphoproteomics of Activated B Cells Using Complementary Metal Ion Functionalized Soluble Nanopolymers

PubMed Central

2015-01-01

Engagement of the B cell receptor for antigen (BCR) leads to immune responses through a cascade of intracellular signaling events. Most studies to date have focused on the BCR and protein tyrosine phosphorylation. Because spleen tyrosine kinase, Syk, is an upstream kinase in multiple BCR-regulated signaling pathways, it also affects many downstream events that are modulated through the phosphorylation of proteins on serine and threonine residues. Here, we report a novel phosphopeptide enrichment strategy and its application to a comprehensive quantitative phosphoproteomics analysis of Syk-dependent downstream signaling events in B cells, focusing on serine and threonine phosphorylation. Using a combination of the Syk inhibitor piceatannol, SILAC quantification, peptide fractionation, and complementary PolyMAC-Ti and PolyMAC-Zr enrichment techniques, we analyzed changes in BCR-stimulated protein phosphorylation that were dependent on the activity of Syk. We identified and quantified over 13 000 unique phosphopeptides, with a large percentage dependent on Syk activity in BCR-stimulated B cells. Our results not only confirmed many known functions of Syk, but more importantly, suggested many novel roles, including in the ubiquitin proteasome pathway, that warrant further exploration. PMID:24905233

Validating the Manchester Acute Coronary Syndromes (MACS) and Troponin-only Manchester Acute Coronary Syndromes (T-MACS) rules for the prediction of acute myocardial infarction in patients presenting to the emergency department with chest pain.

PubMed

Greenslade, Jaimi H; Nayer, Robert; Parsonage, William; Doig, Shaela; Young, Joanna; Pickering, John W; Than, Martin; Hammett, Christopher; Cullen, Louise

2017-08-01

The Manchester Acute Coronary Syndromes (MACS) rule and the Troponin-only MACS (T-MACS) rule risk stratify patients with suspected acute coronary syndrome (ACS). This observational study sought to validate and compare the MACS and T-MACS rules for assessment of acute myocardial infarction (AMI). Prospectively collected data from twoEDs in Australia and New Zealand were analysed. Patients were assigned a probability of ACS based on the MACS and T-MACS rules, incorporating high-sensitivity troponin T, heart-type fatty acid-binding protein, ECG results and clinical symptoms. Patients were then deemed very low risk, low risk, intermediate or high risk if their MACS probability was less than 2%, between 2% and 5%, between 5% and 95% and greater than 95%, respectively. The primary endpoint was 30-day diagnosis of AMI. The secondary endpoint was 30-day major adverse cardiac event (MACE) including AMI, revascularisation or coronary stenosis (>70%). Sensitivity, specificity and predictive values were calculated to assess the accuracy of the MACS and T-MACS rules. Of the 1244 patients, 114 (9.2%) were diagnosed with AMI and 163 (13.1%) with MACE. The MACS and T-MACS rules categorised 133 (10.7%) and 246 (19.8%) patients, respectively, as very low risk and potentially suitable for early discharge from the ED. There was one false negative case for both rules making sensitivity 99.1% (95.2%-100%). MACS and T-MACS accurately risk stratify very low risk patients. The T-MACS rule would allow for more patients to be discharged early. The potential for missed MACE events means that further outpatient testing for coronary artery disease may be required for patients identified as very low risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of Cricoid Pressure on Laryngeal View During Macintosh, McGrath MAC X-Blade and GlideScope Video Laryngoscopies

PubMed Central

Arslan, Zehra İpek; Solak, Mine

2017-01-01

Objective Cricoid pressure is useful in fasted patients requiring emergency intubation. We compared the effect of cricoid pressure on laryngeal view during Macintosh, McGrath MAC X-Blade and GlideScope video laryngoscopy. Methods After obtaining approval from the Human Research Ethics Committee and written informed consent from patients, we enrolled 120 patients (American Society of Anesthesiologists I–II, age 18–65 years) undergoing elective surgery that required endotracheal intubation in this prospective randomised study. Patients were divided into three groups (Macintosh, McGrath MAC X-Blade and GlideScope). Results Demographic and airway variables were similar in the groups. Cormack-Lehane grades were improved or unchanged on using cricoid pressure in Macintosh and McGrath MAC X-Blade groups. However, laryngeal views worsened in 12 patients (30%), remained unchanged in 26 patients (65%) and improved in 2 patients (5%) in the GlideScope group (p<0.001). Insertion and intubation times for Macintosh and McGrath MAC X-Blade video laryngoscopes were similar. Insertion times for GlideScope and Macintosh video laryngoscopes were similar, but were longer than those for the McGrath MAC X-Blade video laryngoscope (p=0.02). Tracheal intubation took longer with the GlideScope video laryngoscope than with the other devices (p<0.001 and p=0.003). Mean arterial pressures after insertion increased significantly in Macintosh and GlideScope groups (p=0.004 and p=0.001, respectively) compared with post-induction values. Heart rates increased after insertion in all three groups compared with post-induction values (p<0.001). Need for optimisation manoeuvres and postoperative minor complications were comparable in all three groups. Conclusion Although all three devices are useful for normal or difficult intubation, cricoid pressure improved Cormack-Lehane grades of Macintosh and McGrath MAC X-Blade video laryngoscopes but statistically significantly worsened that of the GlideScope video laryngoscope. PMID:29359076

A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid.

PubMed

Fernández, Silvina; Córdoba, Mariana

2017-04-01

Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium. Capacitation and acrosome reaction were evaluated by chlortetracycline technique, while plasma membrane and acrosome integrity were determined by trypan blue stain/differential interference contrast microscopy. Heparin capacitated samples had a significant decrease in LDH and CK activities, while in hyaluronic acid capacitated samples LDH and CK activities both increased compared to control samples, in heparin and hyaluronic acid capacitation conditions, respectively. A significant increase in lactate concentration in the incubation medium occurred in hyaluronic acid-treated sperm samples compared to heparin treatment, indicating this energetic metabolite is produced during capacitation. The LDH and CK enzyme activities and lactate concentrations in the incubation medium were decreased with 2',5'-dideoxyadenosine treatment in hyaluronic acid samples. The mAC inhibitor significantly inhibited heparin-induced capacitation of sperm cells, but did not completely inhibit hyaluronic acid capacitation. Therefore, hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a mAC. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by mAC. Copyright © 2017 Elsevier B.V. All rights reserved.

Using the memory activation capture (MAC) procedure to investigate the temporal dynamics of hypothesis generation.

PubMed

Lange, Nicholas D; Buttaccio, Daniel R; Davelaar, Eddy J; Thomas, Rick P

2014-02-01

Research investigating top-down capture has demonstrated a coupling of working memory content with attention and eye movements. By capitalizing on this relationship, we have developed a novel methodology, called the memory activation capture (MAC) procedure, for measuring the dynamics of working memory content supporting complex cognitive tasks (e.g., decision making, problem solving). The MAC procedure employs briefly presented visual arrays containing task-relevant information at critical points in a task. By observing which items are preferentially fixated, we gain a measure of working memory content as the task evolves through time. The efficacy of the MAC procedure was demonstrated in a dynamic hypothesis generation task in which some of its advantages over existing methods for measuring changes in the contents of working memory over time are highlighted. In two experiments, the MAC procedure was able to detect the hypothesis that was retrieved and placed into working memory. Moreover, the results from Experiment 2 suggest a two-stage process following hypothesis retrieval, whereby the hypothesis undergoes a brief period of heightened activation before entering a lower activation state in which it is maintained for output. The results of both experiments are of additional general interest, as they represent the first demonstrations of top-down capture driven by participant-established WM content retrieved from long-term memory.

Identification of Two Novel Mycobacterium avium Allelic Variants in Pig and Human Isolates from Brazil by PCR-Restriction Enzyme Analysis

PubMed Central

Leão, Sylvia Cardoso; Briones, Marcelo R. S.; Sircili, Marcelo Palma; Balian, Simone Carvalho; Mores, Nelson; Ferreira-Neto, José Soares

1999-01-01

Mycobacterium avium complex (MAC) is composed of environmental mycobacteria found widely in soil, water, and aerosols that can cause disease in animals and humans, especially disseminated infections in AIDS patients. MAC consists of two closely related species, M. avium and M. intracellulare, and may also include other, less-defined groups. The precise differentiation of MAC species is a fundamental step in epidemiological studies and for the evaluation of possible reservoirs for MAC infection in humans and animals. In this study, which included 111 pig and 26 clinical MAC isolates, two novel allelic M. avium PCR-restriction enzyme analysis (PRA) variants were identified, differing from the M. avium PRA prototype in the HaeIII digestion pattern. Mutations in HaeIII sites were confirmed by DNA sequencing. Identification of these isolates as M. avium was confirmed by PCR with DT1-DT6 and IS1245 primers, nucleic acid hybridization with the AccuProbe system, 16S ribosomal DNA sequencing, and biochemical tests. The characterization of M. avium PRA variants can be useful in the elucidation of factors involved in mycobacterial virulence and routes of infection and also has diagnostic significance, since they can be misidentified as M. simiae II and M. kansasii I if the PRA method is used in the clinical laboratory for identification of mycobacteria. PMID:10405407

Antioxidant and Antihyperglycemic Properties of Three Banana Cultivars (Musa spp.)

PubMed Central

Oboh, Ganiyu

2016-01-01

Background. This study sought to investigate the antioxidant and antihyperglycemic properties of Musa sapientum (Latundan banana) (MSL), Musa acuminata (Cavendish banana) (MAC), and Musa acuminate (Red Dacca) (MAR). Materials and Methods. The sugar, starch, amylose, and amylopectin contents and glycemic index (GI) of the three banana cultivars were determined. Furthermore, total phenol and vitamin C contents and α-amylase and α-glucosidase inhibitory effects of banana samples were also determined. Results. MAC and MAR had the highest starch, amylose, and amylopectin contents and estimated glycemic index (eGI) with no significant different while MSL had the lowest. Furthermore, MAR (1.07 mg GAE/g) had a higher total phenol content than MAC (0.94 mg GAE/g) and MSL (0.96 mg GAE/g), while there was no significant difference in the vitamin C content. Furthermore, MAR had the highest α-amylase (IC50 = 3.95 mg/mL) inhibitory activity while MAC had the least (IC50 = 4.27 mg/mL). Moreover, MAC and MAR inhibited glucosidase activity better than MSL (IC50 3.47 mg/mL). Conclusion. The low sugar, GI, amylose, and amylopectin contents of the three banana cultivars as well as their α-amylase and α-glucosidase inhibitory activities could be possible mechanisms and justification for their recommendation in the management of type-2 diabetes. PMID:27872791

Antioxidant and Antihyperglycemic Properties of Three Banana Cultivars (Musa spp.).

PubMed

Adedayo, Bukola C; Oboh, Ganiyu; Oyeleye, Sunday I; Olasehinde, Tosin A

2016-01-01

Background . This study sought to investigate the antioxidant and antihyperglycemic properties of Musa sapientum (Latundan banana) (MSL), Musa acuminata (Cavendish banana) (MAC), and Musa acuminate (Red Dacca) (MAR). Materials and Methods. The sugar, starch, amylose, and amylopectin contents and glycemic index (GI) of the three banana cultivars were determined. Furthermore, total phenol and vitamin C contents and α -amylase and α -glucosidase inhibitory effects of banana samples were also determined. Results . MAC and MAR had the highest starch, amylose, and amylopectin contents and estimated glycemic index (eGI) with no significant different while MSL had the lowest. Furthermore, MAR (1.07 mg GAE/g) had a higher total phenol content than MAC (0.94 mg GAE/g) and MSL (0.96 mg GAE/g), while there was no significant difference in the vitamin C content. Furthermore, MAR had the highest α -amylase (IC 50 = 3.95 mg/mL) inhibitory activity while MAC had the least (IC 50 = 4.27 mg/mL). Moreover, MAC and MAR inhibited glucosidase activity better than MSL (IC 50 3.47 mg/mL). Conclusion . The low sugar, GI, amylose, and amylopectin contents of the three banana cultivars as well as their α -amylase and α -glucosidase inhibitory activities could be possible mechanisms and justification for their recommendation in the management of type-2 diabetes.

Computational Modeling of Age-Differences In a Visually Demanding Driving Task: Vehicle Detection

DTIC Science & Technology

1997-10-07

overall estimate of d’ for each scene was calculated from the two levels using the method described in MacMillan and Creelman [13]. MODELING VEHICLE...Scialfa, "Visual and auditory aging," In J. Birren & K. W. Schaie (Eds.) Handbook of the Psychology of Aging (4th edition), 1996, New York: Academic...Computational models of Visual Processing, 1991, Boston MA: MIT Press. [13] N. A. MacMillan & C. D. Creelman , Detection Theory: A User’s Guide, 1991

A gene profiling deconvolution approach to estimating immune cell composition from complex tissues.

PubMed

Chen, Shu-Hwa; Kuo, Wen-Yu; Su, Sheng-Yao; Chung, Wei-Chun; Ho, Jen-Ming; Lu, Henry Horng-Shing; Lin, Chung-Yen

2018-05-08

A new emerged cancer treatment utilizes intrinsic immune surveillance mechanism that is silenced by those malicious cells. Hence, studies of tumor infiltrating lymphocyte populations (TILs) are key to the success of advanced treatments. In addition to laboratory methods such as immunohistochemistry and flow cytometry, in silico gene expression deconvolution methods are available for analyses of relative proportions of immune cell types. Herein, we used microarray data from the public domain to profile gene expression pattern of twenty-two immune cell types. Initially, outliers were detected based on the consistency of gene profiling clustering results and the original cell phenotype notation. Subsequently, we filtered out genes that are expressed in non-hematopoietic normal tissues and cancer cells. For every pair of immune cell types, we ran t-tests for each gene, and defined differentially expressed genes (DEGs) from this comparison. Equal numbers of DEGs were then collected as candidate lists and numbers of conditions and minimal values for building signature matrixes were calculated. Finally, we used v -Support Vector Regression to construct a deconvolution model. The performance of our system was finally evaluated using blood biopsies from 20 adults, in which 9 immune cell types were identified using flow cytometry. The present computations performed better than current state-of-the-art deconvolution methods. Finally, we implemented the proposed method into R and tested extensibility and usability on Windows, MacOS, and Linux operating systems. The method, MySort, is wrapped as the Galaxy platform pluggable tool and usage details are available at https://testtoolshed.g2.bx.psu.edu/view/moneycat/mysort/e3afe097e80a .

TreeMAC: Localized TDMA MAC protocol for real-time high-data-rate sensor networks

USGS Publications Warehouse

Song, W.-Z.; Huang, R.; Shirazi, B.; LaHusen, R.

2009-01-01

Earlier sensor network MAC protocols focus on energy conservation in low-duty cycle applications, while some recent applications involve real-time high-data-rate signals. This motivates us to design an innovative localized TDMA MAC protocol to achieve high throughput and low congestion in data collection sensor networks, besides energy conservation. TreeMAC divides a time cycle into frames and each frame into slots. A parent node determines the children's frame assignment based on their relative bandwidth demand, and each node calculates its own slot assignment based on its hop-count to the sink. This innovative 2-dimensional frame-slot assignment algorithm has the following nice theory properties. First, given any node, at any time slot, there is at most one active sender in its neighborhood (including itself). Second, the packet scheduling with TreeMAC is bufferless, which therefore minimizes the probability of network congestion. Third, the data throughput to the gateway is at least 1/3 of the optimum assuming reliable links. Our experiments on a 24-node testbed show that TreeMAC protocol significantly improves network throughput, fairness, and energy efficiency compared to TinyOS's default CSMA MAC protocol and a recent TDMA MAC protocol Funneling-MAC. Partial results of this paper were published in Song, Huang, Shirazi and Lahusen [W.-Z. Song, R. Huang, B. Shirazi, and R. Lahusen, TreeMAC: Localized TDMA MAC protocol for high-throughput and fairness in sensor networks, in: The 7th Annual IEEE International Conference on Pervasive Computing and Communications, PerCom, March 2009]. Our new contributions include analyses of the performance of TreeMAC from various aspects. We also present more implementation detail and evaluate TreeMAC from other aspects. ?? 2009 Elsevier B.V.

Adaptive Optics Microperimetry and OCT Images Show Preserved Function and Recovery of Cone Visibility in Macular Telangiectasia Type 2 Retinal Lesions

PubMed Central

Wang, Qinyun; Tuten, William S.; Lujan, Brandon J.; Holland, Jennifer; Bernstein, Paul S.; Schwartz, Steven D.; Duncan, Jacque L.; Roorda, Austin

2015-01-01

Purpose. To evaluate visual function and disease progression in the retinal structural abnormalities of three patients from two unrelated families with macular telangiectasia (MacTel) type 2. Methods. Adaptive optics scanning laser ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the structure and function of macular cones in three eyes with MacTel type 2. Cone spacing was estimated using histogram analysis of intercone distances, and registered spectral-domain optical coherence tomography (SD-OCT) scans were used to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and around areas of apparent cone loss. Results. Although overall lesion surface area increased, some initially affected regions subsequently showed clear, contiguous, and normally spaced cone mosaics with recovered photoreceptor inner/outer segment (IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell mosaics (R). At N sites, AOMP threshold values (arbitrary units [au]) increased with increasing eccentricity (slope = 0.054 au/degree, r2 = 0.77). The N thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity everywhere except areas without intact external limiting membrane (ELM) and with diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS) regions on OCT. Conclusions. Visual sensitivity and recovery of cone visibility in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a preserved ELM may contain functioning cones with abnormal scattering and/or waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.) PMID:25587056

MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB-TolC, binds lipopolysaccharide core specifically and with high affinity.

PubMed

Lu, Shuo; Zgurskaya, Helen I

2013-11-01

The Escherichia coli MacAB-TolC transporter has been implicated in efflux of macrolide antibiotics and secretion of enterotoxin STII. In this study, we found that purified MacA, a periplasmic membrane fusion protein, contains one tightly bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was bound specifically to MacA protein with affinity exceeding that of polymyxin B. Sequence analyses showed that MacA contains two high-density clusters of positively charged amino acid residues located in the cytoplasmic N-terminal domain and the periplasmic C-terminal domain. Substitutions in the C-terminal cluster reducing the positive-charge density completely abolished binding of R-LPS. At the same time, these substitutions significantly reduced the functionality of MacA in the protection of E. coli against macrolides in vivo and in the in vitro MacB ATPase stimulation assays. Taken together, our results suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB-TolC.

MacA, a Periplasmic Membrane Fusion Protein of the Macrolide Transporter MacAB-TolC, Binds Lipopolysaccharide Core Specifically and with High Affinity

PubMed Central

Lu, Shuo

2013-01-01

The Escherichia coli MacAB-TolC transporter has been implicated in efflux of macrolide antibiotics and secretion of enterotoxin STII. In this study, we found that purified MacA, a periplasmic membrane fusion protein, contains one tightly bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was bound specifically to MacA protein with affinity exceeding that of polymyxin B. Sequence analyses showed that MacA contains two high-density clusters of positively charged amino acid residues located in the cytoplasmic N-terminal domain and the periplasmic C-terminal domain. Substitutions in the C-terminal cluster reducing the positive-charge density completely abolished binding of R-LPS. At the same time, these substitutions significantly reduced the functionality of MacA in the protection of E. coli against macrolides in vivo and in the in vitro MacB ATPase stimulation assays. Taken together, our results suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB-TolC. PMID:23974027

The effect of nitrous oxide on the minimum alveolar concentration (MAC) and MAC derivatives of isoflurane in dogs

PubMed Central

Voulgaris, Debra A.; Egger, Christine M.; Seddighi, M. Reza; Rohrbach, Barton W.; Love, Lydia C.; Doherty, Thomas J.

2013-01-01

This study investigated the effects of 70% nitrous oxide (N2O) on the minimum alveolar concentration (MAC) of isoflurane (ISO) that prevents purposeful movement, the MAC of ISO at which there is no motor movement (MACNM), and the MAC of ISO at which autonomic responses are blocked (MACBAR) in dogs. Six adult, healthy, mixed-breed, intact male dogs were anesthetized with ISO delivered via mask. Baseline MAC, MACNM, and MACBAR of ISO were determined for each dog using a supra-maximal electrical stimulus (50 V, 50 Hz, 10 ms). Nitrous oxide (70%) was then administered and MAC and its derivatives (N2O-MAC, N2O-MACNM, and N2O-MACBAR) were determined using the same methodology. The values for baseline MAC, MACNM, and MACBAR were 1.39 ± 0.14, 1.59 ± 0.10, and 1.72 ± 0.16, respectively. The addition of 70% N2O decreased MAC, MACNM, and MACBAR by 32%, 15%, and 25%, respectively. PMID:24082405

An Ultra-low-power Medium Access Control Protocol for Body Sensor Network.

PubMed

Li, Huaming; Tan, Jindong

2005-01-01

In this paper, a medium access control (MAC) protocol designed for Body Sensor Network (BSN-MAC) is proposed. BSN-MAC is an adaptive, feedback-based and IEEE 802.15.4-compatible MAC protocol. Due to the traffic coupling and sensor diversity characteristics of BSNs, common MAC protocols can not satisfy the unique requirements of the biomedical sensors in BSN. BSN-MAC exploits the feedback information from the deployed sensors to form a closed-loop control of the MAC parameters. A control algorithm is proposed to enable the BSN coordinator to adjust parameters of the IEEE 802.15.4 superframe to achieve both energy efficiency and low latency on energy critical nodes. We evaluate the performance of BSN-MAC using energy efficiency as the primary metric.

Obstetric and perinatal outcome of babies born from sperm selected by MACS from a randomized controlled trial.

PubMed

Romany, Laura; Garrido, Nicolas; Cobo, Ana; Aparicio-Ruiz, Belen; Serra, Vicente; Meseguer, Marcos

2017-02-01

The purpose of this study is to assess outcomes after magnetic-activated cell sorting (MACS) technology on obstetric and perinatal outcomes compared with those achieved after swim up from randomized controlled trial. This is a two-arm, unicentric, prospective, randomized, and triple-blinded trial and has a total of 237 infertile couples, between October 2010 and January 2013. A total of 65 and 66 newborns from MACS and control group, respectively, were described. MACS had no clinically relevant adverse effects on obstetric and perinatal outcomes. No differences were found for obstetric problems including premature rupture of membranes 6.1% (CI95% 0-12.8) vs. 5.9% (CI95% 0-12.4), 1st trimester bleeding 28.6% (CI95% 15.9-41.2) vs. 23.5% (CI95% 11.9-35.1), invasive procedures as amniocentesis 2.0% (CI95% 0-5.9) vs. 3.9% (CI95% 0-9.2), diabetes 14.3% (CI95% 4.5-24.1) vs. 9.8% (CI95% 1.6-17.9), anemia 6.1% (CI95% 0-12.8) vs. 5.9%(CI95% 0-12.4), 2nd and 3rd trimesters 10.2% (CI95% 1.7-18.7) vs. 5.9% (CI95% 0-12.4), urinary tract infection 8.2% (CI95% 0.5-15.9) vs. 3.9% (CI95% 0-9.2), pregnancy-induced hypertension 6.1% (CI95% 0-12.8) vs. 15.7% (CI95% 5.7-25.7), birth weight (g) 2684.10 (CI95% 2499.48-2868.72) vs. 2676.12 (CI95% 2499.02-2852.21), neonatal height (cm) 48.3 (CI95% 47.1-49.4) vs. 46.5 (CI95% 44.6-48.4), and gestational cholestasis 0%(CI95% 0-0) vs. 3.9% (CI95% 0-9.2), respectively, in MACS group compared with control group. Our data suggest that MACS technology does not increase or decrease Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation adverse obstetric and perinatal outcomes in children conceived when this technology was performed, being the largest randomized control trial with live birth reported results with MACS.

MQ-MAC: A Multi-Constrained QoS-Aware Duty Cycle MAC for Heterogeneous Traffic in Wireless Sensor Networks

PubMed Central

Monowar, Muhammad Mostafa; Rahman, Md. Obaidur; Hong, Choong Seon; Lee, Sungwon

2010-01-01

Energy conservation is one of the striking research issues now-a-days for power constrained wireless sensor networks (WSNs) and hence, several duty-cycle based MAC protocols have been devised for WSNs in the last few years. However, assimilation of diverse applications with different QoS requirements (i.e., delay and reliability) within the same network also necessitates in devising a generic duty-cycle based MAC protocol that can achieve both the delay and reliability guarantee, termed as multi-constrained QoS, while preserving the energy efficiency. To address this, in this paper, we propose a Multi-constrained QoS-aware duty-cycle MAC for heterogeneous traffic in WSNs (MQ-MAC). MQ-MAC classifies the traffic based on their multi-constrained QoS demands. Through extensive simulation using ns-2 we evaluate the performance of MQ-MAC. MQ-MAC provides the desired delay and reliability guarantee according to the nature of the traffic classes as well as achieves energy efficiency. PMID:22163439

Introduction to MAC CRM training

NASA Technical Reports Server (NTRS)

Brown, Donald D.

1987-01-01

The author introduces the Military Airlift Command (MAC) and its mission. A brief history of Cockpit Resource Management (CRM) as it relates to MAC is given. He also states why MAC is currently interested in CRM.

Evaluation of Allogeneic Transplantation in First or Later Minimal Residual Disease-Negative Remission Following Adult-Inspired Therapy for Acute Lymphoblastic Leukemia

PubMed Central

Cassaday, Ryan D.; Alan Potts, D.; Stevenson, Philip A.; Bar, Merav; Georges, George E.; Shustov, Andrei R.; Sorror, Mohamed L.; Wood, Brent L.; Delaney, Colleen; Doney, Kristine C.; Storb, Rainer F.; Sandmaier, Brenda M.

2016-01-01

Comparisons without hematopoietic cell transplantation (HCT) to myeloablative (MAC) or reduced-intensity HCT (RIC) for adults with acute lymphoblastic leukemia (ALL) in first minimal-residual-disease negative remission (MRDNeg CR1) are limited. Further, the importance of MRDNeg following salvage therapy (MRDNeg CR2+) is unknown. We evaluated 89 patients in MRDNeg CR1 after adult-inspired treatment: 33 received MAC (12 Philadelphia chromosome [Ph]+), 17 received RIC (13 Ph+), and 39 Deferred HCT (3 Ph+). 3-year overall survival (OS) estimates for MAC, RIC, and Deferred HCT were 71%, 69%, and 68%, while 3-year event-free survival (EFS) estimates were 65%, 54%, and 28%, respectively. Further, HCT in MRDNeg CR1 performed similarly to MRDNeg CR2+: 3-year OS estimates were 70% and 69%, and 3-year EFS estimates were 62% and 62%, respectively. In conclusion, adults with ALL in MRDNeg CR1 following adult-inspired therapy had similar OS with or without HCT, and HCT in MRDNeg CR2+ can yield long-term survival. PMID:27002921

In vitro and in vivo activity of LS 4477 and LS 4559, novel analogues of the tubulin binder estramustine.

PubMed

Nicholson, K M; Phillips, R M; Shnyder, S D; Bibby, M C

2002-01-01

LS 4477 and LS 4559, two of a series of N-acyl-aminoalkyl phenyl ethers, are rationally designed compounds based on the tubulin binder estramustine. This study investigated their mechanism of action and compared their effectiveness in relation to estramustine in vitro against a panel of human and murine cell lines and in vivo against two murine colon tumour models (MAC). At biologically relevant concentrations, LS 4477 and LS 4559 caused a 59.9 and 56% reduction in tubulin assembly, respectively, compared with a 28.4% reduction in tubulin assembly by estramustine. The analogues were approximately 100 times more potent in chemosensitivity tests in vitro than the parent compound. Both analogues were orally active against the MAC 15A murine tumour model, to a greater extent than estramustine, producing significant growth delays (P<0.01). Significant activity was also shown against the slower growing MAC 26 tumour for LS 4577 (the soluble pro-drug of LS 4559). The results presented in this study suggest these compounds warrant further development with a view to assessing their clinical activity.

EC00-0283-5

NASA Image and Video Library

2000-09-18

Technician Marshall MacCready carefully lays a panel of solar cells into place on a wing section of the Helios Prototype flying wing at AeroVironment's Design Development Center in Simi Valley, California. More than 1,800 panels containing some 64,000 bi-facial cells, fabricated by SunPower, Inc., of Sunnyvale, California, have been installed on the solar-powered aircraft to provide electricity to its 14 motors and operating systems.

Mechanisms of Cell Injury with Hepatotoxic Chemicals

DTIC Science & Technology

1985-05-01

McLean (1982), Dis- sociation of cell death from covalent binding of paracetamol by flavones in a hepatocyte system, Biochem. Pharmacol., 31:3745-3749...MacDonald, and R. D. HarbJson (1977), Effect of N-acetylcysteine on hepatic covalent binding of paracetamol (acetaminophen), Lancet, 1:657-658...Williams (1977), Paracetamol -induced hepatic necrosis in the mouse-relationship between covalent binding, hepatic glutathione depletion, and the

5G small-cell networks leveraging optical technologies with mm-wave massive MIMO and MT-MAC protocols

NASA Astrophysics Data System (ADS)

Papaioannou, S.; Kalfas, G.; Vagionas, C.; Mitsolidou, C.; Maniotis, P.; Miliou, A.; Pleros, N.

2018-01-01

Analog optical fronthaul for 5G network architectures is currently being promoted as a bandwidth- and energy-efficient technology that can sustain the data-rate, latency and energy requirements of the emerging 5G era. This paper deals with a new optical fronthaul architecture that can effectively synergize optical transceiver, optical add/drop multiplexer and optical beamforming integrated photonics towards a DSP-assisted analog fronthaul for seamless and medium-transparent 5G small-cell networks. Its main application targets include dense and Hot-Spot Area networks, promoting the deployment of mmWave massive MIMO Remote Radio Heads (RRHs) that can offer wireless data-rates ranging from 25Gbps up to 400Gbps depending on the fronthaul technology employed. Small-cell access and resource allocation is ensured via a Medium-Transparent (MT-) MAC protocol that enables the transparent communication between the Central Office and the wireless end-users or the lamp-posts via roof-top-located V-band massive MIMO RRHs. The MTMAC is analysed in detail with simulation and analytical theoretical results being in good agreement and confirming its credentials to satisfy 5G network latency requirements by guaranteeing latency values lower than 1 ms for small- to midload conditions. Its extension towards supporting optical beamforming capabilities and mmWave massive MIMO antennas is discussed, while its performance is analysed for different fiber fronthaul link lengths and different optical channel capacities. Finally, different physical layer network architectures supporting the MT-MAC scheme are presented and adapted to different 5G use case scenarios, starting from PON-overlaid fronthaul solutions and gradually moving through Spatial Division Multiplexing up to Wavelength Division Multiplexing transport as the user density increases.

AFRRI Reports, Fourth Quarter 1991

DTIC Science & Technology

1992-01-01

Gallin, E. K. Heat induces intracellular acidification in human A-431 cells : role of Na’-H’ exchange and metabolism. SR91-49: MacVittie, T. J., Monroy, R... induced release of DNA front agarose plugs treated with Not I restriction enzyme As above, wild-type and strain 112 cells were exposed to 2 kGy and...times. Ager and co-workers (1990) found that following irradiation of CHO-KI cells , replication forks showed reduced PFGE- induced migration out of the

A simple phenotypic method for screening of MCR-1-mediated colistin resistance.

PubMed

Coppi, M; Cannatelli, A; Antonelli, A; Baccani, I; Di Pilato, V; Sennati, S; Giani, T; Rossolini, G M

2018-02-01

To evaluate a novel method, the colistin-MAC test, for phenotypic screening of acquired colistin resistance mediated by transferable mcr-1 resistance determinants, based on colistin MIC reduction in the presence of dipicolinic acid (DPA). The colistin-MAC test consists in a broth microdilution method, in which colistin MIC is tested in the absence or presence of DPA (900 μg/mL). Overall, 74 colistin-resistant strains of Enterobacteriaceae (65 Escherichia coli and nine other species), including 61 strains carrying mcr-1-like genes and 13 strains negative for mcr genes, were evaluated with the colistin-MAC test. The presence of mcr-1-like and mcr-2-like genes was assessed by real-time PCR and end-point PCR. For 20 strains, whole-genome sequencing data were also available. A ≥8-fold reduction of colistin MIC in the presence of DPA was observed with 59 mcr-1-positive strains, including 53 E. coli of clinical origin, three E. coli transconjugants carrying MCR-1-encoding plasmids, one Enterobacter cloacae complex and two Citrobacter spp. Colistin MICs were unchanged, increased or at most reduced by twofold with the 13 mcr-negative colistin-resistant strains (nine E. coli and four Klebsiella pneumoniae), but also with two mcr-1-like-positive K. pneumoniae strains. The colistin-MAC test could be a simple phenotypic test for presumptive identification of mcr-1-positive strains among isolates of colistin-resistant E. coli, based on a ≥8-fold reduction of colistin MIC in the presence of DPA. Evaluation of the test with a larger number of strains, species and mcr-type resistance determinants would be of interest. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Methamphetamine-Associated Cardiomyopathy

PubMed Central

Won, Sekon; Hong, Robert A.; Shohet, Ralph V.; Seto, Todd B.; Parikh, Nisha I.

