Gold nano particle decorated graphene core first generation PAMAM dendrimer for label free electrochemical DNA hybridization sensing.

PubMed

Jayakumar, K; Rajesh, R; Dharuman, V; Venkatasan, R; Hahn, J H; Pandian, S Karutha

2012-01-15

A novel first generation (G1) poly(amidoamine) dendrimer (PAMAM) with graphene core (GG1PAMAM) was synthesized for the first time. Single layer of GG1PAMAM was immobilized covalently on mercaptopropionic acid (MPA) monolayer on Au transducer. This allows cost effective and easy deposition of single layer graphene on the Au transducer surface than the advanced vacuum techniques used in the literature. Au nano particles (17.5 nm) then decorated the GG1PAMAM and used for electrochemical DNA hybridization sensing. The sensor discriminates selectively and sensitively the complementary double stranded DNA (dsDNA, hybridized), non-complementary DNA (ssDNA, un-hybridized) and single nucleotide polymorphism (SNP) surfaces. Interactions of the MPA, GG1PAMAM and the Au nano particles were characterized by Ultra Violet (UV), Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), Thermo gravimetric analysis (TGA), Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Cyclic Voltmetric (CV), Impedance spectroscopy (IS) and Differntial Pulse Voltammetry (DPV) techniques. The sensor showed linear range 1×10(-6) to 1×10(-12) M with lowest detection limit 1 pM which is 1000 times lower than G1PAMAM without graphene core. Copyright © 2011 Elsevier B.V. All rights reserved.

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer.

PubMed

Bellini, Reinaldo G; Guimarães, Ana P; Pacheco, Marco A C; Dias, Douglas M; Furtado, Vanessa R; de Alencastro, Ricardo B; Horta, Bruno A C

2015-07-01

The association of the anti-tuberculosis drug rifampicin (RIF) with a 4th-generation poly(amidoamine) (G4-PAMAM) dendrimer was investigated by means of molecular dynamics simulations. The RIF load capacity was estimated to be around 20 RIF per G4-PAMAM at neutral pH. The complex formed by 20 RIF molecules and the dendrimer (RIF20-PAMAM) was subjected to 100 ns molecular dynamics (MD) simulations at two different pH conditions (neutral and acidic). The complex was found to be significantly more stable in the simulation at neutral pH compared to the simulation at low pH in which the RIF molecules were rapidly and almost simultaneously expelled to the solvent bulk. The high stability of the RIF-PAMAM complex under physiological pH and the rapid release of RIF molecules under acidic medium provide an interesting switch for drug targeting since the Mycobacterium resides within acidic domains of the macrophage. Altogether, these results suggest that, at least in terms of stability and pH-dependent release, PAMAM-like dendrimers may be considered suitable drug delivery systems for RIF and derivatives. Copyright © 2015 Elsevier Inc. All rights reserved.

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

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

Bodewein, Lambert

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, withmore » EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish

E-DNA sensor of Mycobacterium tuberculosis based on electrochemical assembly of nanomaterials (MWCNTs/PPy/PAMAM).

PubMed

Miodek, Anna; Mejri, Nawel; Gomgnimbou, Michel; Sola, Christophe; Korri-Youssoufi, Hafsa

2015-09-15

Two-step electrochemical patterning methods have been employed to elaborate composite nanomaterials formed with multiwalled carbon nanotubes (MWCNTs) coated with polypyrrole (PPy) and redox PAMAM dendrimers. The nanomaterial has been demonstrated as a molecular transducer for electrochemical DNA detection. The nanocomposite MWCNTs-PPy has been formed by wrapping the PPy film on MWCNTs during electrochemical polymerization of pyrrole on the gold electrode. The MWCNTs-PPy layer was modified with PAMAM dendrimers of fourth generation (PAMAM G4) with covalent bonding by electro-oxidation method. Ferrocenyl groups were then attached to the surface as a redox marker. The electrochemical properties of the nanomaterial (MWCNTs-PPy-PAMAM-Fc) were studied using both square wave voltammetry and cyclic voltammetry to demonstrate efficient electron transfer. The nanomaterial shows high performance in the electrochemical detection of DNA hybridization leading to a variation in the electrochemical signal of ferrocene with a detection limit of 0.3 fM. Furthermore, the biosensor demonstrates ability for sensing DNA of rpoB gene of Mycobacterium tuberculosis in real PCR samples. Developed biosensor was suitable for detection of sequences with a single nucleotide polymorphism (SNP) T (TCG/TTG), responsible for resistance of M. tuberculosis to rifampicin drug, and discriminating them from wild-type samples without such mutation. This shows potential of such systems for further application in pathogens diagnostic and therapeutic purpose.

Toxicity of PAMAM-coated gold nanoparticles in different unicellular models.

PubMed

Perreault, François; Melegari, Silvia Pedroso; Fuzinatto, Cristiane Funghetto; Bogdan, Nicoleta; Morin, Mario; Popovic, Radovan; Matias, William Gerson

2014-03-01

Polyamidoamine (PAMAM) dendrimers are used for many pharmaceutical and biomedical applications. However, the toxicological risks of several PAMAM-based compounds are still not fully evaluated, despite evidences of PAMAM deleterious effects on biological membranes, leading to toxicity. In this report, we investigated the toxicity of generation 0 PAMAM-coated gold nanoparticles (AuG0 NPs) in four different models to determine how different cellular systems are affected by PAMAM-coated NPs. Toxicity was evaluated in two mammalian cell lines, Neuro 2A and Vero, in the green alga Chlamydomonas reinhardtii and the bacteria Vibrio fischeri. AuG0 NP treatments reduced cell metabolic activity in algal and bacterial cells, measured by esterase enzymatic activity (C. reinhardtii) and luminescence emission (V. fischeri). EC50 value after 30 min of treatment was similar in both organisms, with 0.114 and 0.167 mg mL(-1) for C. reinhardtii and V. fischeri, respectively. On the other hand, AuG0 NPs induced no change of mitochondrial activity in mammalian cells after 24 h of treatment to up to 0.4 mg mL(-1) AuG0 NPs. Change in the absorption spectra of AuG0 NP in the mammalian cell culture media may indicate an alteration of NP properties that contributed to the low toxicity of AuG0 NPs in mammalian cells. For a safe development of PAMAM-based nanomaterials, the difference of sensitivity between mammalian and microbial cells, as well as the modulation of NPs toxicity by medium properties, should be taken into account when designing PAMAM NPs for applications that may lead to their introduction in the environment. Copyright © 2012 Wiley Periodicals, Inc.

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines.

PubMed

Bodewein, Lambert; Schmelter, Frank; Di Fiore, Stefano; Hollert, Henner; Fischer, Rainer; Fenske, Martina

2016-08-15

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96h and human cancer cell lines for 24h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7μM at 24 and 48hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values≥402μM (PAMAMs) and ≤240μM (PPIs) for HepG2 and ≤13.24μM (PAMAMs) and ≤12.84μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

PubMed Central

Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

2015-01-01

The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

Cationic PAMAM dendrimers disrupt key platelet functions

PubMed Central

Jones, Clinton F.; Campbell, Robert A.; Franks, Zechariah; Gibson, Christopher C.; Thiagarajan, Giridhar; Vieira-de-Abreu, Adriana; Sukavaneshvar, Sivaprasad; Mohammad, S. Fazal; Li, Dean Y.; Ghandehari, Hamidreza; Weyrich, Andrew S.; Brooks, Benjamin D.; Grainger, David W.

2012-01-01

Poly(amidoamine) (PAMAM) dendrimers have been proposed for a variety of biomedical applications and are increasingly studied as model nanomaterials for such use. The dendritic structure features both modular synthetic control of molecular size and shape and presentation of multiple equivalent terminal groups. These properties make PAMAM dendrimers highly functionalizable, versatile single-molecule nanoparticles with a high degree of consistency and low polydispersity. Recent nanotoxicological studies showed that intravenous administration of amine-terminated PAMAM dendrimers to mice was lethal, causing a disseminated intravascular coagulation-like condition. To elucidate the mechanisms underlying this coagulopathy, in vitro assessments of platelet functions in contact with PAMAM dendrimers were undertaken. This study demonstrates that cationic G7 PAMAM dendrimers activate platelets and dramatically alter their morphology. These changes to platelet morphology and activation state substantially altered platelet function, including increased aggregation and adherence to surfaces. Surprisingly, dendrimer exposure also attenuated platelet-dependent thrombin generation, indicating that not all platelet functions remained intact. These findings provide additional insight into PAMAM dendrimer effects on blood components and underscore the necessity for further research on the effects and mechanisms of PAMAM-specific and general nanoparticle toxicity in blood. PMID:22497592

Characterization of folic acid-PAMAM conjugates: drug loading efficacy and dendrimer morphology.

PubMed

Chanphai, P; Tajmir-Riahi, H A

2018-05-01

We report the loading efficacy of folic acid (FA) by polyamidoamine (PAMAM-G3 and PAMAM-G4) nanoparticles in aqueous solution at physiological pH. Thermodynamic parameters ΔH = -47.57 (kJ Mol -1 ), ΔS = -122.78 (J Mol -1 , K -1 ) and ΔG = -10.96 (kJ Mol -1 ) showed FA-PAMAM bindings occur via H-bonding and van der Waals contacts. The stability of acid-PAMAM conjugate increased as polymer size increased. The acid loading efficacy was 40 to 50%. TEM images exhibited major polymer morphological changes upon acid encapsulation. PAMAM dendrimers are capable of FA delivery in vitro.

G3.5 PAMAM dendrimers enhance transepithelial transport of SN38 while minimizing gastrointestinal toxicity.

PubMed

Goldberg, Deborah S; Vijayalakshmi, Nirmalkumar; Swaan, Peter W; Ghandehari, Hamidreza

2011-03-30

Poly(amido amine) (PAMAM) dendrimers have shown promise in oral drug delivery. Conjugation of SN38 to PAMAM dendrimers has the potential to improve its oral absorption while minimizing gastrointestinal toxicity. In this work we evaluated G3.5 PAMAM dendrimer-SN38 conjugates with ester-linked glycine and β-alanine spacers for their suitability in oral therapy of hepatic colorectal cancer metastases. G3.5-βAlanine-SN38 was mostly stable while G3.5-Glycine-SN38 showed 10%, 20%, and 56% SN38 release in simulated gastric, intestinal and liver environments for up to 6, 24 and 48 hours, respectively. Short-term treatment of Caco-2 cells with G3.5-SN38 conjugates did not reduce cell viability, while comparable concentrations of SN38 caused significant cytotoxicity. G3.5-Glycine-SN38 and G3.5-βAlanine-SN38 showed IC₅₀ values of 0.60 and 3.59 μM, respectively, in HT-29 cells treated for 48 h, indicating the efficacy of the drug delivery system in colorectal cancer cells with longer incubation time. Both conjugates increased SN38 transepithelial transport compared to the free drug. Transport of G3.5-Glycine-SN38 was highly concentration-dependent whereas transport of G3.5-βAlanine-SN38 was concentration-independent, highlighting the influence of drug loading and spacer chemistry on transport mechanism. Together these results show that PAMAM dendrimers have the potential to improve the oral bioavailability of potent anti-cancer drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

G3.5 PAMAM Dendrimers Enhance Transepithelial Transport of SN38 while minimizing Gastrointestinal Toxicity

PubMed Central

Goldberg, Deborah S.; Vijayalakshmi, Nirmalkumar; Swaan, Peter W.; Ghandehari, Hamidreza

2011-01-01

Poly(amido amine) (PAMAM) dendrimers have shown promise in oral drug delivery. Conjugation of SN38 to PAMAM dendrimers has the potential to improve its oral absorption while minimizing gastrointestinal toxicity. In this work we evaluated G3.5 PAMAM dendrimer-SN38 conjugates with ester-linked glycine and β-alanine spacers for their suitability in oral therapy of hepatic colorectal cancer metastases. G3.5-βAlanine-SN38 was mostly stable while G3.5-Glycine-SN38 showed 10%, 20%, and 56% SN38 release in simulated gastric, intestinal and liver environments for up to 6, 24 and 48 hours, respectively. Short-term treatment of Caco-2 cells with G3.5-SN38 conjugates did not reduce cell viability, while comparable concentrations of SN38 caused significant cytotoxicity. G3.5-Glycine-SN38 and G3.5-βAlanine-SN38 showed IC50 values of 0.60 and 3.59 μM, respectively, in HT-29 cells treated for 48 hours, indicating the efficacy of the drug delivery system in colorectal cancer cells with longer incubation time. Both conjugates increased SN38 transepithelial transport compared to the free drug. Transport of G3.5-Glycine-SN38 was highly concentration-dependent whereas transport of G3.5-βAlanine-SN38 was concentration-independent, highlighting the influence of drug loading and spacer chemistry on transport mechanism. Together these results show that PAMAM dendrimers have the potential to improve the oral bioavailability of potent anti-cancer drugs. PMID:21115079

Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

PubMed

Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

2015-11-02

Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

Drospirenone/ethinyl estradiol 3 mg/20 μg (24/4 day regimen): hormonal contraceptive choices – use of a fourth-generation progestin

PubMed Central

Bachmann, Gloria; Kopacz, Sharon

2009-01-01

The combined oral contraceptive pill (COC) consisting of drospirenone 3 mg/ethinyl estradiol 20 μg (3 mg DRSP/20 μg EE-24/4) supplies 24 days of pills with hormones followed by 4 days of hormone-free pills. This regimen is called the 24/4 regimen. The progesterone component of this oral contraceptive pill (OCP), drospirenone (DRSP), is a fourth-generation progestin that has potent progestogenic, antimineralocorticoid, and antiandrogenic activity, which are unique characteristics compared with the other progestogens contained in most of the other OCPs currently marketed. This formulation, in addition to being an effective long-term OCP, has the additional medical benefit of providing a good parallel treatment for premenstrual dysphoric disorder and moderate acne. The effectiveness of 3 mg DRSP/20 μg EE-24/4, its tolerability and safety, and its additional non-contraceptive benefits are discussed. PMID:19936169

Large PAMAM Dendron Induces Formation of Unusual P4332 Mesophase in Monoolein/Water system.

PubMed

Kumar, Manoj; Patil, Naganath G; Ambade, Ashootosh V; Kumaraswamy, Guruswamy

2018-05-18

Compact macromolecular dendrons have been shown to induce the formation of discontinuous inverse micellar assemblies with Fd3m symmetry in monoolein/water systems. Here, we demonstrate that a large PAMAM dendron (G5: fifth generation) induces the formation a very unusual mesophase with P4332 symmetry. This mesophase had previously been observed in monoolein/water systems only on addition of cytochrome C. The P4332 mesophase can be considered an intermediate phase between the bicontinuous Ia3d and discontinuous micellar mesophases. In this unusual phase, every third rod junction of the Ia3d mesophase is replaced with a spherical micelle. We present a detailed investigation of the phase behaviour of monoolein/water as a function of G5 concentration and temperature. Addition of 1% G5 in 85/15 monoolein/water system induces a transition from the L to Ia3d phase. Further increase in G5 concentration to above 2% induces the formation of the P4332 phase. Thus, incorporation of G5 yields a qualitatively different phase diagram when compared with incorporation of lower generation PAMAM dendrons (G2 - G4) in monoolein/water, where the reverse micellar Fd3m phase forms. PAMAM dendrons of all generations, G2 - G5, bear terminal amine groups that interact with the monoolein head group. The compact molecular architecture of the dendrons and these attractive interactions induce bending of the monoolein bilayer structure. For smaller dendrons, G2 - G4, this results in the formation of the Fd3m phase. However, the large size of the G5 dendron precludes this and a rare intermediate phase between the Ia3d and discontinuous micellar phase, the P4332 mesophase forms instead.

Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

PubMed Central

Shao, Naimin; Su, Yunzhang; Hu, Jingjing; Zhang, Jiahai; Zhang, Hongfeng; Cheng, Yiyun

2011-01-01

Background Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. Methods The dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Results Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Conclusion Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development. PMID:22267921

Encapsulation of micronutrients resveratrol, genistein, and curcumin by folic acid-PAMAM nanoparticles.

PubMed

Chanphai, P; Tajmir-Riahi, H A

2018-05-21

It has been shown that encapsulation of dietary polyphenols leads to increased solubility and bioavailability of these micronutrients. The encapsulation of dietary polyphenols resveratrol, genistein, and curcumin by folic acid-PAMAM-G3 and folic acid-PAMAM-G4 nanoparticles was studied in aqueous solution at physiological conditions, using multiple spectroscopic methods, TEM images, and docking studies. The polyphenol bindings are via hydrophilic, hydrophobic, and H-bonding contacts with resveratrol forming more stable conjugates. As folic acid-PAMAM nanoparticle size increased, the loading efficacy and the stability of polyphenol-polymer conjugates were increased. Polyphenol encapsulation induced major alterations of dendrimer morphology. Folic acid-PAMAM nanoconjugates are capable of delivery of polyphenols in vitro.

The influence of PAMAM dendrimers surface groups on their interaction with porcine pepsin.

PubMed

Ciolkowski, Michal; Rozanek, Monika; Bryszewska, Maria; Klajnert, Barbara

2013-10-01

In this study the ability of three polyamidoamine (PAMAM) dendrimers with different surface charge (positive, neutral and negative) to interact with a negatively charged protein (porcine pepsin) was examined. It was shown that the dendrimer with a positively charged surface (G4 PAMAM-NH2), as well as the dendrimer with a neutral surface (G4 PAMAM-OH), were able to inhibit enzymatic activity of pepsin. It was also found that these dendrimers act as mixed partially non-competitive pepsin inhibitors. The negatively charged dendrimer (G3.5 PAMAM-COOH) was not able to inhibit the enzymatic activity of pepsin, probably due to the electrostatic repulsion between this dendrimer and the protein. No correlation between changes in enzymatic activity of pepsin and alterations in CD spectrum of the protein was observed. It indicates that the interactions between dendrimers and porcine pepsin are complex, multidirectional and not dependent only on disturbances of the secondary structure. © 2013.

The interaction of the excited states of safranine-O with low generation carboxyl terminated PAMAM dendrimers in an aqueous medium.

PubMed

Militello, M Paula; Altamirano, Marcela S; Bertolotti, Sonia G; Previtali, Carlos M

2018-05-16

The interaction of the singlet and triplet excited states of the synthetic dye safranine-O with carboxyl-terminated poly(amidoamine) (PAMAM) dendrimers was investigated in a buffer solution at pH 8. Low half-generation PAMAM dendrimers (G -0.5; G +0.5: G 1.5) were employed. The UV-vis absorption spectrum of the dye presents only a very small red shift in the presence of dendrimers. Fluorescence quenching was detected and it was interpreted by a static mechanism in terms of the association of the dye with the dendrimer. Laser flash photolysis experiments were carried out and transient absorption spectra of the triplet and radicals were obtained. The triplet state is quenched by the dendrimers with rate constants well below the diffusional limit. The quenching process was characterized as an electron transfer process and the quantum yield of radicals was estimated. It was found that radicals are formed with a high efficiency in the triplet quenching reaction.

Surface modification of PAMAM dendrimers modulates the mechanism of cellular internalization.

PubMed

Saovapakhiran, Angkana; D'Emanuele, Antony; Attwood, David; Penny, Jeffrey

2009-04-01

The aim of this study was to investigate the influence of dendrimer surface properties on cellular internalization and intracellular trafficking in the human colon adenocarcinoma HT-29 cell line. Third-generation (G3) polyamidoamine (PAMAM) dendrimers were modified to contain either two lauroyl chains (G3L2), two propranolol molecules (G3P2), or two lauroyl and two propranolol molecules (G3L2P2) at the dendrimer surface. Surface-modified and unmodified dendrimers were labeled with fluorescein isothiocyanate (FITC) at an average molar ratio of 1:1. The mechanisms of cellular internalization and intracellular trafficking of dendrimers were analyzed by confocal laser scanning microscopy and flow cytometry. The internalization of G3 and G3P2 dendrimers involved both caveolae-dependent endocytosis and macropinocytosis pathways; internalization of G3L2P2 dendrimer appeared to involve caveolae-dependent, and possibly clathrin-dependent, endocytosis pathways; and internalization of G3L2 dendrimer occurred via caveolae-dependent, clathrin-dependent, and macropinocytosis pathways. Subcellular colocalization data indicated that unmodified and all surface-modified G3 PAMAM dendrimers were internalized and trafficked to endosomes and lysosomes. It is therefore apparent that the initial mode of dendrimer internalization into HT-29 cells is influenced by the surface properties of G3 PAMAM dendrimer.

The evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 as a drug and as drug carriers: a systematic review and meta-analysis.

PubMed

Jędrych, Marian; Borowska, Katarzyna; Galus, Ryszard; Jodłowska-Jędrych, Barbara

2014-02-28

The purpose of this study was to investigate the evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 (PAMAM G4) as a drug and as drug carriers by a systematic review of literature and meta-analysis. The results obtained from meta-analysis concluded that drug therapy reduces the change of parameters in relation to the control. The impact of the drug administered to change the test parameters are dependent on the type of tissue. PAMAM G4 may be effective in vitro and in vivo as a drug and drug carriers and may have appropriate applications in various fields of medicine. PAMAM G4 dendrimers hold promises for nanomedicine. Copyright © 2013 Elsevier B.V. All rights reserved.

Cationic PAMAM Dendrimers Aggressively Initiate Blood Clot Formation

PubMed Central

Jones, Clinton F.; Campbell, Robert A.; Brooks, Amanda E.; Assemi, Shoeleh; Tadjiki, Soheyl; Thiagarajan, Giridhar; Mulcock, Cheyanne; Weyrich, Andrew S.; Brooks, Benjamin D.; Ghandehari, Hamidreza; Grainger, David W.