2015-01-01

Methamphetamine and related compounds are now the second most commonly used illicit substance worldwide, after cannabis. Reports of methamphetamine-associated cardiomyopathy (MAC) are increasing, but MAC has not been well reviewed. This analysis of MAC will provide an overview of the pharmacology of methamphetamine, historical perspective and epidemiology, a review of case and clinical studies, and a summary of the proposed mechanisms for MAC. Clinically, many questions remain, including the appropriate therapeutic interventions for MAC, the incidence and prevalence of cardiac pathology in methamphetamine users, risk factors for developing MAC, and prognosis of these patients. In conclusion, recognition of the significance of MAC among physicians and other medical caregivers is important given the growing use of methamphetamine and related stimulants worldwide. PMID:24037954

Interaction of Macrophage Antigen 1 and CD40 Ligand Leads to IL-12 Production and Resistance in CD40-Deficient Mice Infected with Leishmania major.

PubMed

Okwor, Ifeoma; Jia, Ping; Uzonna, Jude E

2015-10-01

Although some studies indicate that the interaction of CD40 and CD40L is critical for IL-12 production and resistance to cutaneous leishmaniasis, others suggest that this pathway may be dispensable. In this article, we compared the outcome of Leishmania major infection in both CD40- and CD40L-deficient mice after treatment with rIL-12. We show that although CD40 and CD40L knockout (KO) mice are highly susceptible to L. major, treatment with rIL-12 during the first 2 wk of infection causes resolution of cutaneous lesions and control of parasite replication. Interestingly, although treated CD40 KO mice remained healed, developed long-term immunity, and were resistant to secondary L. major challenge, treated CD40L KO reactivated their lesion after cessation of rIL-12 treatment. Disease reactivation in CD40L KO mice was associated with impaired IL-12 and IFN-γ production and a concomitant increase in IL-4 production by cells from lymph nodes draining the infection site. We show that IL-12 production by dendritic cells and macrophages via CD40L-macrophage Ag 1 (Mac-1) interaction is responsible for the sustained resistance in CD40 KO mice after cessation of rIL-12 treatment. Blockade of CD40L-Mac-1 interaction with anti-Mac-1 mAb led to spontaneous disease reactivation in healed CD40 KO mice, which was associated with impaired IFN-γ response and loss of infection-induced immunity after secondary L. major challenge. Collectively, our data reveal a novel role of CD40L-Mac-1 interaction in IL-12 production, development, and maintenance of optimal Th1 immunity in mice infected with L. major. Copyright © 2015 by The American Association of Immunologists, Inc.

The use of complimentary assays to evaluate the enrichment of human sperm quality in asthenoteratozoospermic and teratozoospermic samples processed with Annexin-V magnetic activated cell sorting.

PubMed

Delbes, G; Herrero, M B; Troeung, E-T; Chan, P T K

2013-09-01

Sperm chromatin integrity may affect the outcomes of assisted reproductive technology (ART). Developing a clinically reliable strategy to enrich sperm samples with high chromatin quality spermatozoa prior to sperm banking or use in ART would thus be advantageous. The objectives of this study were to: (i) assess the sperm chromatin quality in men with different categories of semen parameters; and (ii) evaluate the extents of Annexin-V magnetic-activated cell sorting (MACS) technology coupled with differential density gradient centrifugation (DGC) in improving sperm chromatin quality. Three categories of men from couples attending a university-based fertility clinic were recruited based on their semen parameters: normozoospermic (n = 13), asthenoteratozoospermic (n = 17) and teratozoospermic (n = 12). For each patient, spermatozoa in semen samples were processed first by DGC to enrich the motility and further by MACS to remove spermatozoa showing apoptotic features. The yield and enrichment of sperm quality was evaluated at each step with conventional semen parameters in conjunction with a combination of five complementary assays, to assess sperm maturity, chromatin structure, compaction and DNA integrity (Hyaluronic Binding Assay, SCSA, chromomycine A3 staining and TUNEL and COMET assays). Our results demonstrated that, compared with normozoospermic samples, raw asthenoteratozoospermic and teratozoospermic samples had a higher proportion of spermatozoa containing DNA breaks, but only asthenoteratozoospermic exhibited altered chromatin structure and decreased binding to hyaluronic acid. Interestingly, the DGC appeared to select for more mature spermatozoa with high DNA compaction. More importantly, in all categories of semen samples, Annexin-V MACS allows enrichment of spermatozoa with good chromatin quality as measured by the TUNEL and SCSA. Because effective treatment modalities to improve sperm DNA damage are limited, our results suggest a potential clinical value of MACS as a mean to enhance sperm quality that may improve assisted reproductive outcomes. © 2013 American Society of Andrology and European Academy of Andrology.

TreeMAC: Localized TDMA MAC protocol for real-time high-data-rate sensor networks

USGS Publications Warehouse

Song, W.-Z.; Huang, R.; Shirazi, B.; Husent, R.L.

2009-01-01

Earlier sensor network MAC protocols focus on energy conservation in low-duty cycle applications, while some recent applications involve real-time high-data-rate signals. This motivates us to design an innovative localized TDMA MAC protocol to achieve high throughput and low congestion in data collection sensor networks, besides energy conservation. TreeMAC divides a time cycle into frames and frame into slots. Parent determines children's frame assigmnent based on their relative bandwidth demand, and each node calculates its own slot assignment based on its hop-count to the sink. This innovative 2-dimensional frame-slot assignment algorithm has the following nice theory properties. Firstly, given any node, at any time slot, there is at most one active sender in its neighborhood (includ ing itself). Secondly, the packet scheduling with TreelMAC is bufferless, which therefore minimizes the probability of network congestion. Thirdly, the data throughput to gateway is at least 1/3 of the optimum assuming reliable links. Our experiments on a 24 node test bed demonstrate that TreeMAC protocol significantly improves network throughput and energy efficiency, by comparing to the TinyOS's default CSMA MAC protocol and a recent TDMA MAC protocol Funneling-MAC[8]. ?? 2009 IEEE.

Minimum alveolar concentration (MAC) for sevoflurane and xenon at normothermia and hypothermia in newborn pigs.

PubMed

Liu, X; Dingley, J; Elstad, M; Scull-Brown, E; Steen, P A; Thoresen, M

2013-05-01

Neuroprotection from therapeutic hypothermia increases when combined with the anaesthetic gas xenon in animal studies. A clinical feasibility study of the combined treatment has been successfully undertaken in asphyxiated human term newborns. It is unknown whether xenon alone would be sufficient for sedation during hypothermia eliminating or reducing the need for other sedative or analgesic infusions in ventilated sick infants. Minimum alveolar concentration (MAC) of xenon is unknown in any neonatal species. Eight newborn pigs were anaesthetised with sevoflurane alone and then sevoflurane plus xenon at two temperatures. Pigs were randomised to start at either 38.5°C or 33.5°C. MAC for sevoflurane was determined using the claw clamp technique at the preset body temperature. For xenon MAC determination, a background of 0.5 MAC sevoflurane was used, and 60% xenon added to the gas mixture. The relationship between sevoflurane and xenon MAC is assumed to be additive. Xenon concentrations were changed in 5% steps until a positive clamp reaction was noted. Pigs' temperature was changed to the second target, and two MAC determinations for sevoflurane and 0.5 MAC sevoflurane plus xenon were repeated. MAC for sevoflurane was 4.1% [95% confidence interval (CI): 3.65-4.50] at 38.5°C and 3.05% (CI: 2.63-3.48) at 33.5°C, a significant reduction. MAC for xenon was 120% at 38.5°C and 116% at 33.5°C, not different. In newborn swine sevoflurane, MAC was temperature dependent, while xenon MAC was independent of temperature. There was large individual variability in xenon MAC, from 60% to 120%. © 2013 The Acta Anaesthesiologica Scandinavica Foundation.

The Modulated Annual Cycle: An Alternative Reference Frame for Climate Anomalies

NASA Astrophysics Data System (ADS)

Wu, Z.

2007-12-01

In climate science, an anomaly is the deviation of a quantity from its annual cycle (AC). There are many ways to define annual cycle. Traditionally, the annual cycle is taken to be an exact repetition of itself year after year. This stationary annual cycle may not reflect well the intrinsic nonlinearity of the climate system, especially under external forcing. In this study, we have reexamined the reference frame for anomalies by reexamining the annual cycle. We propose an alternative reference frame, the modulated annual cycle (MAC) that allows the annual cycle to change from year to year, for defining anomalies. In order for this alternative reference frame to be useful, we need to be able to define the instantaneous annual cycle. We therefore also introduce a new method to extract the MAC from climatic data. In the presence of an MAC, modulated in both amplitude and frequency, we can then define an alternative version of an anomaly, this time with respect to the instantaneous MAC rather than a permanent and unchanging AC. Based on this alternative definition of anomalies, we reexamine some familiar physical processes: in particular, the sea surface temperature (SST) reemergence and the ENSO phase locking to the annual cycle. We find that the re-emergence mechanism may be alternatively interpreted as an explanation of the change of the annual cycle instead of the interannual to interdecadal persistence of SST anomalies. We also find that the ENSO phase locking can largely be attributed to the residual annual cycle (the difference of the MAC and the corresponding traditional annual cycle) contained in the traditional anomaly, and, therefore, can be alternatively interpreted as a part of the annual cycle phase locked to the annual cycle itself. Two additional examples are also presented of the implications of using a MAC against which to define anomalies. We show that using MAC as a reference framework for anomaly can bypass the difficulty brought by concepts such as "decadal variability of summer (or winter) climate" for understanding the low-frequency variability of the climate system. We also point out the drawbacks related to the stationary assumption in previous studies of extreme weather and climate and propose instead the appropriateness of choosing a non-stationary framework to study extreme weather and climate events. The concept of an amplitude and frequency modulated annual cycle, a method to extract it, and its implications for the interpretation of physical processes, all may contribute potentially to a more consistent and fruitful way of examining past and future climate variability and change.

The modulated annual cycle: an alternative reference frame for climate anomalies

NASA Astrophysics Data System (ADS)

Wu, Zhaohua; Schneider, Edwin K.; Kirtman, Ben P.; Sarachik, E. S.; Huang, Norden E.; Tucker, Compton J.

2008-12-01

In climate science, an anomaly is the deviation of a quantity from its annual cycle. There are many ways to define annual cycle. Traditionally, this annual cycle is taken to be an exact repeat of itself year after year. This stationary annual cycle may not reflect well the intrinsic nonlinearity of the climate system, especially under external forcing. In this paper, we re-examine the reference frame for anomalies by re-examining the annual cycle. We propose an alternative reference frame for climate anomalies, the modulated annual cycle (MAC) that allows the annual cycle to change from year to year, for defining anomalies. In order for this alternative reference frame to be useful, we need to be able to define the instantaneous annual cycle: we therefore also introduce a new method to extract the MAC from climatic data. In the presence of a MAC, modulated in both amplitude and frequency, we can then define an alternative version of an anomaly, this time with respect to the instantaneous MAC rather than a permanent and unchanging AC. Based on this alternative definition of anomalies, we re-examine some familiar physical processes: in particular SST re-emergence and ENSO phase locking to the annual cycle. We find that the re-emergence mechanism may be alternatively interpreted as an explanation of the change of the annual cycle instead of an explanation of the interannual to interdecadal persistence of SST anomalies. We also find that the ENSO phase locking can largely be attributed to the residual annual cycle (the difference of the MAC and the corresponding traditional annual cycle) contained in the traditional anomaly, and, therefore, can be alternatively interpreted as a part of the annual cycle phase locked to the annual cycle itself. In addition to the examples of reinterpretation of physics of well known climate phenomena, we also present an example of the implications of using a MAC against which to define anomalies. We show that using MAC as a reference framework for anomaly can bypass the difficulty brought by concepts such as “decadal variability of summer (or winter) climate” for understanding the low-frequency variability of the climate system. The concept of an amplitude and frequency modulated annual cycle, a method to extract it, and its implications for the interpretation of physical processes, all may contribute potentially to a more consistent and fruitful way of examining past and future climate variability and change.

The Role of the Transcription Factors MtrR and MtrA in the Fitness of the Pathogen Neisseria gonorrhoeae

DTIC Science & Technology

2007-10-19

MacA -MacB efflux pump is expressed at very low levels in N. gonorrhoeae; however, experimental alteration of the promoter sequence showed that the...specificity (132). The gonococcus expresses four efflux pump systems, namely MtrC-Mtr-D-MtrE (64), FarA-FarB-MtrE (97), NorM (158), and MacA -MacB (161...2005. Characterization of the MacA -MacB efflux system in Neisseria gonorrhoeae. The Journal of antimicrobial chemotherapy 56:856-860. 162. Rouquette, C

Photocopy of drawing (original drawing of MacDill Field in possession ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing (original drawing of MacDill Field in possession of MacDill Air Force Base, Civil Engineering, Tampa, Florida; 1952 architectural drawings by Strategic Air Command, MacDill Air Force Base) BASE LAYOUT, 1952 - MacDill Air Force Base, Bounded by City of Tampa North, Tampa Bay South, Old Tampa Bay West, & Hillsborough Bay East, Tampa, Hillsborough County, FL

The activity of silver nanoparticles against microalgae of the Prototheca genus.

PubMed

Jagielski, Tomasz; Bakuła, Zofia; Pleń, Małgorzata; Kamiński, Michał; Nowakowska, Julita; Bielecki, Jacek; Wolska, Krystyna I; Grudniak, Anna M

2018-05-01

To investigate the in vitro activity of silver NPs (AgNPs) against pathogenic microalgae of the Prototheca genus. The antialgal potential of AgNPs against Prototheca species of both clinical and environmental origin was assessed from minimum inhibitory (algistatic) and algicidal concentrations. The in vitro cytotoxicity of AgNPs against bovine mammary epithelial cell line was evaluated by means of the standard MTT assay. AgNPs showed a strong killing activity toward Prototheca algae, as the minimal algicidal concentration (MAC) values matched perfectly the corresponding minimum inhibitory concentration (MIC) values for all species (MAC = MIC, 1-4 mg/l), except P. stagnora (MIC > 8 mg/l). The concentrations inhibitory to pathogenic Prototheca spp. (MIC, 1-4 mg/l) were below the concentrations at which any toxicity in epithelial cells could be observed (CC 20 > 6 mg/l). The study emphasizes the potential of AgNPs as a new therapeutic tool for the management of Prototheca infections.

Mitral annular calcification in patients undergoing aortic valve replacement for aortic valve stenosis.

PubMed

Takami, Yoshiyuki; Tajima, Kazuyoshi

2016-02-01

Limited data exis t on clinical relevance of aortic valve stenosis (AVS) and mitral annular calcification (MAC), although with similar pathophysiologic basis. We sought to reveal the prevalence of MAC and its clinical features in the patients undergoing aortic valve replacement (AVR) for AVS. We reviewed 106 consecutive patients who underwent isolated AVR from 2004 to 2010. Before AVR, CT scans were performed to identify MAC, whose severity was graded on a scale of 0-4, with grade 0 denoting no MAC and grade 4 indicating severe MAC. Echocardiography was performed before AVR and at follow-up over 2 years after AVR. MAC was identified in 56 patients with grade 1 (30 %), 2 (39 %), 3 (18 %), and 4 (13 %), respectively. Patients with MAC presented older age (72 ± 8 versus 66 ± 11 years), higher rate of dialysis-dependent renal failure (43 versus 4 %), and less frequency of bicuspid aortic valve (9 versus 36 %), when compared to those without MAC. No significant differences were seen in short- and mid-term mortality after AVR between the groups. In patients with MAC, progression of neither mitral regurgitation nor stenosis was observed at follow-up of 53 ± 23 months for 102 survivors, although the transmitral flow velocities were higher than in those without MAC. In conclusion, MAC represented 53 % of the patients undergoing isolated AVR for AVS, usually appeared in dialysis-dependent elder patients with tricuspid AVS. MAC does not affect adversely upon the survival, without progression of mitral valve disease, at least within 2 years after AVR.

Species distribution in human immunodeficiency virus-related mycobacterial infections: implications for selection of initial treatment.

PubMed

Montessori, V; Phillips, P; Montaner, J; Haley, L; Craib, K; Bessuille, E; Black, W

1996-06-01

Management of mycobacterial infection is species specific; however, treatment is prompted by positive smears or cultures, often several weeks before species identification. The objective of this study was to determine the species distribution of mycobacterial isolates from various body sites in patients infected with human immunodeficiency virus (HIV). All mycobacterial isolates recovered at St. Paul's Hospital (Vancouver, British Columbia, Canada) from April 1989 to March 1993 were reviewed. Among 357 HIV-positive patients with mycobacterial infections, 64% (96) of the sputum isolates were Mycobacterium avium complex (MAC), 18% were Mycobacterium tuberculosis, and 17% were Mycobacterium kansasii. Lymph node involvement (25 patients) was due to either MAC (72%) or M. tuberculosis (24%). Two hundred ninety-eight episodes of mycobacteremia were due to MAC (98%), M. tuberculosis (1%), and M. kansasii (1%). Similarly, cultures of 84 bone marrow biopsy specimens (99%), 19 intestinal biopsy specimens (100%), and 30 stool specimens (97%) yielded predominantly MAC. These results have implications for initial therapy, particularly in areas where rapid methods for species identification are not readily available. Because of considerable geographic variation, development of guidelines for selection of initial therapy depends on regional determination of species distribution in HIV-related mycobacterial infections.

Advertisement-Based Energy Efficient Medium Access Protocols for Wireless Sensor Networks

NASA Astrophysics Data System (ADS)

Ray, Surjya Sarathi

One of the main challenges that prevents the large-scale deployment of Wireless Sensor Networks (WSNs) is providing the applications with the required quality of service (QoS) given the sensor nodes' limited energy supplies. WSNs are an important tool in supporting applications ranging from environmental and industrial monitoring, to battlefield surveillance and traffic control, among others. Most of these applications require sensors to function for long periods of time without human intervention and without battery replacement. Therefore, energy conservation is one of the main goals for protocols for WSNs. Energy conservation can be performed in different layers of the protocol stack. In particular, as the medium access control (MAC) layer can access and control the radio directly, large energy savings is possible through intelligent MAC protocol design. To maximize the network lifetime, MAC protocols for WSNs aim to minimize idle listening of the sensor nodes, packet collisions, and overhearing. Several approaches such as duty cycling and low power listening have been proposed at the MAC layer to achieve energy efficiency. In this thesis, I explore the possibility of further energy savings through the advertisement of data packets in the MAC layer. In the first part of my research, I propose Advertisement-MAC or ADV-MAC, a new MAC protocol for WSNs that utilizes the concept of advertising for data contention. This technique lets nodes listen dynamically to any desired transmission and sleep during transmissions not of interest. This minimizes the energy lost in idle listening and overhearing while maintaining an adaptive duty cycle to handle variable loads. Additionally, ADV-MAC enables energy efficient MAC-level multicasting. An analytical model for the packet delivery ratio and the energy consumption of the protocol is also proposed. The analytical model is verified with simulations and is used to choose an optimal value of the advertisement period. Simulations show that the optimized ADV-MAC provides substantial energy gains (50% to 70% less than other MAC protocols for WSNs such as T-MAC and S-MAC for the scenarios investigated) while faring as well as T-MAC in terms of packet delivery ratio and latency. Although ADV-MAC provides substantial energy gains over S-MAC and T-MAC, it is not optimal in terms of energy savings because contention is done twice -- once in the Advertisement Period and once in the Data Period. In the next part of my research, the second contention in the Data Period is eliminated and the advantages of contention-based and TDMA-based protocols are combined to form Advertisement based Time-division Multiple Access (ATMA), a distributed TDMA-based MAC protocol for WSNs. ATMA utilizes the bursty nature of the traffic to prevent energy waste through advertisements and reservations for data slots. Extensive simulations and qualitative analysis show that with bursty traffic, ATMA outperforms contention-based protocols (S-MAC, T-MAC and ADV-MAC), a TDMA based protocol (TRAMA) and hybrid protocols (Z-MAC and IEEE 802.15.4). ATMA provides energy reductions of up to 80%, while providing the best packet delivery ratio (close to 100%) and latency among all the investigated protocols. Simulations alone cannot reflect many of the challenges faced by real implementations of MAC protocols, such as clock-drift, synchronization, imperfect physical layers, and irregular interference from other transmissions. Such issues may cripple a protocol that otherwise performs very well in software simulations. Hence, to validate my research, I conclude with a hardware implementation of the ATMA protocol on SORA (Software Radio), developed by Microsoft Research Asia. SORA is a reprogrammable Software Defined Radio (SDR) platform that satisfies the throughput and timing requirements of modern wireless protocols while utilizing the rich general purpose PC development environment. Experimental results obtained from the hardware implementation of ATMA closely mirror the simulation results obtained for a single hop network with 4 nodes.

Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy.

PubMed

Mock, Ulrike; Nickolay, Lauren; Philip, Brian; Cheung, Gordon Weng-Kit; Zhan, Hong; Johnston, Ian C D; Kaiser, Andrew D; Peggs, Karl; Pule, Martin; Thrasher, Adrian J; Qasim, Waseem

2016-08-01

Novel cell therapies derived from human T lymphocytes are exhibiting enormous potential in early-phase clinical trials in patients with hematologic malignancies. Ex vivo modification of T cells is currently limited to a small number of centers with the required infrastructure and expertise. The process requires isolation, activation, transduction, expansion and cryopreservation steps. To simplify procedures and widen applicability for clinical therapies, automation of these procedures is being developed. The CliniMACS Prodigy (Miltenyi Biotec) has recently been adapted for lentiviral transduction of T cells and here we analyse the feasibility of a clinically compliant T-cell engineering process for the manufacture of T cells encoding chimeric antigen receptors (CAR) for CD19 (CAR19), a widely targeted antigen in B-cell malignancies. Using a closed, single-use tubing set we processed mononuclear cells from fresh or frozen leukapheresis harvests collected from healthy volunteer donors. Cells were phenotyped and subjected to automated processing and activation using TransAct, a polymeric nanomatrix activation reagent incorporating CD3/CD28-specific antibodies. Cells were then transduced and expanded in the CentriCult-Unit of the tubing set, under stabilized culture conditions with automated feeding and media exchange. The process was continuously monitored to determine kinetics of expansion, transduction efficiency and phenotype of the engineered cells in comparison with small-scale transductions run in parallel. We found that transduction efficiencies, phenotype and function of CAR19 T cells were comparable with existing procedures and overall T-cell yields sufficient for anticipated therapeutic dosing. The automation of closed-system T-cell engineering should improve dissemination of emerging immunotherapies and greatly widen applicability. Copyright © 2016. Published by Elsevier Inc.

Treatment Decision-Making Capacity in Children and Adolescents Hospitalized for an Acute Mental Disorder: The Role of Cognitive Functioning and Psychiatric Symptoms

PubMed Central

Sabatello, Ugo; Lapponi, Elisa; Pace, Giulia; Ferrara, Mauro; Ferracuti, Stefano

2017-01-01

Abstract Objective: This study was conducted to assess treatment decision-making capacity (TDMC) in a child and adolescent psychiatric sample and to verify possible associations between TDMC, psychiatric symptom severity, and cognitive functioning. Methods: Twenty-two consecutively recruited patients hospitalized for an acute mental disorder, aged 11–18 years, underwent measurement of TDMC by the MacArthur Competence Assessment Tool for Treatment (MacCAT-T). The MacCAT-T interview focused on patients' current treatment, which comprised second-generation antipsychotics (45.5%), first-generation antipsychotics (13.6%), antiepileptic drugs used as mood stabilizers or lithium carbonate (45.5%), selective serotonin reuptake inhibitors (32%), and benzodiazepines (18%). We moreover measured cognitive functioning (Wechsler Intelligence Scale for Children III) and psychiatric symptom severity (Brief Psychiatric Rating Scale v 4.0). Results: Patients' TDMC varied within the sample, but MacCAT-T scores were good in the sample overall, suggesting that children and adolescents with severe mental disorders could be competent to consent to treatment. The TDMC proved independent of psychiatric diagnosis while being positively associated with cognitive functioning and negatively with excitement. Conclusion: The MacCAT-T proved feasible for measuring TDMC in a child and adolescent psychiatric sample. TDMC in minors with severe mental disorders was not necessarily impaired. These results deserve reconsidering the interplay between minors and surrogate decision-makers as concerning treatment decisions. PMID:27935747

Disruption of mTORC1 in Macrophages Decreases Chemokine Gene Expression and Atherosclerosis

PubMed Central

Ai, Ding; Jiang, Hongfeng; Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Ganda, Anjali; Abramowicz, Sandra; Welch, Carrie; Almazan, Felicidad; Zhu, Yi; Miller, Yury I; Tall, Alan R.

2014-01-01

Rationale The mammalian target of rapamycin complex 1 (mTORC1) inhibitor, rapamycin, has been shown to decrease atherosclerosis, even while increasing plasma LDL levels. This suggests an anti-atherogenic effect possibly mediated by modulation of inflammatory responses in atherosclerotic plaques. Objective To assess the role of macrophage mTORC1 in atherogenesis. Methods and Results We transplanted bone marrow from mice in which a key mTORC1 adaptor, Raptor, was deleted in macrophages by Cre/loxP recombination (Mac-RapKO mice) into Ldlr-/- mice and then fed them the Western-type diet (WTD). Atherosclerotic lesions from Mac-RapKO mice showed decreased infiltration of macrophages, lesion size and chemokine gene expression compared with control mice. Treatment of macrophages with minimally modified LDL (mmLDL) resulted in increased levels of chemokine mRNAs and STAT3 phosphorylation; these effects were reduced in Mac-RapKO macrophages. While wild-type and Mac-RapKO macrophages showed similar STAT3 phosphorylation on Tyr705, Mac-RapKO macrophages showed decreased STAT3 Ser727 phosphorylation in response to mmLDL treatment and decreased Ccl2 promoter binding of STAT3. Conclusions The results demonstrate cross-talk between nutritionally-induced mTORC1 signaling and mmLDL-mediated inflammatory signaling via combinatorial phosphorylation of STAT3 in macrophages, leading to increased STAT3 activity on the CCL2 (MCP-1)promoter with pro-atherogenic consequences. PMID:24687132

The Mobility Assessment Course for the Diagnosis of Spatial Neglect: Taking a Step Forward?

PubMed Central

Grech, Megan; Stuart, Tracey; Williams, Lindy; Chen, Celia; Loetscher, Tobias

2017-01-01

Spatial neglect after stroke can be a challenging syndrome to diagnose under standard neuropsychological assessment. There is now sufficient evidence that those affected might demonstrate neglect behavior in everyday settings despite showing no signs of neglect during common neglect tasks. This discrepancy is attributed to the simplified and unrealistic nature of common pen and paper based tasks that do not match the demanding, novel, and complex environment of everyday life. As such, increasing task demands under more ecologically valid scenarios has become an important method of increasing test sensitivity. The main aim of the current study was to evaluate the diagnostic utility of the Mobility Assessment Course (MAC), an ecological task, for the assessment of neglect. If neglect becomes more apparent under more challenging task demands the MAC could prove to be more diagnostically accurate at detecting neglect than conventional methods, particularly as the time from initial brain damage increases. Data collected by Guide Dogs of SA/NT were retrospectively analyzed. The Receiver Operating Characteristic (ROC) curve, a measure of sensitivity and specificity, was used to investigate the diagnostic utility of the MAC and a series of paper and pencil tests in 67 right hemisphere stroke survivors. While the MAC proved to be a more sensitive neglect test (74.2%) when compared to the Star Cancellation (43.3%) and Line Bisection (35.7%) tests, this was at the expense of relatively low specificity. As a result, the ROC curve analysis showed no statistically discernable differences between tasks (p > 0.12), or between subacute and chronic groups for individual tasks (p > 0.45). It is concluded that, while the MAC is an ecologically valid alternative for assessing neglect, regarding its diagnostic accuracy, there is currently not enough evidence to suggest that it is a big step forward in comparison to the accuracy of conventional tests. PMID:29163331

Comparison of the TruView infant EVO2 PCD™ and C-MAC video laryngoscopes with direct Macintosh laryngoscopy for routine tracheal intubation in infants with normal airways

PubMed Central

Mutlak, Haitham; Rolle, Udo; Rosskopf, Willi; Schalk, Richard; Zacharowski, Kai; Meininger, Dirk; Byhahn, Christian

2014-01-01

OBJECTIVE: Videolaryngoscopy has mainly been developed to facilitate difficult airway intubation. However, there is a lack of studies demonstrating this method's efficacy in pediatric patients. The aim of the present study was to compare the TruView infant EVO2 and the C-MAC videolaryngoscope with conventional direct Macintosh laryngoscopy in children with a bodyweight ≤10 kg in terms of intubation conditions and the time to intubation. METHODS: In total, 65 children with a bodyweight ≤10 kg (0-22 months) who had undergone elective surgery requiring endotracheal intubation were retrospectively analyzed. Our database was screened for intubations with the TruView infant EVO2, the C-MAC videolaryngoscope, and conventional direct Macintosh laryngoscopy. The intubation conditions, the time to intubation, and the oxygen saturation before and after intubation were monitored, and demographic data were recorded. Only children with a bodyweight ≤10 kg were included in the analysis. RESULTS: A total of 23 children were intubated using the C-MAC videolaryngoscope, and 22 children were intubated using the TruView EVO2. Additionally, 20 children were intubated using a standard Macintosh blade. The time required for tracheal intubation was significantly longer using the TruView EVO2 (52 sec vs. 28 sec for C-MAC vs. 26 sec for direct LG). However, no significant difference in oxygen saturation was found after intubation. CONCLUSION: All devices allowed excellent visualization of the vocal cords, but the time to intubation was prolonged when the TruView EVO2 was used. The absence of a decline in oxygen saturation may be due to apneic oxygenation via the TruView scope and may provide a margin of safety. In sum, the use of the TruView by a well-trained anesthetist may be an alternative for difficult airway management in pediatric patients. PMID:24473556

Effect of fentanyl target-controlled infusions on isoflurane minimum anaesthetic concentration and cardiovascular function in red-tailed hawks (Buteo jamaicensis).

PubMed

Pavez, Juan C; Hawkins, Michelle G; Pascoe, Peter J; Knych, Heather K DiMaio; Kass, Philip H

2011-07-01

To determine the impact of three different target plasma concentrations of fentanyl on the minimum anaesthetic concentration (MAC) for isoflurane in the red-tailed hawk and the effects on the haemodynamic profile. Experimental study. Six healthy adult red-tailed hawks (Buteo jamaicensis) of unknown sex with body weights (mean ± SD) of 1.21 ± 0.15 kg. This study was undertaken in two phases. In the first phase anaesthesia was induced with isoflurane in oxygen via facemask and maintained with isoflurane delivered in oxygen via a Bain circuit. Following instrumentation baseline determination of the MAC for isoflurane was made for each animal using the bracketing method and a supramaximal electrical stimulus. End-tidal isoflurane concentration (E'Iso) was then set at 0.75 × MAC and after an appropriate equilibration period a bolus of fentanyl (20 μg kg(-1)) was administered intravenously (IV) in order to determine the pharmacokinetics of fentanyl in the isoflurane-anaesthetized red-tailed hawk. During the second phase anaesthesia was induced in a similar manner and E'Iso was set at 0.75 × MAC for each individual. Fentanyl was infused IV to achieve target plasma concentrations between 8 and 32 ng mL(-1). At each fentanyl plasma concentration, the MAC for isoflurane and cardiovascular variables were determined. Data were analyzed by use of repeated-measures anova. Mean ± SD fentanyl plasma concentrations and isoflurane MACs were 0 ± 0, 8.51 ± 4, 14.85 ± 4.82 and 29.25 ± 11.52 ng mL(-1), and 2.05 ± 0.45%, 1.42 ± 0.53%, 1.14 ± 0.31% and 0.93 ± 0.32% for the target concentrations of 0, 8, 16 and 32 ng mL(-1), respectively. At these concentrations fentanyl significantly (p = 0.0016) decreased isoflurane MAC by 31%, 44% and 55%, respectively. Dose had no significant effect on heart rate, systolic, diastolic or mean arterial blood pressure. Fentanyl produced a dose-related decrease of isoflurane MAC with minimal effects on measured cardiovascular parameters in red-tailed hawks. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Effects of clinically relevant acute hypercapnic and metabolic acidosis on the cardiovascular system: an experimental porcine study

PubMed Central

2013-01-01

Introduction Hypercapnic acidosis (HCA) that accompanies lung-protective ventilation may be considered permissive (a tolerable side effect), or it may be therapeutic by itself. Cardiovascular effects may contribute to, or limit, the potential therapeutic impact of HCA; therefore, a complex physiological study was performed in healthy pigs to evaluate the systemic and organ-specific circulatory effects of HCA, and to compare them with those of metabolic (eucapnic) acidosis (MAC). Methods In anesthetized, mechanically ventilated and instrumented pigs, HCA was induced by increasing the inspired fraction of CO2 (n = 8) and MAC (n = 8) by the infusion of HCl, to reach an arterial plasma pH of 7.1. In the control group (n = 8), the normal plasma pH was maintained throughout the experiment. Hemodynamic parameters, including regional organ hemodynamics, blood gases, and electrocardiograms, were measured in vivo. Subsequently, isometric contractions and membrane potentials were recorded in vitro in the right ventricular trabeculae. Results HCA affected both the pulmonary (increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR)) and systemic (increase in mean arterial pressure (MAP), decrease in systemic vascular resistance (SVR)) circulations. Although the renal perfusion remained unaffected by any type of acidosis, HCA increased carotid, portal, and, hence, total liver blood flow. MAC influenced the pulmonary circulation only (increase in MPAP and PVR). Both MAC and HCA reduced the stroke volume, which was compensated for by an increase in heart rate to maintain (MAC), or even increase (HCA), the cardiac output. The right ventricular stroke work per minute was increased by both MAC and HCA; however, the left ventricular stroke work was increased by HCA only. In vitro, the trabeculae from the control pigs and pigs with acidosis showed similar contraction force and action-potential duration (APD). Perfusion with an acidic solution decreased the contraction force, whereas APD was not influenced. Conclusions MAC preferentially affects the pulmonary circulation, whereas HCA affects the pulmonary, systemic, and regional circulations. The cardiac contractile function was reduced, but the cardiac output was maintained (MAC), or even increased (HCA). The increased ventricular stroke work per minute revealed an increased work demand placed by acidosis on the heart. PMID:24377654

Use of procainamide gels in the purification of human and horse serum cholinesterases.

PubMed Central

Ralston, J S; Main, A R; Kilpatrick, B F; Chasson, A L

1983-01-01

Two large-scale methods based primarily on the use of procainamide-Sepharose gels were developed for the purification of horse and human serum non-specific cholinesterases. With method I, the procainamide-Sepharose 4B gel was used in the first step to handle large volumes of serum. With method II, the procainamide-Sepharose 4B gel was used in the final step to obtain pure enzyme. Although both methods gave electrophoretically pure cholinesterase preparations in good yields, they were significantly more efficient at purifying the horse enzyme than the human enzyme. To study this problem, the relative binding of human and horse cholinesterases to procainamide-, methylacridinium (MAC)-, m-trimethylammoniophenyl (m-PTA)- and p-trimethylammoniophenyl (p-PTA)-Sepharose 4B gels were measured, by using two approaches. In one, binding was measured by a procedure involving equilibration of pure cholinesterase in a small volume of diluted gel slurry (4%, v/v). A partially purified preparation of Electrophorus acetylcholinesterase was included. Pure human cholinesterase bound consistently more tightly to each of the gels than did horse cholinesterase, and the acetylcholinesterase appeared to bind the gels 10-100 times more tightly than did the non-specific cholinesterases. The order of binding for the cholinesterases, beginning with the tightest, was: procainamide-Sepharose 4B, MAC-Sepharose 4B, p-PTA-Sepharose 4B and m-PTA-Sepharose 4B. For the acetylcholinesterase the order was: MAC-Sepharose 4B, procainamide-Sepharose 4B, p-PTA-Sepharose 4B and m-PTA-Sepharose 4B. The second approach involved passing native sera or partially purified sera fractions through 1 ml test columns of each of the four affinity gels to determine their retention capacity for the cholinesterases. With these impure samples, the MAC-Sepharose 4B gels proved superior to the procainamide-Sepharose 4B gels at retaining human cholinesterase, but the opposite was true for the horse cholinesterase. PMID:6870822

Application of the Molecular Adsorber Coating Technology on the Ionospheric Connection Explorer Program

NASA Technical Reports Server (NTRS)

Abraham, Nithin S.; Hasegawa, Mark M.; Secunda, Mark S.

2016-01-01

The Molecular Adsorber Coating (MAC) is a zeolite based highly porous coating technology that was developed by NASA Goddard Space Flight Center (GSFC) to capture outgassed contaminants, such as plastics, adhesives, lubricants, silicones, epoxies, potting compounds, and other similar materials. This paper describes the use of the MAC technology to address molecular contamination concerns on NASAs Ionospheric Connection Explorer (ICON) program led by the University of California (UC) Berkeleys Space Sciences Laboratory. The sprayable paint technology was applied onto plates that were installed within the instrument cavity of ICONs Far Ultraviolet Imaging Spectrograph (FUV). However, due to the instruments particulate sensitivity, the coating surface was vibrationally cleaned through simulated acoustics to reduce the risk of particle fall-out contamination. This paper summarizes the coating application efforts on the FUV adsorber plates, the simulated laboratory acoustic level cleaning test methods, particulation characteristics, and future plans for the MAC technology.

Application of the Molecular Adsorber Coating technology on the Ionospheric Connection Explorer program

NASA Astrophysics Data System (ADS)

Abraham, Nithin S.; Hasegawa, Mark M.; Secunda, Mark S.

2016-09-01

The Molecular Adsorber Coating (MAC) is a zeolite based highly porous coating technology that was developed by NASA Goddard Space Flight Center (GSFC) to capture outgassed contaminants, such as plastics, adhesives, lubricants, silicones, epoxies, potting compounds, and other similar materials. This paper describes the use of the MAC technology to address molecular contamination concerns on NASA's Ionospheric Connection Explorer (ICON) program led by the University of California (UC) Berkeley's Space Sciences Laboratory. The sprayable paint technology was applied onto plates that were installed within the instrument cavity of ICON's Far Ultraviolet Imaging Spectrograph (FUV). However, due to the instrument's particulate sensitivity, the coating surface was vibrationally cleaned through simulated acoustics to reduce the risk of particle fall-out contamination. This paper summarizes the coating application efforts on the FUV adsorber plates, the simulated laboratory acoustic level cleaning test methods, particulation characteristics, and future plans for the MAC technology.

Concurrent and face validity of the MacArthur scale for assessing subjective social status: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Ferreira, Wasney de Almeida; Giatti, Luana; Figueiredo, Roberta Carvalho de; Mello, Heliana Ribeiro de; Barreto, Sandhi Maria

2018-04-01

This work assessed the concurrent and face validity of the MacArthur scale, which attempts to capture subjective social status in society, neighborhood and work contexts. The study population comprised a convenience sample made up of 159 adult participants of the ELSA-Brasil cohort study conducted in Minas Gerais between 2012 and 2014. The analysis was conducted drawing on Conceptual Metaphor Theory and using corpus linguistic methods. Concurrent validity was shown to be moderate for the society ladder (Kappaw = 0.55) and good for the neighborhood (Kappaw = 0.60) and work (Kappaw = 0,67) ladders. Face validity indicated that the MacArthur scale really captures subjective social status across indicators of socioeconomic position, thus confirming that it is a valuable tool for the study of social inequalities in health Brazil.

The influence of donor age on liver regeneration and hepatic progenitor cell populations.

PubMed

Ono, Yoshihiro; Kawachi, Shigeyuki; Hayashida, Tetsu; Wakui, Masatoshi; Tanabe, Minoru; Itano, Osamu; Obara, Hideaki; Shinoda, Masahiro; Hibi, Taizo; Oshima, Go; Tani, Noriyuki; Mihara, Kisyo; Kitagawa, Yuko

2011-08-01

Recent reports suggest that donor age might have a major impact on recipient outcome in adult living donor liver transplantation (LDLT), but the reasons underlying this effect remain unclear. The aims of this study were to compare liver regeneration between young and aged living donors and to evaluate the number of Thy-1+ cells, which have been reported to be human hepatic progenitor cells. LDLT donors were divided into 2 groups (Group O, donor age ≥ 50 years, n = 6 and Group Y, donor age ≤ 30 years, n = 9). The remnant liver regeneration rates were calculated on the basis of computed tomography volumetry on postoperative days 7 and 30. Liver tissue samples were obtained from donors undergoing routine liver biopsy or patients undergoing partial hepatectomy for metastatic liver tumors. Thy-1+ cells were isolated and counted using immunomagnetic activated cell sorting (MACS) technique. Donor liver regeneration rates were significantly higher in young donors compared to old donors (P = .042) on postoperative day 7. Regeneration rates were significantly higher after right lobe resection compared to rates after left lobe resection. The MACS findings showed that the number of Thy-1+ cells in the human liver consistently tended to decline with age. Our study revealed that liver regeneration is impaired with age after donor hepatectomy, especially after right lobe resection. The declining hepatic progenitor cell population might be one of the reasons for impaired liver regeneration in aged donors. Copyright © 2011 Mosby, Inc. All rights reserved.

Engineered Autologous Stromal Cells for the Delivery of Kringle 5, a Potent Endothelial Cell Specific Inhibitor for Anti-Angiogenic Breast Cancer Therapy

DTIC Science & Technology

2006-08-01

immune modulatory properties on blood -derived immune competent cells – in keeping with the observations made by others with angiostatin. To address...factor (vWF) antibody (Fig. 4B, left panel). The number (Fig. 4C) as well as the length (Fig. 4B, right panel) of blood vessels was significantly reduced...from heparinized human peripheral blood were assayed for cell- surface expression of the adhesion marker CD11b (Mac-1) by flow cytometry analysis, and

University of Texas Southwestern Medical Center: U01 Natural Products Screening | Office of Cancer Genomics

Cancer.gov

The goal of this project was to enlarge the chemical space probed by Project 1 (High-Throughput siRNA Screening of a Non-Small Cell Lung Cancer Cell Line Panel) by screening an expanded natural products library (~40,000) in an effort to further define vulnerabilities and therapeutic targets in non-small cell lung cancer. This new library is derived from a diverse collection of marine bacteria (prepared by Dr. John MacMillan, University of Texas Southwestern).

University of Texas Southwestern Medical Center (UTSW): U01 Natural Products Screening | Office of Cancer Genomics

Cancer.gov

The goal of this project was to enlarge the chemical space probed by Project 1 (High-Throughput siRNA Screening of a Non-Small Cell Lung Cancer Cell Line Panel) by screening an expanded natural products library (~40,000) in an effort to further define vulnerabilities and therapeutic targets in non-small cell lung cancer. This new library is derived from a diverse collection of marine bacteria (prepared by Dr. John MacMillan, University of Texas Southwestern).

A European aerosol phenomenology-5: Climatology of black carbon optical properties at 9 regional background sites across Europe

NASA Astrophysics Data System (ADS)

Zanatta, M.; Gysel, M.; Bukowiecki, N.; Müller, T.; Weingartner, E.; Areskoug, H.; Fiebig, M.; Yttri, K. E.; Mihalopoulos, N.; Kouvarakis, G.; Beddows, D.; Harrison, R. M.; Cavalli, F.; Putaud, J. P.; Spindler, G.; Wiedensohler, A.; Alastuey, A.; Pandolfi, M.; Sellegri, K.; Swietlicki, E.; Jaffrezo, J. L.; Baltensperger, U.; Laj, P.

2016-11-01

A reliable assessment of the optical properties of atmospheric black carbon is of crucial importance for an accurate estimation of radiative forcing. In this study we investigated the spatio-temporal variability of the mass absorption cross-section (MAC) of atmospheric black carbon, defined as light absorption coefficient (σap) divided by elemental carbon mass concentration (mEC). σap and mEC have been monitored at supersites of the ACTRIS network for a minimum period of one year. The 9 rural background sites considered in this study cover southern Scandinavia, central Europe and the Mediterranean. σap was determined using filter based absorption photometers and mEC using a thermal-optical technique. Homogeneity of the data-set was ensured by harmonization of all involved methods and instruments during extensive intercomparison exercises at the European Center for Aerosol Calibration (ECAC). Annual mean values of σap at a wavelength of 637 nm vary between 0.66 and 1.3 Mm-1 in southern Scandinavia, 3.7-11 Mm-1 in Central Europe and the British Isles, and 2.3-2.8 Mm-1 in the Mediterranean. Annual mean values of mEC vary between 0.084 and 0.23 μg m-3 in southern Scandinavia, 0.28-1.1 in Central Europe and the British Isles, and 0.22-0.26 in the Mediterranean. Both σap and mEC in southern Scandinavia and Central Europe have a distinct seasonality with maxima during the cold season and minima during summer, whereas at the Mediterranean sites an opposite trend was observed. Annual mean MAC values were quite similar across all sites and the seasonal variability was small at most sites. Consequently, a MAC value of 10.0 m2 g-1 (geometric standard deviation = 1.33) at a wavelength of 637 nm can be considered to be representative of the mixed boundary layer at European background sites, where BC is expected to be internally mixed to a large extent. The observed spatial variability is rather small compared to the variability of values in previous literature, indicating that the harmonization efforts resulted in substantially increased precision of the reported MAC. However, absolute uncertainties of the reported MAC values remain as high as ± 30-70% due to the lack of appropriate reference methods and calibration materials. The mass ratio between elemental carbon and non-light-absorbing matter was used as a proxy for the thickness of coatings around the BC cores, in order to assess the influence of the mixing state on the MAC of BC. Indeed, the MAC was found to increase with increasing values of the coating thickness proxy. This provides evidence that coatings do increase the MAC of atmospheric BC to some extent, which is commonly referred to as lensing effect.

Stochastic-Strength-Based Damage Simulation of Ceramic Matrix Composite Laminates

NASA Technical Reports Server (NTRS)

Nemeth, Noel N.; Mital, Subodh K.; Murthy, Pappu L. N.; Bednarcyk, Brett A.; Pineda, Evan J.; Bhatt, Ramakrishna T.; Arnold, Steven M.

2016-01-01

The Finite Element Analysis-Micromechanics Analysis Code/Ceramics Analysis and Reliability Evaluation of Structures (FEAMAC/CARES) program was used to characterize and predict the progressive damage response of silicon-carbide-fiber-reinforced reaction-bonded silicon nitride matrix (SiC/RBSN) composite laminate tensile specimens. Studied were unidirectional laminates [0] (sub 8), [10] (sub 8), [45] (sub 8), and [90] (sub 8); cross-ply laminates [0 (sub 2) divided by 90 (sub 2),]s; angled-ply laminates [plus 45 (sub 2) divided by -45 (sub 2), ]s; doubled-edge-notched [0] (sub 8), laminates; and central-hole laminates. Results correlated well with the experimental data. This work was performed as a validation and benchmarking exercise of the FEAMAC/CARES program. FEAMAC/CARES simulates stochastic-based discrete-event progressive damage of ceramic matrix composite and polymer matrix composite material structures. It couples three software programs: (1) the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC), (2) the Ceramics Analysis and Reliability Evaluation of Structures Life Prediction Program (CARES/Life), and (3) the Abaqus finite element analysis program. MAC/GMC contributes multiscale modeling capabilities and micromechanics relations to determine stresses and deformations at the microscale of the composite material repeating-unit-cell (RUC). CARES/Life contributes statistical multiaxial failure criteria that can be applied to the individual brittle-material constituents of the RUC, and Abaqus is used to model the overall composite structure. For each FEAMAC/CARES simulation trial, the stochastic nature of brittle material strength results in random, discrete damage events that incrementally progress until ultimate structural failure.

Comparative evaluation of the diagnostic potential of recombinant envelope proteins and native cell culture purified viral antigens of Chikungunya virus.

PubMed

Khan, Mohsin; Dhanwani, Rekha; Kumar, Jyoti S; Rao, P V Lakshmana; Parida, Manmohan

2014-07-01

Despite the fact that Chikungunya resurgence is associated with epidemic of unprecedented magnitude, there are challenges in the field of its clinical diagnosis. However, serological tests in an ELISA format provide a rapid tool for the diagnosis of Chikungunya infection. Indeed, ELISAs based on recombinant proteins hold a great promise as these methods are cost effective and are free from the risk of handling biohazardous material. In this study, the performance of recombinant CHIKV antigens was compared in various ELISA formats for the diagnosis of Chikungunya. Two recombinant antigens derived from the envelope proteins of Chikungunya virus were prepared and evaluated by comparing their competence for detecting circulating antibodies in serum samples of patients infected with CHIKV using MAC-ELISA and indirect IgM-ELISA. The efficacy of the recombinant antigens was also compared with the native antigen. The indirect antibody capture IgM microplate ELISA revealed ≥90% concordance with the native antigen in detecting the CHIKV specific IgM antibodies whereas the recombinant antigen based MAC-ELISA showed 100% specificity. The recombinant antigens used in this study were effective and reliable targets for the diagnosis of CHIKV infection and also provide an alternative for native antigen use which is potentially biohazardous. © 2013 Wiley Periodicals, Inc.

A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix.

PubMed

Hara, Kieko; Saito, Tsuyoshi; Hayashi, Takuo; Yimit, Alkam; Takahashi, Michiko; Mitani, Keiko; Takahashi, Makoto; Yao, Takashi

2015-09-01

Appendiceal mucinous tumors (AMTs) are classified as low-grade appendiceal mucinous neoplasms (LAMNs) or mucinous adenocarcinomas (MACs), although their carcinogenesis is not well understood. As somatic activating mutations of GNAS are considered to be characteristic of LAMNs while TP53 mutations have been shown to be specific to MACs, MACs are unlikely to result from transformation of LAMNs. However, emerging evidence also shows the presence of GNAS mutations in MACs. We examined 16 AMTs (11 LAMNs and 5 MACs) for genetic alterations of GNAS, KRAS, BRAF, TP53, CTNNB1, and TERT promoter in order to elucidate the possibility of a shared genetic background in the two tumor types. Extensive histological examination revealed the presence of a low-grade component in all cases of MAC. GNAS mutations were detected in two LAMNs and in one MAC, although the GNAS mutation in this MAC was a nonsense mutation (Q227X) expected not to be activating mutation. TP53 mutations were detected in three LAMNs; they were frequently detected in MACs. KRAS mutations were detected in three LAMNs and three MACs, and CTNNB1 mutations were detected in two LAMNs. KRAS mutation and activating mutation of GNAS occurred exclusively in AMTs. BRAF and TERT mutations were not detected. Overexpression of p53 was observed in only two MACs, and p53 immunostaining clearly discriminated the high-grade lesion from a low-grade component in one. These findings suggest that p53 overexpression plays an important role in the carcinogenesis of AMTs and that, in addition to mutations of GNAS, KRAS and TP53 alterations might be shared by AMTs, thus providing evidence for the possible progression of LAMNs to MAC. Copyright © 2015 Elsevier GmbH. All rights reserved.

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

PubMed Central

Bagdonaite, Ieva; Wandall, Hans H.; Litvinov, Ivan V.; Nastasi, Claudia; Becker, Jürgen C.; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M.; Zhang, Qian; Wasik, Mariusz A.; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-01-01

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22ΔN), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22ΔN mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22ΔN (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22ΔN and CD22wt in these cells. In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients. PMID:25957418

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients.

PubMed

Bagdonaite, Ieva; Wandall, Hans H; Litvinov, Ivan V; Nastasi, Claudia; Becker, Jürgen C; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M; Zhang, Qian; Wasik, Mariusz A; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-06-10

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22∆N), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22∆N mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22∆N (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22∆N and CD22wt in these cells.In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients.

Adipose tissue macrophages in non-rodent mammals: a comparative study.

PubMed

Ampem, Grace; Azegrouz, Hind; Bacsadi, Árpád; Balogh, Lajos; Schmidt, Susanne; Thuróczy, Julianna; Röszer, Tamás

2016-02-01

The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.

Effects of anticoagulant, processing delay, and assay method (branched DNA versus reverse transcriptase PCR) on measurement of human immunodeficiency virus type 1 RNA levels in plasma.

PubMed

Kirstein, L M; Mellors, J W; Rinaldo, C R; Margolick, J B; Giorgi, J V; Phair, J P; Dietz, E; Gupta, P; Sherlock, C H; Hogg, R; Montaner, J S; Muñoz, A

1999-08-01

We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, -0.12 log(10) copies/ml; RT-PCR, -0.05 log(10) copies/ml) and after 18 h (bDNA assay, -0.27 log(10) copies/ml; RT-PCR, -0.15 log(10) copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, -0.002 log(10) copies/ml; RT-PCR, -0.02 log(10) copies/ml), but it was after 18 h (bDNA assay, -0.09 log(10) copies/ml; RT-PCR, -0.09 log(10) copies/ml). Only 4% of samples processed after 6 h lost more than 50% (>/=0.3 log(10) copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4(+)-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (-0.05 to -0.12 log(10) copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4(+)-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP.

Carbon nanotube-clamped metal atomic chain

PubMed Central

Tang, Dai-Ming; Yin, Li-Chang; Li, Feng; Liu, Chang; Yu, Wan-Jing; Hou, Peng-Xiang; Wu, Bo; Lee, Young-Hee; Ma, Xiu-Liang; Cheng, Hui-Ming

2010-01-01

Metal atomic chain (MAC) is an ultimate one-dimensional structure with unique physical properties, such as quantized conductance, colossal magnetic anisotropy, and quantized magnetoresistance. Therefore, MACs show great potential as possible components of nanoscale electronic and spintronic devices. However, MACs are usually suspended between two macroscale metallic electrodes; hence obvious technical barriers exist in the interconnection and integration of MACs. Here we report a carbon nanotube (CNT)-clamped MAC, where CNTs play the roles of both nanoconnector and electrodes. This nanostructure is prepared by in situ machining a metal-filled CNT, including peeling off carbon shells by spatially and elementally selective electron beam irradiation and further elongating the exposed metal nanorod. The microstructure and formation process of this CNT-clamped MAC are explored by both transmission electron microscopy observations and theoretical simulations. First-principles calculations indicate that strong covalent bonds are formed between the CNT and MAC. The electrical transport property of the CNT-clamped MAC was experimentally measured, and quantized conductance was observed. PMID:20427743

hCG-dependent regulation of angiogenic factors in human granulosa lutein cells.

PubMed

Phan, B; Rakenius, A; Pietrowski, D; Bettendorf, H; Keck, C; Herr, D

2006-07-01

As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), Leptin, connective tissue growth factor (CTGF), meningioma-associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary.

Chip-set for quality of service support in passive optical networks

NASA Astrophysics Data System (ADS)

Ringoot, Edwin; Hoebeke, Rudy; Slabbinck, B. Hans; Verhaert, Michel

1998-10-01

In this paper the design of a chip-set for QoS provisioning in ATM-based Passive Optical Networks is discussed. The implementation of a general-purpose switch chip on the Optical Network Unit is presented, with focus on the design of the cell scheduling and buffer management logic. The cell scheduling logic supports `colored' grants, priority jumping and weighted round-robin scheduling. The switch chip offers powerful buffer management capabilities enabling the efficient support of GFR and UBR services. Multicast forwarding is also supported. In addition, the architecture of a MAC controller chip developed for a SuperPON access network is introduced. In particular, the permit scheduling logic and its implementation on the Optical Line Termination will be discussed. The chip-set enables the efficient support of services with different service requirements on the SuperPON. The permit scheduling logic built into the MAC controller chip in combination with the cell scheduling and buffer management capabilities of the switch chip can be used by network operators to offer guaranteed service performance to delay sensitive services, and to efficiently and fairly distribute any spare capacity to delay insensitive services.

Rasch analysis of the Mini-Mental Adjustment to Cancer Scale (mini-MAC) among a heterogeneous sample of long-term cancer survivors: A cross-sectional study

PubMed Central

2012-01-01

Background The mini-Mental Adjustment to Cancer Scale (mini-MAC) is a well-recognised, popular measure of coping in psycho-oncology and assesses five cancer-specific coping strategies. It has been suggested that these five subscales could be grouped to form the over-arching adaptive and maladptive coping subscales to facilitate the interpretation and clinical application of the scale. Despite the popularity of the mini-MAC, few studies have examined its psychometric properties among long-term cancer survivors, and further validation of the mini-MAC is needed to substantiate its use with the growing population of survivors. Therefore, this study examined the psychometric properties and dimensionality of the mini-MAC in a sample of long-term cancer survivors using Rasch analysis. Methods RUMM 2030 was used to analyse the mini-MAC data (n=851). Separate Rasch analyses were conducted for each of the original mini-MAC subscales as well as the over-arching adaptive and maladaptive coping subscales to examine summary and individual model fit statistics, person separation index (PSI), response format, local dependency, targeting, item bias (or differential item functioning -DIF), and dimensionality. Results For the fighting spirit, fatalism, and helplessness-hopelessness subscales, a revised three-point response format seemed more optimal than the original four-point response. To achieve model fit, items were deleted from four of the five subscales – Anxious Preoccupation items 7, 25, and 29; Cognitive Avoidance items 11 and 17; Fighting Spirit item 18; and Helplessness-Hopelessness items 16 and 20. For those subscales with sufficient items, analyses supported unidimensionality. Combining items to form the adaptive and maladaptive subscales was partially supported. Conclusions The original five subscales required item deletion and/or rescaling to improve goodness of fit to the Rasch model. While evidence was found for overarching subscales of adaptive and maladaptive coping, extensive modifications were necessary to achieve this result. Further exploration and validation of over-arching subscales assessing adaptive and maladaptive coping is necessary with cancer survivors. PMID:22607052

A Fair Contention Access Scheme for Low-Priority Traffic in Wireless Body Area Networks

PubMed Central

Sajeel, Muhammad; Bashir, Faisal; Asfand-e-yar, Muhammad; Tauqir, Muhammad

2017-01-01

Recently, wireless body area networks (WBANs) have attracted significant consideration in ubiquitous healthcare. A number of medium access control (MAC) protocols, primarily derived from the superframe structure of the IEEE 802.15.4, have been proposed in literature. These MAC protocols aim to provide quality of service (QoS) by prioritizing different traffic types in WBANs. A contention access period (CAP)with high contention in priority-based MAC protocols can result in higher number of collisions and retransmissions. During CAP, traffic classes with higher priority are dominant over low-priority traffic; this has led to starvation of low-priority traffic, thus adversely affecting WBAN throughput, delay, and energy consumption. Hence, this paper proposes a traffic-adaptive priority-based superframe structure that is able to reduce contention in the CAP period, and provides a fair chance for low-priority traffic. Simulation results in ns-3 demonstrate that the proposed MAC protocol, called traffic- adaptive priority-based MAC (TAP-MAC), achieves low energy consumption, high throughput, and low latency compared to the IEEE 802.15.4 standard, and the most recent priority-based MAC protocol, called priority-based MAC protocol (PA-MAC). PMID:28832495

Determination and validation of an aquatic Maximum Acceptable Concentration-Environmental Quality Standard (MAC-EQS) value for the agricultural fungicide azoxystrobin.

PubMed

Rodrigues, Elsa Teresa; Pardal, Miguel Ângelo; Gante, Cristiano; Loureiro, João; Lopes, Isabel

2017-02-01

The main goal of the present study was to determine and validate an aquatic Maximum Acceptable Concentration-Environmental Quality Standard (MAC-EQS) value for the agricultural fungicide azoxystrobin (AZX). Assessment factors were applied to short-term toxicity data using the lowest EC 50 and after the Species Sensitivity Distribution (SSD) method. Both ways of EQS generation were applied to a freshwater toxicity dataset for AZX based on available data, and to marine toxicity datasets for AZX and Ortiva ® (a commercial formulation of AZX) obtained by the present study. A high interspecific variability in AZX sensitivity was observed in all datasets, being the copepoda Eudiaptomus graciloides (LC 50,48h  = 38 μg L -1 ) and the gastropod Gibbula umbilicalis (LC 50,96h  = 13 μg L -1 ) the most sensitive freshwater and marine species, respectively. MAC-EQS values derived using the lowest EC 50 (≤0.38 μg L -1 ) were more protective than those derived using the SSD method (≤3.2 μg L -1 ). After comparing the MAC-EQS values estimated in the present study to the smallest AA-EQS available, which protect against the occurrence of prolonged exposure of AZX, the MAC-EQS values derived using the lowest EC 50 were considered overprotective and a MAC-EQS of 1.8 μg L -1 was validated and recommended for AZX for the water column. This value was derived from marine toxicity data, which highlights the importance of testing marine organisms. Moreover, Ortiva affects the most sensitive marine species to a greater extent than AZX, and marine species are more sensitive than freshwater species to AZX. A risk characterization ratio higher than one allowed to conclude that AZX might pose a high risk to the aquatic environment. Also, in a wider conclusion, before new pesticides are approved, we suggest to improve the Tier 1 prospective Ecological Risk Assessment by increasing the number of short-term data, and apply the SSD approach, in order to ensure the safety of aquatic organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

GENETIC FINGERPRINTING OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS ISOLATED FROM HOSPITAL PATIENTS AND THE ENVIRONMENT

EPA Science Inventory

A particularly pathogenic group of mycobacteria belong to the Mycobacterium avium complex (MAC), which includes M. avium and M. intracellulare. MAC organisms cause disease in children, the elderly, and immuno-compromised individuals. A critical step in preventing MAC infections...

Discriminative validity of the MacAndrew Alcoholism Scale with Cluster B personality disorders.

PubMed

Smith, S R; Hilsenroth, M J

2001-06-01

This study was designed to assess the ability of the Minnesota Multiphasic Personality Inventory (MMPI-2) MacAndrew Alcoholism Scale (MAC-R) to differentiate between outpatients with personality disorders with Substance-Related Disorders (SRDs) and without SRDs. MMPI-2 validity, clinical, and MAC-R scale scores were compared in an SRD Cluster B group (comprised of Narcissistic, Antisocial, Borderline, and Histrionic; n = 15), a non-SRD Cluster B group (n = 33), and a non-SRD group with personality disorders from Clusters A and C (n = 18). Results revealed that the substance-abusing Cluster B group scored significantly higher on the MAC-R ( p <.0001) as well as the Psychopathic Deviate scale ( p <.01). Dimensional analyses illustrated that MAC-R scores were related to the presence of an SRD diagnosis (rpb =.70, p <.0001) and diagnostic criteria for Antisocial Personality Disorder (r =.60, p <.0001). Stepwise regression revealed that (in order of magnitude) the presence of a substance-abuse diagnosis followed by diagnostic criteria for Antisocial and Histrionic Personality Disorders were most related to MAC-R scores (R =.78, R(2) =.60). This indicates that the MAC-R may be more related to the presence of an SRD than has been suggested, and when used in outpatient settings as MacAndrew (1965) intended, the MAC-R may be useful as a screening device for assessing SRD among outpatients with Axis II psychopathology.

Magnetic manipulation device for the optimization of cell processing conditions.

PubMed

Ito, Hiroshi; Kato, Ryuji; Ino, Kosuke; Honda, Hiroyuki

2010-02-01

Variability in human cell phenotypes make it's advancements in optimized cell processing necessary for personalized cell therapy. Here we propose a strategy of palm-top sized device to assist physically manipulating cells for optimizing cell preparations. For the design of such a device, we combined two conventional approaches: multi-well plate formatting and magnetic cell handling using magnetite cationic liposomes (MCLs). From our previous works, we showed the labeling applications of MCL on adhesive cells for various tissue engineering approaches. To feasibly transfer cells in multi-well plate, we here evaluated the magnetic response of MCL-labeled suspension type cells. The cell handling performance of Jurkat cells proved to be faster and more robust compared to MACS (Magnetic Cell Sorting) bead methods. To further confirm our strategy, prototype palm-top sized device "magnetic manipulation device (MMD)" was designed. In the device, the actual cell transportation efficacy of Jurkat cells was satisfying. Moreover, as a model of the most distributed clinical cell processing, primary peripheral blood mononuclear cells (PBMCs) from different volunteers were evaluated. By MMD, individual PBMCs indicated to have optimum Interleukin-2 (IL-2) concentrations for the expansion. Such huge differences of individual cells indicated that MMD, our proposing efficient and self-contained support tool, could assist the feasible and cost-effective optimization of cell processing in clinical facilities. Copyright (c) 2009 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

PAD-MAC: Primary User Activity-Aware Distributed MAC for Multi-Channel Cognitive Radio Networks

PubMed Central

Ali, Amjad; Piran, Md. Jalil; Kim, Hansoo; Yun, Jihyeok; Suh, Doug Young

2015-01-01

Cognitive radio (CR) has emerged as a promising technology to solve problems related to spectrum scarcity and provides a ubiquitous wireless access environment. CR-enabled secondary users (SUs) exploit spectrum white spaces opportunistically and immediately vacate the acquired licensed channels as primary users (PUs) arrive. Accessing the licensed channels without the prior knowledge of PU traffic patterns causes severe throughput degradation due to excessive channel switching and PU-to-SU collisions. Therefore, it is significantly important to design a PU activity-aware medium access control (MAC) protocol for cognitive radio networks (CRNs). In this paper, we first propose a licensed channel usage pattern identification scheme, based on a two-state Markov model, and then estimate the future idle slots using previous observations of the channels. Furthermore, based on these past observations, we compute the rank of each available licensed channel that gives SU transmission success assessment during the estimated idle slot. Secondly, we propose a PU activity-aware distributed MAC (PAD-MAC) protocol for heterogeneous multi-channel CRNs that selects the best channel for each SU to enhance its throughput. PAD-MAC controls SU activities by allowing them to exploit the licensed channels only for the duration of estimated idle slots and enables predictive and fast channel switching. To evaluate the performance of the proposed PAD-MAC, we compare it with the distributed QoS-aware MAC (QC-MAC) and listen-before-talk MAC schemes. Extensive numerical results show the significant improvements of the PAD-MAC in terms of the SU throughput, SU channel switching rate and PU-to-SU collision rate. PMID:25831084

A Comparison of the C-MAC Video Laryngoscope to the Macintosh Direct Laryngoscope for Intubation in the Emergency Department

PubMed Central

Sakles, John C.; Mosier, Jarrod; Chiu, Stephen; Cosentino, Mari; Kalin, Leah

2015-01-01

Study objective We determine the proportion of successful intubations with the C-MAC video laryngoscope (C-MAC) compared with the direct laryngoscope in emergency department (ED) intubations. Methods This was a retrospective analysis of prospectively collected data entered into a continuous quality improvement database during a 28-month period in an academic ED. After each intubation, the operator completed a standardized data form evaluating multiple aspects of the intubation, including patient demographics, indication for intubation, device(s) used, reason for device selection, difficult airway characteristics, number of attempts, and outcome of each attempt. Intubation was considered ultimately successful if the endotracheal tube was correctly inserted into the trachea with the initial device. An attempt was defined as insertion of the device into the mouth regardless of whether there was an attempt to pass the tube. The primary outcome measure was ultimate success. Secondary outcome measures were first-attempt success, Cormack-Lehane view, and esophageal intubation. Multivariate logistic regression analyses, with the inclusion of a propensity score, were performed for the outcome variables ultimate success and first-attempt success. Results During the 28-month study period, 750 intubations were performed with either the C-MAC with a size 3 or 4 blade or a direct laryngoscope with a Macintosh size 3 or 4 blade. Of these, 255 were performed with the C-MAC as the initial device and 495 with a Macintosh direct laryngoscope as the initial device. The C-MAC resulted in successful intubation in 248 of 255 cases (97.3%; 95% confidence interval [CI] 94.4% to 98.9%). A direct laryngoscope resulted in successful intubation in 418 of 495 cases (84.4%; 95% CI 81.0% to 87.5%). In the multivariate regression model, with a propensity score included, the C-MAC was positively predictive of ultimate success (odds ratio 12.7; 95% CI 4.1 to 38.8) and first-attempt success (odds ratio 2.2; 95% CI 1.2 to 3.8). When the C-MAC was used as a video laryngoscope, a Cormack-Lehane grade I or II view (video) was obtained in 117 of 125 cases (93.6%; 95% CI 87.8% to 97.2%), whereas when a direct laryngoscope was used, a grade I or II view was obtained in 410 of 495 cases (82.8%; 95% CI 79.2% to 86.1%). The C-MAC was associated with immediately recognized esophageal intubation in 4 of 255 cases (1.6%; 95% CI 0.4% to 4.0%), whereas a direct laryngoscope was associated with immediately recognized esophageal intubation in 24 of 495 cases (4.8%; 95% CI 3.1% to 7.1%). Conclusion When used for emergency intubations in the ED, the C-MAC was associated with a greater proportion of successful intubations and a greater proportion of Cormack-Lehane grade I or II views compared with a direct laryngoscope. PMID:22560464

Rapid susceptibility testing of mycobacterium avium complex and mycobacterium tuberculosis isolated from AIDS patients

NASA Technical Reports Server (NTRS)

Dhople, Arvind M.