2012-01-01

Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood contacting applications, amine-terminated dendrimers have recently been shown to activate platelets and cause a fatal, disseminated intravascular coagulation (DIC)-like condition in mice and rats. We here demonstrate that, upon addition to blood, cationic G7 PAMAM dendrimers induce fibrinogen aggregation, which may contribute to the in vivo DIC-like phenomenon. We demonstrate that amine-terminated dendrimers act directly on fibrinogen in a thrombin-independent manner to generate dense, high-molecular-weight fibrinogen aggregates with minimal fibrin fibril formation. In addition, we hypothesize this clot-like behavior is likely mediated through electrostatic interactions between the densely charged cationic dendrimer surface and negatively charged fibrinogen domains. Interestingly, cationic dendrimers also induced aggregation of albumin, suggesting that many negatively charged blood proteins may be affected by cationic dendrimers. To investigate this further, zebrafish embryos (ZFE) were employed to more specifically determine the speed of this phenomenon and the pathway- and dose-dependency of the resulting vascular occlusion phenotype. These novel findings show that G7 PAMAM dendrimers significantly and adversely impact many blood components to produce rapid coagulation and strongly suggest that these effects are independent of classic coagulation mechanisms. These results also strongly suggest the need to fully characterize amine-terminated PAMAM dendrimers in regards to their adverse effects on both coagulation and platelets, which may contribute to blood toxicity. PMID:23062017

Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

PubMed

Avaritt, Brittany R; Swaan, Peter W

2014-09-01

Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

On the ability of PAMAM dendrimers and dendrimer/DNA aggregates to penetrate POPC model biomembranes.

PubMed

Ainalem, Marie-Louise; Campbell, Richard A; Khalid, Syma; Gillams, Richard J; Rennie, Adrian R; Nylander, Tommy

2010-06-03

Poly(amido amine) (PAMAM) dendrimers have previously been shown, as cationic condensing agents of DNA, to have high potential for nonviral gene delivery. This study addresses two key issues for gene delivery: the interaction of the biomembrane with (i) the condensing agent (the cationic PAMAM dendrimer) and (ii) the corresponding dendrimer/DNA aggregate. Using in situ null ellipsometry and neutron reflection, parallel experiments were carried out involving dendrimers of generations 2 (G2), 4 (G4), and 6 (G6). The study demonstrates that free dendrimers of all three generations were able to traverse supported palmitoyloleoylphosphatidylcholine (POPC) bilayers deposited on silica surfaces. The model biomembranes were elevated from the solid surfaces upon dendrimer penetration, which offers a promising new way to generate more realistic model biomembranes where the contact with the supporting surface is reduced and where aqueous cavities are present beneath the bilayer. The largest dendrimer (G6) induced partial bilayer destruction directly upon penetration, whereas the smaller dendrimers (G2 and G4) leave the bilayer intact, so we propose that lower generation dendrimers have greater potential as transfection mediators. In addition to the experimental observations, coarse-grained simulations on the interaction between generation 3 (G3) dendrimers and POPC bilayers were performed in the absence and presence of a bilayer-supporting negatively charged surface that emulates the support. The simulations demonstrate that G3 is transported across free-standing POPC bilayers by direct penetration and not by endocytosis. The penetrability was, however, reduced in the presence of a surface, indicating that the membrane transport observed experimentally was not driven solely by the surface. The experimental reflection techniques were also applied to dendrimer/DNA aggregates of charge ratio = 0.5, and while G2/DNA and G4/DNA aggregates interact with POPC bilayers, G6/DNA

Transepithelial Transport of PAMAM Dendrimers across Isolated Rat Jejunal Mucosae in Ussing Chambers

PubMed Central

2015-01-01

Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [14C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery. PMID:24992090

Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.

PubMed

Hubbard, Dallin; Ghandehari, Hamidreza; Brayden, David J

2014-08-11

Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [(14)C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery.

Atomistic computer simulations on multi-loaded PAMAM dendrimers: a comparison of amine- and hydroxyl-terminated dendrimers

NASA Astrophysics Data System (ADS)

Badalkhani-Khamseh, Farideh; Ebrahim-Habibi, Azadeh; Hadipour, Nasser L.

2017-12-01

Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility improvement and increase in drug loading capacity of PAMAM dendrimers. In this work, fully atomistic MD simulations were employed to study the association of 5-Fluorouracil (5-FU) with amine (NH2)- and hydroxyl (OH)-terminated PAMAM dendrimers of generations 3 and 4 (G3 and G4). MD results show a 1:12, 1:1, 1:27, and 1:4 stoichiometry, respectively, for G3NH2-FU, G3OH-FU, G4NH2-FU, and G4OH-FU complexes, which is in good agreement with the isothermal titration calorimetry results. The results obtained showed that NH2-terminated dendrimers assume segmented open structures with large cavities and more drug molecules can encapsulate inside the dendritic cavities of amine terminated dendrimers. However, OH-terminated have a densely packed structure and therefore, 5-FU drug molecules are more stable to locate close to the surface of the dendrimers. Intermolecular hydrogen bonding analysis showed that 5-FU drug molecules have more tendency to form hydrogen bonds with terminal monomers of OH-terminated dendrimers, while in NH2-terminated these occur both in the inner region and the surface. Furthermore, MM-PBSA analysis revealed that van der Waals and electrostatic energies are both important to stabilize the complexes. We found that drug molecules are distributed uniformly inside the amine and hydroxyl terminated dendrimers and therefore, both dendrimers are promising candidates as drug delivery systems for 5-FU drug molecules.

Interactions of PAMAM dendrimers with SDS at the solid-liquid interface.

PubMed

Arteta, Marianna Yanez; Eltes, Felix; Campbell, Richard A; Nylander, Tommy

2013-05-14

This work addresses structural and nonequilibrium effects of the interactions between well-defined cationic poly(amidoamine) PAMAM dendrimers of generations 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) at the hydrophilic silica-water interface. Neutron reflectometry and quartz crystal microbalance with dissipation monitoring were used to reveal the adsorption from premixed dendrimer/surfactant solutions as well as sequential addition of the surfactant to preadsorbed layers of dendrimers. PAMAM dendrimers of both generations adsorb to hydrophilic silica as a compact monolayer, and the adsorption is irreversible upon rinsing with salt solution. SDS adsorbs on the dendrimer layer and at low bulk concentrations causes the expansion of the dendrimer layers on the surface. When the bulk concentration of SDS is increased, the surfactant layer consists of aggregates or bilayer-like structures. The adsorption of surfactant is reversible upon rinsing, but slight changes of the structure of the preadsorbed PAMAM monolayer were observed. The adsorption from premixed solutions close to charge neutrality results in thick multilayers, but the surface excess is lower when the bulk complexes have a net negative charge. A critical examination of the pathway of adsorption for the interactions of SDS with preadsorbed PAMAM monolayers and premixed PAMAM/SDS solutions with hydrophilic silica revealed that nonequilibrium effects are important only in the latter case, and the application of a thermodynamic model to such experimental data would be inappropriate.

Low Concentrations of Cationic PAMAM Dendrimers Affect Lymphocyte Respiration in In vitro Studies.

PubMed

Labieniec-Watala, Magdalena; Szwed, Marzena; Hertel, Joanna; Wisnik, Ewelina

2017-01-01

In this study, the effect of low concentrations of poly(amido)amine dendrimers (G2-G4) on human lymphocytes was studied. Some works revealed that PAMAMs can adversely affect the morphology of blood components and mitochondria functions. In this context, the present report aimed to investigate the in vitro cationic dendrimers' effect on mitochondrial respiration and cell morphology in lymphocytes isolated from human blood. To monitor the mitochondrial changes, the high-resolution respirometer was used, whereas the cell morphology was analyzed using a flow cytometer and fluorescence microscopy. The concentration-dependent dendrimers' influence on lymphocytes morphology was shown. Changes in mitochondrial respiration revealed the concentration- and generation-dependent differences between dendrimer activity. There were no alterations in the routine respiration and in the state of the inner mitochondrial membrane (L/E), but decreased ADP- and FCCP-stimulated respirations were detected after treatment with G3 and G4 dendrimers. The markers of mitochondrial membrane integrity (RCR) and OXPHOS efficiency (P/E) significantly decreased regardless of the dendrimer generation used. Based on these in vitro evaluations, we state that cationic PAMAM dendrimers can impair both the morphology and the bioenergetics of human lymphocytes, even when used at low concentrations and in a short time (up to 1 h). However, these results do not imply that similar findings could be possible for in vivo observations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

An electrospun nanofiber matrix based on organo-clay for biosensors: PVA/PAMAM-Montmorillonite

NASA Astrophysics Data System (ADS)

Unal, Betul; Yalcinkaya, Esra Evrim; Demirkol, Dilek Odaci; Timur, Suna

2018-06-01

Diagnostic techniques based on biomolecules have huge a potential to be applied in the application in various areas such as food/beverage industries, diseases diagnostics, monitoring of bio-processes and environmental pollutants. Immobilization of biomolecules on a transducer is the key parameter to being able to prepare a highly stable diagnostic tests. Electrospun nanofibers are a good alternative to immobilize biomolecules. Here, electrospun nanofibers based on an organoclay were used to design the first generation amperometric enzyme biosensor. PAMAM G2 dendrimers were used to intercalate montmorillonite clay (Mt) and then the modification of Mt by PAMAM was characterized using FTIR, XRD, TGA and zeta potential measurements. After that nanofibers were prepared by electrospinning Mt and PAMAM-Mt using poly(vinyl) alcohol (PVA) as an auxiliary polymer and the formed PVA/PAMAM-Mt electrospun nanofibers were proved by SEM, TEM and AFM techniques. Finally, pyranose oxidases (PyOx) were immobilized on a glassy carbon electrode surface, which was modified using the PVA/PAMAM-Mt electrospun nanofibers. Amperometric measurements were carried out using buffer solution at -0.7 V under stirring conditions. The linear response for glucose was from 0.005 mM to 0.25 mM using PVA/Mt/PyOx and PVA/PAMAM-Mt/PyOx biosensors. The limit of detection was 0.7 μM glucose with PVA/PAMAM-Mt/PyOx biosensor. To detect glucose in real sample, measurements were carried out using soft drink cola as a substrate instead of glucose.

PEGylated PAMAM dendrimer-doxorubicin conjugate-hybridized gold nanorod for combined photothermal-chemotherapy.

PubMed

Li, Xiaojie; Takashima, Munenobu; Yuba, Eiji; Harada, Atsushi; Kono, Kenji

2014-08-01

We prepared pH-sensitive drug-dendrimer conjugate-hybridized gold nanorod as a promising platform for combined cancer photothermal-chemotherapy under in vitro and in vivo conditions. Poly(ethylene glycol)-attached PAMAM G4 dendrimers (PEG-PAMAM) were first covalently linked on the surface of mercaptohexadecanoic acid-functionalized gold nanorod (MHA-AuNR), with subsequent conjugation of anti-cancer drug doxorubicin (DOX) to dendrimer layer using an acid-labile-hydrazone linkage to afford PEG-DOX-PAMAM-AuNR particles. The particles with a high PEG-PAMAM dendrimer coverage density (0.28 per nm(2) AuNR) showed uniform sizes and excellent colloidal stability. In vitro drug release studies demonstrated that DOX released from PEG-DOX-PAMAM-AuNR was negligible under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. The efficient intracellular acid-triggered DOX release inside of lysosomes was confirmed using confocal laser scanning microscopy analysis. Furthermore, the combined photothermal-chemo treatment of cancer cells using PEG-DOX-PAMAM-AuNR for synergistic hyperthermia ablation and chemotherapy was demonstrated both in vitro and in vivo to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of PEG-DOX-PAMAM-AuNR particles for cancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Construction of novel electrochemical immunosensor for detection of prostate specific antigen using ferrocene-PAMAM dendrimers.

PubMed

Çevik, Emre; Bahar, Özlem; Şenel, Mehmet; Abasıyanık, M Fatih

2016-12-15

In this study, an immunosensor was designed to utilize for the detection of prostate specific antigen (PSA) based on three different generations (G1, G2 and G3) of ferrocene (Fc) cored polyamidiamine dendrimers (Fc-PAMAM) gold (Au) electrode. The self-assembled monolayer principle (SAM) was used to fabricate the sensitive, selective and disposable immunosensor electrodes. In electrode fabrication cysteamine (Cys) was the first agent covalently linked on the Au electrode surface. Immobilized redox center (ferrocene) cored PAMAM dendrimers served as a layer for the further binding of biological components. The monoclonal antibody of PSA (anti-PSA) was covalently immobilized on dendrimers which were attached onto the modified Au surface (Au/Cys/Fc-PAMAMs/anti-PSA). PSA levels were quantitatively analyzed by using electrochemical differential pulse voltammetry (DPV) whose lowest detection limit was calculated as 0.001ngmL(-1). The Au/Cys/FcPAMAM/anti-PSA immunosensor showed excellent performance for PSA at the pulse amplitude; 50mV and the scan rate; 10mV/s in a wide linear concentration range of 0.01ng-100ngmL(-1). Analytical performance and specificity assays were carried out using human serum and different proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

Traffic Dimensioning and Performance Modeling of 4G LTE Networks

ERIC Educational Resources Information Center

Ouyang, Ye

2011-01-01

Rapid changes in mobile techniques have always been evolutionary, and the deployment of 4G Long Term Evolution (LTE) networks will be the same. It will be another transition from Third Generation (3G) to Fourth Generation (4G) over a period of several years, as is the case still with the transition from Second Generation (2G) to 3G. As a result,…

Dielectric Properties of Generation 3 Pamam Dendrimer Nanocomposites

NASA Astrophysics Data System (ADS)

Ristić, Sanja; Mijović, Jovan

2008-08-01

Broadband dielectric relaxation spectroscopy (DRS) was employed to study molecular dynamics of blends composed of generation 3 poly(amidoamine) (PAMAM) dendrimers with ethylenediamine core and amino surface groups and four linear polymers: poly(propylene oxide)—PPO, two block copolymers, poly(propylene oxide)/poly(ethylene oxide)—PPO/PEO with different mol ratios (29/6 and 10/31) and poly(ethylene oxide)—PEO. The results were generated over a broad range of frequency. Dielectric spectra of dendrimers in PPO matrix reveal slight shift of normal and segmental processes to higher frequency with increasing concentration of dendrimers. In the 29PPO/6PEO matrix, no effect of concentration on the average relaxation time for normal and segmental processes was observed. In the 10PPO/31PEO matrix the relaxation time of the segmental process increases with increasing dendrimer concentration, while in the PEO matrix, local processes in dendrimers slow down. A detailed analysis of the effect of concentration of dendrimers and morphology of polymer matrix on the dielectric properties of dendrimer nanocomposites will be presented.

TRANSEPITHELIAL TRANSPORT AND TOXICITY OF PAMAM DENDRIMERS: IMPLICATIONS FOR ORAL DRUG DELIVERY

PubMed Central

Sadekar, S.; Ghandehari, H.

2011-01-01

This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer – drug conjugates, as a function of physicochemical properties will further need to be assessed. PMID:21983078

Effect of anionic and cationic polyamidoamine (PAMAM) dendrimers on a model lipid membrane.

PubMed

Lombardo, Domenico; Calandra, Pietro; Bellocco, Ersilia; Laganà, Giuseppina; Barreca, Davide; Magazù, Salvatore; Wanderlingh, Ulderico; Kiselev, Mikhail A

2016-11-01

In spite of the growing variety of biological applications of dendrimer-based nanocarriers, a major problem of their potential applications in bio-medicine is related to the disruption of lipid bilayers and the cytotoxicity caused by the aggregation processes involved onto cellular membranes. With the aim to study model dendrimer-biomembrane interaction, the self-assembly processes of a mixture of charged polyamidoamine (PAMAM) dendrimers and dipalmitoylphosphatidylcholine (DPPC) lipids were investigated by means of Zeta potential analysis, Raman and x-ray scattering. Zwitterionic DPPC liposomes showed substantially different behaviors during their interaction with negatively charged (generation G=2.5) sodium carboxylate terminated (COO - Na + ) dendrimers or positively charged (generation G=3.0) amino terminated (-NH 2 ) dendrimers. More specifically the obtained results evidence the sensitive interactions between dendrimer terminals and lipid molecules at the surface of the liposome, with an enhancement of the liposome surface zeta potential, as well as in the hydrophobic region of the bilayers, where dendrimer penetration produce a perturbation of the hydrophobic alkyl chains of the bilayers. Analysis of the SAXS structure factor with a suitable model for the inter-dendrimers electrostatic potential allows an estimation of an effective charge of 15 ǀeǀ for G=2.5 and 7.6 ǀeǀ for G=3.0 PAMAM dendrimers. Only a fraction (about 1/7) of this charge contributes to the linear increase of liposome zeta-potential with increasing PAMAM/DPPC molar fraction. The findings of our investigation may be applied to rationalize the effect of the nanoparticles electrostatic interaction in solution environments for the design of new drug carriers combining dendrimeric and liposomal technology. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional PEG–PAMAM-Tetraphosphonate Capped NaLnF4 Nanoparticles and their Colloidal Stability in Phosphate Buffer

PubMed Central

2015-01-01

Developing surface coatings for NaLnF4 nanoparticles (NPs) that provide long-term stability in solutions containing competitive ions such as phosphate remains challenging. An amine-functional polyamidoamine tetraphosphonate (NH2-PAMAM-4P) as a multidentate ligand for these NPs has been synthesized and characterized as a ligand for the surface of NaGdF4 and NaTbF4 nanoparticles. A two-step ligand exchange protocol was developed for introduction of the NH2-PAMAM-4P ligand on oleate-capped NaLnF4 NPs. The NPs were first treated with methoxy-poly(ethylene glycol)-monophosphoric acid (Mn = 750) in tetrahydrofuran. The mPEG750-OPO3-capped NPs were stable colloidal solutions in water, where they could be ligand-exchanged with NH2-PAMAM-4P. The surface amine groups on the NPs were available for derivatization to attach methoxy-PEG (Mn = 2000) and biotin-terminated PEG (Mn = 2000) chains. The surface coverage of ligands on the NPs was examined by thermal gravimetric analysis, and by a HABA analysis for biotin-containing NPs. Colloidal stability of the NPs was examined by dynamic light scattering. NaGdF4 and NaTbF4 NPs capped with mPEG2000–PAMAM-4P showed colloidal stability in DI water and in phosphate buffer (10 mM, pH 7.4). A direct comparison with NaTbF4 NPs capped with a mPEG2000-lysine-based tetradentate ligand that we reported previously (Langmuir2012, 28, 12861−1287022906305) showed that both ligands provided long-term stability in phosphate buffer, but that the lysine-based ligand provided better stability in phosphate-buffered saline. PMID:24898128

Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers.

PubMed

Kojima, Chie; Regino, Celeste; Umeda, Yasuhito; Kobayashi, Hisataka; Kono, Kenji

2010-01-04

Dendrimers are a potential drug carrier. Because modification with polyethylene glycol (PEG) is known to improve the blood retention, PEGylated dendrimers have been studied as a useful drug carrier. In this study, three types of PEGylated L-lysine-bearing polyamidoamine dendrimers (PEG2k-Lys-PAMAM (G4), PEG5k-Lys-PAMAM (G4), PEG2k-Lys-PAMAM (G5)) were synthesized, which are composed of a dendrimer of different generations (generations 4 and 5) and PEG chains with different molecular weights (2k and 5k). An acetylated L-lysine-bearing dendrimer was also synthesized as a non-PEGylated dendrimer. Bifunctional diethylenetriaminepentaacetic acid (pSCN-benzyl-DTPA) was bound to the epsilon -amino group of lysine in a dendrimer, to be labeled with radioactive indium-111. These PEGylayed dendrimers showed longer blood retention and lower accumulation in other normal organs such as the kidneys than the non-PEGylated dendrimer. The PEGylated dendrimers with the higher generation and the longer PEG led the greater blood retention.

Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

PubMed

Sadekar, S; Ghandehari, H

2012-05-01

This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

Transport of surface engineered polyamidoamine (PAMAM) dendrimers across IPEC-J2 cell monolayers.

PubMed

Pisal, Dipak S; Yellepeddi, Venkata K; Kumar, Ajay; Palakurthi, Srinath

2008-11-01

The aim of our study was to prepare arginine-and ornithine-conjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM(G4) dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P(app)) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through the oral mucosa.

PAMAM-RGD Conjugates Enhance siRNA Delivery Through a Multicellular Spheroid Model of Malignant Glioma

PubMed Central

Waite, Carolyn L.; Roth, Charles M.

2011-01-01

Generation 5 poly(amidoamine) (PAMAM) dendrimers were modified by the addition of cyclic RGD targeting peptides and were evaluated for their ability to associate with siRNA and mediate siRNA delivery to U87 malignant glioma cells. PAMAM-RGD conjugates were able to complex with siRNA to form complexes of approximately 200 nm in size. Modest siRNA delivery was observed in U87 cells using either PAMAM or PAMAM-RGD conjugates. PAMAM-RGD conjugates prevented the adhesion of U87 cells to fibrinogen coated plates, in a manner that depends on the number of RGD ligands per dendrimer. The delivery of siRNA through three-dimensional multicellular spheroids of U87 cells was enhanced using PAMAM-RGD conjugates compared to the native PAMAM dendrimers, presumably by interfering with integrin-ECM contacts present in a three-dimensional tumor model. PMID:19775120

In Vitro/In Vivo Evaluation of Dexamethasone--PAMAM Dendrimer Complexes for Retinal Drug Delivery.

PubMed

Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Vural, İmran; Ünlü, Nurşen

2015-11-01

Current treatment options for diabetic retinopathy (DR) have side effects because of invasive application and topical application does not generally result in therapeutic levels in the target tissue. Therefore, improving the drug delivery to retina, following topical administration, might be a solution to DR treatment problems. The purpose of this study was to investigate the complexation effects of poly(amidoamine) (PAMAM) dendrimers on ocular absorption of dexamethasone (DEX). Using different PAMAM generations, complex formulations were prepared and characterized. Formulations were evaluated in terms of cytotoxicity and cell permeability, as well as ex vivo transport across ocular tissues. The ocular pharmacokinetic properties of DEX formulations were studied in Sprague-Dawley rats following topical and subconjunctival applications, to evaluate the effect of PAMAM on retinal delivery of DEX. Methyl-thiazol-tetrazolium (MTT) assay indicated that all groups resulted in cell viability comparable to DEX solution (87.5%), with the cell viability being the lowest for G3 complex at 73.5%. Transport study results showed that dendrimer complexation increases DEX transport across both cornea and sclera tissues. The results of in vivo studies were also indicated that especially anionic DEX-PAMAM complex formulations have reached higher DEX concentrations in ocular tissues compared with plain DEX suspension. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

PAMAM dendrimers and graphene: materials for removing aromatic contaminants from water.