1993-01-01

In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of the Human Immunodeficiency Virus (HIV) infection will continue to rise more rapidly worldwide than predicted earlier. The Acquired Immunodeficiency Syndrome (AIDS) patients are susceptible to diseases called opportunistic infections of which tuberculosis and M. avium Complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, Maryland, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. Therefore, we proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis. The work was initiated in June 1992. In the last report, we described our efforts in developing ATP assay method using MAC. Studies were continued further, and during the period of this report, we established the relationship between colony forming units and ATP levels of these organisms during the growth cycle. Also, we evaluated the effects of standard antimycobacterial drugs using ATP assay technique and compared the results with those obtained with conventional tube dilution proportional method.

Time accurate application of the MacCormack 2-4 scheme on massively parallel computers

NASA Technical Reports Server (NTRS)

Hudson, Dale A.; Long, Lyle N.

1995-01-01

Many recent computational efforts in turbulence and acoustics research have used higher order numerical algorithms. One popular method has been the explicit MacCormack 2-4 scheme. The MacCormack 2-4 scheme is second order accurate in time and fourth order accurate in space, and is stable for CFL's below 2/3. Current research has shown that the method can give accurate results but does exhibit significant Gibbs phenomena at sharp discontinuities. The impact of adding Jameson type second, third, and fourth order artificial viscosity was examined here. Category 2 problems, the nonlinear traveling wave and the Riemann problem, were computed using a CFL number of 0.25. This research has found that dispersion errors can be significantly reduced or nearly eliminated by using a combination of second and third order terms in the damping. Use of second and fourth order terms reduced the magnitude of dispersion errors but not as effectively as the second and third order combination. The program was coded using Thinking Machine's CM Fortran, a variant of Fortran 90/High Performance Fortran, and was executed on a 2K CM-200. Simple extrapolation boundary conditions were used for both problems.

78 FR 65541 - Federal Agricultural Mortgage Corporation Funding and Fiscal Affairs; Farmer Mac Liquidity...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... Funding and Fiscal Affairs; Farmer Mac Liquidity Management AGENCY: Farm Credit Administration. ACTION... liquidity management regulations for the Federal Agricultural Mortgage Corporation (Farmer Mac). The purpose of the final rule is to strengthen liquidity risk management at Farmer Mac, improve the quality of...

A New In Vitro Model of Breast Cancer Metastasis to Bone

DTIC Science & Technology

2008-04-01

intravital videomicroscopy [11, 12] have revealed that early stage, pre-angiogenic interactions between the cancer cells and the bone environment are...Chambers AF, MacDonald IC, Schmidt EE, et al. (1995) Steps in tumor metastasis: New concepts from intravital videomicroscopy . 279 - 301 13. Steeg PS

Phase Relations and Miscibility in Polymer Blends Containing Copolymers.

DTIC Science & Technology

1986-04-15

MacKnight, W. J ., Pure Appl. Chem. 52, 409 (1980). 36. Vukovic , R., Kuresevic, V., Karasz, F. E., and MacKnight, W. J ., Thermochim. Acta 54, 349 (1982). 37... Vukovic , R., Karasz, F. E., and MacKnight, W. J ., Polymer 24, 529 (1983). 38. Vukovic , R., Karasz, F. E., and MacKnight, W. J ., J . Appl. Polymer Sci...28, 219 (1983). 39. Zacharius, S. L., ten Brinke, G., MacKnight, W. J ., and Karasz, F. E., Macromolecules 16, 381 (1983). 40. Vukovic , R., Kuresevic

Decay Accelerating Factor (CD55) Protects Neuronal Cells from Chemical Hypoxia-Induced Injury

DTIC Science & Technology

2010-04-09

Pavlakovic G, Isom GE: Dopaminergic neurotoxicity of cyanide: neurochemical, histological and behavioral characterization. Toxicol Appl Pharmacol...provided the original work is properly cited. ResearchDecay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury...deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured

Library Signage: Applications for the Apple Macintosh and MacPaint.

ERIC Educational Resources Information Center

Diskin, Jill A.; FitzGerald, Patricia

1984-01-01

Describes specific applications of the Macintosh computer at Carnegie-Mellon University Libraries, where MacPaint was used as a flexible, easy to use, and powerful tool to produce informational, instructional, and promotional signage. Profiles of system hardware and software, an evaluation of the computer program MacPaint, and MacPaint signage…

Investigation of Carbonaceous Aerosol Optical Properties to Understand Impacts on Air Quality and Composition

NASA Astrophysics Data System (ADS)

Olson, Michael R.

The optical properties of carbonaceous aerosols were investigated to understand the impact source emissions and ambient particulate matter (PM) have on atmospheric radiative forcing. Black carbon (BC) is a strong absorber of visible light and contributes highly to atmospheric radiative forcing, therefore it is important to link BC properties to combustion emission sources. Brown carbon (BrC) is poorly understood and may be an important contributor to both positive and negative radiative forcing. The research investigates these primary knowledge gaps. The optical properties of carbonaceous aerosols were investigated to understand the impact source emissions and ambient particulate matter (PM) have on atmospheric radiative forcing. Black carbon (BC) is a strong absorber of visible light and contributes highly to atmospheric radiative forcing, therefore it is important to link BC properties to combustion emission sources. Brown carbon (BrC) is poorly understood and may be an important contributor to both positive and negative radiative forcing. The research investigates these primary knowledge gaps. Multiple methods were developed and applied to quantify the mass absorption cross-section (MAC) at multiple wavelengths of source and ambient samples. The MAC of BC was determined to be approximately 7.5 m2g-1 at 520nm. However, the MAC was highly variable with OC fraction and wavelength. The BrC MAC was similar for all sources, with the highest absorption in the UV at 370nm; the MAC quickly decreases at larger wavelengths. In the UV, the light absorption by BrC could exceed BC contribution by over 100 times, but only when the OC fraction is large (>90%) as compared to the total carbon. BrC was investigated by measuring the light absorption of solvent extracted fractions in water, dichloromethane, and methanol. Source emissions exhibited greater light absorption in methanol extractions as compared to water and DCM extracts. The BrC MAC was 2.4 to 3.7 m2g-1 at 370nm in methanol. Ambient samples showed similar MACs for the water and methanol extracts. Dichloromethane extracts did not have a significant light absorption characteristics for ambient samples. BrC and BC were measured in Beijing, China. Both were reduced significantly when restrictive air pollution controls were put in place. The industrial regions south and east of Beijing were the highest contributors to ambient BrC and BC. The controls reduced BrC more than BC as compared to observations during the regions heating period. Using the color characteristics of ambient PM, a model was developed to estimate elemental and organic carbon (EC/OC). The method will allow fast and cost effective quantification of PM composition in combination with large climate and health studies, especially in the developing world.

[Effects of xenon preconditioning against ischemia/reperfusion injury and oxidative stress in immature heart].

PubMed

Li, Qian; Lian, Chun-Wei; Fang, Li-Qun; Liu, Bin; Yang, Bo

2014-09-01

To investigate whether xenon preconditioning (PC) could protect immature myocardium against ischemia-reperfusion (I/R) injury in a dose-dependent manner and clarify the role of xenon PC on oxidative stress. Forty-eight isolated perfused immature rabbit hearts were randomly divided into four groups (n = 12): The sham group had the hearts perfused continuously for 300 min. In I/R group, the hearts were subjected to 60 min perfusion followed by 60 min ischemia and 180 min reperfusion. In 1 minimum alveolar concentration (MAC) and 0.5 MAC xenon PC groups, the hearts were preconditioned with 1 MAC or 0.5 MAC xenon respectively, following 60 min ischemia and 180 min reperfusion. The cardiac function, myocardial infarct size, mitochondrial structure, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were determined after reperfusion. Compared with I/R group, both 1 MAC and 0. 5 MAC xenon preconditioning significantly improved cardiac function (P < 0.01), reduced myocardial infarct size (P < 0.01) and mitochondrial damage, increased SOD activity and decreased MDA level (P < 0.01). There were no differences between 1 MAC group and 0.5 MAC xenon group (P > 0.05). Xenon preconditioning at 0. 5 and 1 MAC produce similar cardioprotective effects against I/R injury in isolated perfused immature heart.

Current evidence for the use of C-MAC videolaryngoscope in adult airway management: a review of the literature

PubMed Central

Xue, Fu-Shan; Li, Hui-Xian; Liu, Ya-Yang; Yang, Gui-Zhen

2017-01-01

The C-MAC videolaryngoscope is the first Macintosh-typed videolaryngoscope. Since the advent of its original version video Macintosh system in 1999, this device has been modified several times. A unique feature of C-MAC device is its ability to provide the 2 options of direct and video laryngoscopy with the same device. The available evidence shows that in patients with normal airways, C-MAC videolaryngoscope compared with direct laryngoscopy can provide comparable or better laryngeal views and exerts less force on maxillary incisors, but does not offer conclusive benefits with regard to intubation time, intubation success, number of intubation attempts, the use of adjuncts, and hemodynamic responses to intubation. In patients with predicted or known difficult airways, C-MAC videolaryngoscope can achieve a better laryngeal view, a higher intubation success rate and a shorter intubation time than direct laryngoscopy. Furthermore, the option to perform direct and video laryngoscopy with the same device makes C-MAC videolaryngoscope exceptionally useful for emergency intubation. In addition, the C-MAC videolaryngoscope is a very good tool for tracheal intubation teaching. However, tracheal intubation with C-MAC videolaryngoscope may occasionally fail and introduction of C-MAC videolaryngoscope in clinical practice must be accompanied by formal training programs in normal and difficult airway managements. PMID:28740393

Analysis of expert consultation referrals for anesthesia-related issues (December 2008-July 2010): KSA legislation committee report

PubMed Central

Lee, Kook Hyun; An, Tae-Hun; Choi, Jong Ho; Lim, Dong Gun; Lee, Yeong-Ju

2011-01-01

Background Since 2009, database construction of anesthesia-related adverse events has been initiated through the legislation committee of the Korean Society of Anesthesiologists (KSA), based on expert consultation referrals provided by police departments, civil courts, and criminal courts. Methods This study was a retrospective descriptive analysis of expert consultation referrals on surgical anesthesia-related cases between December 2008 and July 2010. Results During the given period, 46 surgical anesthesia-related cases were referred to the KSA legislation committee for expert consultation. Because six cases were excluded due to insufficient data, 40 cases were included in the final analysis. Of 40 cases, 29 (72.5%) resulted in death. Respiratory events were most common in both surviving/disabled and dead patients (36.4 vs. 51.7%, respectively; P > 0.05). Overall, respiratory depression due to the drugs used for monitored anesthesia care (MAC) was the most common specific mechanism (25%), in which all but one case (profound brain damage) resulted in death. In all of these cases, surgeons or physicians provided MAC without the help of anesthesiologists. Conclusions Overall, the most common damaging mechanism was related to respiratory depression due to sedatives or anesthetics used for MAC. Almost all MAC injury cases are believed to be preventable with the use of additional or better monitoring and an effective response to initial physiological derangement. Thus, it is essential to establish practical MAC guidelines and adhere to these guidelines strictly to reduce the occurrence of severe anesthesia-related adverse outcomes. PMID:21602976

HFC-134a emissions from mobile air conditioning in China from 1995 to 2030

NASA Astrophysics Data System (ADS)

Su, Shenshen; Fang, Xuekun; Li, Li; Wu, Jing; Zhang, Jianbo; Xu, Weiguang; Hu, Jianxin

2015-02-01

Since 1995, 1,1,1,2-tetrafluoroethane (CH2FCF3, HFC-134a) has become the most important substitute of CFC-12 in mobile air conditioning (MAC) in China and MAC sector has dominated all the emissions of HFC-134a. In this study, we developed an accurate, updated and county-level inventory of the HFC-134a emissions from MAC in China for the period of 1995-2030 with an improved bottom-up method. Our estimation indicated that the total HFC-134a emissions kept growing at increase rates of ∼100% per year for 1995-2000 and ∼34% per year for 2001-2010. In 2010, HFC-134a emissions from MAC in China reached 16.7 Gg (10.5-22.7 Gg at 95% confidential interval), equivalent to 21.7 Tg CO2 (CO2-eq). Furthermore, the emissions in China estimated in this study accounted for 9.8% of global HFC-134a emissions and 29.0% of total emissions from Non-Annex_I countries in 2010. Due to the more advanced social-economic conditions and more intensive ownership of automobiles, greater HFC-134a were observed to come from big cities in East China. Under a Business-as-usual (BAU) Scenario, projected emissions will grow to 89.4 (57.9-123.9) Gg (about 75.3-161.1 Tg CO2-eq) in 2030, but under an Alternative Scenario, 88.6% of the projected emissions under BAU scenario could be curbed. Our estimation demonstrates huge emission mitigation potential of HFC-134a in China's MAC sector.

Use of Body-Mounted Cameras to Enhance Data Collection: An Evaluation of Two Arthropod Sampling Techniques.

PubMed

Hagler, James R; Thompson, Alison L; Stefanek, Melissa A; Machtley, Scott A

2018-03-01

A study was conducted that compared the effectiveness of a sweepnet versus a vacuum suction device for collecting arthropods in cotton. The study differs from previous research in that body-mounted action cameras (B-MACs) were used to record the activity of the person conducting the arthropod collections. The videos produced by the B-MACs were then analyzed with behavioral event recording software to quantify various aspects of the sampling process. The sampler's speed and the number of sampling sweeps or vacuum suctions taken over a fixed distance (12.2 m) of cotton were two of the more significant sampling characteristics quantified for each method. The arthropod counts obtained, combined with the analyses of the videos, enabled us to estimate arthropod sampling efficiency for each technique based on fixed distance, time, and sample unit measurements. Data revealed that the vacuuming was the most precise method for collecting arthropods in the relatively small cotton research plots. However, data also indicates that the sweepnet method would be more efficient for collecting most of the cotton-dwelling arthropod taxa, especially if the sampler could continuously sweep for at least 1 min or ≥80 m (e.g., in larger research plots). The B-MACs are inexpensive and non-cumbersome, the video images generated are outstanding, and they can be archived to provide permanent documentation of a research project. The methods described here could be useful for other types of field-based research to enhance data collection efficiency.

Effect of fentanyl and lidocaine on the end-tidal sevoflurane concentration preventing motor movement in dogs.

PubMed

Suarez, Martin A; Seddighi, Reza; Egger, Christine M; Rohrbach, Barton W; Cox, Sherry K; KuKanich, Butch K; Doherty, Thomas J

2017-01-01

OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MAC NM ) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MAC NM (MAC NM-B ) was determined starting 45 minutes after induction of anesthesia. Dogs then received 1 of 3 treatments IV: fentanyl (loading dose, 15 μg/kg; constant rate infusion [CRI], 6 μg/kg/h), lidocaine (loading dose, 2 mg/kg; CRI, 6 mg/kg/h), and the fentanyl-lidocaine combination at the same doses. Determination of treatment MAC NM (MAC NM-T ) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MAC NM measurement for determination of plasma concentrations of fentanyl and lidocaine. RESULTS Mean ± SEM overall MAC NM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MAC NM decreased from MAC NM-B to MAC NM-T by 39%, 21%, and 55% for fentanyl, lidocaine, and the fentanyl-lidocaine combination, respectively. This decrease differed significantly among treatments. Plasma fentanyl concentration was 3.25 and 2.94 ng/mL for fentanyl and the fentanyl-lidocaine combination, respectively. Plasma lidocaine concentration was 2,570 and 2,417 ng/mL for lidocaine and the fentanyl-lidocaine combination, respectively. Plasma fentanyl and lidocaine concentrations did not differ significantly between fentanyl and the fentanyl-lidocaine combination or between lidocaine and the fentanyl-lidocaine combination. CONCLUSIONS AND CLINICAL RELEVANCE CRIs of fentanyl, lidocaine, and the fentanyl-lidocaine combination at the doses used were associated with clinically important and significant decreases in the MAC NM of sevoflurane in dogs.

Refractory inclusions from the ungrouped carbonaceous chondrites MAC 87300 and MAC 88107

NASA Astrophysics Data System (ADS)

Russell, Sara S.; Davis, Andrew M.; MacPherson, Glenn J.; Guan, Yunbin; Huss, Gary R.

2000-09-01

MAC 87300 and MAC 88107 are two unusual carbonaceous chondrites that are intermediate in chemical composition between the CO3 and CM2 meteorite groups. Calcium-aluminum-rich inclusions (CAIs) from these two meteorites are mostly spinel-pyroxene and melilite-rich (Type A) varieties. Spinel-pyroxene inclusions have either a banded or nodular texture, with aluminous diopside rimming iron-poor spinel. Melilite-rich inclusions (4-42) are irregular in shape and contain minor spinel (FeO <1 wt%), perovskite and, more rarely, hibonite. The CAIs in MAC 88107 and MAC 87300 are similar in primary mineralogy to CAIs from low petrologic grade CO3 meteorites, but differ in that they commonly contain phyllosilicates. The two meteorites also differ somewhat from each other: melilite is more abundant and slightly more aluminum-rich in inclusions from MAC 88107 than in those from MAC 87300, and phyllosilicate is more abundant and magnesium-poor in MAC 87300 CAIs relative to that in MAC 88107. These differences suggest that the two meteorites are not paired. CAI sizes and the abundance of melilite-rich CAIs in MAC 88107 and MAC 87300 suggests a genetic relationship to CO3 meteorites, but the CAIs in both have suffered a greater degree of aqueous alteration than is observed in COs. Al-rich melilite in CAIs from both meteorites generally contains excess 26Mg, presumably from the in situ decay of 26Al. Although well-defined isochrons are not observed, the 26Mg excesses are consistent with initial 26Al/27Al ~3-5 ( 10-5. An unusual hibonite-bearing inclusion is isotopically heterogeneous, with two large and abutting hibonite crystals showing significant differences in their degrees of mass-dependent fractionation of 25Mg/24Mg. The two crystals also show differences in their inferred initial 26Al/27Al, 1 ( 10-5 vs. 3 ( 10-6.

The use of the chick embryo chorioallantoic membrane as experimental model to study virus growth and to test the clonal selection hypothesis. The contribution of Sir Mac Farlane Burnet.

PubMed

Ribatti, Domenico

2018-06-07

Sir Mac Farlane Burnet was the most honored of all Australian scientists. In 1960, Burnet shared the Nobel Prize for Medicine with Peter Medawar of Britain for the discovery of acquired immunological tolerance. He developed techniques for growing influenza viruses in the chorioallantoic membrane of the chick embryo. This became a standard laboratory practice. He continued to work with chick embryos long after the use of cell cultures had become general. His virology research resulted in significant discoveries concerning the nature and replication of viruses and their interaction with the immune system. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Comparison of m-Endo LES, MacConkey, and Teepol media for membrane filtration counting of total coliform bacteria in water.

PubMed Central

Grabow, W O; du Preez, M

1979-01-01

Total coliform counts obtained by means of standard membrane filtration techniques, using MacConkey agar, m-Endo LES agar, Teepol agar, and pads saturated with Teepol broth as growth media, were compared. Various combinations of these media were used in tests on 490 samples of river water and city wastewater after different stages of conventional purification and reclamation processes including lime treatment, and filtration, active carbon treatment, ozonation, and chlorination. Endo agar yielded the highest average counts for all these samples. Teepol agar generally had higher counts then Teepol broth, whereas MacConkey agar had the lowest average counts. Identification of 871 positive isolates showed that Aeromonas hydrophila was the species most commonly detected. Species of Escherichia, Citrobacter, Klebsiella, and Enterobacter represented 55% of isolates which conformed to the definition of total coliforms on Endo agar, 54% on Teepol agar, and 45% on MacConkey agar. Selection for species on the media differed considerably. Evaluation of these data and literature on alternative tests, including most probable number methods, indicated that the technique of choice for routine analysis of total coliform bacteria in drinking water is membrane filtration using m-Endo LES agar as growth medium without enrichment procedures or a cytochrome oxidase restriction. PMID:394678

Genetic diversity of clinical Mycobacterium avium subsp. hominissuis and Mycobacterium intracellulare isolates causing pulmonary diseases recovered from different geographical regions.

PubMed

Ichikawa, Kazuya; van Ingen, Jakko; Koh, Won-Jung; Wagner, Dirk; Salfinger, Max; Inagaki, Takayuki; Uchiya, Kei-Ichi; Nakagawa, Taku; Ogawa, Kenji; Yamada, Kiyofumi; Yagi, Tetsuya

2015-12-01

Mycobacterium avium complex (MAC) infections are increasing annually in many countries. MAC strains are the most common nontuberculous mycobacterial pathogens isolated from respiratory samples and predominantly consist of two species, Mycobacterium avium and Mycobacterium intracellulare. The aim of this study was to analyze the molecular epidemiology and genetic backgrounds of clinical MAC isolates collected from The Netherlands, Germany, United States, Korea and Japan. Variable numbers of tandem repeats (VNTR) analysis was used to examine the genetic relatedness of clinical isolates of M. avium subsp. hominissuis (n=261) and M. intracellulare (n=116). Minimum spanning tree and unweighted pair group method using arithmetic averages analyses based on the VNTR data indicated that M. avium subsp. hominissuis isolates from Japan shared a high degree of genetic relatedness with Korean isolates, but not with isolates from Europe or the United States, whereas M. intracellulare isolates did not show any specific clustering by geographic origin. The findings from the present study indicate that strains of M. avium subsp. hominissuis, but not M. intracellulare, exhibit geographical differences in genetic diversity and imply that MAC strains may have different sources, routes of transmission and perhaps clinical manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

Protective responses to sublytic complement in the retinal pigment epithelium

PubMed Central

Tan, Li Xuan; Toops, Kimberly A.; Lakkaraju, Aparna

2016-01-01

The retinal pigment epithelium (RPE) is a key site of injury in inherited and age-related macular degenerations. Abnormal activation of the complement system is a feature of these blinding diseases, yet how the RPE combats complement attack is poorly understood. The complement cascade terminates in the cell-surface assembly of membrane attack complexes (MACs), which promote inflammation by causing aberrant signal transduction. Here, we investigated mechanisms crucial for limiting MAC assembly and preserving cellular integrity in the RPE and asked how these are compromised in models of macular degeneration. Using polarized primary RPE and the pigmented Abca4−/− Stargardt disease mouse model, we provide evidence for two protective responses occurring within minutes of complement attack, which are essential for maintaining mitochondrial health in the RPE. First, accelerated recycling of the membrane-bound complement regulator CD59 to the RPE cell surface inhibits MAC formation. Second, fusion of lysosomes with the RPE plasma membrane immediately after complement attack limits sustained elevations in intracellular calcium and prevents mitochondrial injury. Cholesterol accumulation in the RPE, induced by vitamin A dimers or oxidized LDL, inhibits these defense mechanisms by activating acid sphingomyelinase (ASMase), which increases tubulin acetylation and derails organelle traffic. Defective CD59 recycling and lysosome exocytosis after complement attack lead to mitochondrial fragmentation and oxidative stress in the RPE. Drugs that stimulate cholesterol efflux or inhibit ASMase restore both these critical safeguards in the RPE and avert complement-induced mitochondrial injury in vitro and in Abca4−/− mice, indicating that they could be effective therapeutic approaches for macular degenerations. PMID:27432952

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

PubMed Central

Nowlin, Brian T.; Burdo, Tricia H.; Midkiff, Cecily C.; Salemi, Marco; Alvarez, Xavier; Williams, Kenneth C.

2016-01-01

Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163+) and inflammatory (MAC387+) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2′-deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387+ macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163+ macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU+ cells were MAC387+; however, CD163+BrdU+ macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% ± 1.8%) of macrophages in SIVE lesions were present in the CNS before SIVE lesion formation. There was a 2.9-fold increase in SIVp28+ macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163+ macrophage recruitment to the CNS inversely correlated with time to death (P < 0.03) and increased with SIVE. In SIVE animals, soluble CD163 correlated with CD163+ macrophage recruitment (P = 0.02). Most perivascular macrophages that comprise SIVE lesions and multinucleated giant cells are present in the CNS early, before SIVE lesions are formed. Most SIV-infected macrophages traffic to the CNS terminally with AIDS. PMID:25963554

Photocopy of drawing (original drawing of MacDill Field in possession ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing (original drawing of MacDill Field in possession of MacDill Air Force Base, Civil Engineering, Tampa, Florida; site plan dated December, 1942) BASE LAYOUT, DECEMBER 1942 - MacDill Air Force Base, Bounded by City of Tampa North, Tampa Bay South, Old Tampa Bay West, & Hillsborough Bay East, Tampa, Hillsborough County, FL

Generic Drug Cost Containment in Medicaid: Lessons from Five State MAC Programs

PubMed Central

Abramson, Richard G.; Harrington, Catherine A.; Missmar, Raad; Li, Susan P.; Mendelson, Daniel N.

2004-01-01

In Medicaid, generic drug cost containment revolves around two programs: the Federal upper limit (FUL) program and State maximum allowable cost (MAC) programs. This article analyzes MAC programs in five States and finds considerable variation between these programs and the FUL program in both size and pricing aggressiveness. We conclude that expansion of existing MAC programs and creation of new ones could contribute to cost containment efforts nationwide. Options for States seeking to optimize their efforts include focusing on pricing for drugs with high sales volumes, ensuring that MAC lists include prices for all forms and dosages of listed drug entities, and collaborating with other States or the Federal Government on MAC list operations. PMID:15229994

Effects of carprofen and morphine on the minimum alveolar concentration of isoflurane in dogs.

PubMed

Ko, Jeff C H; Weil, Ann B; Inoue, Tomohito

2009-01-01

The minimum alveolar concentration (MAC) of isoflurane in dogs was determined following carprofen (2.2 mg/kg per os) alone, morphine (1 mg/kg intravenously) alone, carprofen and morphine, and no drug control in eight healthy adult dogs. Isoflurane MAC following administration of morphine alone (0.81%+/-0.18%) or carprofen and morphine (0.68%+/-0.31%) was significantly less than the control MAC (1.24%+/-0.15%). Isoflurane MAC after carprofen alone (1.13%+/-0.13%) was not significantly different from the control value. Results indicated that administration of morphine alone or in combination with carprofen significantly reduced the MAC of isoflurane in dogs. The isoflurane MAC reduction was additive between the effects of carprofen and morphine.

Application of the implicit MacCormack scheme to the PNS equations

NASA Technical Reports Server (NTRS)

Lawrence, S. L.; Tannehill, J. C.; Chaussee, D. S.

1983-01-01

The two-dimensional parabolized Navier-Stokes equations are solved using MacCormack's (1981) implicit finite-difference scheme. It is shown that this method for solving the parabolized Navier-Stokes equations does not require the inversion of block tridiagonal systems of algebraic equations and allows the original explicit scheme to be employed in those regions where implicit treatment is not needed. The finite-difference algorithm is discussed and the computational results for two laminar test cases are presented. Results obtained using this method for the case of a flat plate boundary layer are compared with those obtained using the conventional Beam-Warming scheme, as well as those obtained from a boundary layer code. The computed results for a more severe test of the method, the hypersonic flow past a 15 deg compression corner, are found to compare favorably with experiment and a numerical solution of the complete Navier-Stokes equations.

Functional Study of Genes Essential for Autogamy and Nuclear Reorganization in Paramecium▿§

PubMed Central

Nowak, Jacek K.; Gromadka, Robert; Juszczuk, Marek; Jerka-Dziadosz, Maria; Maliszewska, Kamila; Mucchielli, Marie-Hélène; Gout, Jean-François; Arnaiz, Olivier; Agier, Nicolas; Tang, Thomas; Aggerbeck, Lawrence P.; Cohen, Jean; Delacroix, Hervé; Sperling, Linda; Herbert, Christopher J.; Zagulski, Marek; Bétermier, Mireille

2011-01-01

Like all ciliates, Paramecium tetraurelia is a unicellular eukaryote that harbors two kinds of nuclei within its cytoplasm. At each sexual cycle, a new somatic macronucleus (MAC) develops from the germ line micronucleus (MIC) through a sequence of complex events, which includes meiosis, karyogamy, and assembly of the MAC genome from MIC sequences. The latter process involves developmentally programmed genome rearrangements controlled by noncoding RNAs and a specialized RNA interference machinery. We describe our first attempts to identify genes and biological processes that contribute to the progression of the sexual cycle. Given the high percentage of unknown genes annotated in the P. tetraurelia genome, we applied a global strategy to monitor gene expression profiles during autogamy, a self-fertilization process. We focused this pilot study on the genes carried by the largest somatic chromosome and designed dedicated DNA arrays covering 484 genes from this chromosome (1.2% of all genes annotated in the genome). Transcriptome analysis revealed four major patterns of gene expression, including two successive waves of gene induction. Functional analysis of 15 upregulated genes revealed four that are essential for vegetative growth, one of which is involved in the maintenance of MAC integrity and another in cell division or membrane trafficking. Two additional genes, encoding a MIC-specific protein and a putative RNA helicase localizing to the old and then to the new MAC, are specifically required during sexual processes. Our work provides a proof of principle that genes essential for meiosis and nuclear reorganization can be uncovered following genome-wide transcriptome analysis. PMID:21257794

Impact of divalent metal ions on regulation of adenylyl cyclase isoforms by forskolin analogs.

PubMed

Erdorf, Miriam; Mou, Tung-Chung; Seifert, Roland

2011-12-01

Mammalian membranous adenylyl cyclases (mACs) play an important role in transmembrane signalling events in almost every cell and represent an interesting drug target. Forskolin (FS) is an invaluable research tool, activating AC isoforms 1-8. However, there is a paucity of AC isoform-selective FS analogs. Therefore, we examined the effects of FS and six FS derivatives on recombinant ACs 1, 2 and 5, representing members of different mAC families. Correlations of the pharmacological properties of the different AC isoforms revealed pronounced differences between ACs 1, 2 and 5. Additionally, potencies and efficacies of FS derivatives changed for any given AC isoform, depending on the metal ion, Mg(2+) or Mn(2+). The most striking effects of Mg(2+) and Mn(2+) on the diterpene profile were observed for AC2 where the large inhibitory effect of BODIPY-FS in the presence of Mg(2+) was considerably reduced in the presence of Mn(2+). Sequence alignment and docking experiments confirmed an exceptional position of AC2 compared to ACs 1 and 5 with respect to the structural environment of the catalytic core and cation-dependent diterpene effects. In conclusion, mAC isoforms 1, 2 and 5 exhibit a distinct pharmacological diterpene profile, depending on the divalent cation present. mAC crystal structures and modelling/docking studies provided an explanation for the pharmacological differences between the AC isoforms. Our study constitutes an important step towards the development of isoform-specific diterpenes exhibiting stimulatory or inhibitory effects. Copyright © 2011 Elsevier Inc. All rights reserved.

Immune system cells in healthy ferrets: an immunohistochemical study.