PubMed

DeFever, Ryan S; Geitner, Nicholas K; Bhattacharya, Priyanka; Ding, Feng; Ke, Pu Chun; Sarupria, Sapna

2015-04-07

We present results from experiments and atomistic molecular dynamics simulations on the remediation of naphthalene by polyamidoamine (PAMAM) dendrimers and graphene oxide (GrO). Specifically, we investigate 3rd-6th generation (G3-G6) PAMAM dendrimers and GrO with different levels of oxidation. The work is motivated by the potential applications of these emerging nanomaterials in removing polycyclic aromatic hydrocarbon contaminants from water. Our experimental results indicate that GrO outperforms dendrimers in removing naphthalene from water. Molecular dynamics simulations suggest that the prominent factors driving naphthalene association to these seemingly disparate materials are similar. Interestingly, we find that cooperative interactions between the naphthalene molecules play a significant role in enhancing their association to the dendrimers and GrO. Our findings highlight that while selection of appropriate materials is important, the interactions between the contaminants themselves can also be important in governing the effectiveness of a given material. The combined use of experiments and molecular dynamics simulations allows us to comment on the possible factors resulting in better performance of GrO in removing polyaromatic contaminants from water.

Bendamustine-PAMAM Conjugates for Improved Apoptosis, Efficacy, and in Vivo Pharmacokinetics: A Sustainable Delivery Tactic.

PubMed

Gothwal, Avinash; Khan, Iliyas; Kumar, Pramod; Raza, Kaisar; Kaul, Ankur; Mishra, Anil Kumar; Gupta, Umesh

2018-06-04

Successful delivery of a chemotherapeutic agent like bendamustine still remains a challenge in clinical conditions like chronic lymphatic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma. We have conjugated bendamustine to polyamidoamine (PAMAM) dendrimers after conjugating with N-(hydroxyethyl)maleimide (spacer) via an ester bond. The particle size of PAMAM-bendamustine conjugate was 49.8 ± 2.5 nm. In vitro drug release resulted in sustained release with improved solution stability of drug up to 72 h. In a 24 h cytotoxicity study by MTT assay against human monoblastic leukemia cells (THP-1), the IC50 value for PAMAM-bendamustine was 32.1 ± 4.8 μM compared to 50.42 ± 3.4 μM and 2303 ± 106.5 μM for bendamustine and PAMAM dendrimer, respectively. Significantly higher cell uptake and apoptosis were observed in THP-1 cells by PAMAM-bendamustine conjugate which was confirmed by flow cytometry and confocal laser scanning microscopy. Preliminary in vivo studies undertaken included pharmacokinetics studies, organ distribution studies, and tumor inhibition studies. In healthy Wistar rat model (1CBM IV push model), the pharmacokinetic studies revealed that bioavailability and t 1/2 increased significantly, i.e., almost 8.5-fold (193.8 ± 1.116 vs 22.8 ± 0.158 μg mL -1 /h) and 5.1-fold (0.75 ± 0.005 vs 3.85 ± 0.015 h), respectively, for PAMAM-bendamustine conjugate compared to pure bendamustine ( p < 0.05), however, clearance and volume of distribution were found to be decreased compared to those of free drug. The study suggests that PAMAM-bendamustine conjugate was not only stable for the longer period but also least toxic and highly taken up by THP-1 cells to exert an anticancer effect at the reduced dose. Tumor inhibition and biodistribution studies in tumor-bearing BALB/c mice revealed that PAMAM-bendamustine conjugate was more effective than the pure drug and showed higher accumulation in the tumor.

Fourth Generation Parity

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

Lee, Hye-Sung; Soni, Amarjit

2013-01-01

We present a very simple 4th-generation (4G) model with an Abelian gauge interaction under which only the 4G fermions have nonzero charge. The U(1) gauge symmetry can have a Z_2 residual discrete symmetry (4G-parity), which can stabilize the lightest 4G particle (L4P). When the 4G neutrino is the L4P, it would be a neutral and stable particle and the other 4G fermions would decay into the L4P leaving the trace of missing energy plus the standard model fermions. Because of the new symmetry, the 4G particle creation and decay modes are different from those of the sequential 4G model, andmore » the 4G particles can be appreciably lighter than typical experimental bounds.« less

In vitro antibacterial activity of poly (amidoamine)-G7 dendrimer.

PubMed

Gholami, Mitra; Mohammadi, Rashin; Arzanlou, Mohsen; Akbari Dourbash, Fakhraddin; Kouhsari, Ebrahim; Majidi, Gharib; Mohseni, Seyed Mohsen; Nazari, Shahram

2017-06-05

Nano-scale dendrimers are synthetic macromolecules that frequently used in medical and health field. Traditional anibiotics are induce bacterial resistence so there is an urgent need for novel antibacterial drug invention. In the present study seventh generation poly (amidoamine) (PAMAM-G7) dendrimer was synthesized and its antibacterial activities were evaluated against representative Gram- negative and Gram-positive bacteria. PAMAM-G7 was synthesized with divergent growth method. The structural and surface of PAMAM-G7 were investigated by transmission electron microscopy, scanning electron microscope and fourier transform infrared. Pseudomonas. aeruginosa (n = 15), E. coli (n = 15), Acinetobacter baumanni (n = 15), Shigella dysenteriae (n = 15), Klebsiella pneumoniae (n = 10), Proteus mirabilis (n = 15), Staphylococcus aureus (n = 15) and Bacillus subtilis (n = 10) have been used for antibacterial activity assay. Additionally, representative standard strains for each bacterium were included. Minimum Inhibitory Concentration (MIC) was determined using microdilution method. Subsequently, Minimum Bactericidal Concentration (MBC) was determined by sub-culturing each of the no growth wells onto Mueller Hinton agar medium. The cytotoxicity of PAMAM-G7 dendrimer were evaluated in HCT116 and NIH 3 T3 cells by MTT assay. The average size of each particle was approximately 20 nm. PAMAM-G7 was potentially to inhibit both Gram positive and gram negative growth. The MIC50 and MIC90 values were determined to be 2-4 μg/ml and 4-8 μg/ml, respectively. The MBC50 and MBC90 values were found to be 64-256 μg/ml and 128-256 μg/ml, respectively. The cytotoxity effect of dendrimer on HCT116 and NIH 3 T3 cells is dependent upon exposure time to and concentration of dendrimers. The most reduction (44.63 and 43%) in cell viability for HCT116 and NIH 3 T3 cells was observed at the highest concentration, 0.85 μM after 72 h treatmentm, respectively. This study

Systems Prototyping with Fourth Generation Tools.

ERIC Educational Resources Information Center

Sholtys, Phyllis

1983-01-01

The development of information systems using an engineering approach that uses both traditional programing techniques and fourth generation software tools is described. Fourth generation applications tools are used to quickly develop a prototype system that is revised as the user clarifies requirements. (MLW)

Physico-chemical studies on the interaction of dendrimers with lipid bilayers. 1. Effect of dendrimer generation and liposome surface charge.

PubMed

Roy, Biplab; Panda, Amiya Kumar; Parimi, Srinivas; Ametov, Igor; Barnes, Timothy; Prestidge, Clive A

2014-01-01

Studies on the interaction of different generation poly (amido amine) (PAMAM) dendrimers (2G, 4G and 6G) and liposomes of different compositions were carried out by a combined turbidity, dynamic light scattering and atomic force microscopic measurements. Liposomes comprising soy lecithin (SLC, negative surface charge), 1, 2-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC, mildly positive surface charge), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol (DPPG, negatively charged) and a biologically simulated mixture of DPPC + DPPG (7:3, M/M, negatively charged) were used as model bilayers. 30 wt% cholesterol was used in each combination as it is known to control the fluidity of membrane bilayers. Silica was used as a negatively charged hard sphere model with an aim to compare the results. Both the turbidity and hydrodynamic diameter values of all the liposomes, except DPPC, passed through maxima upon the progressive addition of PAMAM; the effect was insignificant in case of DPPC. Formation of dendriosome, a complex formed between dendrimer and liposome, resulted in the charge reversal of the negatively charged liposomes. Interaction between PAMAM and liposome was found to be governed by electrostatic as well as hydrogen bonding. Generation dependent PAMAM activity followed the order: 6G >4G>2G in terms of overall dendrimer concentration. However, interestingly, the order was reverse when PAMAM activity was considered in terms of total end group concentrations. AFM studies reveal the rupture of bilayer structure upon addition of dendrimer.

PAMAM dendrimers and graphene: Materials for removing aromatic contaminants from water

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

DeFever, Ryan S.; Geitner, Nicholas K.; Bhattacharya, Priyanka

2015-04-07

We present results from experiments and atomistic molecular dynamics simulations on the association of naphthalene with polyamidoamine (PAMAM) dendrimers and graphene oxide (GrO). Specifically, we investigate 3rd-6th generation (G3-G6) PAMAM dendrimers and GrO with different levels of oxidation. The work is motivated by the potential applications of these materials in removing polycyclic aromatic hydrocarbon contaminants from water. Our experimental results indicate that graphene oxide outperforms dendrimers in removing naphthalene from water. Molecular dynamics simulations suggest that the prominent factors driving naphthalene association to these seemingly disparate materials are similar. Interestingly, we find that cooperative interactions between the naphthalene molecules playmore » a significant role in enhancing their association to the dendrimers and graphene oxide. Our findings highlight that while selection of appropriate materials is important, the interactions between the contaminants themselves can also be important in governing the effectiveness of a given material. The combined use of experiments and molecular dynamics simulations allows us to comment on the possible factors resulting in better performance of graphene oxide in removing naphthalene from water.« less

Dentin remineralization in acid challenge environment via PAMAM and calcium phosphate composite.

PubMed

Liang, Kunneng; Weir, Michael D; Xie, Xianju; Wang, Lin; Reynolds, Mark A; Li, Jiyao; Xu, Hockin H K

2016-11-01

The objective of this study was to investigate the effects of poly (amido amine) (PAMAM), composite with nanoparticles of amorphous calcium phosphate (NACP), and the combined PAMAM+NACP nanocomposite treatment, on remineralization of demineralized dentin in a cyclic artificial saliva/lactic acid environment for the first time. Dentin specimens were prepared and demineralized with 37% phosphoric acid for 15s. Four groups were prepared: (1) dentin control, (2) dentin coated with PAMAM, (3) dentin with NACP composite, (4) dentin with PAMAM+NACP. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 21days. Acid neutralization and calcium (Ca) and phosphate (P) ion concentrations were measured. The remineralized dentin specimens were examined by scanning electron microscopy (SEM) and hardness testing. NACP nanocomposite had mechanical properties similar to commercial control composites (p>0.1). NACP composite had acid-neutralization and Ca and P ion release capability. PAMAM or NACP composite each alone achieved remineralization and increased the hardness of demineralized dentin (p<0.05). PAMAM+NACP nanocomposite achieved the greatest mineral regeneration in demineralized dentin and the greatest hardness increase in demineralized dentin, which approached the hardness of healthy dentin (p>0.1). The superior remineralization efficacy of PAMAM+NACP was demonstrated for the first time. PAMAM+NACP induced remineralization in demineralized dentin in an acid challenge environment, when conventional remineralization methods such as PAMAM did not work well. The novel PAMAM+NACP composite approach is promising for a wide range of dental applications to inhibit caries and protect tooth structures. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Combining Bioactive Multifunctional Dental Composite with PAMAM for Root Dentin Remineralization

PubMed Central

Xiao, Shimeng; Liang, Kunneng; Weir, Michael D.; Cheng, Lei; Liu, Huaibing; Zhou, Xuedong; Ding, Yi; Xu, Hockin H. K.

2017-01-01

Objectives. The objectives of this study were to: (1) develop a bioactive multifunctional composite (BMC) via nanoparticles of amorphous calcium phosphate (NACP), 2-methacryloyloxyethyl phosphorylcholine (MPC), dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of silver (NAg); and (2) investigate the effects of combined BMC + poly (amido amine) (PAMAM) on remineralization of demineralized root dentin in a cyclic artificial saliva/lactic acid environment for the first time. Methods. Root dentin specimens were prepared and demineralized with 37% phosphoric acid for 15 s. Four groups were prepared: (1) root dentin control; (2) root dentin with BMC; (3) root dentin with PAMAM; (4) root dentin with BMC + PAMAM. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 21 days. Calcium (Ca) and phosphate (P) ion concentrations and acid neutralization were determined. The remineralized root dentin specimens were examined via hardness testing and scanning electron microscopy (SEM). Results. Mechanical properties of BMC were similar to commercial control composites (p = 0.913). BMC had excellent Ca and P ion release and acid-neutralization capability. BMC or PAMAM alone each achieved slight mineral regeneration in demineralized root dentin. The combined BMC + PAMAM induced the greatest root dentin remineralization, and increased the hardness of pre-demineralized root dentin to match that of healthy root dentin (p = 0.521). Significance. The excellent root dentin remineralization effects of BMC + PAMAM were demonstrated for the first time. BMC + PAMAM induced effective and complete root dentin remineralization in an acid challenge environment. The novel BMC + PAMAM method is promising for Class V and other restorations to remineralize and protect tooth structures. PMID:28772450

Combining Bioactive Multifunctional Dental Composite with PAMAM for Root Dentin Remineralization.

PubMed

Xiao, Shimeng; Liang, Kunneng; Weir, Michael D; Cheng, Lei; Liu, Huaibing; Zhou, Xuedong; Ding, Yi; Xu, Hockin H K

2017-01-22

Objectives . The objectives of this study were to: (1) develop a bioactive multifunctional composite (BMC) via nanoparticles of amorphous calcium phosphate (NACP), 2-methacryloyloxyethyl phosphorylcholine (MPC), dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of silver (NAg); and (2) investigate the effects of combined BMC + poly (amido amine) (PAMAM) on remineralization of demineralized root dentin in a cyclic artificial saliva/lactic acid environment for the first time. Methods . Root dentin specimens were prepared and demineralized with 37% phosphoric acid for 15 s. Four groups were prepared: (1) root dentin control; (2) root dentin with BMC; (3) root dentin with PAMAM; (4) root dentin with BMC + PAMAM. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 21 days. Calcium (Ca) and phosphate (P) ion concentrations and acid neutralization were determined. The remineralized root dentin specimens were examined via hardness testing and scanning electron microscopy (SEM). Results . Mechanical properties of BMC were similar to commercial control composites ( p = 0.913). BMC had excellent Ca and P ion release and acid-neutralization capability. BMC or PAMAM alone each achieved slight mineral regeneration in demineralized root dentin. The combined BMC + PAMAM induced the greatest root dentin remineralization, and increased the hardness of pre-demineralized root dentin to match that of healthy root dentin ( p = 0.521). Significance . The excellent root dentin remineralization effects of BMC + PAMAM were demonstrated for the first time. BMC + PAMAM induced effective and complete root dentin remineralization in an acid challenge environment. The novel BMC + PAMAM method is promising for Class V and other restorations to remineralize and protect tooth structures.

G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin.

PubMed

Qi, Rong; Zhang, Heran; Xu, Lu; Shen, Wenwen; Chen, Cong; Wang, Chao; Cao, Yini; Wang, Yunan; van Dongen, Mallory A; He, Bing; Wang, Siling; Liu, George; Banaszak Holl, Mark M; Zhang, Qiang

2015-07-01

This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery. Various carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Design, Synthesis, and Biological Evaluations of Asymmetric Bow-Tie PAMAM Dendrimer-Based Conjugates for Tumor-Targeted Drug Delivery.

PubMed

Wang, Tao; Zhang, Yaozhong; Wei, Longfei; Teng, Yuhan G; Honda, Tadashi; Ojima, Iwao

2018-04-30

A unique asymmetric bow-tie poly(amidoamine) (PAMAM) dendrimer (ABTD) scaffold was designed and developed as a well-defined macromolecular carrier for tumor-targeted drug delivery. The ABTD scaffold in this study consists of a G3-half-dendron (G3-HD) unit and a G1-half-dendron (G1-HD) unit, bearing thiol moiety in each unit and a bis(maleimide) linker unit, which undergo sequential thiol-maleimide coupling to assemble the scaffold. This assembly methodology is applicable to all other combinations of different generations of PAMAM dendrimers. In the prototype ABTD in this study, 16 biotin moieties were tethered to the G3-HD unit and 4 payloads (new-generation taxoid) to the G1-HD via a self-immolative linker to form an ABTD-tumor-targeting conjugate (ABTD-TTC-1). Two other ABTD-TTCs were synthesized, wherein the G1-HD unit was tethered to a fluorescence-labeled taxoid or to a fluorescent probe. These three ABTD-TTCs were constructed by using a common key ABTD 6 bearing a terminal acetylene group in the G1-HD unit, which was fully characterized as a single molecule by high-resolution mass spectrometry and NMR despite its high molecular weight ( M w : 12 876). Then, the click reaction was employed to couple ABTD 6 with a small-molecule payload or fluorescence probe unit bearing a terminal azide moiety. ABTD-TTC-3, as a surrogate of ABTD-TTC-2, showed substantially enhanced internalization into two cancer cell lines via receptor-mediated endocytosis, attributed to multibinding effect. ABTD-TTC-1 exhibited a remarkable selectivity to cancer cells (1400-7500 times) compared to human normal cells, which demonstrates the salient feature and bright prospect of the ABTD-based tumor-targeted drug-delivery system.

Mobile Applications and 4G Wireless Networks: A Framework for Analysis

ERIC Educational Resources Information Center

Yang, Samuel C.

2012-01-01

Purpose: The use of mobile wireless data services continues to increase worldwide. New fourth-generation (4G) wireless networks can deliver data rates exceeding 2 Mbps. The purpose of this paper is to develop a framework of 4G mobile applications that utilize such high data rates and run on small form-factor devices. Design/methodology/approach:…

Mechanism of gene transfection by polyamidoamine (PAMAM) dendrimers modified with ornithine residues.

PubMed

Kumar, Ajay; Yellepeddi, Venkata K; Vangara, Kiran K; Strychar, Kevin B; Palakurthi, Srinath

2011-11-01

The aim of this study was to prepare and investigate the mechanism of uptake of the dendriplexes prepared with ornithine-conjugated polyamidoamine (PAMAM) G4 dendrimers. Ornithine-conjugated PAMAMG4 dendrimers were prepared by Fmoc synthesis. A comparative transfection study in NCI H157G cells and polyamine transport-deficient cell line NCI H157R was performed to confirm the role of the polyamine transporter system (PAT) in the dendriplex uptake. Transfection efficiency significantly increased with increase in generation number and extent of ornithine conjugation. Transfection efficiency of the PAMAMG4-ORN60 dendrimers significantly decreased in presence of excess of ornithine (P < 0.05) and paraquat (P < 0.01) but not of PAMAMG4 dendrimers. Transfection efficiency of PAMAMG4-ORN60 was significantly low in NCI H157R (31.66 ± 3.95%, RFU: 17.87 ± 1.34) as compared to NCI H157G cell line (63.07 ± 6.8%, relative fluorescence units (RFU): 23.28 ± 0.66). Results indicate the role of PAT in addition to charge-mediated endocytosis in the internalization of ornithine-conjugated PAMAMG4 dendrimers. Cytotoxicity analysis (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay) in human embryonic kidney cell line (HEK) 293T cells showed that the dendriplexes were non-toxic at N/P 10.

Biofunctionalization of PAMAM-montmorillonite decorated poly (Ɛ-caprolactone)-chitosan electrospun nanofibers for cell adhesion and electrochemical cytosensing.

PubMed

Kirbay, Fatma Ozturk; Yalcinkaya, Esra Evrim; Atik, Gozde; Evren, Gizem; Unal, Betul; Demirkol, Dilek Odaci; Timur, Suna

2018-06-30

The construction and biofunctionalization of the poly (Ɛ-caprolactone) (PCL)-chitosan (CHIT) nanofibrous mats, which included Polyamidoamine (PAMAM) dendrimer modified montmorillonite (Mt), for the cell adhesion and electrochemical cytosensing were accomplished in this report. After the intercalation of the PAMAM generation zero dendrimer into the Mt, PAMAM-Mt decorated PCL-CHIT electrospun nanofibers were formed. The addition of PAMAM caused the decrease of contact angle of PCL-CHIT nanofibers. The covalent immobilization of a tripeptide namely Arginylglycylaspartate (RGD) on both the PCL-CHIT/Mt and PCL-CHIT/PAMAM-Mt surface was carried out. U87-MG and HaCaT (negative control) cell lines were incubated on the PCL-CHIT/Mt/RGD and PCL-CHIT/PAMAM-Mt/RGD. The proliferation studies and imaging of the cells were carried out on these fibers. Finally, electrochemical measurements were performed after each modification step by differential pulse/cyclic voltammetry and electrochemical impedance spectroscopy. U87-MG cells were grown better than HaCaT cells on the PCL-CHIT/PAMAM-Mt/RGD surfaces. To the best of our knowledge, there is no study that developed electrochemical cytosensor using electrospun nanofibers as a cell adhesion platform. Copyright © 2018 Elsevier B.V. All rights reserved.

Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations.

PubMed

Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh

2017-03-01

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH 2 ) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH 2 ). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2mM G5-PPI-NH 2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH10.0, respectively (p<0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH 2 dendrimers because it has more hydrophobic interior than G4-PAMAM-NH 2 dendrimers. The release of BTZ from G5-PPI-NH 2 complex was comparatively slower than G4-PAMAM-NH 2 . The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

Fate and transformation products of amine-terminated PAMAM dendrimers under ozonation and irradiation.

PubMed

Santiago-Morales, Javier; Rosal, Roberto; Hernando, María D; Ulaszewska, Maria M; García-Calvo, Eloy; Fernández-Alba, Amadeo R

2014-02-15

This article deals with the degradation of a third-generation (G3) poly(amidoamine) (PAMAM) dendrimer under ozonation and irradiation. The identification and quantification of G3 PAMAM dendrimer and its transformation products has been performed by liquid chromatography-electrospray ionization-hybrid quadrupole time-of-flight-mass spectrometry. The dendrimer was completely depleted by ozone in less than 1 min. The effect of ultraviolet irradiation was attributed to hydroxyl-mediated oxidation. The transformation products were attributed to the oxidation of amines, which resulted in highly oxidized structures with abundance of carboxylic acids, which started from the formation of amine oxide and the scission of the CN bond of the amide group. We studied the toxicity of treated mixtures for six different organisms: the acute toxicity for the bacterium Vibrio fischeri and the microcrustacean Daphnia magna, the multigenerational growth inhibition of the alga Pseudokirchneriella subcapitata, and the seed germination phytotoxicity of Licopersicon esculentum, Lactuca sativa and Lolium perenne. Ozonation and irradiation originated transformation products are more toxic than the parent dendrimer. The toxicity of the dendrimer for the green alga was linked to a strong increase of intracellular reactive oxygen species with intense lipid peroxidation. Copyright © 2013 Elsevier B.V. All rights reserved.