PubMed

Vidaña, B; Majó, N; Pérez, M; Montoya, M; Martorell, J; Martínez, J

2014-07-01

The ferret has emerged as an excellent animal model to characterize several physiologic and pathologic conditions. The distribution and characterization of different types of immune system cells were studied in healthy ferret tissues. Eight primary antibodies were tested for immunohistochemistry in formalin-fixed tissues: anti-CD3, anti-CD79α, anti-CD20, anti-HLA-DR, anti-lysozyme, anti-CD163, anti-SWC3, and anti-Mac387. The anti-CD3 antibody labeled T cells mainly in interfollicular and paracortical areas of lymph nodes, cortex and thymic medulla, and periarteriolar lymphoid sheaths in the spleen. The anti-CD79α and anti-CD20 antibodies immunolabeled B cells located in lymphoid follicles at lymph nodes, spleen, and Peyer patches. The CD79α and CD20 antibodies also labeled cells with nonlymphoid morphology in atypical B-cell locations. The anti-HLA-DR antibody labeled macrophages, some populations of B and T lymphocytes, and different populations of dendritic cells in lymph nodes, Peyer patches, spleen, and thymus. The anti-lysozyme antibody immunolabeled macrophages in the liver, lymph nodes, spleen, and thymus. The Mac-387, CD163, and SWC3 antibodies did not show any positive reaction in formalin-fixed or frozen tissues. To elucidate the origin of the uncommon CD79α/CD20 positive cells, a double immunohistochemistry was carried out using the anti-HLA-DR + the anti-CD79α, the anti-HLA-DR + the anti-CD20, and the anti-lysozyme + the anti-CD79α antibodies. Double labeling was mainly observed when the anti-HLA-DR + the anti-CD79α antibodies were combined. The immunohistologic characterization and distribution of these immune system cells in healthy ferret tissues should be of value in future comparative studies of diseases in ferrets. © The Author(s) 2013.

An extended smart utilization medium access control (ESU-MAC) protocol for ad hoc wireless systems

NASA Astrophysics Data System (ADS)

Vashishtha, Jyoti; Sinha, Aakash

2006-05-01

The demand for spontaneous setup of a wireless communication system has increased in recent years for areas like battlefield, disaster relief operations etc., where a pre-deployment of network infrastructure is difficult or unavailable. A mobile ad-hoc network (MANET) is a promising solution, but poses a lot of challenges for all the design layers, specifically medium access control (MAC) layer. Recent existing works have used the concepts of multi-channel and power control in designing MAC layer protocols. SU-MAC developed by the same authors, efficiently uses the 'available' data and control bandwidth to send control information and results in increased throughput via decreasing contention on the control channel. However, SU-MAC protocol was limited for static ad-hoc network and also faced the busy-receiver node problem. We present the Extended SU-MAC (ESU-MAC) protocol which works mobile nodes. Also, we significantly improve the scheme of control information exchange in ESU-MAC to overcome the busy-receiver node problem and thus, further avoid the blockage of control channel for longer periods of time. A power control scheme is used as before to reduce interference and to effectively re-use the available bandwidth. Simulation results show that ESU-MAC protocol is promising for mobile, ad-hoc network in terms of reduced contention at the control channel and improved throughput because of channel re-use. Results show a considerable increase in throughput compared to SU-MAC which could be attributed to increased accessibility of control channel and improved utilization of data channels due to superior control information exchange scheme.

THE ISOLATION AND IDENTIFICATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) RECOVERED FROM LOS ANGELES POTABLE WATER, A POSSIBLE SOURCE OF INFECTION IN AIDS PATIENTS

EPA Science Inventory

Los Angeles water was investigated as a possible source of Mycobacterium avium complex (MAC) infection in patients with AIDS. MAC consists of M.avium (MA), M. intracellulare (MI) and Mycobacterium X (MX)(positive for MAC by DNA probe but not MA or MI). The study included 13 reser...

33 CFR 165.768 - Security Zone; MacDill Air Force Base, Tampa Bay, FL.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Security Zone; MacDill Air Force....768 Security Zone; MacDill Air Force Base, Tampa Bay, FL. (a) Location. The following area is a... title. All waters within Tampa Bay, Florida in the vicinity of MacDill Air Force Base, including...

Introduction to MacDraft. High-Technology Training Module.

ERIC Educational Resources Information Center

Traxler, Gene

This training module on MacDraft is part of a computer drafting skills unit on communications technology for grades 9-12. The objective is for each student to complete a drawing on the MacIntosh computer using the MacDraft software program. This drawing is to be dimensioned with a dual system and is to include a border and title block. This module…

Genetics Home Reference: Langerhans cell histiocytosis

MedlinePlus

... Oct;29(5):853-73. doi: 10.1016/j.hoc.2015.06.005. Epub 2015 Aug 18. Review. Citation on PubMed Nelson DS, van Halteren A, Quispel WT, van den Bos C, Bovée JV, Patel B, Badalian-Very G, van Hummelen P, Ducar M, Lin L, MacConaill LE, Egeler RM, ...

[Spanish validation of the MacArthur Competence Assessment Tool for Treatment interview to assess patients competence to consent treatment].

PubMed

Alvarez Marrodán, Ignacio; Baón Pérez, Beatriz; Navío Acosta, Mercedes; López-Antón, Raul; Lobo Escolar, Elena; Ventura Faci, Tirso

2014-09-09

To validate the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) Spanish version, which assesses the mental capacity of patients to consent treatment, by examining 4 areas (Understanding, Appreciation, Reasoning and Expressing a choice). 160 subjects (80 Internal Medicine inpatients, 40 Psychiatric inpatients and 40 healthy controls). MacCAT-T, Mini-Mental Status Examination (MMSE). Feasibility study, reliability and validity calculations (against to gold standard of clinical expert). Mean duration of the MacCAT-T interview was 18min. Inter-rater reliability: Intraclass correlation coefficient for Understanding=0.98, Appreciation=0.97, Reasoning=0.98, Expressing a choice=0.91. Internal consistency (Cronbach's alpha): Understanding=0.87, for Appreciation=0.76, for Reasoning=0.86. Patients considered to be incapable (gold standard) scored lower in all the MacCAT-T areas. Poor performance on the MacCAT-T was related to cognitive impairment assessed by MMSE. Spanish version of the MacCAT-T is feasible, reliable, and valid for assessing the capacity of patients to consent treatment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Serrated adenocarcinoma morphology in colorectal mucinous adenocarcinoma is associated with improved patient survival

PubMed Central

Lee, Chung-Ta; Chow, Nan-Haw; Su, Pei-Fang; Ho, Chung-Liang; Tsai, Hung-Wen; Chen, Yi-Lin; Lin, Shao-Chieh; Lin, Bo-Wen; Lin, Peng-Chan; Lee, Jenq-Chang

2017-01-01

Colorectal mucinous adenocarcinoma (MAC) and serrated adenocarcinoma (SAC) share many characteristics, including right-side colon location, frequent mucin production, and various molecular features. This study examined the frequency of SAC morphology in MACs. We assessed the correlation of SAC morphology with clinicopathological parameters, molecular characteristics, and patient prognosis. Eighty-eight colorectal MACs were collected and reviewed for SAC morphology according to Makinen's criteria. We sequenced KRAS and BRAF, assessed CpG island methylator phenotype (CIMP) frequency, and analyzed DNA mismatch repair enzyme levels using immunohistochemistry in tumor samples. SAC morphology was observed in 38% of MACs, and was associated with proximal location (P=0.001), BRAF mutation (P=0.042), CIMP-positive status (P=0.023), and contiguous traditional serrated adenoma (P=0.019). Multivariate analysis revealed that MACs without both SAC morphology and CIMP-positive status exhibited 3.955 times greater risk of cancer relapse than MACs having both characteristics or either one (P=0.035). Our results show that two MAC groups with distinct features can be identified using Makinen's criteria, and suggest a favorable prognostic role for the serrated neoplastic pathway in colorectal MAC. PMID:28422723

Considerations for Improving the Capacity and Performance of AeroMACS

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Kamali, Behnam; Apaza, Rafael D.; Wilson, Jeffrey D.; Dimond, Robert P.

2014-01-01

The Aeronautical Mobile Airport Communications System (AeroMACS) has progressed from concept through prototype development, testing, and standards development and is now poised for the first operational deployments at nine US airports by the Federal Aviation Administration. These initial deployments will support fixed applications. Mobile applications providing connectivity to and from aircraft and ground-based vehicles on the airport surface will occur at some point in the future. Given that many fixed applications are possible for AeroMACS, it is necessary to now consider whether the existing capacity of AeroMACS will be reached even before the mobile applications are ready to be added, since AeroMACS is constrained by both available bandwidth and transmit power limitations. This paper describes some concepts that may be applied to improve the future capacity of AeroMACS, with a particular emphasis on gains that can be derived from the addition of IEEE 802.16j multihop relays to the AeroMACS standard, where a significant analysis effort has been undertaken.

An energy-efficient MAC protocol using dynamic queue management for delay-tolerant mobile sensor networks.

PubMed

Li, Jie; Li, Qiyue; Qu, Yugui; Zhao, Baohua

2011-01-01

Conventional MAC protocols for wireless sensor network perform poorly when faced with a delay-tolerant mobile network environment. Characterized by a highly dynamic and sparse topology, poor network connectivity as well as data delay-tolerance, delay-tolerant mobile sensor networks exacerbate the severe power constraints and memory limitations of nodes. This paper proposes an energy-efficient MAC protocol using dynamic queue management (EQ-MAC) for power saving and data queue management. Via data transfers initiated by the target sink and the use of a dynamic queue management strategy based on priority, EQ-MAC effectively avoids untargeted transfers, increases the chance of successful data transmission, and makes useful data reach the target terminal in a timely manner. Experimental results show that EQ-MAC has high energy efficiency in comparison with a conventional MAC protocol. It also achieves a 46% decrease in packet drop probability, 79% increase in system throughput, and 25% decrease in mean packet delay.

An Energy-Efficient MAC Protocol Using Dynamic Queue Management for Delay-Tolerant Mobile Sensor Networks

PubMed Central

Li, Jie; Li, Qiyue; Qu, Yugui; Zhao, Baohua

2011-01-01

Conventional MAC protocols for wireless sensor network perform poorly when faced with a delay-tolerant mobile network environment. Characterized by a highly dynamic and sparse topology, poor network connectivity as well as data delay-tolerance, delay-tolerant mobile sensor networks exacerbate the severe power constraints and memory limitations of nodes. This paper proposes an energy-efficient MAC protocol using dynamic queue management (EQ-MAC) for power saving and data queue management. Via data transfers initiated by the target sink and the use of a dynamic queue management strategy based on priority, EQ-MAC effectively avoids untargeted transfers, increases the chance of successful data transmission, and makes useful data reach the target terminal in a timely manner. Experimental results show that EQ-MAC has high energy efficiency in comparison with a conventional MAC protocol. It also achieves a 46% decrease in packet drop probability, 79% increase in system throughput, and 25% decrease in mean packet delay. PMID:22319385

SACRB-MAC: A High-Capacity MAC Protocol for Cognitive Radio Sensor Networks in Smart Grid

PubMed Central

Yang, Zhutian; Shi, Zhenguo; Jin, Chunlin

2016-01-01

The Cognitive Radio Sensor Network (CRSN) is considered as a viable solution to enhance various aspects of the electric power grid and to realize a smart grid. However, several challenges for CRSNs are generated due to the harsh wireless environment in a smart grid. As a result, throughput and reliability become critical issues. On the other hand, the spectrum aggregation technique is expected to play an important role in CRSNs in a smart grid. By using spectrum aggregation, the throughput of CRSNs can be improved efficiently, so as to address the unique challenges of CRSNs in a smart grid. In this regard, we proposed Spectrum Aggregation Cognitive Receiver-Based MAC (SACRB-MAC), which employs the spectrum aggregation technique to improve the throughput performance of CRSNs in a smart grid. Moreover, SACRB-MAC is a receiver-based MAC protocol, which can provide a good reliability performance. Analytical and simulation results demonstrate that SACRB-MAC is a promising solution for CRSNs in a smart grid. PMID:27043573

SACRB-MAC: A High-Capacity MAC Protocol for Cognitive Radio Sensor Networks in Smart Grid.

PubMed

Yang, Zhutian; Shi, Zhenguo; Jin, Chunlin

2016-03-31

The Cognitive Radio Sensor Network (CRSN) is considered as a viable solution to enhance various aspects of the electric power grid and to realize a smart grid. However, several challenges for CRSNs are generated due to the harsh wireless environment in a smart grid. As a result, throughput and reliability become critical issues. On the other hand, the spectrum aggregation technique is expected to play an important role in CRSNs in a smart grid. By using spectrum aggregation, the throughput of CRSNs can be improved efficiently, so as to address the unique challenges of CRSNs in a smart grid. In this regard, we proposed Spectrum Aggregation Cognitive Receiver-Based MAC (SACRB-MAC), which employs the spectrum aggregation technique to improve the throughput performance of CRSNs in a smart grid. Moreover, SACRB-MAC is a receiver-based MAC protocol, which can provide a good reliability performance. Analytical and simulation results demonstrate that SACRB-MAC is a promising solution for CRSNs in a smart grid.

Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders.

PubMed

Slack, James; Albert, Michael H; Balashov, Dmitry; Belohradsky, Bernd H; Bertaina, Alice; Bleesing, Jack; Booth, Claire; Buechner, Jochen; Buckley, Rebecca H; Ouachée-Chardin, Marie; Deripapa, Elena; Drabko, Katarzyna; Eapen, Mary; Feuchtinger, Tobias; Finocchi, Andrea; Gaspar, H Bobby; Ghosh, Sujal; Gillio, Alfred; Gonzalez-Granado, Luis I; Grunebaum, Eyal; Güngör, Tayfun; Heilmann, Carsten; Helminen, Merja; Higuchi, Kohei; Imai, Kohsuke; Kalwak, Krzysztof; Kanazawa, Nubuo; Karasu, Gülsün; Kucuk, Zeynep Y; Laberko, Alexandra; Lange, Andrzej; Mahlaoui, Nizar; Meisel, Roland; Moshous, D; Muramatsu, Hideki; Parikh, Suhag; Pasic, Srdjan; Schmid, Irene; Schuetz, Catharina; Schulz, Ansgar; Schultz, Kirk R; Shaw, Peter J; Slatter, Mary A; Sykora, Karl-Walter; Tamura, Shinobu; Taskinen, Mervi; Wawer, Angela; Wolska-Kuśnierz, Beata; Cowan, Morton J; Fischer, Alain; Gennery, Andrew R

2018-01-01

Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m 2 fludarabine or less and 40 mg/kg cyclophosphamide or less were used. Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P = .006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P = .45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved. RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Interference Analysis Status and Plans for Aeronautical Mobile Airport Communications System (AeroMACS)

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Wilson, Jeffrey D.

2010-01-01

Interference issues related to the operation of an aeronautical mobile airport communications system (AeroMACS) in the C-Band (specifically 5091-5150 MHz) is being investigated. The issue of primary interest is co-channel interference from AeroMACS into mobile-satellite system (MSS) feeder uplinks. The effort is focusing on establishing practical limits on AeroMACS transmissions from airports so that the threshold of interference into MSS is not exceeded. The analyses are being performed with the software package Visualyse Professional, developed by Transfinite Systems Limited. Results with omni-directional antennas and plans to extend the models to represent AeroMACS more accurately will be presented. These models should enable realistic analyses of emerging AeroMACS designs to be developed from NASA Test Bed, RTCA 223, and European results.

ACME: Automated Cell Morphology Extractor for Comprehensive Reconstruction of Cell Membranes

PubMed Central

Mosaliganti, Kishore R.; Noche, Ramil R.; Xiong, Fengzhu; Swinburne, Ian A.; Megason, Sean G.

2012-01-01

The quantification of cell shape, cell migration, and cell rearrangements is important for addressing classical questions in developmental biology such as patterning and tissue morphogenesis. Time-lapse microscopic imaging of transgenic embryos expressing fluorescent reporters is the method of choice for tracking morphogenetic changes and establishing cell lineages and fate maps in vivo. However, the manual steps involved in curating thousands of putative cell segmentations have been a major bottleneck in the application of these technologies especially for cell membranes. Segmentation of cell membranes while more difficult than nuclear segmentation is necessary for quantifying the relations between changes in cell morphology and morphogenesis. We present a novel and fully automated method to first reconstruct membrane signals and then segment out cells from 3D membrane images even in dense tissues. The approach has three stages: 1) detection of local membrane planes, 2) voting to fill structural gaps, and 3) region segmentation. We demonstrate the superior performance of the algorithms quantitatively on time-lapse confocal and two-photon images of zebrafish neuroectoderm and paraxial mesoderm by comparing its results with those derived from human inspection. We also compared with synthetic microscopic images generated by simulating the process of imaging with fluorescent reporters under varying conditions of noise. Both the over-segmentation and under-segmentation percentages of our method are around 5%. The volume overlap of individual cells, compared to expert manual segmentation, is consistently over 84%. By using our software (ACME) to study somite formation, we were able to segment touching cells with high accuracy and reliably quantify changes in morphogenetic parameters such as cell shape and size, and the arrangement of epithelial and mesenchymal cells. Our software has been developed and tested on Windows, Mac, and Linux platforms and is available publicly under an open source BSD license (https://github.com/krm15/ACME). PMID:23236265

Research in Biological and Medical Sciences Including Biochemistry, Communicable Disease and Immunology, Internal Medicine, Physiology, Psychiatry, Surgery, and Veterinary Medicine. Volume 1

DTIC Science & Technology

1979-09-01

and R.P. MacDermott. Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K-lymphocytes and monocytes are effective...malaria research. During the reporting period, research activities have included analyses of: 1) a hemagglutination inhibition test for early detection of...radioiodination or sodium borohydride reduction. Evaluate the potential roles of activity for each protein isolated. Compare the composition of isolated

STS-115 MS MacLean holds Yeast GAP in the FWD MDDK of the Space Shuttle Atlantis during Joint Operations

NASA Image and Video Library

2006-09-19

S115-E-07273 (9-21 Sept. 2006) --- Astronaut Heidemarie M. Stefanyshyn-Piper, STS-115 mission specialist, works with the Yeast-Group Activation Packs (Yeast-GAP) on the middeck of Space Shuttle Atlantis. Yeast-GAP experiment studies the effects of genetic changes of yeast cells exposed to the space environment. The results will help scientists to understand how cells respond to radiation and microgravity.

STS-115 MS MacLean holds Yeast GAP in the FWD MDDK of the Space Shuttle Atlantis during Joint Operations

NASA Image and Video Library

2006-09-19

S115-E-07274 (9-21 Sept. 2006) --- Astronaut Heidemarie M. Stefanyshyn-Piper, STS-115 mission specialist, works with the Yeast-Group Activation Packs (Yeast-GAP) on the middeck of Space Shuttle Atlantis. Yeast-GAP experiment studies the effects of genetic changes of yeast cells exposed to the space environment. The results will help scientists to understand how cells respond to radiation and microgravity.

Development and validation of an ELISA kit (YF MAC-HD) to detect IgM to yellow fever virus.

PubMed

Basile, Alison Jane; Goodman, Christin; Horiuchi, Kalanthe; Laven, Janeen; Panella, Amanda J; Kosoy, Olga; Lanciotti, Robert S; Johnson, Barbara W

2015-12-01

Yellow fever virus (YFV) is endemic in tropical and sub-tropical regions of the world, with around 180,000 human infections a year occurring in Africa. Serologic testing is the chief laboratory diagnostic means of identifying an outbreak and to inform the decision to commence a vaccination campaign. The World Health Organization disseminates the reagents for YFV testing to African reference laboratories, and the US Centers for Disease Control and Prevention (CDC) is charged with producing and providing these reagents. The CDC M-antibody capture ELISA is a 2-day test, requiring titration of reagents when new lots are received, which leads to inconsistency in testing and wastage of material. Here we describe the development of a kit-based assay (YF MAC-HD) based upon the CDC method, that is completed in approximately 3.5h, with equivocal samples being reflexed to an overnight protocol. The kit exhibits >90% accuracy when compared to the 2-day test. The kits were designed for use with a minimum of equipment and are stored at 4°C, removing the need for freezing capacity. This kit is capable of tolerating temporary sub-optimal storage conditions which will ease shipping or power outage concerns, and a shelf life of >6 months was demonstrated with no deterioration in accuracy. All reagents necessary to run the YF MAC-HD are included in the kit and are single-use, with 8 or 24 sample options per kit. Field trials are envisioned for the near future, which will enable refinement of the method. The use of the YF MAC-HD is anticipated to reduce materials wastage, and improve the quality and consistency of YFV serologic testing in endemic areas. Published by Elsevier B.V.

Inference for occupancy and occupancy dynamics

USGS Publications Warehouse

O'Connell, Allan F.; Bailey, Larissa L.; O'Connell, Allan F.; Nichols, James D.; Karanth, K. Ullas

2011-01-01

This chapter deals with the estimation of occupancy as a state variable to assess the status of, and track changes in, species distributions when sampling with camera traps. Much of the recent interest in occupancy estimation and modeling originated from the models developed by MacKenzie et al. (2002, 2003), although similar methods were developed independently (Azuma et al. 1990; Bayley and Petersen 2001; Nichols and Karanth, 2002; Tyre et al. 2003), all of which deal with species occurrence information and imperfect detection. Less than a decade after these publications, the modeling and estimation of species occurrence and occupancy dynamics have increased significantly. Special features of scientific journals have explored innovative uses of detection–nondetection data with occupancy models (Vojta 2005), and an entire volume has synthesized the use and application of occupancy estimation methods (MacKenzie et al. 2006). Reviews of the topical concepts, philosophical considerations, and various sampling designs that can be used for occupancy estimation are now readily available for a range of audiences (MacKenzie and Royle 2005; MacKenzie et al. 2006; Bailey et al. 2007; Royle and Dorazio 2008; Conroy and Carroll 2009; Kendall and White 2009; Hines et al. 2010; Link and Barker 2010). As a result, it would be pointless here to recast all that these publications have so eloquently articulated, but that said, a review of any scientific topic requires sufficient context and relevant background information, especially when relatively new methodologies and techniques such as occupancy estimation and camera traps are involved. This is especially critical in a digital age where new information is published at warp speed, making it increasingly difficult to stay abreast of theoretical advances and research developments.

Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator.

PubMed

Carlson, Signe; Helterline, Deri; Asbe, Laura; Dupras, Sarah; Minami, Elina; Farris, Stephen; Stempien-Otero, April

2017-07-01

Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3±6.5 and 70.3±36, fold change vs UI, n=8, P<0.007). There was significant up-regulation of cardiac mac Arg1 and YM1 with MI in both WT and uPA null mice (n=4-9 per genotype and condition). Treatment with plasmin increased expression of Arg1 and YM1 in cultured cardiac macs. Histologic analysis revealed increased density of activated fibroblasts and M2 macs in SR-uPA hearts post-infarction with associated increases in fibrosis. Cardiac macs isolated from human hearts with ischemic heart disease expressed increased levels of the M2 marker CD206 in comparison to blood-derived macs (4.9±1.3). Cardiac macs in mouse and human hearts adopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Constraints on voltage sensor movement in the shaker K+ channel.

PubMed

Darman, Rachel B; Ivy, Allison A; Ketty, Vina; Blaustein, Robert O

2006-12-01

In nerve and muscle cells, the voltage-gated opening and closing of cation-selective ion channels is accompanied by the translocation of 12-14 elementary charges across the membrane's electric field. Although most of these charges are carried by residues in the S4 helix of the gating module of these channels, the precise nature of their physical movement is currently the topic of spirited debate. Broadly speaking, two classes of models have emerged: those that suggest that small-scale motions can account for the extensive charge displacement, and those that invoke a much larger physical movement. In the most recent incarnation of the latter type of model, which is based on structural and functional data from the archaebacterial K(+) channel KvAP, a "voltage-sensor paddle" comprising a helix-turn-helix of S3-S4 translocates approximately 20 A through the bilayer during the gating cycle (Jiang, Y., A. Lee, J. Chen, V. Ruta, M. Cadene, B.T. Chait, and R. MacKinnon. 2003. Nature. 423:33-41; Jiang, Y., V. Ruta, J. Chen, A. Lee, and R. MacKinnon. 2003. Nature. 423:42-48.; Ruta, V., J. Chen, and R. MacKinnon. 2005. Cell. 123:463-475). We used two methods to test for analogous motions in the Shaker K(+) channel, each examining the aqueous exposure of residues near S3. In the first, we employed a pore-blocking maleimide reagent (Blaustein, R.O., P.A. Cole, C. Williams, and C. Miller. 2000. Nat. Struct. Biol. 7:309-311) to probe for state-dependent changes in the chemical reactivity of substituted cysteines; in the second, we tested the state-dependent accessibility of a tethered biotin to external streptavidin (Qiu, X.Q., K.S. Jakes, A. Finkelstein, and S.L. Slatin. 1994. J. Biol. Chem. 269:7483-7488; Slatin, S.L., X.Q. Qiu, K.S. Jakes, and A. Finkelstein. 1994. Nature. 371:158-161). In both types of experiments, residues predicted to lie near the top of S3 did not exhibit any change in aqueous exposure during the gating cycle. This lack of state dependence argues against large-scale movements, either axially or radially, of Shaker's S3-S4 voltage-sensor paddle.

Constraints on Voltage Sensor Movement in the Shaker K+ Channel

PubMed Central

Darman, Rachel B.; Ivy, Allison A.; Ketty, Vina; Blaustein, Robert O.

2006-01-01

In nerve and muscle cells, the voltage-gated opening and closing of cation-selective ion channels is accompanied by the translocation of 12–14 elementary charges across the membrane's electric field. Although most of these charges are carried by residues in the S4 helix of the gating module of these channels, the precise nature of their physical movement is currently the topic of spirited debate. Broadly speaking, two classes of models have emerged: those that suggest that small-scale motions can account for the extensive charge displacement, and those that invoke a much larger physical movement. In the most recent incarnation of the latter type of model, which is based on structural and functional data from the archaebacterial K+ channel KvAP, a “voltage-sensor paddle” comprising a helix-turn-helix of S3–S4 translocates ∼20 Å through the bilayer during the gating cycle (Jiang, Y., A. Lee, J. Chen, V. Ruta, M. Cadene, B.T. Chait, and R. MacKinnon. 2003. Nature. 423:33–41; Jiang, Y., V. Ruta, J. Chen, A. Lee, and R. MacKinnon. 2003. Nature. 423:42–48.; Ruta, V., J. Chen, and R. MacKinnon. 2005. Cell. 123:463–475). We used two methods to test for analogous motions in the Shaker K+ channel, each examining the aqueous exposure of residues near S3. In the first, we employed a pore-blocking maleimide reagent (Blaustein, R.O., P.A. Cole, C. Williams, and C. Miller. 2000. Nat. Struct. Biol. 7:309–311) to probe for state-dependent changes in the chemical reactivity of substituted cysteines; in the second, we tested the state-dependent accessibility of a tethered biotin to external streptavidin (Qiu, X.Q., K.S. Jakes, A. Finkelstein, and S.L. Slatin. 1994. J. Biol. Chem. 269:7483–7488; Slatin, S.L., X.Q. Qiu, K.S. Jakes, and A. Finkelstein. 1994. Nature. 371:158–161). In both types of experiments, residues predicted to lie near the top of S3 did not exhibit any change in aqueous exposure during the gating cycle. This lack of state dependence argues against large-scale movements, either axially or radially, of Shaker's S3–S4 voltage-sensor paddle. PMID:17101817

Self-Anchored Catalyst Interface Enables Ordered Via Array Formation from Submicrometer to Millimeter Scale for Polycrystalline and Single-Crystalline Silicon.

PubMed

Kim, Jeong Dong; Kim, Munho; Kong, Lingyu; Mohseni, Parsian K; Ranganathan, Srikanth; Pachamuthu, Jayavel; Chim, Wai Kin; Chiam, Sing Yang; Coleman, James J; Li, Xiuling

2018-03-14

Defying text definitions of wet etching, metal-assisted chemical etching (MacEtch), a solution-based, damage-free semiconductor etching method, is directional, where the metal catalyst film sinks with the semiconductor etching front, producing 3D semiconductor structures that are complementary to the metal catalyst film pattern. The same recipe that works perfectly to produce ordered array of nanostructures for single-crystalline Si (c-Si) fails completely when applied to polycrystalline Si (poly-Si) with the same doping type and level. Another long-standing challenge for MacEtch is the difficulty of uniformly etching across feature sizes larger than a few micrometers because of the nature of lateral etching. The issue of interface control between the catalyst and the semiconductor in both lateral and vertical directions over time and over distance needs to be systematically addressed. Here, we present a self-anchored catalyst (SAC) MacEtch method, where a nanoporous catalyst film is used to produce nanowires through the pinholes, which in turn physically anchor the catalyst film from detouring as it descends. The systematic vertical etch rate study as a function of porous catalyst diameter from 200 to 900 nm shows that the SAC-MacEtch not only confines the etching direction but also enhances the etch rate due to the increased liquid access path, significantly delaying the onset of the mass-transport-limited critical diameter compared to nonporous catalyst c-Si counterpart. With this enhanced mass transport approach, vias on multistacks of poly-Si/SiO 2 are also formed with excellent vertical registry through the polystack, even though they are separated by SiO 2 which is readily removed by HF alone with no anisotropy. In addition, 320 μm square through-Si-via (TSV) arrays in 550 μm thick c-Si are realized. The ability of SAC-MacEtch to etch through poly/oxide/poly stack as well as more than half millimeter thick silicon with excellent site specificity for a wide range of feature sizes has significant implications for 2.5D/3D photonic and electronic device applications.

Unrelated cord blood transplantation in adults with myelodysplasia or secondary acute myeloblastic leukemia: a survey on behalf of Eurocord and CLWP of EBMT.

PubMed

Robin, M; Sanz, G F; Ionescu, I; Rio, B; Sirvent, A; Renaud, M; Carreras, E; Milpied, N; Mohty, M; Beguin, Y; Bordigoni, P; de Witte, T; Picardi, A; Purtill, D; Gluckman, E; Kroger, N; Rocha, V

2011-01-01

The aim of our study was to evaluate, through the Eurocord and European Group for Blood and Marrow Transplantation (EBMT) registries, outcomes and risk factors for outcomes in adult patients who underwent single or double unrelated cord blood transplantation (UCBT) for myelodysplastic syndrome (MDS) or secondary acute myeloblastic leukemia (sAML). A total of 180 adults with MDS (n=39) or sAML (n=69) were analyzed. Risk factors for outcomes were analyzed using the Fine and Gray method and the Cox model. Median age was 43 (18-72) years. In all, 77 patients (71%) received a single UCBT. Myeloablative conditioning regimen (MAC) was given to 57 (53%) patients. Median numbers of nucleated and CD34(+) cells at freezing were 3.6 × 10(7) and 1.1 × 10(5) kg. At 60 days, cumulative incidence of neutrophil recovery was 78±4% and was independently associated with the number of CD34(+) cells per kg (>1.1 × 10(5); P=0.005) and advanced disease status (blasts <5% at time of UCBT, P=0.016). A 2-year non-relapse mortality (NRM) was significantly higher after MAC (62 vs 34%; P=0.009). A 2-year disease-free-survival (DFS) and overall survival (OS) were 30 and 34%, respectively. In multivariate analysis, patients with high-risk disease (blasts >5% and International Prognostic scoring system (IPSS) intermediate-2 or high in MDS) had significant poorer DFS (hazard ratio (HR): 1.76; P=0.047). In spite of high NRM, these data indicate that UCBT is an acceptable alternative option to treat adults with high-risk MDS or sAML, without a suitable human leukocyte antigen (HLA)-matched donor.

42 CFR 423.2110 - MAC reviews on its own motion.

Code of Federal Regulations, 2011 CFR

2011-10-01

... its own motion, it will mail the results of its action to the enrollee and to CMS or the IRE, as... 42 Public Health 3 2011-10-01 2011-10-01 false MAC reviews on its own motion. 423.2110 Section 423..., and Judicial Review § 423.2110 MAC reviews on its own motion. (a) General rule. The MAC may decide on...

Effect of CLA and other C18 unsaturated fatty acids on DGAT in bovine milk fat biosynthetic systems.

PubMed

Sørensen, Brent M; Chris Kazala, E; Murdoch, Gordon K; Keating, Aileen F; Cruz-Hernandez, Cristina; Wegner, Jochen; Kennelly, John J; Okine, Erasmus K; Weselake, Randall J

2008-10-01

Production of dairy products with increased amounts of nutraceutic FA such as conjugated linoleic acid (CLA) represents a recent approach for dairy producers and processors to increase the value of their products. The effect of CLA and other FA on the expression of diacylglycerol acyltransferase-1 (DGAT-1) and DGAT-2, and DGAT activity were investigated in bovine mammary gland epithelial (MAC-T) cells. DGAT gene expression analyses were also conducted using bovine mammary gland tissue from dairy cows. In the studies with MAC-T cells, there were no significant effects of CLA isomers or other FA on DGAT1 expression, whereas all FA tested showed enhanced DGAT2 expression (P < 0.05 to P < 0.001), with alpha-linolenic acid (alpha-18:3) having the greatest effect. Additionally, DGAT2 expression was co-ordinated with expression of lysophosphatidic acid acyltransferase (LPAAT), an observation that was also apparent in mammary gland from lactating dairy cows. In contrast, treatment of MAC-T cells with trans-10, cis-12 18:2 or alpha-18:3 resulted in a significant (P < 0.05) decrease in overall DGAT enzyme activity, although the mechanisms resulting in these effects are unclear. Competition assays using microsomes from bovine mammary gland tissue and 1-[(14)C]oleoyl-CoA suggested that DGAT activity was more selective for oleoyl (cis-9 18:1)-CoA than cis-9, trans-11 18:2-, trans-10, cis-12 18:2- or cis-9, cis-12 18:2-CoA. Collectively, the results suggest the relationship between trans-10, cis-12 18:2 and reduced TAG production in bovine milk is not linked to the production of DGAT1 or DGAT2 transcripts, but probably involves effects of this CLA isomer at events beyond transcription, such as post-translational and/or enzyme activity effects.