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

NASA Astrophysics Data System (ADS)

Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

2013-09-01

Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase ( p < 0.05) in expression of apoptotic genes ( Bcl2, Bax, p53) and 13.2- to 27.1-fold increase ( p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

Size effect of Au/PAMAM contrast agent on CT imaging of reticuloendothelial system and tumor tissue

NASA Astrophysics Data System (ADS)

Wang, Wei; Li, Jian; Liu, Ransheng; Zhang, Aixu; Yuan, Zhiyong

2016-09-01

Polyamidoamine (PAMAM)-entrapped Au nanoparticles were synthesized with distinct sizes to figure out the size effect of Au-based contrast agent on CT imaging of passively targeted tissues. Au/PAMAM nanoparticles were first synthesized with narrow distribution of particles size of 22.2 ± 3.1, 54.2 ± 3.7, and 104.9 ± 4.7 nm in diameters. Size effect leads no significant difference on X-ray attenuation when Au/PAMAM was ≤0.05 mol/L. For CT imaging of a tumor model, small Au/PAMAM were more easily internalized via endocytosis in the liver, leading to more obviously enhanced contrast. Similarly, contrast agents with small sizes were more effective in tumor imaging because of the enhanced permeability and retention effect. Overall, the particle size of Au/PAMAM heavily affected the efficiency of CT enhancement in imaging RES and tumors.

Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin.

PubMed

Sadekar, S; Thiagarajan, G; Bartlett, K; Hubbard, D; Ray, A; McGill, L D; Ghandehari, H

2013-11-01

Oral delivery of camptothecin has a treatment advantage but is limited by low bioavailability and gastrointestinal toxicity. Poly(amido amine) or PAMAM dendrimers have shown promise as intestinal penetration enhancers, drug solubilizers and drug carriers for oral delivery in vitro and in situ. There have been very limited studies in vivo to evaluate PAMAM dendrimers for oral drug delivery. In this study, camptothecin (5 mg/kg) was formulated and co-delivered with cationic, amine-terminated PAMAM dendrimer generation 4.0 (G4.0) (100 and 300 mg/kg) and anionic, carboxylate-terminated PAMAM generation 3.5 (G3.5) (300 and 1000 mg/kg) in CD-1 mice. Camptothecin associated to a higher extent with G4.0 than G3.5 in the formulation, attributed to an electrostatic interaction on the surface of G4.0. Both PAMAM G4.0 and G3.5 increased camptothecin solubilization in simulated gastric fluid and caused a 2-3 fold increase in oral absorption of camptothecin when delivered at 2 h. PAMAM G4.0 and G3.5 did not increase mannitol transport suggesting that the oral absorption of camptothecin was not due to tight junction modulation. Histologic observations of the epithelial layer of small intestinal segments of the gastrointestinal tract (GIT) at 4 h post dosing supported no evidence of toxicity at the evaluated doses of PAMAM dendrimers. This study demonstrates that both cationic (G.4) and anionic (G3.5) PAMAM dendrimers were effective in enhancing the oral absorption of camptothecin. Results suggest that drug inclusion in PAMAM interior controlled solubilization in simulated gastric and intestinal fluids, and increased oral bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

A Comparative Study on the Photophysics and Photochemistry of Xanthene Dyes in the Presence of Polyamidoamine (PAMAM) Dendrimers.

PubMed

Arbeloa, Ernesto Maximiliano; Previtali, Carlos Mario; Bertolotti, Sonia Graciela

2018-04-17

The photophysical and photochemical properties of the xanthene dyes Eosin Y, Erythrosin B, and Rose Bengal are evaluated in the presence of amino-terminated polyamidoamine (PAMAM) dendrimers of relatively high generation (G3-G5) in alkaline aqueous solution. UV/Vis absorption and fluorescence spectra of the dyes show bathochromic shifts, which correlate with the size of the dendrimer. Binding constants (K bind ) are calculated from absorption data. The resulting high K bind values indicate strong interactions between both molecules. Triplet-triplet absorption spectra of the dyes are recorded by laser flash photolysis, and a decrease in the triplet lifetimes is observed in the presence of dendrimers. At the same time, an increase in the absorption of the semireduced form of the dyes is observed. Rate constants for triplet quenching ( 3 k q ) and radical quantum yields (Φ R ) are obtained. The results are explained by a very efficient electron-transfer process from PAMAM to xanthene dyes for all of the dye/dendrimer couples that are evaluated. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

All-atomistic molecular dynamics (AA-MD) studies and pharmacokinetic performance of PAMAM-dendrimer-furosemide delivery systems.

PubMed

Otto, Daniel P; de Villiers, Melgardt M

2018-06-13

Improvement of problematic dissolution and solubility properties of a model drug, furosemide, was investigated for poly(amidoamine) (PAMAM) dendrimer complexes of the drug. Full and half generation dendrimers with amino and ester terminals respectively, were studied. In vitro release performance of these complexes was investigated at drug loads ranging 5-60% using simulated gastric fluids. Full generation dendrimers accommodated higher drug loads, outperformed half-generation complexes, and free drug. Pharmacokinetic studies in rats indicated that the dendrimer complexes markedly improved in the bioavailability of the drug compared to the unformulated drug. The G3.0-PAMAM dendrimer complex showed a two-fold increase in C max and a 1.75-fold increase in AUC over the free drug. Additionally, T max was shortened from approximately 25 to 20 min. One of the first all-atomistic molecular dynamics (AA-MD) simulation studies was performed to evaluate low-generation dendrimer-drug complexes as well as its pharmacokinetic performance. AA-MD provided insight into the intermolecular interactions that take place between the dendrimer and drug. It is suggested that the dendrimer not only encapsulates the drug, but can also orientate the drug in stabilized dispersion to prevent drug clustering which could impact release and bioavailability negatively. AA-MD can be a useful tool to develop dendrimer-based drug delivery systems. Copyright © 2018. Published by Elsevier B.V.

In vitro evaluation of the cytotoxicity and cellular uptake of CMCht/PAMAM dendrimer nanoparticles by glioblastoma cell models

NASA Astrophysics Data System (ADS)

Pojo, M.; Cerqueira, S. R.; Mota, T.; Xavier-Magalhães, A.; Ribeiro-Samy, S.; Mano, J. F.; Oliveira, J. M.; Reis, R. L.; Sousa, N.; Costa, B. M.; Salgado, A. J.

2013-05-01

Glioblastoma (GBM) is simultaneously the most common and most malignant subtype tumor of the central nervous system. These are particularly dramatic diseases ranking first among all human tumor types for tumor-related average years of life lost and for which curative therapies are not available. Recently, the use of nanoparticles as drug delivery systems (DDS) for tumor treatment has gained particular interest. In an attempt to evaluate the potential of carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles as a DDS, we aimed to evaluate its cytotoxicity and internalization efficiency in GBM cell models. CMCht/PAMAM-mediated cytotoxicity was evaluated in a GBM cell line (U87MG) and in human immortalized astrocytes (hTERT/E6/E7) by MTS and double-stranded DNA quantification. CMCht/PAMAM internalization was assessed by double fluorescence staining. Both cells lines present similar internalization kinetics when exposed to a high dose (400 μg/mL) of these nanoparticles. However, the internalization rate was higher in tumor GBM cells as compared to immortalized astrocytes when cells were exposed to lower doses (200 μg/mL) of CMCht/PAMAM for short periods (<24 h). After 48 h of exposure, both cell lines present 100 % of internalization efficiency for the tested concentrations. Importantly, short-term exposures (1, 6, 12, 24, and 48 h) did not show cytotoxicity, and long-term exposures (7 days) to CMCht/PAMAM induced only low levels of cytotoxicity in both cell lines ( 20 % of decrease in metabolic activity). The high efficiency and rate of internalization of CMCht/PAMAM we show here suggest that these nanoparticles may be an attractive DDS for brain tumor treatment in the future.

Glassy carbon electrodes sequentially modified by cysteamine-capped gold nanoparticles and poly(amidoamine) dendrimers generation 4.5 for detecting uric acid in human serum without ascorbic acid interference.

PubMed

Ramírez-Segovia, A S; Banda-Alemán, J A; Gutiérrez-Granados, S; Rodríguez, A; Rodríguez, F J; Godínez, Luis A; Bustos, E; Manríquez, J

2014-02-17

Glassy carbon electrodes (GCE) were sequentially modified by cysteamine-capped gold nanoparticles (AuNp@cysteamine) and PAMAM dendrimers generation 4.5 bearing 128-COOH peripheral groups (GCE/AuNp@cysteamine/PAMAM), in order to explore their capabilities as electrochemical detectors of uric acid (UA) in human serum samples at pH 2. The results showed that concentrations of UA detected by cyclic voltammetry with GCE/AuNp@cysteamine/PAMAM were comparable (deviation <±10%; limits of detection (LOD) and quantification (LOQ) were 1.7×10(-4) and 5.8×10(-4) mg dL(-1), respectively) to those concentrations obtained using the uricase-based enzymatic-colorimetric method. It was also observed that the presence of dendrimers in the GCE/AuNp@cysteamine/PAMAM system minimizes ascorbic acid (AA) interference during UA oxidation, thus improving the electrocatalytic activity of the gold nanoparticles. Copyright © 2013 Elsevier B.V. All rights reserved.

Path Loss Prediction Formula in Urban Area for the Fourth-Generation Mobile Communication Systems

NASA Astrophysics Data System (ADS)

Kitao, Koshiro; Ichitsubo, Shinichi

A site-general type prediction formula is created based on the measurement results in an urban area in Japan assuming that the prediction frequency range required for Fourth-Generation (4G) Mobile Communication Systems is from 3 to 6GHz, the distance range is 0.1 to 3km, and the base station (BS) height range is from 10 to 100m. Based on the measurement results, the path loss (dB) is found to be proportional to the logarithm of the distance (m), the logarithm of the BS height (m), and the logarithm of the frequency (GHz). Furthermore, we examine the extension of existing formulae such as the Okumura-Hata, Walfisch-Ikegami, and Sakagami formulae for 4G systems and propose a prediction formula based on the Extended Sakagami formula.

Mixed Matrix PVDF Membranes With in Situ Synthesized PAMAM Dendrimer-Like Particles: A New Class of Sorbents for Cu(II) Recovery from Aqueous Solutions by Ultrafiltration.

PubMed

Kotte, Madhusudhana Rao; Kuvarega, Alex T; Cho, Manki; Mamba, Bhekie B; Diallo, Mamadou S

2015-08-18

Advances in industrial ecology, desalination, and resource recovery have established that industrial wastewater, seawater, and brines are important and largely untapped sources of critical metals and elements. A Grand Challenge in metal recovery from industrial wastewater is to design and synthesize high capacity, recyclable and robust chelating ligands with tunable metal ion selectivity that can be efficiently processed into low-energy separation materials and modules. In our efforts to develop high capacity chelating membranes for metal recovery from impaired water, we report a one-pot method for the preparation of a new family of mixed matrix polyvinylidene fluoride (PVDF) membranes with in situ synthesized poly(amidoamine) [PAMAM] particles. The key feature of our new membrane preparation method is the in situ synthesis of PAMAM dendrimer-like particles in the dope solutions prior to membrane casting using low-generation dendrimers (G0 and G1-NH2) with terminal primary amine groups as precursors and epichlorohydrin (ECH) as cross-linker. By using a combined thermally induced phase separation (TIPS) and nonsolvent induced phase separation (NIPS) casting process, we successfully prepared a new family of asymmetric PVDF ultrafiltration membranes with (i) neutral and hydrophilic surface layers of average pore diameters of 22-45 nm, (ii) high loadings (∼48 wt %) of dendrimer-like PAMAM particles with average diameters of ∼1.3-2.4 μm, and (iii) matrices with sponge-like microstructures characteristics of membranes with strong mechanical integrity. Preliminary experiments show that these new mixed matrix PVDF membranes can serve as high capacity sorbents for Cu(II) recovery from aqueous solutions by ultrafiltration.

Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy.

PubMed

Li, Jun; Liang, Huamin; Liu, Jing; Wang, Ziyuan

2018-07-30

Poly (amidoamine) (PAMAM) dendrimers are well-defined, highly branched macromolecules with numerous active amine groups on the surface. Because of their unique properties, PAMAM dendrimers have steadily grown in popularity in drug delivery, gene therapy, medical imaging and diagnostic application. This review focuses on the recent developments on the application in PAMAM dendrimers as effective carriers for drug and gene (pDNA, siRNA) delivery in cancer therapy, including: a) PAMAM for anticancer drug delivery; b) PAMAM and gene therapy; c) PAMAM used in overcoming tumor multidrug resistance; d) PAMAM used for hybrid nanoparticles; and e) PAMAM linked or loaded in other nanoparticles. Copyright © 2018 Elsevier B.V. All rights reserved.

Cationic PAMAM dendrimers as pore-blocking binary toxin inhibitors.

PubMed

Förstner, Philip; Bayer, Fabienne; Kalu, Nnanya; Felsen, Susanne; Förtsch, Christina; Aloufi, Abrar; Ng, David Y W; Weil, Tanja; Nestorovich, Ekaterina M; Barth, Holger

2014-07-14

Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria.

PAMAM dendrimer hydrogel film—biocompatible material to an efficient dermal delivery of drugs

NASA Astrophysics Data System (ADS)

Magalhães, Thamiris Machado; Guerra, Rodrigo Cinti; San Gil, Rosane Aguiar da Silva; Valente, Ana Paula; Simão, Renata Antoun; Soares, Bluma Guenther; Mendes, Thamara de Carvalho; Pyrrho, Alexandre dos Santos; Sousa, Valeria Pereira de; Rodrigues-Furtado, Vanessa Lúcia

2017-08-01

We report the preparation, characterization, and drug release kinetics of a pH-responsive hydrogel film from a dendrimer megamer. The megamer (GP32) is a three-dimensional reticulated structure with a mean diameter of 71.16 nm (PDI 0.150) and was prepared by the reaction between Poly(amidoamine) generation4 (PAMAM G4) dendrimer and glutaraldehyde (G:P molar ratio 32). The crosslinking units in the megamer are provided mainly by the bicyclic dimer 2-hydroxy-3,4,4a,7,8,8a-hexahydro-2 H-chromene-6-carbaldehyde as determined by high-resolution (800 MHz) 1H NMR and FTIR. The hydrogel film (F[GP32]) is formed upon evaporation of a methanolic solution of the megamer and has a high degree of organization and homogeneity. Further crosslinking with glutaraldehyde (CLF[GP32]) enhanced the mechanical properties of the hydrogel film. The chemical constitution and unique megamer architecture enable the hydrogel film to carry both lipophilic and hydrophilic substances. The film did not cause any dermal irritation or clinical signs of toxicity in tests on rabbits, allowed for a sustained release of ketoprofen and played an important role in the process of drug delivery into the receptor medium. This performance taken together with the absence of toxicity makes this hydrogel film a good choice for dermal sustained drug release. [Figure not available: see fulltext.

Quantitative assessment of surface functionality effects on microglial uptake and retention of PAMAM dendrimers

NASA Astrophysics Data System (ADS)

Liaw, Kevin; Gök, Ozgul; DeRidder, Louis B.; Kannan, Sujatha; Kannan, Rangaramanujam M.

2018-04-01

Dendrimers are a promising class of polymeric nanoparticles for delivery of therapeutics and diagnostics. Polyamidoamine (PAMAM) dendrimers have shown significant efficacy in many animal models, with performance dependent on surface functionalities. Understanding the effects of end groups on biological interactions is critical for rational design of dendrimer-mediated therapies. In this study, we quantify the cellular trafficking kinetics (endocytosis and exocytosis) of generation 4 neutral (D4-OH), cationic (D4-NH2), anionic (D3.5-COOH), and generation 6 neutral (D6-OH) PAMAM dendrimers to investigate the nanoscale effects of surface functionality and size on cellular interactions. Resting and LPS-activated microglia were studied due to their central roles in dendrimer therapies for central nervous system disorders. D4-OH exhibits greater cellular uptake and lower retention than the larger D6-OH. D4-OH and D3.5-COOH exhibit similar trafficking kinetics, while D4-NH2 exhibits significant membrane interactions, resulting in faster cell association but lower internalization. Cationic charge may also enhance vesicular escape for greater cellular retention and preferential partitioning to nuclei. LPS activation further improves uptake of dendrimers, with smaller and cationic dendrimers experiencing the greatest increases in uptake compared to resting microglia. These studies have implications for the dependence of trafficking pathway on dendrimer properties and inform the design of dendrimer constructs tailored to specific therapeutic needs. Cationic dendrimers are ideal for delivering genetic materials to nuclei, but toxicity may be a limiting factor. Smaller, neutral dendrimers are best suited for delivering high levels of therapeutics in acute neuroinflammation, while larger or cationic dendrimers provide robust retention for sustained release of therapeutics in longer-term diseases.

Dendrimer ligands-capped CH3NH3PbBr3 perovskite nanocrystals with delayed halide exchange and record stability against both moisture and water.

PubMed

Xu, Yiren; Xu, Shuhong; Shao, Haibao; Jiang, Han; Cui, Yiping; Wang, Chunlei

2018-06-08

CH 3 NH 3 PbBr 3 perovskite nanocrystals (NCs) suffer from poor stability because of their high sensitivity to environmental moisture and water. To solve this problem, previous works mainly focus on embedding perovskite NCs into water-resistant matrix to form large composites (size of microns or larger). As an alternative solution without serious changing of NC size, enhancing the stability of perovskite NCs themselves by ligand engineering is rarely reported. In this work, we used hyperbranched polyamidoamine (PAMAM) dendrimers with two different generations (G0 and G4) to synthesize CH 3 NH 3 PbBr 3 perovskite NCs with high photoluminescence (PL) quantum yields (QY) above 70% and a new record stability. A novel dendrimers generation-dependent stability of perovskite NCs was observed. The water-resistance time is 18 h (27 h) for perovskite NCs capped by G0 (G4) generation of PAMAM, which is 7 times (11 times) longer than that of traditional oleic acid-capped NCs. Similar PAMAM generation-related stability is also observed in moisture-resistance tests. The stability time against moisture is 500 h (800 h) for G0 (G4) generation of PAMAM-capped perovskite NCs, which is a new record stability time against moisture for CH 3 NH 3 PbBr 3 perovskite NCs. In addition, our results also indicate that PAMAM ligands outside perovskite NCs can dramatically slow down the speed of halide exchange. Even for the mixture of perovskite NCs with two different halide composition, the original luminescence properties of PAMAM-capped perovskite NCs can retain after mixing. In view of slow halide exchange speed, excellent water and moisture stability, PAMAM dendrimers-capped perovskite NCs and their mixture are available as color conversion single layer in fabrication of light-emitting diodes (LED).

Dendrimer ligands-capped CH3NH3PbBr3 perovskite nanocrystals with delayed halide exchange and record stability against both moisture and water

NASA Astrophysics Data System (ADS)

Xu, Yiren; Xu, Shuhong; Shao, Haibao; Jiang, Han; Cui, Yiping; Wang, Chunlei

2018-06-01

CH3NH3PbBr3 perovskite nanocrystals (NCs) suffer from poor stability because of their high sensitivity to environmental moisture and water. To solve this problem, previous works mainly focus on embedding perovskite NCs into water-resistant matrix to form large composites (size of microns or larger). As an alternative solution without serious changing of NC size, enhancing the stability of perovskite NCs themselves by ligand engineering is rarely reported. In this work, we used hyperbranched polyamidoamine (PAMAM) dendrimers with two different generations (G0 and G4) to synthesize CH3NH3PbBr3 perovskite NCs with high photoluminescence (PL) quantum yields (QY) above 70% and a new record stability. A novel dendrimers generation-dependent stability of perovskite NCs was observed. The water-resistance time is 18 h (27 h) for perovskite NCs capped by G0 (G4) generation of PAMAM, which is 7 times (11 times) longer than that of traditional oleic acid-capped NCs. Similar PAMAM generation-related stability is also observed in moisture-resistance tests. The stability time against moisture is 500 h (800 h) for G0 (G4) generation of PAMAM-capped perovskite NCs, which is a new record stability time against moisture for CH3NH3PbBr3 perovskite NCs. In addition, our results also indicate that PAMAM ligands outside perovskite NCs can dramatically slow down the speed of halide exchange. Even for the mixture of perovskite NCs with two different halide composition, the original luminescence properties of PAMAM-capped perovskite NCs can retain after mixing. In view of slow halide exchange speed, excellent water and moisture stability, PAMAM dendrimers-capped perovskite NCs and their mixture are available as color conversion single layer in fabrication of light-emitting diodes (LED).

Nanoscale Investigation of Generation 1 PAMAM Dendrimers Interaction with a Protein Nanopore.

PubMed

Asandei, Alina; Ciuca, Andrei; Apetrei, Aurelia; Schiopu, Irina; Mereuta, Loredana; Seo, Chang Ho; Park, Yoonkyung; Luchian, Tudor

2017-07-21

Herein, we describe at uni-molecular level the interactions between poly(amidoamine) (PAMAM) dendrimers of generation 1 and the α-hemolysin protein nanopore, at acidic and neutral pH, and ionic strengths of 0.5 M and 1 M KCl, via single-molecule electrical recordings. The results indicate that kinetics of dendrimer-α-hemolysin reversible interactions is faster at neutral as compared to acidic pH, and we propose as a putative explanation the fine interplay among conformational and rigidity changes on the dendrimer structure, and the ionization state of the dendrimer and the α-hemolysin. From the analysis of the dendrimer's residence time inside the nanopore, we posit that the pH- and salt-dependent, long-range electrostatic interactions experienced by the dendrimer inside the ion-selective α-hemolysin, induce a non-Stokesian diffusive behavior of the analyte inside the nanopore. We also show that the ability of dendrimer molecules to adapt their structure to nanoscopic spaces, and control the flow of matter through the α-hemolysin nanopore, depends non-trivially on the pH- and salt-induced conformational changes of the dendrimer.

Understanding AuNP interaction with low-generation PAMAM dendrimers: a CIELab and deconvolution study

NASA Astrophysics Data System (ADS)

Jimenez-Ruiz, A.; Carnerero, J. M.; Castillo, P. M.; Prado-Gotor, R.

2017-01-01

Low-generation polyamidoamine (PAMAM) dendrimers are known to adsorb on the surface of gold nanoparticles (AuNPs) causing aggregation and color changes. In this paper, a thorough study of this affinity using absorption spectroscopy, colorimetric, and emission methods has been carried out. Results show that, for citrate-capped gold nanoparticles, interaction with the dendrimer is not only of an electrostatic character but instead occurs, at least in part, through the dendrimer's uncharged internal amino groups. The possibilities of the CIELab chromaticity system parameters' evolution have also been explored in order to quantify dendrimer interaction with the red-colored nanoparticles. By measuring and quantifying 17 nm citrate-capped AuNP color changes, which are strongly dependant on their aggregation state, binding free energies are obtained for the first time for these systems. Results are confirmed via an alternate fitting method which makes use of deconvolution parameters from absorbance spectra. Binding free energies obtained through the use of both means are in good agreement with each other.

Preferential and Increased Uptake of Hydroxyl-Terminated PAMAM Dendrimers by Activated Microglia in Rabbit Brain Mixed Glial Culture.

PubMed

Alnasser, Yossef; Kambhampati, Siva P; Nance, Elizabeth; Rajbhandari, Labchan; Shrestha, Shiva; Venkatesan, Arun; Kannan, Rangaramanujam M; Kannan, Sujatha

2018-04-27

Polyamidoamine (PAMAM) dendrimers are multifunctional nanoparticles with tunable physicochemical features, making them promising candidates for targeted drug delivery in the central nervous system (CNS). Systemically administered dendrimers have been shown to localize in activated glial cells, which mediate neuroinflammation in the CNS. These dendrimers delivered drugs specifically to activated microglia, producing significant neurological improvements in multiple brain injury models, including in a neonatal rabbit model of cerebral palsy. To gain further insight into the mechanism of dendrimer cell uptake, we utilized an in vitro model of primary glial cells isolated from newborn rabbits to assess the differences in hydroxyl-terminated generation 4 PAMAM dendrimer (D4-OH) uptake by activated and non-activated glial cells. We used fluorescently-labelled D4-OH (D-Cy5) as a tool for investigating the mechanism of dendrimer uptake. D4-OH PAMAM dendrimer uptake was determined by fluorescence quantification using confocal microscopy and flow cytometry. Our results indicate that although microglial cells in the mixed cell population demonstrate early uptake of dendrimers in this in vitro system, activated microglia take up more dendrimer compared to resting microglia. Astrocytes showed delayed and limited uptake. We also illustrated the differences in mechanism of uptake between resting and activated microglia using different pathway inhibitors. Both resting and activated microglia primarily employed endocytotic pathways, which are enhanced in activated microglial cells. Additionally, we demonstrated that hydroxyl terminated dendrimers are taken up by primary microglia using other mechanisms including pinocytosis, caveolae, and aquaporin channels for dendrimer uptake.

Cationic PAMAM Dendrimers as Pore-Blocking Binary Toxin Inhibitors

PubMed Central

2015-01-01

Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria. PMID:24954629

Multifunctional Triblock Nanocarrier (PAMAM-PEG-PLL) for the Efficient Intracellular siRNA Delivery and Gene Silencing

PubMed Central

2011-01-01

A novel triblock poly(amido amine)-poly(ethylene glycol)-poly-l-lysine (PAMAM-PEG-PLL) nanocarrier was designed, synthesized, and evaluated for the delivery of siRNA. The design of the nanocarrier is unique and provides a solution to most of the common problems associated with the delivery and therapeutic applications of siRNA. Every component in the triblock nanocarrier plays a significant role and performs multiple functions: (1) tertiary amine groups in the PAMAM dendrimer work as a proton sponge and play a vital role in the endosomal escape and cytoplasmic delivery of siRNA; (2) PEG, a linker connecting PLL and PAMAM dendrimers renders nuclease stability and protects siRNA in human plasma; (3) PLL provides primary amines to form polyplexes with siRNA through electrostatic interaction and also acts as penetration enhancer; and (4) conjugation to PEG and PAMAM reduced toxicity of PLL and the entire triblock nanocarrier PAMAM-PEG-PLL. The data obtained show that the polyplexes resulted from the conjugation of siRNA, and the proposed nanocarriers were effectively taken up by cancer cells and induced the knock down of the target BCL2 gene. In addition, triblock nanocarrier/siRNA polyplexes showed excellent stability in human plasma. PMID:21322531

Molecular Dynamics Study of the Structure, Flexibility, and Hydrophilicity of PETIM Dendrimers: A Comparison with PAMAM Dendrimers.

PubMed

Kanchi, Subbarao; Suresh, Gorle; Priyakumar, U Deva; Ayappa, K G; Maiti, Prabal K

2015-10-15

A new class of dendrimers, the poly(propyl ether imine) (PETIM) dendrimer, has been shown to be a novel hyperbranched polymer having potential applications as a drug delivery vehicle. Structure and dynamics of the amine terminated PETIM dendrimer and their changes with respect to the dendrimer generation are poorly understood. Since most drugs are hydrophobic in nature, the extent of hydrophobicity of the dendrimer core is related to its drug encapsulation and retention efficacy. In this study, we carry out fully atomistic molecular dynamics (MD) simulations to characterize the structure of PETIM (G2-G6) dendrimers in salt solution as a function of dendrimer generation at different protonation levels. Structural properties such as radius of gyration (Rg), radial density distribution, aspect ratio, and asphericity are calculated. In order to assess the hydrophilicity of the dendrimer, we compute the number of bound water molecules in the interior of dendrimer as well as the number of dendrimer-water hydrogen bonds. We conclude that PETIM dendrimers have relatively greater hydrophobicity and flexibility when compared with their extensively investigated PAMAM counterparts. Hence PETIM dendrimers are expected to have stronger interactions with lipid membranes as well as improved drug encapsulation and retention properties when compared with PAMAM dendrimers. We compute the root-mean-square fluctuation of dendrimers as well as their entropy to quantify the flexibility of the dendrimer. Finally we note that structural and solvation properties computed using force field parameters derived based on the CHARMM general purpose force field were in good quantitative agreement with those obtained using the generalized Amber force field (GAFF).

Functional PEG-PAMAM-tetraphosphonate capped NaLnF₄ nanoparticles and their colloidal stability in phosphate buffer.

PubMed

Zhao, Guangyao; Tong, Lemuel; Cao, Pengpeng; Nitz, Mark; Winnik, Mitchell A

2014-06-17

Developing surface coatings for NaLnF4 nanoparticles (NPs) that provide long-term stability in solutions containing competitive ions such as phosphate remains challenging. An amine-functional polyamidoamine tetraphosphonate (NH2-PAMAM-4P) as a multidentate ligand for these NPs has been synthesized and characterized as a ligand for the surface of NaGdF4 and NaTbF4 nanoparticles. A two-step ligand exchange protocol was developed for introduction of the NH2-PAMAM-4P ligand on oleate-capped NaLnF4 NPs. The NPs were first treated with methoxy-poly(ethylene glycol)-monophosphoric acid (M(n) = 750) in tetrahydrofuran. The mPEG750-OPO3-capped NPs were stable colloidal solutions in water, where they could be ligand-exchanged with NH2-PAMAM-4P. The surface amine groups on the NPs were available for derivatization to attach methoxy-PEG (M(n) = 2000) and biotin-terminated PEG (M(n) = 2000) chains. The surface coverage of ligands on the NPs was examined by thermal gravimetric analysis, and by a HABA analysis for biotin-containing NPs. Colloidal stability of the NPs was examined by dynamic light scattering. NaGdF4 and NaTbF4 NPs capped with mPEG2000-PAMAM-4P showed colloidal stability in DI water and in phosphate buffer (10 mM, pH 7.4). A direct comparison with NaTbF4 NPs capped with a mPEG2000-lysine-based tetradentate ligand that we reported previously (Langmuir 2012, 28, 12861-12870) showed that both ligands provided long-term stability in phosphate buffer, but that the lysine-based ligand provided better stability in phosphate-buffered saline.

Fourth Generation Light Sources

NASA Astrophysics Data System (ADS)

Winick, Herman

1997-05-01

Concepts and designs are now being developed at laboratories around the world for light sources with performance levels that exceed present sources, including the very powerful and successful third generation synchrotron radiation sources that have come on line in the past few years. Workshops (M. Cornacchia and H. Winick (eds), Workshop on Fourth Generation Light Sources, Feb. 24-27, 1992, SSRL Report 92/02) (J.-L. Laclare (ed), ICFA Workshop on Fourth Generation Light Sources, Jan. 22-25, 1996, ESRF Report) have been held to review directions for future sources. A main thrust is to increase the brightness and coherence of the radiation using storage rings with lower electron-beam emittance or free-electron lasers (FELs). In the infra-red part of the spectrum very high brightness and coherence is already provided by FEL user facilities driven by linacs and storage rings. It now appears possible to extend FEL operation to the VUV, soft X-ray and even hard X-ray spectral range, to wavelengths down to the angstrom range, using high energy linacs equipped with high-brightness rf photoinjectors and bunch-length compressors. R&D to develop such sources is in progress at BNL, DESY, KEK, SLAC and other laboratories. In the absence of mirrors to form optical cavities, short wavelengths are reached in FEL systems in which a high peak current, low-emittance electron beam becomes bunch-density modulated at the optical wavelength in a single pass through a long undulator by self-amplified spontaneous emission (SASE); i.e.; startup from noise. A proposal to use the last kilometer of the three kilometer SLAC linac (the first two kilometers will be used for injection to the PEP II B-Factory) to provide 15 GeV electron beams to reach 1.5 Angstroms by SASE in a 100 m long undulator is in preparation.

Characterization of basic amino acids-conjugated PAMAM dendrimers as gene carriers for human adipose-derived mesenchymal stem cells.

PubMed

Bae, Yoonhee; Lee, Sunray; Green, Eric S; Park, Jung Hyun; Ko, Kyung Soo; Han, Jin; Choi, Joon Sig

2016-03-30

Since mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple cell types, the delivery of genes to this type of cell can be an important tool in the emerging field of tissue regeneration and engineering. However, development of more efficient and safe nonviral vectors for gene delivery to stem cells in particular still remains a great challenge. In this study, we describe a group of nonviral gene delivery vectors, conjugated PAMAM derivatives (PAMAM-H-R, PAMAM-H-K, and PAMAM-H-O), displaying affinity toward human adipose-derived mesenchymal stem cells (AD-MSCs). Transfection efficiency using pDNA encoding for luciferase (Luc) and enhanced green fluorescent protein (EGFP), and cytotoxicity assays were performed in human AD-MSCs. The results show that transfection efficiencies of conjugated PAMAM derivatives are improved significantly compared to native PAMAM dendrimer, and that among PAMAM derivatives, cytotoxicity of PAMAM-H-K and PAMAM-H-O were very low. Also, treatment of human AD-MSCs to polyplex formation in conjugated PAMAM derivatives, their cellular uptake and localization were analyzed by flow cytometry and confocal microscopy. Copyright © 2016 Elsevier B.V. All rights reserved.

Polyamidoamine dendrimer as a spacer for the immobilization of glucose oxidase in capillary enzyme microreactor.

PubMed

Wang, Siming; Su, Ping; Hongjun, E; Yang, Yi

2010-10-15

Polyamidoamine dendrimer (PAMAM) is one of a number of dendritic polymers with precise molecular structure, highly geometric symmetry, and a large number of terminal groups. In this study, different generations of PAMAM (G0-G4) were introduced onto the inner wall of fused-silica capillaries by microwave irradiation and a new type of glucose oxidase (GOx) capillary enzyme microreactor was developed based on enzyme immobilization in the prepared PAMAM-grafted fused-silica capillaries. The optimal enzymolysis conditions for beta-d-glucose in the microreactor were evaluated by capillary zone electrophoresis. In addition, the enzymolysis efficiencies of different generations of PAMAM-GOx capillary enzyme microreactor were compared. The results indicate that enzymolysis efficiency increased with increasing generations of PAMAM. The experimental results provide the possibility for the development and application of an online immobilized capillary enzyme microreactor. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.

Interactions of poly(amidoamine) dendrimers with human serum albumin: binding constants and mechanisms.

PubMed

Giri, Jyotsnendu; Diallo, Mamadou S; Simpson, André J; Liu, Yi; Goddard, William A; Kumar, Rajeev; Woods, Gwen C

2011-05-24

The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K(b)) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To gain insight into the mechanisms of HSA binding to PAMAM dendrimers, we combined (1)H NMR, saturation transfer difference (STD) NMR, and NMR diffusion ordered spectroscopy (DOSY) of dendrimer-HSA complexes with atomistic molecular dynamics (MD) simulations of dendrimer conformation in aqueous solutions. The binding measurements show that the HSA binding constants (K(b)) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR (1)H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The (1)H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH(2)vs G4-NH(2)) and terminal groups (G4-NH(2)vs G4-OH with amidoethanol groups), suggest that PAMAM dendrimers adopt backfolded configurations as they form weak complexes with HSA proteins in aqueous solutions at physiological pH (7.4).

Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier.

PubMed

Hemmati, Mohammad; Kazemi, Bahram; Najafi, Farhood; Zarebkohan, Amir; Shirkoohi, Reza

2016-01-01

Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p < 0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM-Glu20 in MDA-MB231 cells, 173.56 ± 1.37%, was significantly higher than that of MCF7 cells, 65.00 ± 1.73% (p < 0.05). The results indicated that hPAMAM-Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM-glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.

The effects of an RGD-PAMAM dendrimer conjugate in 3D spheroid culture on cell proliferation, expression and aggregation.

PubMed

Jiang, Li-Yang; Lv, Bing; Luo, Ying

2013-04-01

By presenting biomolecular ligands on the surface in high density, ligand-decorated dendrimers are capable of binding to membrane receptors and cells with specificity and avidity. Despite the various uses, fundamental investigations on ligand-dendrimer conjugates have mainly focused on their binding behavior with cells, whereas their potential bioactivity and applications in multicellular systems, especially in three-dimensional (3D) culture systems, remains untapped. In this study, a typical adhesive peptide ligand - RGD - was modified to generation 4 polyamidoamine (PAMAM), and the bioactivity of suspended RGD-PAMAM conjugates was investigated on cells cultured as multicellular spheroids. Our results demonstrate that the RGD-PAMAM conjugates, after being incorporated into the 3D spheroids, were able to promote cellular proliferation and aggregation, and affect the mRNA expression of extracellular factors by NIH 3T3 cells. These bioactive functions were multivalency-dependent, as none of similar effects was observed for monovalent RGD ligand. Our study suggests that multivalent ligand-dendrimer conjugates may act as a unique type of artificial factors to mediate the cellular microenvironment in 3D culture, a property attributable to the spatial organization of the ligands and possible "cell-gluing" function of multivalent conjugates. This new finding opens the door for further exploring multivalent ligand-dendrimer conjugates for applications in 3D cell culture and tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adoption of 4G Mobile Services from the Female Student's Perspective: Case of Princess Nora University

ERIC Educational Resources Information Center

Rawashdeh, Awni

2015-01-01

The aim this study was to examine the relationship between the perceived usefulness, perceived ease of use, perceived entertainment, attitude and the users' intention toward using the fourth-generation (4G) wireless mobile services. Data of this study were collected by survey with a cross sectional approach. The data were analyzed with factor…

DNA assisted self-assembly of PAMAM dendrimers.

PubMed

Mandal, Taraknath; Kumar, Mattaparthi Venkata Satish; Maiti, Prabal K

2014-10-09

We report DNA assisted self-assembly of polyamidoamine (PAMAM) dendrimers using all atom Molecular Dynamics (MD) simulations and present a molecular level picture of a DNA-linked PAMAM dendrimer nanocluster, which was first experimentally reported by Choi et al. (Nano Lett., 2004, 4, 391-397). We have used single stranded DNA (ssDNA) to direct the self-assembly process. To explore the effect of pH on this mechanism, we have used both the protonated (low pH) and nonprotonated (high pH) dendrimers. In all cases studied here, we observe that the DNA strand on one dendrimer unit drives self-assembly as it binds to the complementary DNA strand present on the other dendrimer unit, leading to the formation of a DNA-linked dendrimer dimeric complex. However, this binding process strongly depends on the charge of the dendrimer and length of the ssDNA. We observe that the complex with a nonprotonated dendrimer can maintain a DNA length dependent inter-dendrimer distance. In contrast, for complexes with a protonated dendrimer, the inter-dendrimer distance is independent of the DNA length. We attribute this observation to the electrostatic complexation of a negatively charged DNA strand with the positively charged protonated dendrimer.

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

PubMed

Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery.

PubMed

Luong, Duy; Kesharwani, Prashant; Deshmukh, Rahul; Mohd Amin, Mohd Cairul Iqbal; Gupta, Umesh; Greish, Khaled; Iyer, Arun K

2016-10-01

Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers. It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Molecular dynamics study of the structure and interparticle interactions of polyethylene glycol-conjugated PAMAM dendrimers.

PubMed

Lee, Hwankyu; Larson, Ronald G

2009-10-08

We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 , 1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like brushes, with layer thickness in agreement with theory for starlike polymers. Two dendrimer-PEG complexes in the box drift away from each other, indicating that no aggregation is induced by either short or long PEG chains, conflicting with a recent view that the cytotoxicity of some PEGylated particles might be due to particle aggregation for long PEG lengths.

Anomalous single production of the fourth generation quarks at the CERN LHC

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

Ciftci, R.

Possible anomalous single productions of the fourth standard model generation up and down type quarks at CERN Large Hadron Collider are studied. Namely, pp{yields}u{sub 4}(d{sub 4})X with subsequent u{sub 4}{yields}bW{sup +} process followed by the leptonic decay of the W boson and d{sub 4}{yields}b{gamma} (and its H.c.) decay channel are considered. Signatures of these processes and corresponding standard model backgrounds are discussed in detail. Discovery limits for the quark mass and achievable values of the anomalous coupling strength are determined.

Accuracy of a Fourth-Generation Subcutaneous Continuous Glucose Sensor.

PubMed

Christiansen, Mark P; Garg, Satish K; Brazg, Ronald; Bode, Bruce W; Bailey, Timothy S; Slover, Robert H; Sullivan, Ashley; Huang, Suiying; Shin, John; Lee, Scott W; Kaufman, Francine R

2017-08-01

This study evaluated the accuracy and performance of a fourth-generation subcutaneous glucose sensor (Guardian ™ Sensor 3) in the abdomen and arm. Eighty-eight subjects (14-75 years of age, mean ± standard deviation [SD] of 42.0 ± 19.1 years) with type 1 or type 2 diabetes participated in the study. Subjects wore two sensors in the abdomen that were paired with either a MiniMed ™ 640G insulin pump, or an iPhone ® or iPod ® touch ® running a glucose monitoring mobile application (Guardian Connect system) and a third sensor in the arm, which was connected to a glucose sensor recorder (GSR). Subjects were also asked to undergo in-clinic visits of 12-14 h on study days 1, 3, and 7 for frequent blood glucose sample testing using a Yellow Springs Instrument (YSI) reference. The overall mean absolute relative difference (MARD ± SD) between abdomen sensor glucose (SG) and YSI reference values was 9.6% ± 9.0% and 9.4% ± 9.8% for the MiniMed 640G insulin pump and Guardian Connect system, respectively; and 8.7% ± 8.0% between arm SG and YSI reference values. The percentage of SG values within 20% agreement of the YSI reference value (for YSI >80 mg/dL) was 90.7% with the MiniMed 640G insulin pump, 91.8% with the Guardian Connect system, and 93.1% for GSR-connected arm sensors. Mean functional sensor life, when calibrating 3-4 times/day, was 145.9 ± 39.3 h for sensors paired with the MiniMed 640G insulin pump, 146.1 ± 41.6 h for sensors paired with the Guardian Connect system, and 147.6 ± 40.4 h for sensors connected to the GSR. Responses to survey questions regarding sensor comfort and ease of use were favorable. The Guardian Sensor 3 glucose sensor, whether located in abdomen or the arm, provided accurate glucose readings when compared with the YSI reference and demonstrated functional life commensurate with the intended 7-day use. ClinicalTrials.gov : NCT02246582.

Probing the binding of cationic lipids with dendrimers.

PubMed

Mandeville, J S; Bourassa, P; Tajmir-Riahi, H A

2013-01-14

Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell. We report the bindings of several lipids cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane(DOTAP), dioctadecyldimethylammoniumbromide (DDAB), and dioleoylphosphatidylethanolamine (DOPE) to dendrimers of different compositions such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) under physiological conditions. FTIR, UV-visible spectroscopic, methods and molecular modeling were used to analyze the lipid binding mode, the binding constant, and the effects of lipid complexation on the dendrimer structure. The structural analysis showed that lipids bind dendrimers through both hydrophilic and hydrophobic contacts with overall binding constants of K(chol-mPEG-G3) = 1.7 × 10(3) M(-1), K(chol-mPEG-PAMAM-G4) = 2.7 × 10(3) M(-1), K(chol-PAMAM-G4) = 1.0 × 10(3) M(-1), K(DOPE-mPEG-G3) = 1.5 × 10(3) M(-1), K(DOPE-mPEG-PAMAM-G4) = 1.6 × 10(3) M(-1), K(DOPE-PAMAM-G4) = 5.3 × 10(2) M(-1), K(DDAB-mPEG-G3) = 1.5 × 10(3) M(-1), K(DDAB-mPEG-PAMAM-G4) = 1.9 × 10(2) M(-1), K(DDAB-PAMAM-G4) = 7.0 × 10(2) M(-1), K(DOTAP-mPEG-G3) = 1.9 × 10(3) M(-1), K(DOTAP-mPEG-PAMAM-G4) = 1.5 × 10(3) M(-1), and K(DOTAP-PAMAM-G4) = 5.7 × 10(2) M(-1). Weaker interaction was observed as dendrimer cationic charges increased. The free binding energies from docking were -5.15 (cholesterol), -5.79 (DDAB), and -5.36 kcal/mol (DOTAP) with the order of stability DDAB-PAMAM-G-4 > DOTAP-PAMAM-G4 > cholesterol-PAMAM-G4, consistent with the spectroscopic results. Dendrimers might act as carriers to transport lipids in vitro.