Predictors of Use of Monitored Anesthesia Care for Outpatient Gastrointestinal Endoscopy in a Capitated Payment System.

PubMed

Adams, Megan A; Prenovost, Katherine M; Dominitz, Jason A; Holleman, Robert G; Kerr, Eve A; Krein, Sarah L; Saini, Sameer D; Rubenstein, Joel H

2017-12-01

Use of monitored anesthesia care (MAC) for gastrointestinal endoscopy has increased in the Veterans Health Administration (VHA) as in fee-for-service environments, despite the absence of financial incentives. We investigated factors associated with use of MAC in an integrated health care delivery system with a capitated payment model. We performed a retrospective cohort study using multilevel logistic regression, with MAC use modeled as a function of procedure year, patient- and provider-level factors, and facility effects. We collected data from 2,091,590 veterans who underwent outpatient esophagogastroduodenoscopy and/or colonoscopy during fiscal years 2000-2013 at 133 facilities. The adjusted rate of MAC use in the VHA increased 17% per year (odds ratio for increase, 1.17; 95% confidence interval, 1.09-1.27) from fiscal year 2000 through 2013. The most rapid increase occurred starting in 2011. VHA use of MAC was associated with patient-level factors that included obesity, obstructive sleep apnea, higher comorbidity, and use of prescription opioids and/or benzodiazepines, although the magnitude of these effects was small. Provider-level and facility factors were also associated with use of MAC, although again the magnitude of these associations was small. Unmeasured facility-level effects had the greatest effect on the trend of MAC use. In a retrospective study of veterans who underwent outpatient esophagogastroduodenoscopy and/or colonoscopy from fiscal year 2000 through 2013, we found that even in a capitated system, patient factors are only weakly associated with use of MAC. Facility-level effects are the most prominent factor influencing increasing use of MAC. Future studies should focus on better defining the role of MAC and facility and organizational factors that affect choice of endoscopic sedation. It will also be important to align resources and incentives to promote appropriate allocation of MAC based on clinically meaningful patient factors. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

The effects of ketamine on the minimum alveolar concentration of isoflurane in cats.

PubMed

Pascoe, Peter J; Ilkiw, Janet E; Craig, Carolyn; Kollias-Baker, Cynthia

2007-01-01

To determine the minimum alveolar concentration (MAC) of isoflurane during the infusion of ketamine. Prospective, experimental trial. Twelve adult spayed female cats weighing 5.1 +/- 0.9 kg. Six cats were anesthetized with isoflurane in oxygen, intubated and attached to a circle-breathing system with mechanical ventilation. Catheters were placed in a peripheral vein for the infusion of fluids and ketamine, and the jugular vein for blood sampling for the measurement of ketamine concentrations. An arterial catheter was placed to allow blood pressure measurement and sampling for the measurement of PaCO2, PaO2 and pH. PaCO2 was maintained between 29 and 41 mmHg (3.9-5.5 kPa) and body temperature was kept between 37.8 and 39.3 degrees C. Following instrumentation, the MAC of isoflurane was determined in triplicate using a tail clamp method. A loading dose (2 mg kg(-1) over 5 minutes) and an infusion (23 microg kg(-1) minute(-1)) of ketamine was started and MAC was redetermined starting 30 minutes later. Two further loading doses and infusions were used, 2 mg kg(-1) and 6 mg kg(-1) with 46 and 115 microg kg(-1) minute(-1), respectively and MAC was redetermined. Cardiopulmonary measurements were taken before application of the noxious stimulus. The second group of six cats was used for the measurement of steady state plasma ketamine concentrations at each of the three infusion rates used in the initial study and the appropriate MAC value determined from the first study. The MAC decreased by 45 +/- 17%, 63 +/- 18%, and 75 +/- 17% at the infusion rates of 23, 46, and 115 microg kg(-1) minute(-1). These infusion rates corresponded to ketamine plasma concentrations of 1.75 +/- 0.21, 2.69 +/- 0.40, and 5.36 +/- 1.19 microg mL(-1). Arterial blood pressure and heart rate increased significantly with ketamine. Recovery was protracted. The MAC of isoflurane was significantly decreased by an infusion of ketamine and this was accompanied by an increase in heart rate and blood pressure. Because of the prolonged recovery in our cats, further work needs to be performed before using this in patients.

Coronary artery calcification correlates with the presence and severity of valve calcification.

PubMed

Koulaouzidis, G; Nicoll, R; MacArthur, T; Jenkins, P J; Henein, M Y

2013-10-15

To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both. This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score. AVC was more prevalent than MAC (64% vs. 2.5%, p < 0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC+MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score >400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score >400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC. The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification. © 2013.

Girardia dorotocephala transcriptome sequence, assembly, and validation through characterization of piwi homologs and stem cell progeny markers

PubMed Central

Almazan, Eugene Matthew P.; Lesko, Sydney L.; Markey, Michael P.; Rouhana, Labib

2017-01-01

Planarian flatworms are popular models for the study of regeneration and stem cell biology in vivo. Technical advances and increased availability of genetic information have fueled the discovery of molecules responsible for stem cell pluripotency and regeneration in flatworms. Unfortunately, most of the planarian research performed worldwide utilizes species that are not natural habitants of North America, which limits their availability to newcomer laboratories and impedes their distribution for educational activities. In order to circumvent these limitations and increase the genetic information available for comparative studies, we sequenced the transcriptome of Girardia dorotocephala, a planarian species pandemic and commercially available in North America. A total of 254,802,670 paired sequence reads were obtained from RNA extracted from intact individuals, regenerating fragments, as well as freshly excised auricles of a clonal line of G. dorotocephala (MA-C2), and used for de novo assembly of its transcriptome. The resulting transcriptome draft was validated through functional analysis of genetic markers of stem cells and their progeny in G. dorotocephala. Akin to orthologs in other planarian species, G. dorotocephala Piwi1 (GdPiwi1) was found to be a robust marker of the planarian stem cell population and GdPiwi2 an essential component for stem cell-driven regeneration. Identification of G. dorotocephala homologs of the early stem cell descendent marker PROG-1 revealed a family of lysine-rich proteins expressed during epithelial cell differentiation. Sequences from the MA-C2 transcriptome were found to be 98–99% identical to nucleotide sequences from G. dorotocephala populations with different chromosomal number, demonstrating strong conservation regardless of karyotype evolution. Altogether, this work establishes G. dorotocephala as a viable and accessible option for analysis of gene function in North America. PMID:28774726

Selection of Single Domain Antibodies from Immune Libraries Displayed on the Surface of E. coli Cells with Two β-Domains of Opposite Topologies

PubMed Central

Martínez-Arteaga, Rocio; Ruano-Gallego, David; Fraile, Sofía; Margolles, Yago; Teira, Xema; Gutierrez, Carlos; Bodelón, Gustavo; Fernández, Luis Ángel

2013-01-01

Screening of antibody (Ab) libraries by direct display on the surface of E. coli cells is hampered by the presence of the outer membrane (OM). In this work we demonstrate that the native β-domains of EhaA autotransporter and intimin, two proteins from enterohemorrhagic E. coli O157:H7 (EHEC) with opposite topologies in the OM, are effective systems for the display of immune libraries of single domain Abs (sdAbs) from camelids (nanobodies or VHH) on the surface of E. coli K-12 cells and for the selection of high affinity sdAbs using magnetic cell sorting (MACS). We analyzed the capacity of EhaA and intimin β-domains to display individual sdAbs and sdAb libraries obtained after immunization with the extracellular domain of the translocated intimin receptor from EHEC (TirMEHEC). We demonstrated that both systems displayed functional sdAbs on the surface of E. coli cells with little proteolysis and cellular toxicity, although E. coli cells displaying sdAbs with the β-domain of intimin showed higher antigen-binding capacity. Both E. coli display libraries were screened for TirMEHEC binding clones by MACS. High affinity binders were selected by both display systems, although more efficiently with the intimin β-domain. The specificity of the selected clones against TirMEHEC was demonstrated by flow cytometry of E. coli cells, along with ELISA and surface plasmon resonance with purified sdAbs. Finally, we employed the E. coli cell display systems to provide an estimation of the affinity of the selected sdAb by flow cytometry analysis under equilibrium conditions. PMID:24086454

Chronic upregulation of activated microglia immunoreactive for galectin-3/Mac-2 and nerve growth factor following diffuse axonal injury

PubMed Central

2010-01-01

Background Diffuse axonal injury in patients with traumatic brain injury (TBI) can be associated with morbidity ranging from cognitive difficulties to coma. Magnetic resonance imaging scans now allow early detection of axonal injury following TBI, and have linked cognitive disability in these patients to white matter signal changes. However, little is known about the pathophysiology of this white matter injury, and the role of microglial activation in this process. It is increasingly recognized that microglia constitute a heterogeneous population with diverse roles following injury. In the present studies, we tested the hypothesis that following diffuse axonal injury involving the corpus callosum, there is upregulation of a subpopulation of microglia that express the lectin galectin-3/Mac-2 and are involved in myelin phagocytosis. Methods Adult mice were subject to midline closed skull injury or sham operation and were sacrificed 1, 8, 14 or 28 days later. Immunohistochemistry and immunofluorescence techniques were used to analyze patterns of labelling within the corpus callosum qualitatively and quantitatively. Results Activated microglia immunoreactive for galectin-3/Mac-2 were most abundant 1 day following injury. Their levels were attenuated at later time points after TBI but still were significantly elevated compared to sham animals. Furthermore, the majority of galectin-3/Mac-2+ microglia were immunoreactive for nerve growth factor in both sham and injured animals. Conclusions Our results suggest that galectin-3/Mac-2+ microglia play an important role in the pathogenesis of diffuse axonal injury both acutely and chronically and that they mediate their effects, at least in part by releasing nerve growth factor. PMID:20507613

Toxic aluminium and heavy metals in groundwater of middle Russia: health risk assessment.

PubMed

Momot, Olga; Synzynys, Boris

2005-08-01

Two approaches are distinguished in modern ecological monitoring. The first one is physicochemical analysis of environmental objects with respect to maximum allowable concentrations (MACs) of chemical substances, which is performed by standards methods in accordance with state regulations. The second approach (biological monitoring) is based on the methodology of biotesting and bio indication. The task of this work is to create biotests for estimation of Al and other metals toxicity in ground water and to compare these results with physicochemical analysis dates. Risk assessment for heavy metals contaminated groundwater was also performed. Risk assessment was performed accordingly EPA US recommendation and gave results about 90 per 100000 citizens for Al and 402 per 100000 for mixture of different heavy metals. For comparison: risk for earth background radiation for Middle Russia is (Individual dose 1 millisivert per year) consist 5 per 100000 people. It was shown that groundwater consist HCO3- ions (360 mg/l), sometimes Al compounds 0.21-0.65 mg/l (MAC for Al is 0.5 mg/l for Russia). Other groundwater contain Hg - 0.004 mg/l (MAC - 0.0005 mg/l); Cr - 0.072 mg/l (MAC - 0.05 mg/l); As - less than 0.03 mg/l (MAC - 0.05 mg/l). We developed plant biotest for estimation of groundwater quality with barley roots, tradescatia and others. Some biotests parameters correlate with HCO3-, Cl-, SO(4)2- and metal ions content positively, for another biotest this correlation is strongly negative. The quality of groundwater near Obninsk and in Kaluga Region is very different but hasnit been changed since the year 1998.

Randomized controlled study comparing the hemodynamic response to laryngoscopy and endotracheal intubation with McCoy, Macintosh, and C-MAC laryngoscopes in adult patients

PubMed Central

Buhari, Faiza Sulaiman; Selvaraj, Venkatesh

2016-01-01

Background and Aims: Earlier studies have shown that the type of laryngoscope blade influences the degree of hemodynamic response to endotracheal intubation. The aim of the study was to evaluate the hemodynamic response to oral endotracheal intubation with C-MAC laryngoscopy and McCoy laryngoscopy compared to that of Macintosh laryngoscopy in adult patients under general anesthesia. Material and Methods: This is a prospective randomized parallel group study. Ninety American Society of Anesthesiologists I patients were randomly allotted into three groups. Group A – Macintosh laryngoscopy (control group). Group B – laryngoscopy with McCoy laryngoscope. Group C – laryngoscopy with C-MAC video laryngoscope. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were monitored at baseline (just before induction), just before intubation (T0), 1 min (T1), 3 min (T3), 5 min (T5), and 10 min (T10) after intubation. Intergroup comparison of study parameters was done by unpaired sample t-test for normal data and Mann-Whitney U-test for skewed data. For within-group comparison, the repeated measures of ANOVA for normal data and Friedman followed by Wilcoxon signed rank test for skewed data were performed. Results: In C-MAC group, the HR was significantly higher than the Macintosh group at 3 min after intubation, whereas SBP, DBP, and MAP were significantly higher at 1 min. McCoy group showed a similar response compared to Macintosh group at all time intervals. Conclusion: C-MAC video laryngoscope has a comparatively greater hemodynamic response than Macintosh laryngoscope. PMID:28096584

Feasibility of cord blood transplantation in chemosensitive adult T-cell leukemia/lymphoma: a retrospective analysis of the Nagasaki Transplantation Network.

PubMed

Fukushima, Takuya; Itonaga, Hidehiro; Moriuchi, Yukiyoshi; Yoshida, Shinichiro; Taguchi, Jun; Imaizumi, Yoshitaka; Imanishi, Daisuke; Tsushima, Hideki; Sawayama, Yasushi; Matsuo, Emi; Hata, Tomoko; Miyazaki, Yasushi

2013-04-01

It has been reported that cord blood transplantation (CBT) for patients with aggressive adult T-cell leukemia/lymphoma (ATL) results in poorer outcomes than transplantation using other stem cell sources. To identify a subset of ATL in which CBT is feasible, we retrospectively analyzed 27 patients treated with CBT at three institutions in Nagasaki Prefecture, Japan. The estimated overall survival (OS) rate at 3 years was 27.4 %. Of 16 patients who received CBT during remission (complete, CR, or partial, PR), the OS rate at 3 years was 50 %, while during refractory periods (non-CR or non-PR), the OS rate was 9.1 %. Reduced intensity conditioning (RIC) was given to 18 patients, and myeloablative conditioning (MAC) was used in nine, with 3-year OS of 50.0 and 0 %, respectively. Of the 19 deaths, nine were due to progressive disease, eight (five MAC and three RIC) to infection, and two to multiple organ failure. These results suggest that CBT provides similar results with those in other transplantation procedures for selected ATL patients, such as those in CR or PR. Further studies are needed to evaluate the use of CBT in aggressive ATL.

KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation

PubMed Central

Goodman, Wendy A.; Omenetti, Sara; Date, Dipali; Di Martino, Luca; De Salvo, Carlo; Kim, Gun-Dong; Chowdhry, Saleem; Bamias, Giorgos; Cominelli, Fabio; Pizarro, Theresa T.; Mahabeleshwar, Ganapati H.

2016-01-01

Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of NFκB signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of STAT3 signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate-sodium (DSS) and found that Mac-KLF6-KO mice were protected against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation. PMID:26838049

EISCAT observations during MAC/SINE and MAC/Epsilon

NASA Technical Reports Server (NTRS)

Roettger, J.; Hoppe, U.-P.; Hall, C.

1989-01-01

The EISCAT incoherent scatter radar facility in Tromsoe, Norway was operated during the MAC/SINE campaign for 78 hours in the period 10 June to 17 July 1987, and during the MAC/Epsilon campaign for 90 hours in the period 15 October to 5 November 1987. The VHF (224 MHz) radar operations during MAC/SINE yielded most interesting observations of strong coherent echoes from the mesopause region. Characteristic data of these polar mesospheric summer echoes are presented. The UHF (933 MHz) radar operations during MAC/Epsilon were done with 18 deg off zenith beam and allows the deduction of meridonal and horizontal wind components as well as radial velocity spectra in addition to the usual electron density profiles in the D and lower E regions. Some results from the VHF and UHF radars indicating the presence of gravity waves are examined.

Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia-anophthalmia-coloboma (MAC) spectrum cases.

PubMed

Gonzalez-Rodriguez, J; Pelcastre, E L; Tovilla-Canales, J L; Garcia-Ortiz, J E; Amato-Almanza, M; Villanueva-Mendoza, C; Espinosa-Mattar, Z; Zenteno, J C

2010-08-01

Microphthalmia-anophthalmia-coloboma (MAC) are congenital eye malformations causing a significant percentage of visually impairments in children. Although these anomalies can arise from prenatal exposure to teratogens, mutations in well-defined genes originate potentially heritable forms of MAC. Mutations in genes such as CHX10, GDF6, RAX, SOX2 and OTX2, among others, have been recognised in dominant or recessive MAC. SOX2 and OTX2 are the two most commonly mutated genes in monogenic MAC. However, as more numerous samples of MAC subjects would be analysed, a better estimation of the actual involvement of specific MAC-genes could be made. Here, a comprehensive mutational analysis of the CHX10, GDF6, RAX, SOX2 and OTX2 genes was performed in 50 MAC subjects. PCR amplification and direct automated DNA sequencing of all five genes in 50 unrelated subjects. Eight mutations (16% prevalence) were recognised, including four GDF6 mutations (one novel), two novel RAX mutations, one novel OTX2 mutation and one SOX2 mutation. Anophthalmia and nanophthalmia, not previously associated with GDF6 mutations, were observed in two subjects carrying defects in this gene, expanding the spectrum of GDF6-linked ocular anomalies. Our study underscores the importance of genotyping large groups of patients from distinct ethnic origins for improving the estimation of the global involvement of particular MAC-causing genes.

A Cross-Layer Duty Cycle MAC Protocol Supporting a Pipeline Feature for Wireless Sensor Networks

PubMed Central

Tong, Fei; Xie, Rong; Shu, Lei; Kim, Young-Chon

2011-01-01

Although the conventional duty cycle MAC protocols for Wireless Sensor Networks (WSNs) such as RMAC perform well in terms of saving energy and reducing end-to-end delivery latency, they were designed independently and require an extra routing protocol in the network layer to provide path information for the MAC layer. In this paper, we propose a new cross-layer duty cycle MAC protocol with data forwarding supporting a pipeline feature (P-MAC) for WSNs. P-MAC first divides the whole network into many grades around the sink. Each node identifies its grade according to its logical hop distance to the sink and simultaneously establishes a sleep/wakeup schedule using the grade information. Those nodes in the same grade keep the same schedule, which is staggered with the schedule of the nodes in the adjacent grade. Then a variation of the RTS/CTS handshake mechanism is used to forward data continuously in a pipeline fashion from the higher grade to the lower grade nodes and finally to the sink. No extra routing overhead is needed, thus increasing the network scalability while maintaining the superiority of duty-cycling. The simulation results in OPNET show that P-MAC has better performance than S-MAC and RMAC in terms of packet delivery latency and energy efficiency. PMID:22163895

The microassay on a card: A rugged, portable immunoassay

NASA Technical Reports Server (NTRS)

Kidwell, David

1991-01-01

The Microassay on a Card (MAC) is a portable, hand-held, non-instrumental immunoassay that can test for the presence of a wide variety of substances in the environment. The MAC is a simple device to use. A drop of test solution is placed on one side of the card and within five minutes a color is developed on the other side in proportion to the amount of substance in the test solution, with sensitivity approaching 10 ng/ml. The MAC is self-contained and self-timed; no reagents or timing is necessary. The MAC may be configured with multiple wells to provide simultaneous testing for multiple species. As envisioned, the MAC will be employed first as an on-site screen for drugs of abuse in urine or saliva. If the MAC can be used as a screen of saliva for drugs of abuse, it could be applied to driving while intoxicated, use of drugs on the job, or testing of the identity of seized materials. With appropriate modifications, the MAC also could be used to test for environmental toxins or pollutants.

AeroMACS system characterization and demonstrations

NASA Astrophysics Data System (ADS)

Kerczewski, R. J.; Apaza, R. D.; Dimond, R. P.

This The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past three years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

AeroMACS System Characterization and Demonstrations

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Apaza, Rafael D.; Dimond, Robert P.

2013-01-01

This The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past 3 years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

AeroMACS System Characterization and Demonstrations

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Apaza, Rafael D.; Dimond, Robert P.

2013-01-01

The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past three years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

McMAC: Towards a MAC Protocol with Multi-Constrained QoS Provisioning for Diverse Traffic in Wireless Body Area Networks

PubMed Central

Monowar, Muhammad Mostafa; Hassan, Mohammad Mehedi; Bajaber, Fuad; Al-Hussein, Musaed; Alamri, Atif

2012-01-01

The emergence of heterogeneous applications with diverse requirements for resource-constrained Wireless Body Area Networks (WBANs) poses significant challenges for provisioning Quality of Service (QoS) with multi-constraints (delay and reliability) while preserving energy efficiency. To address such challenges, this paper proposes McMAC, a MAC protocol with multi-constrained QoS provisioning for diverse traffic classes in WBANs. McMAC classifies traffic based on their multi-constrained QoS demands and introduces a novel superframe structure based on the “transmit-whenever-appropriate” principle, which allows diverse periods for diverse traffic classes according to their respective QoS requirements. Furthermore, a novel emergency packet handling mechanism is proposed to ensure packet delivery with the least possible delay and the highest reliability. McMAC is also modeled analytically, and extensive simulations were performed to evaluate its performance. The results reveal that McMAC achieves the desired delay and reliability guarantee according to the requirements of a particular traffic class while achieving energy efficiency. PMID:23202224

Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Weixin; Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang; Wu, Mingchai

Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies.more » The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia/reperfusion (I/R) injury in vivo. • Compound 14p functioned through both antioxidant and anti-apoptotic pathways. • Compound 14p limited myocardial I/R injury as a promising antioxidant.« less

Vibrational, DFT, and thermal analysis of 2,4,6-triamino-1,3,5-triazin-1-ium 3-(prop-2-enoyloxy) propanoate acrylic acid monosolvate monohydrate

NASA Astrophysics Data System (ADS)

Sangeetha, V.; Govindarajan, M.; Kanagathara, N.; Marchewka, M. K.; Drozd, M.; Anbalagan, G.

2013-12-01

New organic crystals of 2,4,6-triamino-1,3,5-triazin-1-ium 3-(prop-2-enoyloxy) propanoate acrylic acid monosolvate monohydrate (MAC) have been obtained from aqueous solution by the slow solvent evaporation method at room temperature. Single crystal X-ray diffraction analysis reveals that the compound crystallises in the triclinic system with centrosymmetric space group P-1. FT-IR and FT-Raman spectra of MAC have been recorded and analyzed. The molecular geometry and vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimization based on density functional theory (DFT) B3LYP method with 6-31G(d,p) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction data. The theoretical results show that the optimized geometry can well reproduce the crystal structure, and the calculated vibrational frequency values show good agreement with experimental values. A study of the electronic properties, such as HOMO and LUMO energies and Molecular electrostatic potential (MEP) were performed. Mulliken charges and NBO charges of the title molecule were also calculated and interpreted. Thermogravimetric analysis has been done to study the thermal behaviour of MAC. The 13C and 1H nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results.

33 CFR 334.630 - Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base... Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base...

33 CFR 334.630 - Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base... Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base...

33 CFR 334.630 - Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base... Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base...

33 CFR 334.630 - Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base... Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base...

Impact of MAC Delay on AUV Localization: Underwater Localization Based on Hyperbolic Frequency Modulation Signal

PubMed Central

2018-01-01

Medium Access Control (MAC) delay which occurs between the anchor node’s transmissions is one of the error sources in underwater localization. In particular, in AUV localization, the MAC delay significantly degrades the ranging accuracy. The Cramer-Rao Low Bound (CRLB) definition theoretically proves that the MAC delay significantly degrades the localization performance. This paper proposes underwater localization combined with multiple access technology to decouple the localization performance from the MAC delay. Towards this goal, we adopt hyperbolic frequency modulation (HFM) signal that provides multiplexing based on its good property, high-temporal correlation. Owing to the multiplexing ability of the HFM signal, the anchor nodes can transmit packets without MAC delay, i.e., simultaneous transmission is possible. In addition, the simulation results show that the simultaneous transmission is not an optional communication scheme, but essential for the localization of mobile object in underwater. PMID:29373518

Impact of MAC Delay on AUV Localization: Underwater Localization Based on Hyperbolic Frequency Modulation Signal.

PubMed

Kim, Sungryul; Yoo, Younghwan

2018-01-26

Medium Access Control (MAC) delay which occurs between the anchor node's transmissions is one of the error sources in underwater localization. In particular, in AUV localization, the MAC delay significantly degrades the ranging accuracy. The Cramer-Rao Low Bound (CRLB) definition theoretically proves that the MAC delay significantly degrades the localization performance. This paper proposes underwater localization combined with multiple access technology to decouple the localization performance from the MAC delay. Towards this goal, we adopt hyperbolic frequency modulation (HFM) signal that provides multiplexing based on its good property, high-temporal correlation. Owing to the multiplexing ability of the HFM signal, the anchor nodes can transmit packets without MAC delay, i.e., simultaneous transmission is possible. In addition, the simulation results show that the simultaneous transmission is not an optional communication scheme, but essential for the localization of mobile object in underwater.

Research on low-latency MAC protocols for wireless sensor networks

NASA Astrophysics Data System (ADS)

He, Chenguang; Sha, Xuejun; Lee, Chankil

2007-11-01

Energy-efficient should not be the only design goal in MAC protocols for wireless sensor networks, which involve the use of battery-operated computing and sensing devices. Low-latency operation becomes the same important as energy-efficient in the case that the traffic load is very heavy or the real-time constrain is used in applications like tracking or locating. This paper introduces some causes of traditional time delays which are inherent in a multi-hops network using existing WSN MAC protocols, illuminates the importance of low-latency MAC design for wireless sensor networks, and presents three MACs as examples of low-latency protocols designed specially for sleep delay, wait delay and wakeup delay in wireless sensor networks, respectively. The paper also discusses design trade-offs with emphasis on low-latency and points out their advantages and disadvantages, together with some design considerations and suggestions for MAC protocols for future applications and researches.

The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils

PubMed Central

Lupia, Enrico; Del Sorbo, Lorenzo; Bergerone, Serena; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-01-01

Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia–reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN). In the present study, we investigated the role of the membrane attack complex (MAC) of complement in the PLN-induced synthesis of PAF. In vivo, we showed a correlation between the levels of soluble terminal complement components (sC5b-9) and the concentrations of PAF detected in blood of patients with AMI infused with SK. In vitro both EC and polymorphonuclear neutrophils (PMN), incubated in the presence of PLN and normal human serum, showed an intense staining for the MAC neoepitope, while no staining was detected when they were incubated with PLN in the presence of heat-inactivated normal human serum. Moreover, the insertion of MAC on EC and PMN plasmamembrane elicited the synthesis of PAF. In conclusion, our results elucidate the mechanisms involved in PAF production during the activation of the fibrinolytic system, showing a role for complement products in this setting. The release of PAF may increase the inflammatory response, thus limiting the beneficial effects of thrombolytic therapy. Moreover, it may have a pathogenic role in other pathological conditions, such as transplant rejection, tumoral angiogenesis, and septic shock, where fibrinolysis is activated. PMID:12871223

The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils.

PubMed

Lupia, Enrico; Del Sorbo, Lorenzo; Bergerone, Serena; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-08-01

Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia-reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN). In the present study, we investigated the role of the membrane attack complex (MAC) of complement in the PLN-induced synthesis of PAF. In vivo, we showed a correlation between the levels of soluble terminal complement components (sC5b-9) and the concentrations of PAF detected in blood of patients with AMI infused with SK. In vitro both EC and polymorphonuclear neutrophils (PMN), incubated in the presence of PLN and normal human serum, showed an intense staining for the MAC neoepitope, while no staining was detected when they were incubated with PLN in the presence of heat-inactivated normal human serum. Moreover, the insertion of MAC on EC and PMN plasmamembrane elicited the synthesis of PAF. In conclusion, our results elucidate the mechanisms involved in PAF production during the activation of the fibrinolytic system, showing a role for complement products in this setting. The release of PAF may increase the inflammatory response, thus limiting the beneficial effects of thrombolytic therapy. Moreover, it may have a pathogenic role in other pathological conditions, such as transplant rejection, tumoral angiogenesis, and septic shock, where fibrinolysis is activated.

Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment.

PubMed

Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

2012-10-01

The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6-65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan-Meier survival curves (log-rank test). It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Viral CTL escape mutants are generated in lymph nodes and subsequently become fixed in plasma and rectal mucosa during acute SIV infection of macaques.

PubMed

Vanderford, Thomas H; Bleckwehl, Chelsea; Engram, Jessica C; Dunham, Richard M; Klatt, Nichole R; Feinberg, Mark B; Garber, David A; Betts, Michael R; Silvestri, Guido

2011-05-01

SIV(mac239) infection of rhesus macaques (RMs) results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL) response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitudinally assessed the presence of CTL escape variants in two MamuA*01-restricted immunodominant epitopes (Tat-SL8 and Gag-CM9) in the plasma, PBMCs, lymph nodes (LN), and rectal biopsies (RB) of fifteen SIV(mac239)-infected RMs. As expected, Gag-CM9 did not exhibit signs of escape before day 84 post infection. In contrast, Tat-SL8 escape mutants were apparent in all tissues by day 14 post infection. Interestingly LNs and plasma exhibited the highest level of escape at day 14 and day 28 post infection, respectively, with the rate of escape in the RB remaining lower throughout the acute infection. The possibility that CTL escape occurs in LNs before RBs is confirmed by the observation that the specific mutants found at high frequency in LNs at day 14 post infection became dominant at day 28 post infection in plasma, PBMC, and RB. Finally, the frequency of escape mutants in plasma at day 28 post infection correlated strongly with the level Tat-SL8-specific CD8 T cells in the LN and PBMC at day 14 post infection. These results indicate that LNs represent the primary source of CTL escape mutants during the acute phase of SIV(mac239) infection, suggesting that LNs are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants.

The LS-STAG immersed boundary/cut-cell method for non-Newtonian flows in 3D extruded geometries

NASA Astrophysics Data System (ADS)

Nikfarjam, F.; Cheny, Y.; Botella, O.

2018-05-01

The LS-STAG method is an immersed boundary/cut-cell method for viscous incompressible flows based on the staggered MAC arrangement for Cartesian grids, where the irregular boundary is sharply represented by its level-set function, results in a significant gain in computer resources (wall time, memory usage) compared to commercial body-fitted CFD codes. The 2D version of LS-STAG method is now well-established (Cheny and Botella, 2010), and this paper presents its extension to 3D geometries with translational symmetry in the z direction (hereinafter called 3D extruded configurations). This intermediate step towards the fully 3D implementation can be applied to a wide variety of canonical flows and will be regarded as the keystone for the full 3D solver, since both discretization and implementation issues on distributed memory machines are tackled at this stage of development. The LS-STAG method is then applied to various Newtonian and non-Newtonian flows in 3D extruded geometries (axisymmetric pipe, circular cylinder, duct with an abrupt expansion) for which benchmark results and experimental data are available. The purpose of these investigations are (a) to investigate the formal order of accuracy of the LS-STAG method, (b) to assess the versatility of method for flow applications at various regimes (Newtonian and shear-thinning fluids, steady and unsteady laminar to turbulent flows) (c) to compare its performance with well-established numerical methods (body-fitted and immersed boundary methods).

Accuracy of the MacArthur competence assessment tool for clinical research (MacCAT-CR) for measuring children's competence to consent to clinical research.

PubMed

Hein, Irma M; Troost, Pieter W; Lindeboom, Robert; Benninga, Marc A; Zwaan, C Michel; van Goudoever, Johannes B; Lindauer, Ramón J L

2014-12-01

An objective assessment of children's competence to consent to research participation is currently not possible. Age limits for asking children's consent vary considerably between countries, and, to our knowledge, the correlation between competence and children's age has never been systematically investigated. To test a standardized competence assessment instrument for children by modifying the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), to investigate its reliability and validity, and to examine the correlation of its assessment with age and estimate cutoff ages. This prospective study included children and adolescents aged 6 to 18 years in the inpatient and outpatient departments of allergology, gastroenterology, oncology, ophthalmology, and pulmonology from January 1, 2012, through January 1, 2014. Participants were eligible for clinical research studies, including observational studies and randomized clinical trials. Competence judgments by experts aware of the 4 relevant criteria-understanding, appreciation, reasoning, and choice-were used to establish the reference standard. The index test was the MacCAT-CR, which used a semistructured interview format. Interrater reliability, validity, and dimensionality of the MacCAT-CR and estimated cutoff ages for competence. Of 209 eligible patients, we included 161 (mean age, 10.6 years; 47.2% male). Good reproducibility of MacCAT-CR total and subscale scores was observed (intraclass correlation coefficient range, 0.68-0.92). We confirmed unidimensionality of the MacCAT-CR. By the reference standard, we judged 54 children (33.5%) to be incompetent; by the MacCAT-CR, 61 children (37.9%). Criterion-related validity of MacCAT-CR scores was supported by high overall accuracy in correctly classifying children as competent against the reference standard (area under the receiver operating characteristics curve, 0.78). Age was a good predictor of competence on the MacCAT-CR (area under the receiver operating characteristics curve, 0.90). In children younger than 9.6 years, competence was unlikely (sensitivity, 90%); in those older than 11.2 years, competence was probable (specificity, 90%). The optimal cutoff age was 10.4 years (sensitivity, 81%; specificity, 84%). The MacCAT-CR demonstrated strong psychometric properties. In children aged 9.6 to 11.2 years, consent may be justified when competence can be demonstrated in individual cases by the MacCAT-CR. The results contribute to a scientific underpinning of regulations for clinical research directed toward children.

Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease

PubMed Central

Wang, Jian; Mou, Yaru; Zhang, Qiangye; Zhang, Fan; Yang, Hongchao; Zhang, Wentong; Li, Aiwu

2013-01-01

Purpose The aim of this study was to investigate the expression and significance of neuroligins in myenteric cells of Cajal (ICC-MY) in Hirschsprung’s disease (HSCR). Methods Longitudinal muscle with adherent myenteric plexus (LMMP) from surgical excision waste colon of HSCR children were prepared by peeling off the mucous layer, sub-mucosal layer and circular muscle. Neuroligins, c-Kit (c-Kit-immunoreactivity representing ICC) and their relationship were assessed by double labeling immunofluorescence staining. ICC-MY were dissociated and cultured from LMMP by enzymolysis method, and were purified and analyzed using a combination of magnetic-activated cell sorting (MACS) and flow cytometry (FCM). Western-blot analysis was applied to compare and evaluate the expression levels of neuroligins in ICC-MY which were dissociated from different segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment). Results Neuroligins and c-Kit were expressed on the same cells (ICC-MY); ICC-MY were dissociated, cultured and purified. For HSCR, neuroligins were expressed significantly in ICC-MY from ganglionic colonic segments, moderately in those from transitional colonic segments and down-regulated significantly in those from aganglionic colonic segments. Conclusions Neuroligins were expressed in ICC-MY of human beings, and the expression varies from different segments of HSCR. This abnormal expression might play an important role in the pathogenesis of this disease through affecting the synaptic function of ICC-MY. PMID:23840625

Effect of Mitral Annular Calcium on Left Ventricular Diastolic Parameters.

PubMed

Codolosa, Jose N; Koshkelashvili, Nikoloz; Alnabelsi, Talal; Goykhman, Igor; Romero-Corral, Abel; Pressman, Gregg S

2016-03-01

Assessment of left ventricular (LV) diastolic function by Doppler flow imaging and tissue Doppler is an integral part of the echocardiographic examination. Mitral annular calcium (MAC) is frequently encountered on echocardiography. The aim of this study was to assess the impact of MAC, quantitatively measured by computed tomography scan, on echocardiographic LV diastolic parameters. We included 155 patients aged ≥65 years. Computed tomography reconstructions of the mitral annulus were created, and calcium identified and quantified by Agatston technique. Calcium locations were assigned using an overlaid template depicting the annular segments in relation to surrounding anatomic structures. Echocardiographic assessment of diastolic function was performed in standard fashion. Mean age was 77 years; 49% were men; and 43% were black. Patients with MAC had lower septal e' (p = 0.003), lateral e' (p = 0.04), and average e' (p = 0.01) compared with those without MAC. They also had a higher E-wave velocity (p = 0.01) and E/e' ratio (p <0.001). When evaluated by severity of MAC, and after adjustment for multiple clinical factors, there was a graded (inverse) relation between MAC severity and septal e' (p = 0.01), lateral e' (p = 0.01), and average e' (p = 0.01). In conclusion, LV diastolic parameters, as measured by Doppler echocardiography, are altered in the presence of MAC. This could be due to direct effects of MAC on annular function or might reflect truly reduced diastolic function. Interpretation of diastolic parameters in patients with MAC should be performed with caution. Copyright © 2016 Elsevier Inc. All rights reserved.

M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

PubMed

Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

2015-05-01

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.

MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer.

PubMed

Eyking, Annette; Reis, Henning; Frank, Magdalena; Gerken, Guido; Schmid, Kurt W; Cario, Elke

2016-01-01

Mucinous adenocarcinoma (MAC) represents a distinct histopathological entity of colorectal cancer (CRC), which is associated with disease progression and poor prognosis. Here, we found that expression levels of miR-205 and miR-373 were specifically upregulated only in patients with mucinous colon cancers, but not in CRC that lack mucinous components. To investigate the effects of miR-205 and miR-373 on intestinal epithelial cell (IEC) biology by gain- and loss-of-function experiments in a proof-of-concept approach, we chose previously established in-vitro human Caco-2-based models of differentiated, non-invasive (expressing TLR4 wild-type; termed Caco-2[WT]) versus undifferentiated, invasive (expressing TLR4 mutant D299G; termed Caco-2[D299G]) IEC. Enterocyte-like Caco-2[WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in colorectal carcinoma-like Caco-2[D299G], thus resembling the miRNA expression pattern of paired normal versus tumor samples from MAC patients. Using stable transfection, we generated miR-205- or miR-373-expressing and miR-205- or miR-373-inhibiting subclones of these IEC lines. We found that introduction of miR-205 into Caco-2[WT] led to expansion of mucus-secreting goblet cell-like cells, which was associated with induction of KLF4, MUC2 and TGFβ1 expression. Activation of miR-205 in Caco-2[WT] induced chemoresistance, while inhibition of miR-205 in Caco-2[D299G] promoted chemosensitivity. Caco-2[WT] overexpressing miR-373 showed mitotic abnormalities and underwent morphologic changes (loss of epithelial polarity, cytoskeletal reorganization, and junctional disruption) associated with epithelial-mesenchymal transition and progression to inflammation-associated colonic carcinoma, which correlated with induction of phosphorylated STAT3 and N-CADHERIN expression. Functionally, introduction of miR-373 into Caco-2[WT] mediated loss of cell-cell adhesion and increased proliferation and invasion. Reversely, inhibition of miR-373 allowed mesenchymal IEC to regain epithelial properties, which correlated with absence of neoplastic progression. Using xenografts in mice demonstrated miR-373-mediated acceleration of malignant intestinal tumor growth. In conclusion, our results provide first evidence that miR-205 and miR-373 may differentially contribute to the aggressive phenotype of MAC in CRC.

High-throughput and low-latency 60GHz small-cell network architectures over radio-over-fiber technologies

NASA Astrophysics Data System (ADS)

Pleros, N.; Kalfas, G.; Mitsolidou, C.; Vagionas, C.; Tsiokos, D.; Miliou, A.

2017-01-01

Future broadband access networks in the 5G framework will need to be bilateral, exploiting both optical and wireless technologies. This paper deals with new approaches and synergies on radio-over-fiber (RoF) technologies and how those can be leveraged to seamlessly converge wireless technology for agility and mobility with passive optical networks (PON)-based backhauling. The proposed convergence paradigm is based upon a holistic network architecture mixing mm-wave wireless access with photonic integration, dynamic capacity allocation and network coding schemes to enable high bandwidth and low-latency fixed and 60GHz wireless personal area communications for gigabit rate per user, proposing and deploying on top a Medium-Transparent MAC (MT-MAC) protocol as a low-latency bandwidth allocation mechanism. We have evaluated alternative network topologies between the central office (CO) and the access point module (APM) for data rates up to 2.5 Gb/s and SC frequencies up to 60 GHz. Optical network coding is demonstrated for SCM-based signaling to enhance bandwidth utilization and facilitate optical-wireless convergence in 5G applications, reporting medium-transparent network coding directly at the physical layer between end-users communicating over a RoF infrastructure. Towards equipping the physical layer with the appropriate agility to support MT-MAC protocols, a monolithic InP-based Remote Antenna Unit optoelectronic PIC interface is shown that ensures control over the optical resource allocation assisting at the same time broadband wireless service. Finally, the MT-MAC protocol is analysed and simulation and analytical theoretical results are presented that are found to be in good agreement confirming latency values lower than 1msec for small- to mid-load conditions.

Effects of Anticoagulant, Processing Delay, and Assay Method (Branched DNA versus Reverse Transcriptase PCR) on Measurement of Human Immunodeficiency Virus Type 1 RNA Levels in Plasma

PubMed Central

Kirstein, Lynn M.; Mellors, John W.; Rinaldo, Charles R.; Margolick, Joseph B.; Giorgi, Janis V.; Phair, John P.; Dietz, Edith; Gupta, Phalguni; Sherlock, Christopher H.; Hogg, Robert; Montaner, J. S. G.; Muñoz, Alvaro

1999-01-01

We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, −0.12 log10 copies/ml; RT-PCR, −0.05 log10 copies/ml) and after 18 h (bDNA assay, −0.27 log10 copies/ml; RT-PCR, −0.15 log10 copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, −0.002 log10 copies/ml; RT-PCR, −0.02 log10 copies/ml), but it was after 18 h (bDNA assay, −0.09 log10 copies/ml; RT-PCR, −0.09 log10 copies/ml). Only 4% of samples processed after 6 h lost more than 50% (≥0.3 log10 copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4+-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (−0.05 to −0.12 log10 copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4+-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP. PMID:10405379

Purification of human induced pluripotent stem cell-derived neural precursors using magnetic activated cell sorting.

PubMed

Rodrigues, Gonçalo M C; Fernandes, Tiago G; Rodrigues, Carlos A V; Cabral, Joaquim M S; Diogo, Maria Margarida

2015-01-01

Neural precursor (NP) cells derived from human induced pluripotent stem cells (hiPSCs), and their neuronal progeny, will play an important role in disease modeling, drug screening tests, central nervous system development studies, and may even become valuable for regenerative medicine treatments. Nonetheless, it is challenging to obtain homogeneous and synchronously differentiated NP populations from hiPSCs, and after neural commitment many pluripotent stem cells remain in the differentiated cultures. Here, we describe an efficient and simple protocol to differentiate hiPSC-derived NPs in 12 days, and we include a final purification stage where Tra-1-60+ pluripotent stem cells (PSCs) are removed using magnetic activated cell sorting (MACS), leaving the NP population nearly free of PSCs.

Spermatozoa with numerical chromosomal abnormalities are more prone to be retained by Annexin V-MACS columns.

PubMed

Esbert, M; Godo, A; Soares, S R; Florensa, M; Amorós, D; Ballesteros, A; Vidal, F

2017-07-01

Colloidal super-paramagnetic microbeads conjugated with annexin V are effective for separating apoptotic spermatozoa by MACS as a result of the high affinity of annexin V for externalized PS molecules. The effectiveness of the procedure in reducing the percentage of sperm with fragmented DNA and abnormal morphology has also been reported. However, it is still unknown if it could decrease the percentage of aneuploid spermatozoa. The objective of our prospective study, performed on 16 males with abnormal FISH on spermatozoa, was to assess if MACS columns were useful tools to retain spermatozoa carrying chromosomal abnormalities in semen samples processed after density gradient centrifugation (DGC). The pellet obtained after DGC was subjected to MACS, and sperm FISH analyses were performed both in the eluded fraction and in the fraction retained in the column. The observed frequencies of disomy and nullisomy 13, 18, and 21, X and Y, as well as the diploidy rates in the MACS eluded fraction and the fraction retained in the MACS column were recorded. We observed that the frequencies of aneuploidies in the eluded fraction were lower than in the fraction retained in the MACS column (0.59% vs. 0.75%; p = 0.010). DGC determined a significant reduction in sperm concentration (z-ratio = 2.83; p = 0.005) and a significant increase in sperm progressive motility (z-ratio = -3.5; p < 0.001). MACS also led to a significant reduction in sperm concentration (z-ratio = 3.14; p = 0.002) and a significant increase in progressive motility (z-ratio = -2.59; p = 0.01) when compared with the post-DGC sample. Sperm concentration was similar in the two fractions generated by MACS (z-ratio = 0.63; p = 0.52), while progressive motility was significantly higher in the MACS eluded fraction (z-ratio = 2.42; p = 0.02). According to our results, MACS columns are able to selectively retain spermatozoa carrying chromosomal abnormalities. Furthermore, the performance of DGC and MACS on semen samples leads to an enrichment of progressive motility. © 2017 American Society of Andrology and European Academy of Andrology.

Traffic Management for Emergency Vehicle Priority Based on Visual Sensing.

PubMed

Nellore, Kapileswar; Hancke, Gerhard P

2016-11-10

Vehicular traffic is endlessly increasing everywhere in the world and can cause terrible traffic congestion at intersections. Most of the traffic lights today feature a fixed green light sequence, therefore the green light sequence is determined without taking the presence of the emergency vehicles into account. Therefore, emergency vehicles such as ambulances, police cars, fire engines, etc. stuck in a traffic jam and delayed in reaching their destination can lead to loss of property and valuable lives. This paper presents an approach to schedule emergency vehicles in traffic. The approach combines the measurement of the distance between the emergency vehicle and an intersection using visual sensing methods, vehicle counting and time sensitive alert transmission within the sensor network. The distance between the emergency vehicle and the intersection is calculated for comparison using Euclidean distance, Manhattan distance and Canberra distance techniques. The experimental results have shown that the Euclidean distance outperforms other distance measurement techniques. Along with visual sensing techniques to collect emergency vehicle information, it is very important to have a Medium Access Control (MAC) protocol to deliver the emergency vehicle information to the Traffic Management Center (TMC) with less delay. Then only the emergency vehicle is quickly served and can reach the destination in time. In this paper, we have also investigated the MAC layer in WSNs to prioritize the emergency vehicle data and to reduce the transmission delay for emergency messages. We have modified the medium access procedure used in standard IEEE 802.11p with PE-MAC protocol, which is a new back off selection and contention window adjustment scheme to achieve low broadcast delay for emergency messages. A VANET model for the UTMS is developed and simulated in NS-2. The performance of the standard IEEE 802.11p and the proposed PE-MAC is analysed in detail. The NS-2 simulation results have shown that the PE-MAC outperforms the IEEE 802.11p in terms of average end-to-end delay, throughput and energy consumption. The performance evaluation results have proven that the proposed PE-MAC prioritizes the emergency vehicle data and delivers the emergency messages to the TMC with less delay compared to the IEEE 802.11p. The transmission delay of the proposed PE-MAC is also compared with the standard IEEE 802.15.4, and Enhanced Back-off Selection scheme for IEEE 802.15.4 protocol [EBSS, an existing protocol to ensure fast transmission of the detected events on the road towards the TMC] and the comparative results have proven the effectiveness of the PE-MAC over them. Furthermore, this research work will provide an insight into the design of an intelligent urban traffic management system for the effective management of emergency vehicles and will help to save lives and property.

Mycobacterium avium complex--the role of potable water in disease transmission.

PubMed

Whiley, H; Keegan, A; Giglio, S; Bentham, R

2012-08-01

Mycobacterium avium complex (MAC) is a group of opportunistic pathogens of major public health concern. It is responsible for a wide spectrum of disease dependent on subspecies, route of infection and patients pre-existing conditions. Presently, there is limited research on the incidence of MAC infection that considers both pulmonary and other clinical manifestations. MAC has been isolated from various terrestrial and aquatic environments including natural waters, engineered water systems and soils. Identifying the specific environmental sources responsible for human infection is essential in minimizing disease prevalence. This paper reviews current literature and case studies regarding the wide spectrum of disease caused by MAC and the role of potable water in disease transmission. Potable water was recognized as a putative pathway for MAC infection. Contaminated potable water sources associated with human infection included warm water distribution systems, showers, faucets, household drinking water, swimming pools and hot tub spas. MAC can maintain long-term contamination of potable water sources through its high resistance to disinfectants, association with biofilms and intracellular parasitism of free-living protozoa. Further research is required to investigate the efficiency of water treatment processes against MAC and into construction and maintenance of warm water distribution systems and the role they play in MAC proliferation. No claim to Australian Government works Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Light scattering and extinction measurements combined with laser-induced incandescence for the real-time determination of soot mass absorption cross section.

PubMed

Wei, Yiyi; Ma, Lulu; Cao, Tingting; Zhang, Qing; Wu, Jun; Buseck, Peter R; Thompson, J E

2013-10-01

An aerosol albedometer was combined with laser-induced incandescence (LII) to achieve simultaneous measurements of aerosol scattering, extinction coefficient, and soot mass concentration. Frequency doubling of a Nd:YAG laser line resulted in a colinear beam of both λ = 532 and 1064 nm. The green beam was used to perform cavity ring-down spectroscopy (CRDS), with simultaneous measurements of scattering coefficient made through use of a reciprocal sphere nephelometer. The 1064 nm beam was selected and directed into a second integrating sphere and used for LII of light-absorbing kerosene lamp soot. Thermal denuder experiments showed the LII signals were not affected by the particle mixing state when laser peak power was 1.5-2.5 MW. The combined measurements of optical properties and soot mass concentration allowed determination of mass absorption cross section (M.A.C., m(2)/g) with 1 min time resolution when soot concentrations were in the low microgram per cubic meter range. Fresh kerosene nanosphere soot (ns-soot) exhibited a mean M.A.C and standard deviation of 9.3 ± 2.7 m(2)/g while limited measurements on dry ambient aerosol yielded an average of 8.2 ± 5.9 m(2)/g when soot was >0.25 μg/m(3). The method also detected increases in M.A.C. values associated with enhanced light absorption when polydisperse, laboratory-generated ns-soot particles were embedded within or coated with ammonium nitrate, ammonium sulfate, and glycerol. Glycerol coatings produced the largest fractional increase in M.A.C. (1.41-fold increase), while solid coatings of ammonium sulfate and ammonium nitrate produced increases of 1.10 and 1.06, respectively. Fresh, ns-soot did not exhibit increased M.A.C. at high relative humidity (RH); however, lab-generated soot coated with ammonium nitrate and held at 85% RH exhibited M.A.C. values nearly double the low-humidity case. The hybrid instrument for simultaneously tracking soot mass concentration and aerosol optical properties in real time is a valuable tool for probing enhanced absorption by soot at atmospherically relevant concentrations.

Effects of group metacognitive training (MCT) on mental capacity and functioning in patients with psychosis in a secure forensic psychiatric hospital: a prospective-cohort waiting list controlled study

PubMed Central

2012-01-01

Background Metacognitive Training (MCT) is a manualised cognitive intervention for psychosis aimed at transferring knowledge of cognitive biases and providing corrective experiences. The aim of MCT is to facilitate symptom reduction and protect against relapse. In a naturalistic audit of clinical effectiveness we examined what effect group MCT has on mental capacity, symptoms of psychosis and global function in patients with a psychotic illness, when compared with a waiting list comparison group. Methods Of 93 patients detained in a forensic mental health hospital under both forensic and civil mental health legislation, 19 were assessed as suitable for MCT and 11 commenced. These were compared with 8 waiting list patients also deemed suitable for group MCT who did not receive it in the study timeframe. The PANSS, GAF, MacArthur Competence Assessment Tool- Treatment (MacCAT-T) and MacArthur Competence Assessment Tool-Fitness to Plead (MacCAT-FP) were recorded at baseline and repeated after group MCT or following treatment as usual in the waiting list group. Results When baseline functioning was accounted for, patients that attended MCT improved in capacity to consent to treatment as assessed by the MacCAT-T (p = 0.019). The more sessions attended, the greater the improvements in capacity to consent to treatment, mainly due to improvement in MacCAT-T understanding (p = 0.014) and reasoning . The GAF score improved in patients who attended the MCT group when compared to the waiting list group (p = 0.038) but there were no changes in PANSS scores. Conclusion Measures of functional mental capacity and global function can be used as outcome measures for MCT. MCT can be used successfully even in psychotic patients detained in a forensic setting. The restoration of elements of decision making capacity such as understanding and reasoning may be a hither-to unrecognised advantage of such treatment. Because pharmacotherapy can be optimised and there is likely to be enough time to complete the course, there are clear opportunities to benefit from such treatment programmes in forensic settings. PMID:22709616

Mitral Annular Calcification as a Possible Nidus for Endocarditis: A Descriptive Series with Bacteriological Differences Noted.

PubMed

Pressman, Gregg S; Rodriguez-Ziccardi, Mary; Gartman, Charles H; Obasare, Edinrin; Melendres, Emmanuel; Arguello, Vivian; Bhalla, Vikas

2017-06-01

Mitral annular calcification (MAC) is a chronic inflammatory process with similarities to atherosclerosis. It is common in elderly patients and those with renal dysfunction. Although MAC is associated with cardiovascular morbidity, its relationship to infective endocarditis is unclear. The aim of this study was to test the hypothesis that MAC would be prevalent in patients with mitral valve vegetations and that vegetations would frequently occur on calcific nodules. A secondary aim was to look for possible bacteriological differences between vegetations attached to the calcified annulus versus leaflet vegetations. We retrospectively reviewed all echocardiographic studies of patients with native mitral valve vegetations from January 2007 to August 2015 (N = 56). We searched for (1) presence of MAC, (2) location of MAC, and (3) vegetation location (on calcium deposits or distant). MAC was defined as focal echo brightness in a nodular or band-like pattern. The modified Duke criteria were used to confirm the diagnosis of infective endocarditis. Transthoracic, transesophageal, and three-dimensional echocardiograms (when available) at the time of infection were evaluated by a single reader. Twenty-eight subjects were infected with Staphylococcus aureus, 17 with a streptococcal species, and five with other organisms; blood cultures were sterile in 6. Thirty-four (61%) subjects had some degree of MAC, while 22 (39%) had none. Among those with MAC, the vegetation was located on the calcium deposits in 22 (65%), versus in 12 (35%) where it was not. Among all 56 subjects, when S. aureus was the infecting organism it was present on MAC in 16/28 (57%) versus 6/28 (21%; P = .01) for other bacterial species. By contrast, streptococcal infections more frequently involved the leaflets (16/17 [94%]) versus nonstreptococcal infections (18/39 [46%]; P = .0008). MAC may act as a nidus for infection especially with S. aureus. Differences in mechanism of attachment between S. aureus and streptococci may account for the observed difference in frequency of attachment of vegetations to MAC. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes.

PubMed

Bertolini, Marta; Uchida, Youhei; Paus, Ralf

2015-11-01

Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I-presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the-as yet elusive-key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA.

C-MAC videolaryngoscope versus Macintosh laryngoscope for tracheal intubation: A systematic review and meta-analysis with trial sequential analysis.

PubMed

Hoshijima, Hiroshi; Mihara, Takahiro; Maruyama, Koichi; Denawa, Yohei; Mizuta, Kentaro; Shiga, Toshiya; Nagasaka, Hiroshi

2018-06-09

The C-MAC laryngoscope (C-MAC) is a videolaryngoscope that uses a modified Macintosh blade. Although several anecdotal reports exist, it remains unclear whether the C-MAC is superior to the Macintosh laryngoscope for tracheal intubation in the adult population. Systematic review, meta-analysis. Operating room, intensive care unit. For inclusion in our analysis, studies had to be prospective randomised trials which compared the C-MAC with the Macintosh laryngoscope for tracheal intubation in the adult population. Data on success rates, intubation time, glottic visualisation and incidence of external laryngeal manipulations (ELM) during tracheal intubation were extracted from the identified studies. In subgroup analysis, we separated those parameters to assess the influence of the airway condition (normal or difficult) and laryngoscopists (novice or experienced). We conducted a trial sequential analysis (TSA). Sixteen articles with 18 trials met the inclusion criteria. The C-MAC provided better glottic visualisation compared to the Macintosh (RR, 1.08; 95% CI, 1.03-1.14). TSA corrected the CI to 1.01-1.19; thus, total sample size reached the required information size (RIS). Success rates and intubation time did not differ significantly between the laryngoscopes. TSA showed that total sample size reached the RIS for success rates. The TSA Z curve surpassed the futility boundary. The C-MAC required less ELM compared to the Macintosh (RR, 0.83; 95% CI, 0.72-0.96). TSA corrected the CI to 0.67-1.03; 52.3% of the RIS was achieved. In difficult airways, the C-MAC showed superior success rates, glottic visualisation, and less ELM compared to the Macintosh. Among experienced laryngoscopists, the C-MAC offered better glottic visualisation with less ELM than the Macintosh. The C-MAC provided better glottic visualisation and less ELM (GRADE: Very Low or Moderate), with improved success rates, glottic visualisation, and less ELM in difficult airways. Copyright © 2018 Elsevier Inc. All rights reserved.

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential.

PubMed

Heber, Elisa M; Kueffer, Peter J; Lee, Mark W; Hawthorne, M Frederick; Garabalino, Marcela A; Molinari, Ana J; Nigg, David W; Bauer, William; Hughes, Andrea Monti; Pozzi, Emiliano C C; Trivillin, Verónica A; Schwint, Amanda E

2012-05-01

Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

David W. Nigg

2012-05-01

Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1)more » MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.« less

33 CFR 334.630 - Tampa Bay south of MacDill Air Force Base, Fla.; small-arms firing range and aircraft jettison, U...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base... Force Base, Fla.; small-arms firing range and aircraft jettison, U.S. Air Force, MacDill Air Force Base...″, longitude 82°33′02.44″; and thence to a point on the shore line of MacDill Air Force Base at latitude 27°50...

Characteristics of Notch2(+) pancreatic cancer stem-like cells and the relationship with centroacinar cells.

PubMed

Zhou, Zhu-Chao; Dong, Qiang-Gang; Fu, De-Liang; Gong, Yi-Yi; Ni, Quan-Xing

2013-08-01

Notch2, a surface marker in cell lines, is used to isolate, identify and localise pancreatic cancer stem-like cells and is a target for therapy of these cells. Sphere formation was induced in Panc-1 and Bxpc-3 pancreatic cancer cell lines, and Notch2(+) cells were separated from Bxpc-3 and Panc-1 cell lines by magnetic activated cell sorting (MACS). Expression of stem cell-related markers, OCT4, Nanog and PDX1, were measured by immunofluorescent (IF) staining. Expression of Notch2 was also determined immunohistochemically in pancreatic tissues. Notch2(+) cells were transplanted in subcutaneous of mice. AQP1 and AQP5 were also measured by IF in Bxpc-3 cells. The Notch signal pathway inhibitor, Compound E (CE), was used to treat Notch2(+) Bxpc-3 cells, and their vitalities were subsequently measured by the CCK-8 method. Positive expression of OCT4, Nanog and PDX1 was observed in Notch2(+) cells. Notch2(+) cells at centroacinar cell (CAC) and terminal ductal locations expressed AQP1 and AQP5. They were strongly tumourigenic in mice, and CE inhibited proliferation of Notch2(+) Bxpc-3 cells to some degree. OCT4 and Nanog can be used as markers of self-renewal in pancreatic cancer stem cells. Notch2(+) cells in human pancreatic cancer Bxpc-3 and Panc-1 cell lines had the properties of cancer stem cells. The results suggest that Notch2(+) pancreatic cancer stem-like cells had a close relationship with CAC. © 2013 International Federation for Cell Biology.

C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 2: Test Bed Performance Evaluation and Final AeroMACS Recommendations

NASA Technical Reports Server (NTRS)

Hall, Edward; Magner, James

2011-01-01

This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II (this document) describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 1: Concepts of Use, Initial System Requirements, Architecture, and AeroMACS Design Considerations

NASA Technical Reports Server (NTRS)

Hall, Edward; Isaacs, James; Henriksen, Steve; Zelkin, Natalie

2011-01-01

This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I (this document) is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

Resting heart rate and the incidence and progression of valvular calcium: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Amoakwa, Kojo; Fashanu, Oluwaseun E; Tibuakuu, Martin; Zhao, Di; Guallar, Eliseo; Whelton, Seamus P; O'Neal, Wesley T; Post, Wendy S; Budoff, Matthew J; Michos, Erin D

2018-06-01

Left-sided valvular calcification is associated with cardiovascular disease (CVD) morbidity and mortality. Resting heart rate (RHR) may influence valvular calcium progression through shear stress. Whether RHR, an established CVD risk factor, is associated with valvular calcium progression is unknown. We assessed whether RHR predicts incidence and progression of mitral annular calcium (MAC) and aortic valve calcium (AVC) in a community-based cohort free of CVD at baseline. RHR was obtained from baseline electrocardiograms of 5498 MESA participants. MAC and AVC were quantified using Agatston scoring from cardiac computed tomography scans obtained at baseline and at a second examination during follow-up. We examined associations of RHR with incident MAC/AVC and annual change in MAC/AVC scores, after adjusting for demographics, CVD risk factors, physical activity, and atrioventricular nodal blocker use. At baseline, participants had mean age of 62 ± 10 years and mean RHR of 63 ± 10 bpm; 12.3% and 8.9% had prevalent AVC and MAC, respectively. Over a median of 2.3 years, 4.1% and 4.5% developed incident AVC and MAC, respectively. Each 10 bpm higher RHR was significantly associated with incident MAC [Risk Ratio 1.17 (95% CI 1.03-1.34)], but not incident AVC. However, RHR was associated with AVC progression [β = 1.62 (0.45-2.80) Agatston units/year for every 10 bpm increment], but not MAC progression. Higher RHR was associated with MAC incidence and AVC progression, independent of traditional CVD risk factors. Future studies are needed to determine whether modification of RHR through lifestyle or pharmacologic interventions can reduce valvular calcium incidence or progression. Copyright © 2018 Elsevier B.V. All rights reserved.

Electromyographic activation reveals cortical and sub-cortical dissociation during emergence from general anesthesia.

PubMed

Hight, Darren F; Voss, Logan J; García, Paul S; Sleigh, Jamie W

2017-08-01

During emergence from anesthesia patients regain their muscle tone (EMG). In a typical population of surgical patients the actual volatile gas anesthetic concentrations in the brain (C e MAC) at which EMG activation occurs remains unknown, as is whether EMG activation at higher C e MACs is correlated with subsequent severe pain, or with cortical activation. Electroencephalographic (EEG) and EMG activity was recorded from the forehead of 273 patients emerging from general anesthesia following surgery. We determined C e MAC at time of EMG activation and at return of consciousness. Pain was assessed immediately after return of consciousness using an 11 point numerical rating scale. The onset of EMG activation during emergence was associated with neither discernible muscle movement nor with the presence of exogenous stimulation in half the patients. EMG activation could be modelled as two distinct processes; termed high- and low-C e MAC (occurring higher or lower than 0.07 C e MAC). Low-C e MAC activation was typically associated with simultaneous EMG activation and consciousness, and the presence of a laryngeal mask. In contrast, high-C e MAC EMG activation occurred independently of return of consciousness, and was not associated with severe post-operative pain, but was more common in the presence of an endotracheal tube. Patients emerging from general anesthesia with an endotracheal tube in place are more likely to have an EMG activation at higher C e MAC concentrations. These activations are not associated with subsequent high-pain, nor with cortical arousal, as evidenced by continuing delta waves in the EEG. Conversely, patients emerging from general anesthesia with a laryngeal mask demonstrate marked neural inertia-EMG activation occurs at a low C e MAC, and is closely temporally associated with return of consciousness.

Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion.

PubMed

Xiao, Zhihua; Visentin, Gian P; Dayananda, Kannayakanahalli M; Neelamegham, Sriram

2008-08-15

We tested the possibility that immune complexes formed following platelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate neutrophil activation, similar to previous reports with platelets. Monoclonal Abs against PF4 and IgG from a heparin-induced thrombocytopenia (HIT) patient were applied. We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil function, costimulation with both reagents resulted in approximately 3-fold increase in cell surface Mac-1 expression, enhanced cell adhesion via L-selectin and CD18 integrins, and degranulation of secondary and tertiary granules. The level of Mac-1 up-regulation peaked at an intermediate PF4 dose, suggesting that functional response varies with antigen-antibody stoichiometry. PF4 binding to neutrophils was blocked by chondroitinase ABC. Cell activation was inhibited by both chondroitinase ABC and anti-CD32/FcgammaRII blocking mAb, IV.3. Confocal microscopy demonstrated that immune complexes colocalize with CD32a. Studies with HIT IgG demonstrated that neutrophils could be activated in the absence of exogenous heparin. These data, together, show that leukocyte surface chondroitin sulfates promote neutrophil activation by enhancing immune-complex binding to CD32a. Studies with recombinant PF4 suggest a role for arginine 49 in stabilizing PF4-chondroitin binding. Neutrophils activated via this mechanism may contribute to thrombosis and inflammation in patients mounting an immune response to PF4-heparin.

Design, synthesis, and anticancer evaluation of long-chain alkoxylated mono-carbonyl analogues of curcumin.