Role of PAMAM-OH dendrimers against the fibrillation pathway of biomolecules.

PubMed

Sekar, Gajalakshmi; Florance, Ida; Sivakumar, A; Mukherjee, Amitava; Chandrasekaran, Natarajan

2016-12-01

The binding behavior of nanoparticle with proteins determines its biocompatibility. This study reports the interaction of ten different biomolecules (proteins-BSA, HSA, haemoglobin, gamma globulin, transferrin and enzymes-hog and bacillus amylase, lysozyme from chicken and human and laccases from Tramates versicolor) with a surface group hydroxylated Poly AMido AMide dendrimer (PAMAM) of generation 5. The study has utilized various spectroscopic methods like UV-vis spectroscopy, Fluorescence emission, Synchronous, 3-D spectroscopy and Circular Dichroism to detect the binding induced structural changes in biomolecules that occur upon interaction with mounting concentration of the dendrimers. Aggregation of proteins results in the formation of amyloid fibrils causing several human diseases. In this study, fibrillar samples of all ten biomolecules formed in the absence and the presence of dendrimers were investigated with Congo Red absorbance and ThT Assay to detect fibril formation, Trp Emission and 3-D scan to evaluate the effect of fibrillation on aromatic environment of biomolecules, and CD spectroscopy to measure the conformational changes in a quantitative manner. These assays have generated useful information on the role of dendrimers in amyloid fibril formation of biomolecules. The outcomes of the study remain valuable in evaluating the biological safety of PAMAM-OH dendrimers for their biomedical application in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Gender Differences in Inference Generation by Fourth-Grade Students

ERIC Educational Resources Information Center

Clinton, Virginia; Seipel, Ben; Broek, Paul; McMaster, Kristen L.; Kendeou, Panayiota; Carlson, Sarah E.; Rapp, David N.

2014-01-01

The purpose of this study was to determine if there are gender differences among elementary school-aged students in regard to the inferences they generate during reading. Fourth-grade students (130 females; 126 males) completed think-aloud tasks while reading one practice and one experimental narrative text. Females generated a larger number and a…

Functionalization of silica-gel with polyamidoamine and 2-mercaptobenzothiazole and its adsorption property for lead

NASA Astrophysics Data System (ADS)

Wu, X. Z.; Liu, Y.; Luo, L. L.; Chen, Z. Y.

2018-01-01

Adsorbents PAMAM-n.0MBTSG (n=1-4) have been prepared by immobilizing polyamidoamine (PAMAM) and 2-mercaptobenzothiazole (MBT) on silica-gel. Characterized with FTIR, SEM, TGA, the preconcentration of Pb2+ with PAMAM-n.0MBTSG(n=1-4) has been investigated by graphite furnace atomic absorption spectroscopy (GFAAS). SEM showed that the surface morphology of adsorbent changed with the generation increase of PAMAM. Adsorption capacity of PAMAM-n.0MBTSG for Pb2+ (n=1-4) reached 16.22, 19.84, 22.92 and 27.56 mg g-1 respectively. Pb2+ (1.0 ng mL-1) in 2000 mL solution could be quantitatively absorbed with PAMAM-4.0MBTSG and eluted to obtain a preconcentration factor (PF) of 200. GFAAS method for analysis of Pb2+ with PAMAM-4.0MBTSG as adsorbent was proposed and successfully applied to analysis of Pb2+ of standard reference material, sea water and squid sample.

Sensitive electrochemical immunosensor for α-synuclein based on dual signal amplification using PAMAM dendrimer-encapsulated Au and enhanced gold nanoparticle labels.

PubMed

An, Yarui; Jiang, Xiaoli; Bi, Wenji; Chen, Hua; Jin, Litong; Zhang, Shengping; Wang, Chuangui; Zhang, Wen

2012-02-15

A novel electrochemical immunosensor for sensitive detection of α-synuclein (α-SYN), a very important neuronal protein, has been developed based on dual signal amplification strategy. Herein, G4-polyamidoamine dendrimer-encapsulated Au nanoparticles (PAMAM-Au nanocomposites) were covalently bound on the poly-o-aminobenzoic acid (poly-o-ABA), which was initially electropolymerized on the electrode surface to perform abundant carboxyl groups. The formed immunosensor platform, PAMAM-Au, was proved to provide numerous amino groups to allow highly dense immobilization of antigen, and facilitate the improvement of electrochemical responses as well. Subsequently, the enhanced gold nanoparticle labels ({HRP-Ab(2)-GNPs}) were fabricated by immobilizing horseradish peroxidase-secondary antibody (HRP-Ab(2)) on the surface of gold nanoparticles (GNPs). After an immunoassay process, the {HRP-Ab(2)-GNPs} labels were introduced onto the electrode surface, and produced an electrocatalytic response by reduction of hydrogen peroxide (H(2)O(2)) in the presence of enzymatically oxidized thionine. On the basis of the dual signal amplification of PAMAM-Au and {HRP-Ab(2)-GNPs} labels, the designed immunosensor displayed an excellent analytical performance with high sensitivity and stability. This developed strategy was successfully proved as a simple, cost-effective method, and could be easily extended to other protein analysis schemes. Copyright © 2011 Elsevier B.V. All rights reserved.

para-Sulfonatocalix[4]arene and polyamidoamine dendrimer nanocomplexes as delivery vehicles for a novel platinum anticancer agent.

PubMed

Pang, Chi Ting; Ammit, Alaina J; Ong, Yu Qing Elysia; Wheate, Nial J

2017-11-01

Novel para-sulfonatocalix[4]arene (sCX[4]) and polyamidoamine (PAMAM) dendrimer nanocomplexes were evaluated as delivery vehicles for the platinum anticancer agent [(1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] chloride (PHENSS). Different ratios of sCX[4] to PHENSS were tested for their compatibility, with a ratio of 6:1 sCX[4]:PHENSS having the best solubility. The loading of sCX[4], and sCX[4]-bound PHENSS, onto three different generations of PAMAM dendrimers (G3.0-5.0) was examined using UV-visible spectrophotometry. The quantity of sCX[4] bound was found to increase exponentially with dendrimer size: G3, 15 sCX[4] molecules per dendrimer; G4, 37; and G5, 78. Similarly, the loading of sCX[4]-bound PHENSS also increased with increasing dendrimer size: G3, 7 PHENSS molecules per dendrimer; G4, 14; and G5, 28.5. The loading of sCX[4]-bound PHENSS molecules is significantly lower when compared with that of sCX[4], which indicates that less than half of the binding sites were occupied (45, 44, and 44%, respectively). By 1 H NMR and UV-vis analysis, the nanocomplex was found to be stable in NaCl solutions at concentrations up to 150mM. While PHENSS is more active in vitro than cisplatin against the human breast cancer cell line, MCF-7, delivery of PHENSS using the sCX[4]-dendrimer nanocomplexes, regardless of dendrimer generation, had little effect on PHENSS cytotoxicity. The results of this study may have application in the delivery of a variety of small molecule metal-based drugs for which chemical conjugation to a nanoparticle is undesired or not feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

Accuracy of a Fourth-Generation Subcutaneous Continuous Glucose Sensor

PubMed Central

Garg, Satish K.; Brazg, Ronald; Bode, Bruce W.; Bailey, Timothy S.; Slover, Robert H.; Sullivan, Ashley; Huang, Suiying; Shin, John; Lee, Scott W.; Kaufman, Francine R.

2017-01-01

Abstract Background: This study evaluated the accuracy and performance of a fourth-generation subcutaneous glucose sensor (Guardian™ Sensor 3) in the abdomen and arm. Methods: Eighty-eight subjects (14–75 years of age, mean ± standard deviation [SD] of 42.0 ± 19.1 years) with type 1 or type 2 diabetes participated in the study. Subjects wore two sensors in the abdomen that were paired with either a MiniMed™ 640G insulin pump, or an iPhone® or iPod® touch® running a glucose monitoring mobile application (Guardian Connect system) and a third sensor in the arm, which was connected to a glucose sensor recorder (GSR). Subjects were also asked to undergo in-clinic visits of 12–14 h on study days 1, 3, and 7 for frequent blood glucose sample testing using a Yellow Springs Instrument (YSI) reference. Results: The overall mean absolute relative difference (MARD ± SD) between abdomen sensor glucose (SG) and YSI reference values was 9.6% ± 9.0% and 9.4% ± 9.8% for the MiniMed 640G insulin pump and Guardian Connect system, respectively; and 8.7% ± 8.0% between arm SG and YSI reference values. The percentage of SG values within 20% agreement of the YSI reference value (for YSI >80 mg/dL) was 90.7% with the MiniMed 640G insulin pump, 91.8% with the Guardian Connect system, and 93.1% for GSR-connected arm sensors. Mean functional sensor life, when calibrating 3–4 times/day, was 145.9 ± 39.3 h for sensors paired with the MiniMed 640G insulin pump, 146.1 ± 41.6 h for sensors paired with the Guardian Connect system, and 147.6 ± 40.4 h for sensors connected to the GSR. Responses to survey questions regarding sensor comfort and ease of use were favorable. Conclusions: The Guardian Sensor 3 glucose sensor, whether located in abdomen or the arm, provided accurate glucose readings when compared with the YSI reference and demonstrated functional life commensurate with the intended 7-day use. ClinicalTrials.gov: NCT

Installing an Integrated System and a Fourth-Generation Language.

ERIC Educational Resources Information Center

Ridenour, David; Ferguson, Linda

1987-01-01

In the spring of 1986 Indiana State University converted to the Series Z software of Information Associates, an IBM mainframe, and Information Builders' FOCUS fourth-generation language. The beginning of the planning stage to product selection, training, and implementation is described. (Author/MLW)

Antibacterial activity of amino- and amido- terminated poly (amidoamine)-G6 dendrimer on isolated bacteria from clinical specimens and standard strains.

PubMed

Rastegar, Ayoob; Nazari, Shahram; Allahabadi, Ahmad; Falanji, Farahnaz; Akbari Dourbash, Fakhreddin Akbari Dourbash; Rezai, Zahra; Alizadeh Matboo, Soudabeh; Hekmat-Shoar, Reza; Mohseni, Seyed Mohsen; Majidi, Gharib

2017-01-01

Background: Nanoscale poly (amidoamine) dendrimers have been investigated for their biological demands, but their antibacterial activity has not been widely discovered. Thus, the sixth generation of poly (amidoamine) dendrimer (PAMAM-G6) was synthesized and its antibacterial activities were evaluated on Gram-negative bacteria; P. aeruginosa, E. coli, A. baumannii, S. typhimurium, S. dysenteriae, K. pneumoniae, P. mirabilis , and Gram-positive bacteria, and S.aureus and B. subtilis , which were isolated from different clinical specimens and standard strains of these bacteria. Methods: In this study, 980 specimens including urine (47%), blood (27%), sputum (13%), wounds (8%), and burns (5%) were collected from clinical specimens of 16 hospitals and clinics in city of Sabzevar, Iran. Then, the target bacteria were isolated and identified using standard methods. Minimum inhibitory concentration and minimum bactericidal concentrations against Gram-positive and Gram-negative bacteria were determined according to guidelines described by clinical and laboratory standards institute (CLSI). Standard discs were prepared using 0.025, 0.25, 2.5, and 25 μg/mL concentrations of PAMAM-G6 on Mueller-Hinton agar plates to determinate the zone of inhibition. The cytotoxicity of PAMAM-G6 dendrimer was evaluated in HCT116 cells by MTT assay. Results: The most important isolated bacteria were E. coli (23.65%), S. aureus (24.7%), P. aeruginosa (10.49%), B. subtilis (7.7%), S. typhimurium (8.87%), A. baumannii (7.02%), K. pneumoniae (7.1%), P. mirabilis (6.46%), and S. dysenteriae (3.6%). Moreover, it was found that poly (amidoamine)-G6 exhibited more antibacterial efficacy on standard strains than isolated bacteria from clinical samples (p<0.05). The cytotoxicity of PAMAM-G6 to the cells showed that cytotoxicity depended on the concentration level and exposure time. Conclusion: The PAMAM-G6 dendrimer showed a positive impact on the removal of dominant bacterial isolated from clinical

Antibacterial activity of amino- and amido- terminated poly (amidoamine)-G6 dendrimer on isolated bacteria from clinical specimens and standard strains

PubMed Central

Rastegar, Ayoob; Nazari, Shahram; Allahabadi, Ahmad; Falanji, Farahnaz; Akbari Dourbash, Fakhreddin Akbari Dourbash; Rezai, Zahra; Alizadeh Matboo, Soudabeh; Hekmat-Shoar, Reza; Mohseni, Seyed Mohsen; Majidi, Gharib

2017-01-01

Background: Nanoscale poly (amidoamine) dendrimers have been investigated for their biological demands, but their antibacterial activity has not been widely discovered. Thus, the sixth generation of poly (amidoamine) dendrimer (PAMAM-G6) was synthesized and its antibacterial activities were evaluated on Gram-negative bacteria; P. aeruginosa, E. coli, A. baumannii, S. typhimurium, S. dysenteriae, K. pneumoniae, P. mirabilis, and Gram-positive bacteria, and S.aureus and B. subtilis, which were isolated from different clinical specimens and standard strains of these bacteria. Methods: In this study, 980 specimens including urine (47%), blood (27%), sputum (13%), wounds (8%), and burns (5%) were collected from clinical specimens of 16 hospitals and clinics in city of Sabzevar, Iran. Then, the target bacteria were isolated and identified using standard methods. Minimum inhibitory concentration and minimum bactericidal concentrations against Gram-positive and Gram-negative bacteria were determined according to guidelines described by clinical and laboratory standards institute (CLSI). Standard discs were prepared using 0.025, 0.25, 2.5, and 25 μg/mL concentrations of PAMAM-G6 on Mueller-Hinton agar plates to determinate the zone of inhibition. The cytotoxicity of PAMAM-G6 dendrimer was evaluated in HCT116 cells by MTT assay. Results: The most important isolated bacteria were E. coli (23.65%), S. aureus (24.7%), P. aeruginosa (10.49%), B. subtilis (7.7%), S. typhimurium (8.87%), A. baumannii (7.02%), K. pneumoniae (7.1%), P. mirabilis (6.46%), and S. dysenteriae (3.6%). Moreover, it was found that poly (amidoamine)–G6 exhibited more antibacterial efficacy on standard strains than isolated bacteria from clinical samples (p<0.05). The cytotoxicity of PAMAM-G6 to the cells showed that cytotoxicity depended on the concentration level and exposure time. Conclusion: The PAMAM-G6 dendrimer showed a positive impact on the removal of dominant bacterial isolated from clinical

Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy.

PubMed

Menjoge, Anupa R; Rinderknecht, Amber L; Navath, Raghavendra S; Faridnia, Masoud; Kim, Chong J; Romero, Roberto; Miller, Richard K; Kannan, Rangaramanujam M

2011-03-30

Dendrimers offer significant potential as nanocarriers for targeted delivery of drugs and imaging agents. The objectives of this study were to evaluate the transplacental transport, kinetics and biodistribution of PAMAM dendrimers ex-vivo across the human placenta in comparison with antipyrine, a freely diffusible molecule, using dually perfused re-circulating term human placental lobules. The purpose of this study is to determine if dendrimers as drug carriers can be used to design drug delivery systems directed at selectively treating either the mother or the fetus. The transplacental transfers of fluorescently (Alexa 488) tagged PAMAM dendrimer (16 kDa) and antipyrine (188 Da) from maternal to fetal circulation were measured using HPLC/dual UV and fluorescent detector (sensitivity of 10 ng/mL for dendrimer and 100 ng/mL for antipyrine respectively). C(max) for the dendrimer-Alexa (DA) in maternal perfusate (T(max)=15 min) was 18 times higher than in the fetal perfusate and never equilibrated with the maternal perfusate during 5.5 h of perfusion (n=4). DA exhibited a measurable but low transplacental transport of 2.26±0.12 μg/mL during 5.5h, where the mean transplacental transfer was 0.84±0.11% of the total maternal concentration and the feto-maternal ratio as percent was 0.073%±0.02. The biochemical and physiological analysis of the placentae perfused with DA demonstrated normal function throughout the perfusion. The immunofluorescence histochemistry confirmed that the biodistribution of DA in perfused placenta was sparsely dispersed, and when noted was principally seen in the inter-villous spaces and outer rim of the villous branches. In a few cases, DA was found internalized and localized in nuclei and cytoplasm of syncytiotrophoblast and inside the villous core; however, DA was mostly absent from the villous capillaries. In conclusion, the PAMAM dendrimers exhibited a low rate of transfer from maternal to the fetal side across the perfused human placenta

A novel acute HIV infection staging system based on 4th generation immunoassay.

PubMed

Ananworanich, Jintanat; Fletcher, James L K; Pinyakorn, Suteeraporn; van Griensven, Frits; Vandergeeten, Claire; Schuetz, Alexandra; Pankam, Tippawan; Trichavaroj, Rapee; Akapirat, Siriwat; Chomchey, Nitiya; Phanuphak, Praphan; Chomont, Nicolas; Michael, Nelson L; Kim, Jerome H; de Souza, Mark

2013-05-29

Fourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging). Screening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2. Using 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.

PubMed

Lin, Yulian; Fujimori, Takeo; Kawaguchi, Naoko; Tsujimoto, Yuiko; Nishimi, Mariko; Dong, Zhengqi; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

2011-01-05

Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine. Copyright © 2010 Elsevier B.V. All rights reserved.

HPLC analysis of functionalized poly(amidoamine) dendrimers and the interaction between a folate-dendrimer conjugate and folate binding protein.

PubMed

Shi, Xiangyang; Bi, Xiangdong; Ganser, T Rose; Hong, Seungpyo; Myc, Lukasz A; Desai, Ankur; Holl, Mark M Banaszak; Baker, James R

2006-07-01

Poly(amidoamine) (PAMAM) dendrimers of different generations with carboxyl, acetyl, and hydroxyl terminal groups and a folic acid (FA)-dendrimer conjugate were separated and analyzed using reverse-phase high performance liquid chromatography (HPLC). Analysis of both the individual PAMAM derivatives and the separation of mixed generations can be achieved using a linear gradient 0-50% acetonitrile (ACN) (balance water) within 40 min. We also show that PAMAMs with defined acetylation and carboxylation degrees can be analyzed using HPLC. Furthermore, a generation 5 dendrimer-FA conjugate (G5.75Ac-FA4; Ac denotes acetyl) was analyzed and its specific binding with a bovine folic acid binding protein (FBP) was monitored. The HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results indicate the formation of three complexes after the binding of G5.75Ac-FA4 with FBP. Dendrimers with FA moieties show much higher specific binding capability with FBP than those without FA moieties. Findings from this study indicate that HPLC is an effective technique not only for characterization and separation of functionalized PAMAM dendrimers and conjugates but also for investigation of the interaction between dendrimers and biomolecules.

Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

NASA Astrophysics Data System (ADS)

Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad

2016-05-01

Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and 1H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol40 %) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

A Sensitive Electrochemical Immunosensor Based on PAMAM Dendrimer-Encapsulated Au for Detection of Norfloxacin in Animal-Derived Foods.

PubMed

Liu, Bing; Li, Min; Zhao, Yaoshuai; Pan, Mingfei; Gu, Ying; Sheng, Wei; Fang, Guozhen; Wang, Shuo

2018-06-15

In this work, a sensitive electrochemical immunosensor has been reported for the determination of norfloxacin in animal-derived foods. The poly (amidoamine) dendrimer encapsulated gold nanoparticles (PAMAM-Au) played dual roles in the proposed sensing platform which not only accelerated the electron transfer process of sensing, but also increased the efficiency of the immobilized antibody. The HRP-labeled antigen, as the signal labels in the immunosensor, was introduced to catalyze the following reaction of the substrate hydroquinone with the aid of H₂O₂ in the competitive reaction. On the basis of the signal amplification of PAMAM-Au, the signal intensity was linearly related to the concentration of norfloxacin in the range of 1 μg·L −1 ⁻10 mg·L −1 . All the results showed that the proposed strategy with low LOD (0.3837 μg·L −1 ) and favorable recovery (91.6⁻106.1%) in the practical sample, and it could provide a suitable protocol for norfloxacin detection in animal-derived foods with high sensitivity, good accuracy, and stability.

A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.

PubMed

Li, Yan; He, Hai; Jia, Xinru; Lu, Wan-Liang; Lou, Jinning; Wei, Yen

2012-05-01

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fluorescent hydroxylamine derived from the fragmentation of PAMAM dendrimers for intracellular hypochlorite recognition.

PubMed

Wu, Te-Haw; Liu, Ching-Ping; Chien, Chih-Te; Lin, Shu-Yi

2013-08-26

Herein, a promising sensing approach based on the structure fragmentation of poly(amidoamine) (PAMAM) dendrimers for the selective detection of intracellular hypochlorite (OCl(-)) is reported. PAMAM dendrimers were easily disrupted by a cascade of oxidations in the tertiary amines of the dendritic core to produce an unsaturated hydroxylamine with blue fluorescence. Specially, the novel fluorophore was only sensitive to OCl(-), one of reactive oxygen species (ROS), resulting in an irreversible fluorescence turn-off. The fluorescent hydroxylamine was selectively oxidised by OCl(-) to form a labile oxoammonium cation that underwent further degradation. Without using any troublesomely synthetic steps, the novel sensing platform based on the fragmentation of PAMAM dendrimers, can be applied to detect OCl(-) in macrophage cells. The results suggest that the sensing approach may be useful for the detection of intracellular OCl(-) with minimal interference from biological matrixes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Higgs data does not rule out a sequential fourth generation with an extended scalar sector

NASA Astrophysics Data System (ADS)

Das, Dipankar; Kundu, Anirban; Saha, Ipsita

2018-01-01

Contrary to common perception, we show that the current Higgs data does not eliminate the possibility of a sequential fourth generation that get their masses through the same Higgs mechanism as the first three generations. The inability to fix the sign of the bottom-quark Yukawa coupling from the available data plays a crucial role in accommodating a chiral fourth generation which is consistent with the bounds on the Higgs signal strengths. We show that effects of such a fourth generation can remain completely hidden not only in the production of the Higgs boson through gluon fusion but also to its subsequent decay to γ γ and Z γ . This, however, is feasible only if the scalar sector of the standard model is extended. We also provide a practical example illustrating how our general prescription can be embedded in a realistic model.

Photocatalytic activity of CdS and Ag2S quantum dots deposited on poly(amidoamine) functionalized carbon nanotubes

PubMed Central

Neelgund, Gururaj M.; Oki, Aderemi

2011-01-01

Two novel ternary nanocatalysts, f-MWCNTs-CdS and f-MWCNTs-Ag2S were successfully constructed by covalent grafting of fourth generation (G4) hyperbranched, crosslinked poly(amidoamine) (PAMAM) to carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) and subsequent deposition of CdS or Ag2S quantum dots (QDs). The structural transformation, surface potential, and morphology of functionalized MWCNTs (f-MWCNTs) and nanocatalysts were characterized by UV-vis spectrophotometer, Fourier transform infrared spectroscopy, powder X-ray diffraction, Raman spectroscopy, thermogravimetric analysis, scanning electron microscopy and energy dispersive spectroscopy. Transmission electron microscopy reveals the effective anchoring of QDs on f-MWCNTs. The catalytic activity of nanocatalysts was evaluated by photodegradation of methyl orange under illumination of UV light. The coupling of MWCNTs, PAMAM and CdS or Ag2S QDs significantly enhanced the catalytic efficiency of nanocatalysts. The rate constants for degradation of methyl orange in presence of nanocatalysts were calculated using the Langmuir-Hinshelwood model. Overall, the excellence in photodegradation was accomplished by hybridizing f-MWCNTs with CdS or Ag2S PMID:22267895

G4RNA: an RNA G-quadruplex database

PubMed Central

Garant, Jean-Michel; Luce, Mikael J.; Scott, Michelle S.

2015-01-01

Abstract G-quadruplexes (G4) are tetrahelical structures formed from planar arrangement of guanines in nucleic acids. A simple, regular motif was originally proposed to describe G4-forming sequences. More recently, however, formation of G4 was discovered to depend, at least in part, on the contextual backdrop of neighboring sequences. Prediction of G4 folding is thus becoming more challenging as G4 outlier structures, not described by the originally proposed motif, are increasingly reported. Recent observations thus call for a comprehensive tool, capable of consolidating the expanding information on tested G4s, in order to conduct systematic comparative analyses of G4-promoting sequences. The G4RNA Database we propose was designed to help meet the need for easily-retrievable data on known RNA G4s. A user-friendly, flexible query system allows for data retrieval on experimentally tested sequences, from many separate genes, to assess G4-folding potential. Query output sorts data according to sequence position, G4 likelihood, experimental outcomes and associated bibliographical references. G4RNA also provides an ideal foundation to collect and store additional sequence and experimental data, considering the growing interest G4s currently generate. Database URL: scottgroup.med.usherbrooke.ca/G4RNA PMID:26200754

The complex of PAMAM-OH dendrimer with Angiotensin (1-7) prevented the disuse-induced skeletal muscle atrophy in mice.

PubMed

Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

2017-01-01

Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier. Bioinformatics analysis showed that the Ang-(1-7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1-7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1-7)/PAMAM-OH complex, but not Ang-(1-7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1-7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1-7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1-7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1-7)/PAMAM-OH complex is an efficient delivery method for Ang-(1-7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

PAMAM-Based Dendrimers with Different Alkyl Chains Self-Assemble on Silica Surfaces: Controllable Layer Structure and Molecular Aggregation.

PubMed

Zhang, Minghui; Yang, Hui; Wang, Shujuan; Zhang, Wei; Hou, Qingfeng; Guo, Donghong; Liu, Fanghui; Chen, Ting; Wu, Xu; Wang, Jinben

2018-06-20

Amphiphilic poly(amidoamine) (PAMAM) dendrimers are a well-known dendritic family due to their remarkable ability to self-assemble on solid surface. However, the relationship between molecular conformation (or adsorption kinetics) of a self-assembled layer and molecular amphiphilicity of such kind of dendrimer is still lacking, which limits the development of modulating self-assembling structures and surface functionality. With this in mind, we synthesized a series of amphiphilic PAMAM-based dendrimers, denoted as G 1 C n , with different alkyl chains ( n = 8, 12, and 16), and investigated the molecular aggregation on silica surfaces by means of quartz crystal microbalance with dissipation, atomic force microscopy, and contact angle. After rinsing, remaining adsorption amounts of G 1 C 12 were higher than those of G 1 C 8 at high concentrations, suggesting that G 1 C 12 adlayers were more stable due to the stronger intermolecular hydrophobic interactions, whereas it preferred to adopt the intramolecular hydrophobic interactions for G 1 C 16 , with low adsorption amounts and unstable adlayers. Bilayer-like structures were inferred in G 1 C 8 and G 1 C 12 adlayers with loose conformation, whereas monolayer structures were likely to exist in the sparse adsorption film of G 1 C 16 . Our results provided more detailed understanding of the effect of molecular structure on the self-assembled structures of amphiphilic dendrimers on solid surfaces, shedding light on the controlled microstructure and wettability of functional surface by modulating the length of hydrophobic chains of dendrimers and a potential application of dendrimer-substrate combinations.

Study of Adsorption Mechanism of Congo Red on Graphene Oxide/PAMAM Nanocomposite

PubMed Central

Rafi, Mohammad; Samiey, Babak; Cheng, Chil-Hung

2018-01-01

Graphene oxide/poly(amidoamine) (GO/PAMAM) nanocomposite adsorbed high quantities of congo red (CR) anionic dye in 0.1 M NaCl solution, with the maximum adsorption capacity of 198 mg·g−1. The kinetics and thermodynamics of adsorption were investigated to elucidate the effects of pH, temperature, shaking rate, ionic strength, and contact time. Kinetic data were analyzed by the KASRA model and the KASRA, ISO, and pore-diffusion equations. Adsorption adsorption isotherms were studied by the ARIAN model and the Henry, Langmuir, and Temkin equations. It was shown that adsorption sites of GO/PAMAM at experimental conditions were phenolic hydroxyl groups of GO sheets and terminal amine groups of PAMAM dendrimer. Analysis of kinetic data indicated that amine sites were located on the surface, and that hydroxyl sites were placed in the pores of adsorbent. CR molecules interacted with the adsorption sites via hydrogen bonds. The molecules were adsorbed firstly on the amine sites, and then on the internal hydroxyl sites. Adsorption kinetic parameters indicated that the interaction of CR to the –NH3+ sites was the rate-controlling step of adsorption of CR on this site and adsorption activation energies calculated for different parts of this step. On the other hand, kinetic parameters showed that the intraparticle diffusion was the rate-controlling step during the interaction of CR molecules to –OH sites and activation energy of this step was not calculable. Finally, the used GO/PAMAM was completely regenerated by using ethylenediamine. PMID:29587463

Accuracy and trending ability of the fourth-generation FloTrac/Vigileo System™ in patients undergoing abdominal aortic aneurysm surgery.

PubMed

Maeda, Takuma; Hattori, Kohshi; Sumiyoshi, Miho; Kanazawa, Hiroko; Ohnishi, Yoshihiko

2018-06-01

The fourth-generation FloTrac/Vigileo™ improved its algorithm to follow changes in systemic vascular resistance index (SVRI). This revision may improve the accuracy and trending ability of CI even in patients who undergo abdominal aortic aneurysm (AAA) surgery which cause drastic change of SVRI by aortic clamping. The purpose of this study is to elucidate the accuracy and trending ability of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery by comparing the FloTrac/Vigileo™-derived CI (CI FT ) with that measured by three-dimensional echocardiography (CI 3D ). Twenty-six patients undergoing elective AAA surgery were included in this study. CI FT and CI3 D were determined simultaneously in eight points including before and after aortic clamp. We used CI 3D as the reference method. In the Bland-Altman analysis, CI FT had a wide limit of agreement with CI 3D showing a percentage error of 46.7%. Subgroup analysis showed that the percentage error between CO 3D and CO FT was 56.3% in patients with cardiac index < 2.5 L/min/m 2 and 28.4% in patients with cardiac index ≥ 2.5 L/min/m 2 . SVRI was significantly higher in patients with cardiac index < 2.5 L/min/m 2 (1703 ± 330 vs. 2757 ± 798; p < 0.001). The tracking ability of fourth generation of FloTrac/Vigileo™ after aortic clamp was not clinically acceptable (26.9%). The degree of accuracy of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery was not acceptable. The tracking ability of the fourth-generation FloTrac/Vigileo™ after aortic clamp was below the acceptable limit.

Fourth-generation Mars vehicle concepts

NASA Astrophysics Data System (ADS)

Sherwood, Brent

1994-09-01

Conceptual designs for fourth-generation crew-carrying Mars transfer and excursion vehicles, fully integrated to state-of-the-art standards, are presented. The resulting vehicle concepts are sized for six crew members, and can support all opposition and conjunction opportunities in or after 2014. The modular, reusable transfer ship is launched to Earth orbit on six 185-ton-class boosters and assembled there robotically. Its dual nuclear-thermal rocket engines use liquid hydrogen propollant. The payload consists of a microgravity habitation system and an expendable lift-to-drag = 1.6 lander capable of aeromaneuvering to sites within +/- 20 deg of the equator. This lander can deliver either an expendable, storable-bipropellant crew-carrying ascent vehicle, or 40 tons of cargo, and it is capable of limited surface mobility to support base buildup. Multiple cargo landers sent ahead on robotic transfer vehicles deliver the supplies and equipment required for long-duration surface missions.

Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue.

PubMed

Hubbard, Dallin; Bond, Tanner; Ghandehari, Hamidreza

2015-12-01

Intestinal permeability of PAMAM dendrimers has been observed, giving rationale for their use in oral drug delivery as potential carriers of associated molecules. This study assessed the apparent permeability coefficients (Papp) of dendrimers across isolated rat intestinal regional mucosae, along with estimation of the maximum non-toxic concentration. Caco-2 monolayers were also used to assess the comparative Papp values between isolated mucosae and cell culture models. Concentrations from 0.1 to 10 mM of anionic and cationic dendrimers were tested in mucosae to assess their Papp, membrane TEER, [(14)C]-mannitol Papp, and histology. 0.1 mM concentrations of dendrimers were assessed over 120 min in Caco-2 cell monolayers as concentrations above that were cytotoxic. Jejunal transport of dendrimers was higher than transport in colonic epithelium. Monolayer Papp values of dendrimers were comparable to those of jejunal mucosae. Mucosae exposed to dendrimer concentrations of 10 mM for 120 min caused significant reduction in TEER and changes in tissue morphology; however, G3.5 was the only analogue that caused significant TEER reduction and morphological changes at 1 mM concentrations. Transport in jejunal mucosae appears to be the greatest indicating that the small intestinal will be the most likely region to target for oral drug delivery using PAMAM dendrimers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Validated Open-Source Multisolver Fourth-Generation Composite Femur Model.

PubMed

MacLeod, Alisdair R; Rose, Hannah; Gill, Harinderjit S

2016-12-01

Synthetic biomechanical test specimens are frequently used for preclinical evaluation of implant performance, often in combination with numerical modeling, such as finite-element (FE) analysis. Commercial and freely available FE packages are widely used with three FE packages in particular gaining popularity: abaqus (Dassault Systèmes, Johnston, RI), ansys (ANSYS, Inc., Canonsburg, PA), and febio (University of Utah, Salt Lake City, UT). To the best of our knowledge, no study has yet made a comparison of these three commonly used solvers. Additionally, despite the femur being the most extensively studied bone in the body, no freely available validated model exists. The primary aim of the study was primarily to conduct a comparison of mesh convergence and strain prediction between the three solvers (abaqus, ansys, and febio) and to provide validated open-source models of a fourth-generation composite femur for use with all the three FE packages. Second, we evaluated the geometric variability around the femoral neck region of the composite femurs. Experimental testing was conducted using fourth-generation Sawbones® composite femurs instrumented with strain gauges at four locations. A generic FE model and four specimen-specific FE models were created from CT scans. The study found that the three solvers produced excellent agreement, with strain predictions being within an average of 3.0% for all the solvers (r2 > 0.99) and 1.4% for the two commercial codes. The average of the root mean squared error against the experimental results was 134.5% (r2 = 0.29) for the generic model and 13.8% (r2 = 0.96) for the specimen-specific models. It was found that composite femurs had variations in cortical thickness around the neck of the femur of up to 48.4%. For the first time, an experimentally validated, finite-element model of the femur is presented for use in three solvers. This model is freely available online along with all the supporting validation data.

Review on the targeted conjugation of anticancer drugs doxorubicin and tamoxifen with synthetic polymers for drug delivery.

PubMed

Sanyakamdhorn, S; Agudelo, D; Tajmir-Riahi, H A

2017-08-01

In this review, the binding and loading efficacy (LE) of anticancer drugs doxorubicin (DOX), tamoxifen (Tam) and its metabolites 4-hydroxytamoxifen (4-Hydroxytam) and endoxifen (Endox) with several synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3), and polyamidoamine (PAMAM-G4) dendrimers were compared in aqueous solution at pH 7.4. The results of multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling of conjugated drug-polymer were examined. Structural analysis showed that drug-polymer conjugation occurs mainly via H-bonding and hydrophobic contacts. The order of binding is PAMAM-G4 > mPEG-PAMAM-G3 > PEG-6000 with 4-hydroxttamoxifen forming more stable conjugate than tamoxifen and endoxifen. Doxorubicin shows stronger affinity for PAMAM-G4 than tamoxifen and its metabolites. The drug LE was 30-55%. TEM showed significant changes in the carrier morphology upon drug encapsulation. Modeling also showed that drug is located in the surface and in the internal cavities of PAMAM with DOX forming more stable polymer conjugates.

Toward a fourth-generation x-ray source.

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

Monction, D. E.

1999-05-19

The field of synchrotron radiation research has grown rapidly over the last 25 years due to both the push of the accelerator and magnet technology that produces the x-ray beams and the pull of the extraordinary scientific research that is possible with them. Three successive generations of synchrotrons radiation facilities have resulted in beam brilliances 11 to 12 orders of magnitude greater than the standard laboratory x-ray tube. However, greater advances can be easily imagined given the fact that x-ray beams from present-day facilities do not exhibit the coherence or time structure so familiar with the optical laser. Theoretical workmore » over the last ten years or so has pointed to the possibility of generating hard x-ray beams with laser-like characteristics. The concept is based on self-amplified spontaneous emission (SASE) in flee-electron lasers. A major facility of this type based upon a superconducting linac could produce a cost-effective facility that spans wave-lengths from the ultraviolet to the hard x-ray regime, simultaneously servicing large numbers experimenters from a wide range of disciplines. As with each past generation of synchrotrons facilities, immense new scientific opportunities would result from fourth-generation sources.« less

A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells

PubMed Central

Zhou, Yanfang; Li, Jiemei; Lu, Fang; Deng, Junjie; Zhang, Jiahua; Fang, Peijie; Peng, Xinsheng; Zhou, Shu-Feng

2015-01-01

Dendrimers are hyperbranched macromolecules with well-defined topological structures and multivalent functionalization sites, but they may cause cytotoxicity due to the presence of cationic charge. Recently, we have introduced alkyne-terminated poly(amidoamine) (PAMAM) dendrons of different generations (G=2,3) into chitosan to obtain dendronized chitosan derivatives [Cs-g-PAMAM (G=2,3)], which exhibited a better water solubility and enhanced plasmid DNA transfection efficiency. In this study, we attempted to examine the impact of Cs-g-PAMAM (G=2,3) at different concentrations (25 μg/mL, 50 μg/mL, and 100 μg/mL) on the morphology, surface structure, and viability of rat red blood cells (RBCs). The results showed that treatment of RBCs with Cs-g-PAMAM (G=2,3) at 50 μg/mL and 100 μg/mL induced a slightly higher hemolysis than Cs, and Cs-g-PAMAM (G=3) caused a slightly higher hemolysis than Cs-g-PAMAM (G=2), but all values were <5.0%. Optical microscopic and atomic force microscopic examinations indicated that Cs-g-PAMAM (G=2,3) caused slight RBC aggregation and lysis. Treatment of RBCs with 100 μg/mL Cs-g-PAMAM (G=3) induced echinocytic transformation, and RBCs displayed characteristic irregular contour due to the folding of the periphery. Drephanocyte-like RBCs were observed when treated with 100 μg/mL Cs-g-PAMAM (G=3). Erythrocytes underwent similar shape transition upon treatment with Cs-g-PAMAM (G=2) or Cs. The roughness values (Rms) of RBCs incubated with Cs-g-PAMAM (G=2,3) were significantly larger than those for RBCs incubated with physiological saline (P<0.01), but the Rms showed no difference for Cs and Cs-g-PAMAM (G=2,3) (P>0.05). Furthermore, Cs-g-PAMAM (G=2,3) exhibited a lower cytotoxicity in human kidney 293T cells. These results indicate that Cs-g-PAMAM (G=2,3) are hemocompatible but may disturb membrane and lipid structures at higher concentrations. Further safety and biocompatibility evaluations are warranted for Cs-g-PAMAM. Our findings prove

The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

PubMed Central

Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

2017-01-01

Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle. PMID:28331320

Magnetic layering transitions in a polyamidoamine (PAMAM) dendrimer nano-structure: Monte Carlo study

NASA Astrophysics Data System (ADS)

Ziti, S.; Aouini, S.; Labrim, H.; Bahmad, L.

2017-02-01

We study the magnetic layering transitions in a polyamidoamine (PAMAM) dendrimer nano-structure, under the effect of an external magnetic field. We examine the magnetic properties, of this model of the spin S=1 Ising ferromagnetic in real nanostructure used in several scientific domains. For T=0, we give and discuss the ground state phase diagrams. At non null temperatures, we applied the Monte Carlo simulations giving important results summarized in the form of the phase diagrams. We also analyzed the effect of varying the external magnetic field, and found the layering transitions in the polyamidoamine (PAMAM) dendrimer nano-structure.

Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

NASA Astrophysics Data System (ADS)

Kurtoglu, Yunus Emre

The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

PAMAM Dendrimers Cross the Blood-Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice.

PubMed

Srinageshwar, Bhairavi; Peruzzaro, Sarah; Andrews, Melissa; Johnson, Kayla; Hietpas, Allison; Clark, Brittany; McGuire, Crystal; Petersen, Eric; Kippe, Jordyn; Stewart, Andrew; Lossia, Olivia; Al-Gharaibeh, Abeer; Antcliff, Aaron; Culver, Rebecca; Swanson, Douglas; Dunbar, Gary; Sharma, Ajit; Rossignol, Julien

2017-03-14

Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH₂ and G4-NH₂) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders.

PAMAM Dendrimers Cross the Blood–Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice

PubMed Central

Srinageshwar, Bhairavi; Peruzzaro, Sarah; Andrews, Melissa; Johnson, Kayla; Hietpas, Allison; Clark, Brittany; McGuire, Crystal; Petersen, Eric; Kippe, Jordyn; Stewart, Andrew; Lossia, Olivia; Al-Gharaibeh, Abeer; Antcliff, Aaron; Culver, Rebecca; Swanson, Douglas; Dunbar, Gary; Sharma, Ajit; Rossignol, Julien

2017-01-01

Drug delivery into the central nervous system (CNS) is challenging due to the blood–brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH2 and G4-NH2) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders PMID:28335421

Charge-dependent conformations and dynamics of pamam dendrimers revealed by neutron scattering and molecular dynamics

NASA Astrophysics Data System (ADS)

Wu, Bin

, at neutral condition, the exterior residues folding back into interior would necessarily lead to higher entropy and equivalently lower free energy and thereby is energetically favored. As one decreases the pH condition of PAMAM dendrimers, the constituent residues would carry positive charges. The resultant inter-residue Coulomb repulsion would naturally result in conformational evolution. We found from CVSANS analysis that when dendrimers are charged by different acids, this conformational evolution is not the same. For dendrimers charged by DCl, the mass is seen to relocate from molecular interior to periphery. Nevertheless, those acidified by D 2SO4 exhibit surprisingly minor structural change under variation of molecular charge. To explain the above observation, we performed MD simulations and calculated the excess free energy of Cl- and SO 42- counterions. The binding between sulfate ions and charged amines of PAMAM dendrimers are found to be much stronger than the case for chlorides. This more energetic binding would serve as better screening effect among charged residues. Consequently, electrostatic repulsion triggered outstretching tendency is effectively diminished. In order to make direct comparison between MD simulations and neutron scattering experiments, we proposed and implemented a rigorous method, which incorporates the contribution from those invasive water molecules, to calculate scattering functions of a single PAMAM dendrimer using equilibrium MD trajectories. The bridge between neutron scattering experiments and MD simulation is successfully established. Aside from structural comparisons between MD simulations and experiments, we utilized MD simulation to decipher the previously reported QENS experimental observation that the segmental dynamics of PAMAM dendrimer would enhance with increasing molecular charge. We pursued the mechanism from the perspective of hydrocarbon component of dendrimer and solvent (water) interaction as a form similar to

Nanopore-based fourth-generation DNA sequencing technology.

PubMed

Feng, Yanxiao; Zhang, Yuechuan; Ying, Cuifeng; Wang, Deqiang; Du, Chunlei

2015-02-01

Nanopore-based sequencers, as the fourth-generation DNA sequencing technology, have the potential to quickly and reliably sequence the entire human genome for less than $1000, and possibly for even less than $100. The single-molecule techniques used by this technology allow us to further study the interaction between DNA and protein, as well as between protein and protein. Nanopore analysis opens a new door to molecular biology investigation at the single-molecule scale. In this article, we have reviewed academic achievements in nanopore technology from the past as well as the latest advances, including both biological and solid-state nanopores, and discussed their recent and potential applications. Copyright © 2015 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

American Military History and its Insights into Fourth Generation Warfare

DTIC Science & Technology

2006-01-01

8William S . Lind, Colonel Keith Nightengale (USA), Captain John F. Schmitt (USMC), Colonel Joseph W. Sutton (USA), and Lieutenant Colonel Gary I. Wilson...Lind, William S ., Colonel Keith Nightengale (USA), Captain John F. Schmitt (USMC), Colonel Joseph W. Sutton (USA), and Lieutenant Colonel Gary I...military history and its insights into fourth generation warfare. 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S

Transepithelial and endothelial transport of poly (amidoamine) dendrimers.