PubMed

Weng, Qiaoyou; Fu, Lili; Chen, Gaozhi; Hui, Junguo; Song, Jingjing; Feng, Jianpeng; Shi, Dengjian; Cai, Yuepiao; Ji, Jiansong; Liang, Guang

2015-10-20

Curcumin is a nontoxic phenolic compound that modulates the activity of several cellular targets that have been linked with cancers and other chronic diseases. However, the efficacy of curcumin in the clinic has been limited by its poor bioavailability and rapid metabolism in vivo. We have previously reported the design and discovery of series of 5-carbon linker-containing mono-carbonyl analogues of curcumin (MACs) as anti-cancer agents. In continuation of our ongoing research, we designed and synthesized 37 novel long-chain alkoxylated MACs for anti-cancer evaluation here. The MTS assay was used to determine the cytotoxicity of compounds in gastrointestinal cancer cells. Compounds 5, 28, and 29 showed strongest inhibition against gastric cancer cell proliferation and were subjected to further analysis. The effects of 5, 28, and 29 on cell apoptosis were measured by flow cytometry. Expression levels of Bcl-2, cleaved poly ADP-ribose polymerase (PARP), and pro-caspase-3 were detected by western blotting. Compounds 5, 28, and 29 induced apoptosis in human gastric carcinoma cells, increased PARP cleavage, and decreased expression of Bcl-2 and pro-caspase-3 protein. We then showed that compound 28, which possessed the strongest activity among the test compounds in vitro, exhibited significant tumor inhibition in SGC7901-driven xenograft mouse model. Taken together, the novel compound 28 could be further explored as an effective anticancer agent for the treatment of human gastric cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Operational effectiveness of a Multiple Aquila Control System (MACS)

NASA Technical Reports Server (NTRS)

Brown, R. W.; Flynn, J. D.; Frey, M. R.

1983-01-01

The operational effectiveness of a multiple aquila control system (MACS) was examined under a variety of remotely piloted vehicle (RPV) mission configurations. The set of assumptions and inputs used to form the rules under which a computerized simulation of MACS was run is given. The characteristics that are to govern MACS operations include: the battlefield environment that generates the requests for RPV missions, operating time-lines of the RPV-peculiar equipment, maintenance requirements, and vulnerability to enemy fire. The number of RPV missions and the number of operation days are discussed. Command, control, and communication data rates are estimated by determining how many messages are passed and what information is necessary in them to support ground coordination between MACS sections.

Fluorinated methacrylamide chitosan sequesters reactive oxygen species to relieve oxidative stress while delivering oxygen.

PubMed

Patil, Pritam S; Leipzig, Nic D

2017-08-01

Antioxidants play an important role in regulating overabundant reactive oxygen species (ROS) in wound healing to reduce oxidative stress and inflammation. In this work, we demonstrate for the first time that functionalization of methacrylamide chitosan (MAC) with aliphatic pentadecafluoro chains, to synthesize pentadecafluoro-octanoyl methacrylamide chitosan (MACF), enhances the antioxidant capacity of the MAC base hydrogel material, while being able to deliver oxygen for future enhanced wound healing applications. As such, MACF was shown to sequester more nitric oxide (p < 0.01) and hydroxyl (p < 0.0001) radicals as compared to the negative control even when delivering additional oxygen. MACF's beneficial antioxidant capacity was further confirmed in in vitro cell culture experiments using human dermal fibroblasts stressed with 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2368-2374, 2017. © 2017 Wiley Periodicals, Inc.

Collective Leadership Measurement for the U.S. Army

DTIC Science & Technology

2014-03-01

methods employed were adapted from standard texts on survey research methods (e.g., Podsakoff, MacKenzie, Lee, & Podsakoff, 2003; Shadish, Cook...members of the research team, as well as procedures for interviews in standard research methods texts (e.g., Campion, Palmer, & Campion, 1997; Latham...critical incident protocol was based on procedures for critical incidents in standard research methods texts (e.g., Flanagan, 1954; Lowenberg, 1979

I-MAC: an incorporation MAC for wireless sensor networks

NASA Astrophysics Data System (ADS)

Zhao, Jumin; Li, Yikun; Li, Dengao; Lin, Xiaojie

2017-11-01

This paper proposes an innovative MAC protocol called I-MAC. Protocol for wireless sensor networks, which combines the advantages of collision tolerance and collision cancellation. The protocol increases the number of antenna in wireless sensor nodes. The purpose is to monitor the occurrence of packet collisions by increasing the number of antenna in real time. The built-in identity structure is used in the frame structure in order to help the sending node to identify the location of the receiving node after a data packet collision is detected. Packets can be recovered from where the conflict occurred. In this way, we can monitor the conflict for a fixed period of time. It can improve the channel utilisation through changing the transmission probability of collision nodes and solve the problem of hidden terminal through collision feedback mechanism. We have evaluated our protocol. Our results show that the throughput of I-MAC is 5 percentage points higher than that of carrier sense multiple access/collision notification. The network utilisation of I-MAC is more than 92%.

The 50th Anniversary of Brown v. Board of Education: Continued Impacts on Minority Life Science Education

ERIC Educational Resources Information Center

Ricks, Irelene

2004-01-01

This article provides a brief history of affirmative action in the United States. The author describes the impact of the "Brown v. Board of Education" on minority life science education. She also discusses how The American Society for Cell Biology (ASCB) Minorities Affairs Committee (MAC) can improve the minority science pipeline.…

The Bacterial Gene IfpA Influences the Potent Induction of Calcitonin Receptor and Osteoclast-Related Genes in Burkholderia Pseudomallei-Induced TRAP-Positive Multinucleated Giant Cells

DTIC Science & Technology

2006-06-13

with arithmetic mean ( UPGMA ) using random tie breaking and uncorrected pairwise distances in MacVector 7.0 (Oxford Molecular). Numbers on branches...denote the UPGMA bootstrap percentage using a highly stringent number (1000) of replications (Felsenstein, 1985). All bootstrap values are 50%, as shown

A MacCormack-TVD finite difference method to simulate the mass flow in mountainous terrain with variable computational domain

NASA Astrophysics Data System (ADS)

Ouyang, Chaojun; He, Siming; Xu, Qiang; Luo, Yu; Zhang, Wencheng

2013-03-01

A two-dimensional mountainous mass flow dynamic procedure solver (Massflow-2D) using the MacCormack-TVD finite difference scheme is proposed. The solver is implemented in Matlab on structured meshes with variable computational domain. To verify the model, a variety of numerical test scenarios, namely, the classical one-dimensional and two-dimensional dam break, the landslide in Hong Kong in 1993 and the Nora debris flow in the Italian Alps in 2000, are executed, and the model outputs are compared with published results. It is established that the model predictions agree well with both the analytical solution as well as the field observations.

Spectroscopic investigation of the interaction of water-soluble azocalix[4]arenes with bovine serum albumin.

PubMed

Fan, Ping; Wan, Lu; Shang, Yunshan; Wang, Jun; Liu, Yulong; Sun, Xiaoyu; Chen, Chen

2015-02-01

In this work, three hydrosoluble azocalix[4]arene derivatives, 5-(o-methylphenylazo)-25,26,27-tris(carboxymethoxy)-28-hydroxycalix[4]arene (o-MAC-Calix), 5-(m-methylphenylazo)-25,26,27-tris(carboxymethoxy)-28-hydroxycalix[4]arene (m-MAC-Calix) and 5-(p-methylphenylazo)-25,26,27-tris(carboxymethoxy)-28-hydroxycalix[4]arene (p-MAC-Calix) were synthesized. Their structures were characterized by infrared spectrum (IR), nuclear magnetic resonance spectrum (1H NMR and 13C NMR) and mass spectrum (MS). The interactions between these compounds and bovine serum albumin (BSA) were studied by fluorescence spectroscopy, UV-vis spectrophotometry and circular dichroic spectroscopy. According to experimental results, three azocalix[4]arene derivatives can efficiently bind to BSA molecules and the o-MAC-Calix displays more efficient interactions with BSA molecules than m-MAC-Calix and p-MAC-Calix. Molecular docking showed that the o-MAC-Calix was embedded in the hydrophobic cavity of helical structure of BSA molecular and the tryptophan (Trp) residue of BSA molecular had strong interaction with o-MAC-Calix. The fluorescence quenching of BSA caused by azocalix[4]arene derivatives is attributed to the static quenching process. In addition, the synchronous fluorescence spectroscopy indicates that these azocalix[4]arene derivatives are more accessible to Trp residues of BSA molecules than the tyrosine (Tyr) residues. The circular dichroic spectroscopy further verified the binding of azocalix[4]arene derivatives and BSA. Copyright © 2014 Elsevier Inc. All rights reserved.

Median effective dose of isoflurane, sevoflurane, and desflurane in green iguanas.

PubMed

Barter, Linda S; Hawkins, Michelle G; Brosnan, Robert J; Antognini, Joseph F; Pypendop, Bruno H

2006-03-01

To determine the median effective dose (ED(50); equivalent to the minimum alveolar concentration [MAC]) of isoflurane, sevoflurane, and desflurane for anesthesia in iguanas. 6 healthy adult green iguanas. In unmedicated iguanas, anesthesia was induced and maintained with each of the 3 volatile drugs administered on separate days according to a Latin square design. Iguanas were endotracheally intubated, mechanically ventilated, and instrumented for cardiovascular and respiratory measurements. During each period of anesthesia, MAC was determined in triplicate. The mean value of 2 consecutive expired anesthetic concentrations, 1 that just permitted and 1 that just prevented gross purposeful movement in response to supramaximal electrical stimulus, and that were not different by more than 15%, was deemed the MAC. Mean +/- SD values for the third MAC determination for isoflurane, sevoflurane, and desflurane were 1.8 +/- 0.3%, 3.1 +/- 1.0%, and 8.9 +/- 2.1% of atmospheric pressure, respectively. The MAC for all inhaled agents was, on average, 22% greater for the first measurement than for the third measurement. Over time, MACs decreased for all 3 agents. Final MAC measurements were similar to values reported for other species. The decrease in MACs over time may be at least partly explained by limitations of anesthetic uptake and distribution imposed by the reptilian cardiorespiratory system. Hence, for a constant end-tidal anesthetic concentration in an iguana, the plane of anesthesia may deepen over time, which could contribute to increased morbidity during prolonged procedures.

Assessment of parental decision-making in neonatal cardiac research: a pilot study.

PubMed

Nathan, Aruna T; Hoehn, K Sarah; Ittenbach, Richard F; Gaynor, J William; Nicolson, Susan; Wernovsky, Gil; Nelson, Robert M

2010-02-01

To assess parental permission for a neonate's research participation using the MacArthur competence assessment tool for clinical research (MacCAT-CR), specifically testing the components of understanding, appreciation, reasoning and choice. Quantitative interviews using study-specific MacCAT-CR tools. Parents of critically ill newborns would produce comparable MacCAT-CR scores to healthy adult controls despite the emotional stress of an infant with critical heart disease or the urgency of surgery. Parents of infants diagnosed prenatally would have higher MacCAT-CR scores than parents of infants diagnosed postnatally. There would be no difference in MacCAT-CR scores between parents with respect to gender or whether they did or did not permit research participation. Parents of neonates undergoing cardiac surgery who had made decisions about research participation before their neonate's surgery. The MacCAT-CR. 35 parents (18 mothers; 17 fathers) of 24 neonates completed 55 interviews for one or more of three studies. Total scores: magnetic resonance imaging (mean 36.6, SD 7.71), genetics (mean 38.8, SD 3.44), heart rate variability (mean 37.7, SD 3.30). Parents generally scored higher than published subject populations and were comparable to published control populations with some exceptions. The MacCAT-CR can be used to assess parental permission for neonatal research participation. Despite the stress of a critically ill neonate requiring surgery, parents were able to understand study-specific information and make informed decisions to permit their neonate's participation.

Pre- and postconditioning effect of Sevoflurane on myocardial dysfunction after cardiopulmonary resuscitation in rats.

PubMed

Knapp, Jürgen; Bergmann, Greta; Bruckner, Thomas; Russ, Nicolai; Böttiger, Bernd W; Popp, Erik

2013-10-01

Post-resuscitation myocardial dysfunction is an important cause of death in the intensive care unit after initially successful cardiopulmonary resuscitation (CPR) of pre-hospital cardiac arrest (CA) patients. Volatile anaesthetics reduce ischaemic-reperfusion injury in regional ischaemia in beating hearts. This effect, called anaesthetic-induced pre- or postconditioning, can be shown when the volatile anaesthetic is given either before regional ischaemia or in the reperfusion phase. However, up to now, little data exist for volatile anaesthetics after global ischaemia due to CA. Therefore, the goal of this study was to clarify whether Sevoflurane improves post-resuscitation myocardial dysfunction after CA in rats. Following institutional approval by the Governmental Animal Care Committee, 144 male Wistar rats (341±19g) were randomized either to a control group or to one of the 9 interventional groups receiving 0.25 MAC, 0.5 MAC or 1 MAC of Sevoflurane for 5min either before resuscitation (SBR), during resuscitation (SDR) or after resuscitation (SAR). After 6min of electrically induced ventricular fibrillation CPR was performed. Before CA (baseline) as well as 1h and 24h after restoration of spontaneous circulation (ROSC), continuous measurement of ejection fraction (EF), and preload adjusted maximum power (PAMP) as primary outcome parameters and end systolic pressure (ESP), end diastolic volume (EDV) and maximal slope of systolic pressure increment (dP/dtmax) as secondary outcome parameters was performed using a conductance catheter. EF was improved in all Sevoflurane treated groups 1h after ROSC in comparison to control, except for the 0.25 MAC SDR and 0.25 MAC SAR group (0.25 MAC SBR: 38±8, p=0.02; 0.5 MAC SBR: 39±7, p=0.04; 1 MAC SBR: 40±6, p=0.007; 0.5 MAC SDR: 38±7, p=0.02; 1 MAC SDR: 40±6, p=0.006; 0.5 MAC SAR: 39±6, p=0.01; 1 MAC SAR: 39±6, p=0.002, vs. 30±7%). Twenty-four hours after ROSC, EF was higher than control in all interventional groups (p<0.05 for all groups). EF recovered to baseline values 24h after ROSC in all SBR and SAR groups. PAMP was improved in comparison to control (4.6±3.0mW/μl(2)) 24h after ROSC in 0.5 MAC SBR (9.4±6.9mW/μl(2), p=0.04), 1 MAC SBR (8.9±4.4mW/μl(2), p=0.04), 1 MAC SDR (8.0±5.7mW/μl(2), p=0.04), and 1 MAC SAR (7.3±3.5mW/μl(2), p=0.04). ESP, EDV, and dP/dtmax was not different from control 1h as well as 24h after ROSC with the exception of 1 MAC SDR with a reduced ESP 1h after ROSC (89±16 vs. 103±22mmHg, p=0.04). Sevoflurane treatment did not affect survival rate. This animal study of CA and resuscitation provides the hypothesis that pharmacological pre- or postconditioning with the volatile anaesthetic Sevoflurane - administered before CA, during resuscitation or after ROSC - results in an improved myocardial inotropy 24h after ROSC. Sevoflurane treatment seems to improve EF even in the early phase of reperfusion 1h after ROSC. Therefore further targeted studies on the optimal dose and time point of administration of Sevoflurane in cardiopulmonary resuscitation seem to be worthwhile (Institutional protocol number: 35-9185.81/G-24/08). Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Simulation of Water Sources and Precipitation Recycling for the MacKenzie, Mississippi and Amazon River Basins

NASA Technical Reports Server (NTRS)

Bosilovich, Michael G.; Chern, Jiun-Dar

2005-01-01

An atmospheric general circulation model simulation for 1948-1997 of the water budgets for the MacKenzie, Mississippi and Amazon River basins is presented. In addition to the water budget, we include passive tracers to identify the geographic sources of water for the basins, and the analysis focuses on the mechanisms contributing to precipitation recycling in each basin. While each basin s precipitation recycling has a strong dependency on evaporation during the mean annual cycle, the interannual variability of the recycling shows important relationships with the atmospheric circulation. The MacKenzie River basin has only a weak interannual dependency on evaporation, where the variations in zonal moisture transport from the Pacific Ocean can affect the basin water cycle. On the other hand, the Mississippi River basin has strong interannual dependencies on evaporation. While the precipitation recycling weakens with increased low level jet intensity, the evaporation variations exert stronger influence in providing water vapor for convective precipitation at the convective cloud base. High precipitation recycling is also found to be partly connected to warm SSTs in the tropical Pacific Ocean. The Amazon River basin evaporation exhibits small interannual variations, so that the interannual variations of precipitation recycling are related to atmospheric moisture transport from the tropical south Atlantic Ocean. Increasing SSTs over the 50-year period are causing increased easterly transport across the basin. As moisture transport increases, the Amazon precipitation recycling decreases (without real time varying vegetation changes). In addition, precipitation recycling from a bulk diagnostic method is compared to the passive tracer method used in the analysis. While the mean values are different, the interannual variations are comparable between each method. The methods also exhibit similar relationships to the terms of the basin scale water budgets.

Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

PubMed

Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A; Villinger, Francois; Mori, Kazuyasu

2017-07-01

Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4 + T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4 + T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3 + CCR5 + CD4 + T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3 + T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14 + CD16 + monocytes and MAC387 + macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387 + macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages. IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4 + T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3 + CCR5 + CD4 + T (Th1) cells during the primary infection, thereby compromising the cellular immune response. Thus, we hypothesized that distinct host responses are elicited by the infections with two different viruses. We found that SIVmac239 induced distinctly higher levels of inflammatory Th1 responses than Δ5G. In particular, SIVmac239 infection elicited robust expression of CXCL10, a chemokine for CXCR3 + cells, in CD14 + CD16 + monocytes and MAC387 + macrophages recently infiltrated in SLOs. In contrast, Δ5G infection elicited only modest inflammatory responses. These results suggest that the glycosylation of Env modulates the inflammatory/Th1 responses through the monocyte/macrophage subsets and elicits marked differences in SIV infection and clinical outcomes. Copyright © 2017 American Society for Microbiology.

Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets

PubMed Central

Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J.; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A.; Villinger, Francois

2017-01-01

ABSTRACT Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4+ T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4+ T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323–9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3+ CCR5+ CD4+ T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3+ T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14+ CD16+ monocytes and MAC387+ macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387+ macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages. IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4+ T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323–9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3+ CCR5+ CD4+ T (Th1) cells during the primary infection, thereby compromising the cellular immune response. Thus, we hypothesized that distinct host responses are elicited by the infections with two different viruses. We found that SIVmac239 induced distinctly higher levels of inflammatory Th1 responses than Δ5G. In particular, SIVmac239 infection elicited robust expression of CXCL10, a chemokine for CXCR3+ cells, in CD14+ CD16+ monocytes and MAC387+ macrophages recently infiltrated in SLOs. In contrast, Δ5G infection elicited only modest inflammatory responses. These results suggest that the glycosylation of Env modulates the inflammatory/Th1 responses through the monocyte/macrophage subsets and elicits marked differences in SIV infection and clinical outcomes. PMID:28424283

Effect of Emdogain enamel matrix derivative and BMP-2 on the gene expression and mineralized nodule formation of alveolar bone proper-derived stem/progenitor cells.

PubMed

Fawzy El-Sayed, Karim M; Dörfer, Christof; Ungefroren, Hendrick; Kassem, Neemat; Wiltfang, Jörg; Paris, Sebastian

2014-07-01

The objective of this study was to evaluate the effect of Emdogain (Enamel Matrix Derivative, EMD) and Bone Morphogenetic Protein-2 (BMP-2), either solely or in combination, on the gene expression and mineralized nodule formation of alveolar bone proper-derived stem/progenitor cells. Stem/progenitor cells were isolated from human alveolar bone proper, magnetically sorted using STRO-1 antibodies, characterized flowcytometrically for their surface markers' expression, and examined for colony formation and multilineage differentiation potential. Subsequently, cells were treated over three weeks with 100 μg/ml Emdogain (EMD-Group), or 100 ng/ml BMP-2 (BMP-Group), or a combination of 100 ng/ml BMP-2 and 100 μg/ml Emdogain (BMP/EMD-Group). Unstimulated stem/progenitor cells (MACS(+)-Group) and osteoblasts (OB-Group) served as controls. Osteogenic gene expression was analyzed using RTq-PCR after 1, 2 and 3 weeks (N = 3/group). Mineralized nodule formation was evaluated by Alizarin-Red staining. BMP and EMD up-regulated the osteogenic gene expression. The BMP Group showed significantly higher expression of Collagen-I, III, and V, Alkaline phosphatase and Osteonectin compared to MACS(+)- and OB-Group (p < 0.05; Two-way ANOVA/Bonferroni) with no mineralized nodule formation. Under in-vitro conditions, Emdogain and BMP-2 up-regulate the osteogenic gene expression of stem/progenitor cells. The combination of BMP-2 and Emdogain showed no additive effect and would not be recommended for a combined clinical stimulation. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Bactericidal and Anti-biofilm Effects of Polyhexamethylene Biguanide in Models of Intracellular and Biofilm of Staphylococcus aureus Isolated from Bovine Mastitis

PubMed Central

Kamaruzzaman, Nor F.; Chong, Stacy Q. Y.; Edmondson-Brown, Kamina M.; Ntow-Boahene, Winnie; Bardiau, Marjorie; Good, Liam

2017-01-01

Staphylococcus aureus infection is a common cause of mastitis, reducing milk yield, affecting animal welfare and causing huge economic losses within the dairy industry. In addition to the problem of acquired drug resistance, bacterial invasion into udder cells and the formation of surface biofilms are believed to reduce antibiotic efficacy, leading to treatment failure. Here, we investigated the antimicrobial activities of enrofloxacin, an antibiotic that is commonly used in mastitis therapy and polyhexamethylene biguanide (PHMB), an antimicrobial polymer. The antimicrobial activities were tested against intracellular S. aureus in infected Mac-T cells (host cells). Also, fluorescein-tagged PHMB was used to study PHMB uptake and localization with S. aureus within the infected Mac-T cells. Anti-biofilm activities were tested by treating S. aureus biofilms and measuring effects on biofilm mass in vitro. Enrofloxacin and PHMB at 15 mg/L killed between 42 to 92 and 99.9% of intracellular S. aureus, respectively. PHMB-FITC entered and colocalized with the intracellular S. aureus, suggesting direct interaction of the drug with the bacteria inside the host cells. Enrofloxacin and PHMB at 15 mg/L reduced between 10 to 27% and 28 to 37% of biofilms’ mass, respectively. The half-maximal inhibitory concentrations (IC50) obtained from a cytotoxicity assay were 345 ± 91 and 21 ± 2 mg/L for enrofloxacin and PHMB, respectively; therefore, both compounds were tolerated by the host cells at high concentrations. These findings suggest that both antimicrobials are effective against intracellular S. aureus and can disrupt biofilm structures, with PHMB being more potent against intracellular S. aureus, highlighting the potential application of PHMB in mastitis therapy. PMID:28848527

MacMouse. Developing Preschool Readiness Concepts and Skills with HyperCard and MacRecorder.

ERIC Educational Resources Information Center

Fitterman, L. Jeffrey

Through developments with the use of the "Apple Macintosh" computer, "HyperCard," and "MacRecorder," children in preschool handicapped programs are now capable of participating in appropriate computerized learning experiences. "HyperCard" allows educators to produce their own computerized instructional…

Roderick MacKinnon - Patents

Science.gov Websites

CHANNEL PROTEINS, MUTANT PROKARYOTIC CATION CHANNEL PROTEINS, AND USES THEREOF - MacKinnon, Roderick cation channel proteins, and potentially have uses in treating conditions related to the function of SENSOR DOMAINS OF VOLTAGE-DEPENDENT ION CHANNEL PROTEINS AND USES THEREOF - MacKinnon, Roderick; et. al

Markovian Monte Carlo program EvolFMC v.2 for solving QCD evolution equations

NASA Astrophysics Data System (ADS)

Jadach, S.; Płaczek, W.; Skrzypek, M.; Stokłosa, P.

2010-02-01

We present the program EvolFMC v.2 that solves the evolution equations in QCD for the parton momentum distributions by means of the Monte Carlo technique based on the Markovian process. The program solves the DGLAP-type evolution as well as modified-DGLAP ones. In both cases the evolution can be performed in the LO or NLO approximation. The quarks are treated as massless. The overall technical precision of the code has been established at 5×10. This way, for the first time ever, we demonstrate that with the Monte Carlo method one can solve the evolution equations with precision comparable to the other numerical methods. New version program summaryProgram title: EvolFMC v.2 Catalogue identifier: AEFN_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEFN_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including binary test data, etc.: 66 456 (7407 lines of C++ code) No. of bytes in distributed program, including test data, etc.: 412 752 Distribution format: tar.gz Programming language: C++ Computer: PC, Mac Operating system: Linux, Mac OS X RAM: Less than 256 MB Classification: 11.5 External routines: ROOT ( http://root.cern.ch/drupal/) Nature of problem: Solution of the QCD evolution equations for the parton momentum distributions of the DGLAP- and modified-DGLAP-type in the LO and NLO approximations. Solution method: Monte Carlo simulation of the Markovian process of a multiple emission of partons. Restrictions:Limited to the case of massless partons. Implemented in the LO and NLO approximations only. Weighted events only. Unusual features: Modified-DGLAP evolutions included up to the NLO level. Additional comments: Technical precision established at 5×10. Running time: For the 10 6 events at 100 GeV: DGLAP NLO: 27s; C-type modified DGLAP NLO: 150s (MacBook Pro with Mac OS X v.10.5.5, 2.4 GHz Intel Core 2 Duo, gcc 4.2.4, single thread).

THE EFFECTS OF A SIMPLE METHOD FOR CRYOPRESERVATION AND THAWING PROCEDURES ON CORD BLOOD DERIVED DC-BASED ESOPHAGEAL CARCINOMA VACCINE.

PubMed

Yu, J; Xie, L; Chen, S; Zhang, J; Guo, G; Chen, B

Producing sufficient numbers of DCs at one time point and subsequently cryopreserving the generated DCs in ready-for-use aliquots for clinical application is useful in cancer treatment. To study the effects of a simplified cryopreservation method and thawing procedures acting on the biological characteristics and specific cytotoxic activity of cord blood derived DC-based esophageal carcinoma vaccine. CD34+ hematopoietic stem cells were isolated from cord blood using CD34+ Progenitor Cell Isolation Kit by magnetic cell sorting system (MACS). The CD34+ cells were expanded with cytokines as DCs, and fused with EC109 cells by PEG-3600. The fused cells were transferred to a freezing tube without rate-controlled freezing and stored at -80 degree C for three weeks. During cryopreservation, 2.5% DMSO, 2.5% glucose and 10% FCS at final concentration was used as stock solution. After thawing, cells were assayed for Typan blue viability, morphology, immunophenotypes and T-cell stimulatory capacity, and specific CTL activity. Cryopreservation does not cause significant changes in the phenotypes expression or morphology of the fused cells, and the viability were well preserved (Typan blue viability was 77.2±1.8%). After being stimulated by DC-based esophageal carcinoma vaccine either before or after cryopreservation, the numbers of CD3+T/CD4+T and CD3+T/CD8+T lymphocytes increased obviously, especially for CD3+T/CD4+T, and the ratio of CD4/CD8 changed from 0.85 to 1.29 and 1.25 respectively. Specific CTL activity were well preserved (compare to the fresh fused vaccine, P>0.05). A simple -80 degree C freezing and storage method is practical for cord blood derived DC-based esophageal carcinoma vaccine. It will greatly facilitate the clinical use of DC-based vaccine for immunotherapy.

Rapid fibroblast removal from high density human embryonic stem cell cultures.

PubMed

Turner, William S; McCloskey, Kara E

2012-10-28

Mouse embryonic fibroblasts (MEFs) were used to establish human embryonic stem cells (hESCs) cultures after blastocyst isolation(1). This feeder system maintains hESCs from undergoing spontaneous differentiation during cell expansion. However, this co-culture method is labor intensive, requires highly trained personnel, and yields low hESC purity(4). Many laboratories have attempted to minimize the number of feeder cells in hESC cultures (i.e. incorporating matrix-coated dishes or other feeder cell types(5-8)). These modified culture systems have shown some promise, but have not supplanted the standard method for culturing hESCs with mitomycin C-treated mouse embyronic fibroblasts in order to retard unwanted spontaneous differentiation of the hESC cultures. Therefore, the feeder cells used in hESC expansion should be removed during differentiation experiments. Although several techniques are available for purifying the hESC colonies (FACS, MACS, or use of drug resistant vectors) from feeders, these techniques are labor intensive, costly and/or destructive to the hESC. The aim of this project was to invent a method of purification that enables the harvesting of a purer population of hESCs. We have observed that in a confluent hESC culture, the MEF population can be removed using a simple and rapid aspiration of the MEF sheet. This removal is dependent on several factors, including lateral cell-to-cell binding of MEFs that have a lower binding affinity to the styrene culture dish, and the ability of the stem cell colonies to push the fibroblasts outward during the generation of their own "niche". The hESC were then examined for SSEA-4, Oct3/4 and Tra 1-81 expression up to 10 days after MEF removal to ensure maintenance of pluripotency. Moreover, hESC colonies were able to continue growing from into larger formations after MEF removal, providing an additional level of hESC expansion.

Antibacterial Activity of 7-Epiclusianone and Its Novel Copper Metal Complex on Streptococcus spp. Isolated from Bovine Mastitis and Their Cytotoxicity in MAC-T Cells.

PubMed

de Barros, Mariana; Perciano, Pedro Griffo; Dos Santos, Marcelo Henrique; De Oliveira, Leandro Licursi; Costa, Éderson D'Martin; Moreira, Maria Aparecida Scatamburlo

2017-05-17

Mastitis is an inflammation of mammary gland parenchyma that adversely affects bovine health and dairy production worldwide despite significant efforts to eradicate it. The aim of this work was to characterize the antimicrobial activity of 7-epiclusianone (7-epi), a compound extracted from the Rheedia brasiliensis fruit, its complex with copper against Streptococcus spp. isolated from bovine mastitis, and to assess their cytotoxicity to bovine mammary alveolar cells (MAC-T). The complex 7-epiclusianone-Cu (7-epi-Cu) was an amorphous green solid with optical activity. Its vibrational spectrum in the infrared region showed absorption bands in the high-frequency region, as well as bands that can be attributed to the unconjugated and conjugated stretching of the free ligand. The complex was anhydrous. One of the tested bacterial strains was not sensitive to the compounds, while the other three had MIC values of 7.8 µg mL -1 and minimum bactericidal concentration (MBC) values between 15.6 and 31.3 µg mL -1 . These two compounds are bacteriostatic, did not cause damage to the cell wall and, at sub-inhibitory concentrations, did not induce bacterial adhesion. The compounds were not cytotoxic. Based on these results, 7-epi and 7-epi-Cu exhibited desirable antimicrobial properties and could potentially be used in bovine mastitis treatment.

The Parker-Sochacki Method--A Powerful New Method for Solving Systems of Differential Equations

NASA Astrophysics Data System (ADS)

Rudmin, Joseph W.

2001-04-01

The Parker-Sochacki Method--A Powerful New Method for Solving Systems of Differential Equations Joseph W. Rudmin (Physics Dept, James Madison University) A new system of solving systems of differential equations will be presented, which has been developed by J. Edgar Parker and James Sochacki, of the James Madison University Mathematics Department. The method produces MacClaurin Series solutions to systems of differential equations, with the coefficients in either algebraic or numerical form. The method yields high-degree solutions: 20th degree is easily obtainable. It is conceptually simple, fast, and extremely general. It has been applied to over a hundred systems of differential equations, some of which were previously unsolved, and has yet to fail to solve any system for which the MacClaurin series converges. The method is non-recursive: each coefficient in the series is calculated just once, in closed form, and its accuracy is limited only by the digital accuracy of the computer. Although the original differential equations may include any mathematical functions, the computational method includes ONLY the operations of addition, subtraction, and multiplication. Furthermore, it is perfectly suited to parallel -processing computer languages. Those who learn this system will never use Runge-Kutta or predictor-corrector methods again. Examples will be presented, including the classical many-body problem.

Intrusion Detection for Defense at the MAC and Routing Layers of Wireless Networks

DTIC Science & Technology

2007-01-01

Space DoS Denial of Service DSR Dynamic Source Routing IDS Intrusion Detection System LAR Location-Aided Routing MAC Media Access Control MACA Multiple...different mobility parameters. 10 They simulate interaction between three MAC protocols ( MACA , 802.11 and CSMA) and three routing protocols (AODV, DSR

12 CFR 652.61 - Capital planning.

Code of Federal Regulations, 2014 CFR

2014-01-01

... progressively severe stress scenarios developed by Farmer Mac appropriate to its business model and portfolios... stress testing, Farmer Mac must provide to OSMO a description of the expected and stressed scenarios that Farmer Mac intends to use to conduct its annual stress test under this section. (B) A description of all...

42 CFR 423.2110 - MAC reviews on its own motion.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false MAC reviews on its own motion. 423.2110 Section 423.2110 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Reopening, ALJ Hearings, MAC review...

THE EFFECT OF TEMPERATURE ON THE GROWTH OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS

EPA Science Inventory

MAC organisms are able to grow, persist, and colonize in water distribution systems and may amplify in hospital hot water systems. This study examined the response of MAC organisms (M. avium, M. intracellulare, and MX) to a range of temperatures commonly associated with drinking...

MacIntyre, Rival Traditions and Education

ERIC Educational Resources Information Center

Stolz, Steven A.

2016-01-01

This paper critically discusses MacIntyre's thesis that education is essentially a contested concept. In order to contextualise my discussion, I discuss both whether rival educational traditions of education found in MacIntyre's work--which I refer to as instrumental and non-instrumental justifications of education--can be rationally resolved…