PubMed

Kitchens, Kelly M; El-Sayed, Mohamed E H; Ghandehari, Hamidreza

2005-12-14

This article summarizes our efforts to evaluate the potential of poly (amidoamine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the permeability of a series of cationic PAMAM-NH2 (G0-G4) dendrimers across Caco-2 cell monolayers was evaluated as a function of dendrimer generation, concentration, and incubation time. The influence of dendrimer surface charge on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers was monitored by measuring the transepithelial electrical resistance (TEER), 14C-mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. Microvascular extravasation of PAMAM-NH2 dendrimers in relation to their size, molecular weight, and molecular geometry is also discussed. Results of these studies show that transepithelial transport and microvascular extravasation of PAMAM dendrimers are dependent on their structural features including molecular size, molecular geometry, and surface chemistry. These results suggest that by optimizing the size and surface charge of PAMAM dendrimers, it is possible to develop oral delivery systems based on these carriers for targeted drug delivery.

Solid surface fluorescence immunosensor for ultrasensitive detection of hepatitis B virus surface antigen using PAMAM/CdTe@CdS QDs nanoclusters.

PubMed

Babamiri, Bahareh; Hallaj, Rahman; Salimi, Abdollah

2018-06-20

In the present study, we constructed an ultrasensitive solid surface fluorescence-immunosensor based on highly luminescent CdTe@CdS-PAMAM structures as nanoprobe for determination of HBsAg by monitoring fluorescence intensity. This strategy was achieved by using PAMAM as a signal amplifier; the PAMAM dendrimer with the many functional amine groups can amplify the fluorescence signal of QDs by covalent attachment of CdTe@CdS on PAMAM and hence, improve the sensitivity of the proposed method significantly. A sandwich type immunosensor was formed after the addition of HBsAg and the PAMAM-QD-Ab 2 , respectively. Under optimal conditions, the designed immunosensor demonstrates a good analytical performance for the HBsAg detection in an excellent linear range from 5 fg ml -1 to 0.15 ng ml -1 with the detection limit (LOD) of 0.6 fg ml -1 at a S/N ratio of 3. In addition, the analysis of human serum samples shows that the fluorescent immunoassay has the great potential for early diagnosis of hepatitis B and can be used for the detection of other tumor markers in clinical applications.

Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

PubMed Central

Nomani, Alireza; Haririan, Ismaeil; Rahimnia, Ramin; Fouladdel, Shamileh; Gazori, Tarane; Dinarvand, Rassoul; Omidi, Yadollah; Azizi, Ebrahim

2010-01-01

To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer. AFM images also showed that such nanoparticles were spherical. The stability of the antisense content of the nanoparticles was investigated over different charge ratios using polyacrylamide gel electrophoresis. It was clear from such analyses that much more than charge neutrality point was required to obtain stable nanoparticles. For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5’-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture. This investigation also shows that the cytotoxicity of the nanoparticles was dependent upon the generation and charge ratio of the PAMAM dendrimer, and the antisense concentration had no significant effect on the cytotoxicity. PMID:20517481

Conformal completion of the standard model with a fourth generation

NASA Astrophysics Data System (ADS)

Ho, Chiu Man; Hung, Pham Q.; Kephart, Thomas W.

2012-06-01

We study dynamical electroweak symmetry breaking with a fourth generation within the Z n orbifolded AdS 5 ⊗ S 5 framework. A realistic Z 7 example is discussed. The initial theory reduces dynamically, due to the induced condensates, to a four-family trinification near a TeV-scale conformal fixed point where the gauge hierarchy problem does not exist. We predict new gauge bosons and bifundamental fermions and scalars accessible by the LHC.

Secure Military Communications on 3G, 4G and WiMAX

DTIC Science & Technology

2013-09-01

per bit, low latency, good quality of service, good coverage and support for mobility at high speeds. Thus, 4G wireless technologies are based on 3G ...security for military communications. 87 LIST OF REFERENCES [1] C. Blanchard, “Security for the third generation ( 3G ) mobile system,” Elsevier Science...COMMUNICATIONS ON 3G , 4G AND WIMAX by Panagiotis Schoinas September 2013 Thesis Advisor: Gurminder Singh Co-Advisor: John H. Gibson

SCALS: a fourth-generation study of assisted living technologies in their organisational, social, political and policy context.

PubMed

Greenhalgh, Trisha; Shaw, Sara; Wherton, Joe; Hughes, Gemma; Lynch, Jenni; A'Court, Christine; Hinder, Sue; Fahy, Nick; Byrne, Emma; Finlayson, Alexander; Sorell, Tom; Procter, Rob; Stones, Rob

2016-02-15

Research to date into assisted living technologies broadly consists of 3 generations: technical design, experimental trials and qualitative studies of the patient experience. We describe a fourth-generation paradigm: studies of assisted living technologies in their organisational, social, political and policy context. Fourth-generation studies are necessarily organic and emergent; they view technology as part of a dynamic, networked and potentially unstable system. They use co-design methods to generate and stabilise local solutions, taking account of context. SCALS (Studies in Co-creating Assisted Living Solutions) consists (currently) of 5 organisational case studies, each an English health or social care organisation striving to introduce technology-supported services to support independent living in people with health and/or social care needs. Treating these cases as complex systems, we seek to explore interdependencies, emergence and conflict. We employ a co-design approach informed by the principles of action research to help participating organisations establish, refine and evaluate their service. To that end, we are conducting in-depth ethnographic studies of people's experience of assisted living technologies (micro level), embedded in evolving organisational case studies that use interviews, ethnography and document analysis (meso level), and exploring the wider national and international context for assisted living technologies and policy (macro level). Data will be analysed using a sociotechnical framework developed from structuration theory. Research ethics approval for the first 4 case studies has been granted. An important outcome will be lessons learned from individual co-design case studies. We will document the studies' credibility and rigour, and assess the transferability of findings to other settings while also recognising unique aspects of the contexts in which they were generated. Academic outputs will include a cross-case analysis and

SCALS: a fourth-generation study of assisted living technologies in their organisational, social, political and policy context

PubMed Central

Greenhalgh, Trisha; Shaw, Sara; Wherton, Joe; Hughes, Gemma; Lynch, Jenni; A'Court, Christine; Hinder, Sue; Fahy, Nick; Byrne, Emma; Finlayson, Alexander; Sorell, Tom; Procter, Rob; Stones, Rob

2016-01-01

Introduction Research to date into assisted living technologies broadly consists of 3 generations: technical design, experimental trials and qualitative studies of the patient experience. We describe a fourth-generation paradigm: studies of assisted living technologies in their organisational, social, political and policy context. Fourth-generation studies are necessarily organic and emergent; they view technology as part of a dynamic, networked and potentially unstable system. They use co-design methods to generate and stabilise local solutions, taking account of context. Methods and analysis SCALS (Studies in Co-creating Assisted Living Solutions) consists (currently) of 5 organisational case studies, each an English health or social care organisation striving to introduce technology-supported services to support independent living in people with health and/or social care needs. Treating these cases as complex systems, we seek to explore interdependencies, emergence and conflict. We employ a co-design approach informed by the principles of action research to help participating organisations establish, refine and evaluate their service. To that end, we are conducting in-depth ethnographic studies of people's experience of assisted living technologies (micro level), embedded in evolving organisational case studies that use interviews, ethnography and document analysis (meso level), and exploring the wider national and international context for assisted living technologies and policy (macro level). Data will be analysed using a sociotechnical framework developed from structuration theory. Ethics and dissemination Research ethics approval for the first 4 case studies has been granted. An important outcome will be lessons learned from individual co-design case studies. We will document the studies’ credibility and rigour, and assess the transferability of findings to other settings while also recognising unique aspects of the contexts in which they were generated

Electrostatic theory of the assembly of PAMAM dendrimers and DNA.

PubMed

Perico, Angelo

2016-05-01

The electrostatic interactions mediated by counterions between a cationic PAMAM dendrimer, modelized as a sphere of radius and cationic surface charge highly increasing with generation, and a DNA, modelized as an anionic elastic line, are analytically calculated in the framework of condensation theory. Under these interactions the DNA is wrapped around the sphere. For excess phosphates relative to dendrimer primary amines, the free energy of the DNA-dendrimer complex displays an absolute minimum when the complex is weakly negatively overcharged. This overcharging opposes gene delivery. For a highly positive dendrimer and a DNA fixed by experimental conditions to a number of phosphates less than the number of dendrimer primary amines, excess amine charges, the dendrimer may at the same time bind stably DNA and interact with negative cell membranes to activate cell transfection in fair agreement with molecular simulations and experiments. © 2016 Wiley Periodicals, Inc.

Modulated regeneration of acid-etched human tooth enamel by a functionalized dendrimer that is an analog of amelogenin.

PubMed

Chen, Mei; Yang, Jiaojiao; Li, Jiyao; Liang, Kunneng; He, Libang; Lin, Zaifu; Chen, Xingyu; Ren, Xiaokang; Li, Jianshu

2014-10-01

In the bioinspired repair process of tooth enamel, it is important to simultaneously mimic the organic-matrix-induced biomineralization and increase the binding strength at the remineralization interface. In this work, a fourth-generation polyamidoamine dendrimer (PAMAM) is modified by dimethyl phosphate to obtain phosphate-terminated dendrimer (PAMAM-PO3H2) since it has a similar dimensional scale and peripheral functionalities to that of amelogenin, which plays important role in the natural development process of enamel. Its phosphate group has stronger affinity for calcium ion than carboxyl group and can simultaneously provide strong hydroxyapatite (HA)-binding capability. The MTT assay demonstrates the low cytotoxicity of PAMAM-PO3H2. Adsorption tests indicate that PAMAM-PO3H2 can be tightly adsorbed on the human tooth enamel. Scanning electron microscopy and X-ray diffraction are used to analyze the remineralization process. After being incubated in artificial saliva for 3weeks, there is a newly generated HA layer of 11.23μm thickness on the acid-etched tooth enamel treated by PAMAM-PO3H2, while the thickness for the carboxyl-terminated one (PAMAM-COOH) is only 6.02μm. PAMAM-PO3H2 can regulate the remineralization process to form ordered new crystals oriented along the Z-axis and produce an enamel prism-like structure that is similar to that of natural tooth enamel. The animal experiment also demonstrates that PAMAM-PO3H2 can induce significant HA regeneration in the oral cavity of rats. Thus PAMAM-PO3H2 shows great potential as a biomimetic restorative material for human tooth enamel. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Development of a fourth generation predictive capability maturity model.

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

Hills, Richard Guy; Witkowski, Walter R.; Urbina, Angel

2013-09-01

The Predictive Capability Maturity Model (PCMM) is an expert elicitation tool designed to characterize and communicate completeness of the approaches used for computational model definition, verification, validation, and uncertainty quantification associated for an intended application. The primary application of this tool at Sandia National Laboratories (SNL) has been for physics-based computational simulations in support of nuclear weapons applications. The two main goals of a PCMM evaluation are 1) the communication of computational simulation capability, accurately and transparently, and 2) the development of input for effective planning. As a result of the increasing importance of computational simulation to SNLs mission, themore » PCMM has evolved through multiple generations with the goal to provide more clarity, rigor, and completeness in its application. This report describes the approach used to develop the fourth generation of the PCMM.« less

A serum-resistant polyamidoamine-based polypeptide dendrimer for gene transfection.

PubMed

Wu, H M; Pan, S R; Chen, M W; Wu, Y; Wang, C; Wen, Y T; Zeng, X; Wu, C B

2011-02-01

A serum tolerant polycation gene vector, G(2) PAMAM-PGlu-G(1) PAMAMs (ALA), was designed, synthesized, characterized and evaluated. A honeycomb-like molecular structure model for mechanistic explanation of ALA was postulated and discussed. Designed as a star-shaped polyamidoamine (PAMAM)-based polypeptide dendrimer through peptide bond linkages, ALA was with non-toxic low generation G(2) PAMAM (G(2)) as its central core, polyglutamate (PGlu)s as its star-shaped backbone branches and G(1) PAMAM (G(1))s as its branch grafts and peripheral terminals. IR, (1)H NMR demonstrated its successful combination. As a gene carrier, ALA exhibited good DNA binding and condensation capacity with particle size (approximately 87 nm for N/P 40, approximately 170 nm for N/P 30) and ζ-potential (approximately 16 mV for N/P 30-40), negligible cytotoxicity, exciting serum tolerant capacity and significant serum-promoted (serum-containing 56.6%>serum-free 32.7%), cell line dependent (Hek 293 > Bel 7402 > Hela), incubation period dependent (38 h > 18 h > 12 h > 9 h > 4 h > 2 h > 1 h) and sustained (peak transfection appeared at 30 h incubation) transfection efficiency. The presence of serum had not only no inhibition on, but also prominent promotion to, the transfection activity of ALA. All above features differentiated ALA clearly from most other serum-inhibitive nonviral gene carriers, and proved ALA the promising and challenging potential efficient gene vector for practical clinical application. 2010 Elsevier Ltd. All rights reserved.

Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: molecular mechanism of IgG4 reaction in cancer tissue.

PubMed

Harada, Kenichi; Shimoda, Shinji; Kimura, Yasushi; Sato, Yasunori; Ikeda, Hiroko; Igarashi, Saya; Ren, Xiang-Shan; Sato, Hirohide; Nakanuma, Yasuni

2012-07-01

IgG4 reactions consisting of marked infiltration by immunoglobulin G4 (IgG4)-positive plasma cells in affected organs is found in cancer patients as well as patients with IgG4-related diseases. Notably, extrahepatic cholangiocarcinomas accompanying marked IgG4 reactions clinicopathologically mimic IgG4-related sclerosing cholangitis. The regulatory cytokine interleukin (IL)-10 is thought to induce the differentiation of IgG4-positive cells. In this study, to clarify the mechanism of the IgG4 reaction in extrahepatic cholangiocarcinoma, we investigated nonprofessional antigen-presenting cells (APCs) generating IL-10-producing regulatory T cells (anergy T cells) and Foxp3-positive regulatory cells producing IL-10. Immunohistochemistry targeting IgG4, HLA-DR, CD80, CD86, and Foxp3 was performed using 54 cholangiocarcinoma specimens from 24 patients with gallbladder cancer, 22 patients with common bile duct cancer, and eight patients with cancer of the Papilla of Vater. Moreover, a molecular analysis of Foxp3 and IL-10 was performed using a cultured human cholangiocarcinoma cell line. Consequently, 43% of the cholangiocarcinomas were found to be abundant in IgG4. Those expressing HLA-DR but lacking costimulatory molecules (CD80 and CD86) and those expressing Foxp3 detected by an antibody recognizing the N terminus accounted for 54% and 39% of cases, respectively. Moreover, the number of IgG4-positive cells was larger in these cases than in other groups. In cultured cells, the presence of a splicing variant of Foxp3 messenger RNA and the expression of IL-10 were demonstrated. Extrahepatic cholangiocarcinoma is often accompanied by significant infiltration of IgG4-positive cells. Cholangiocarcinoma cells could play the role of nonprofessional APCs and Foxp3-positive regulatory cells, inducing IgG4 reactions via the production of IL-10 indirectly and directly, respectively. Copyright © 2012 American Association for the Study of Liver Diseases.

4. RAMP FOR BENJAMIN FRANKLIN BRIDGE (FOURTH ST.) BETWEEN VINE ...

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

4. RAMP FOR BENJAMIN FRANKLIN BRIDGE (FOURTH ST.) BETWEEN VINE AND RACE STS., LOOKING NORTHWEST - Independence National Historical Park, Walnut, Sixth, Chestnut & Second Streets, Philadelphia, Philadelphia County, PA

Combining UASB and the "fourth generation" down-flow hanging sponge reactor for municipal wastewater treatment.

PubMed

Tandukar, M; Uemura, S; Ohashi, A; Harada, H

2006-01-01

A "fourth generation" down-flow hanging sponge (DHS) Reactor has been developed and proposed as an improved variant of post-treatment system for UASB treating domestic wastewater. This paper evaluates the potential of the proposed combination of UASB and DHS as a sewage treatment system, especially for developing countries. A pilot-scale UASB (1.15 m3) and DHS (0.38 m3; volume of sponge) was installed in a municipal sewage treatment site and constantly monitored for 2 years. UASB was operated at an HRT of 6 h corresponding to an organic load of 2.15 kg-COD/m3 per day. Subsequently, the organic load in DHS was 2.35 kg-COD/m3 per day, operated at an HRT of 2 h. Organic removal by the whole system was satisfactory, accomplishing 96% of unfiltered BOD removal and 91% of unfiltered COD removal. However, nitrification decreased from 56% during the startup period to 28% afterwards. Investigation on DHS sludge was made by quantifying it and evaluating oxygen uptake rates with various substrates. Average concentration of trapped biomass was 26 g-VSS/L of sponge volume, increasing the SRT of the system to 100-125 d. Removal of coliforms obtained was 3-4 log10 with the final count of 10(3) to 10(4) MPN/100 ml in DHS effluent.

Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity.

PubMed

Jevprasesphant, Rachaneekorn; Penny, Jeffrey; Attwood, David; McKeown, Neil B; D'Emanuele, Antony

2003-10-01

To evaluate the cytotoxicity, permeation, and transport mechanisms of PAMAM dendrimers and surface-modified cationic PAMAM dendrimers using monolayers of the human colon adenocarcinoma cell line, Caco-2. Cytotoxicity was determined using the MTT assay. The effect of dendrimers on monolayer integrity was determined from measurements of transepithelial electrical resistance (TEER) and [14C]mannitol apparent permeability coefficient (Papp). The Papp of dendrimers through monolayers was measured in both the apical (A)-to-basolateral (B) and B --> A directions at 4 degrees C and 37 degrees C and also in the presence and absence of ethylenediamine tetraacetic acid (EDTA) and colchicine. The cytotoxicity and permeation of dendrimers increased with both concentration and generation. The cytotoxicity of cationic dendrimers (G2, G3, G4) was greater than that of anionic dendrimers (G2.5, G3.5) but was reduced by conjugation with lauroyl chloride: the least cytotoxic conjugates were those with six attached lauroyl chains. At 37 degrees C the Papp of cationic dendrimers was higher than that of anionic dendrimers and, in general, increased with the number of attached lipid chains. Cationic dendrimers decreased TEER and significantly increased the Papp of mannitol. Modified dendrimers also reduced TEER and caused a more marked increase in the Papp of mannitol. The Papp values of dendrimers and modified dendrimers were higher in the presence of EDTA, lower in the presence of colchicine, and lower at 4 degrees C than at 37 degrees C. The properties of dendrimers may be significantly modified by surface engineering. Conjugation of cationic PAMAM dendrimers with lauroyl chloride decreased their cytotoxicity and increased their permeation through Caco-2 cell monolayers. Both PAMAM dendrimers and lauroyl-PAMAM dendrimer conjugates can cross epithelial monolayers by paracellular and transcellular pathways.

Applying Fourth Generation Management to Access Services: Reinventing Customer Service and Process Management

ERIC Educational Resources Information Center

Hasty, Douglas F.

2004-01-01

Are librarians doing all they can to ensure that customer services are delivered with the customer in mind? Librarians are great at helping, but we sometimes need help with identifying customers, defining their needs, developing services, and reviewing the processes behind the services. Fourth Generation Management provides new insight for…

Polyamidoamine dendrimers as sweeping agent and stationary phase for rapid and sensitive open-tubular capillary electrophoretic determination of heavy metal ions.

PubMed

Ge, Ying; Guo, Yujun; Qin, Weidong

2014-04-01

Polyamidoamine (PAMAM) dendrimer generation 2.5 was synthesized and evaluated as sweeping agent for in-column enrichment and as stationary phase for capillary electrochromatographic separation of heavy metal ions, viz., Pb(II), Cu(II), Hg(II), Zn(II) and Co(II), in a running buffer containing 4-(2-pyridylazo)resorcinol (PAR) as a chromogenic reagent. During experiment, a plug of aqueous PAMAM generation 2.5 solution was first introduced to the capillary, followed by electrokinetic injection of the heavy metal ions under a positive voltage. In this step, PAMAM acted as a sweeping agent, stacking the metal ions on the analyte/PAMAM boundary by forming metal ion-PAMAM complexes. The second preconcentration process occurred when PAR, a stronger ligand, moving toward the injection end under the electric field, reached and re-swept the metal ion-PAMAM zone, forming metal ion-PAR complexes. During separation, the neutral PAMAM moved toward the detector with the electroosmotic flow, dynamically coating the capillary wall, forming stationary phases that affected the separation of the metal ions. Due to the function of PAMAM, the detection sensitivity and resolution of the heavy metal ions improved significantly. Under the optimum conditions, the detection limits were 0.299, 0.184, 0.774, 0.182 and 0.047 μg/L for Pb(II), Cu(II), Hg(II), Zn(II) and Co(II), respectively. The method was successfully applied to the determination of heavy metals in snow, tap and rain water samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer: an 17O and 1H relaxation study of its Gd(III) complex.

PubMed

Lebdusková, Petra; Sour, Angélique; Helm, Lothar; Tóth, Eva; Kotek, Jan; Lukes, Ivan; Merbach, André E

2006-07-28

A DTPA-based chelate containing one phosphinate group was conjugated to a generation 5 polyamidoamine (PAMAM) dendrimer via a benzylthiourea linkage. The Gd(III) complex of this novel conjugate has potential as a contrast agent for magnetic resonance imaging (MRI). The chelates bind Gd3+via three nitrogen atoms, four carboxylates and one phosphinate oxygen, and one water molecule completes the inner coordination sphere. The monomer Gd(III) chelates bearing nitrobenzyl and aminobenzyl groups ([Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-) as well as the dendrimeric Gd(III) complex G5-(Gd(DTTAP))63) were studied by multiple-field, variable temperature 17O and 1H NMR. The rate of water exchange is faster than that of [Gd(DTPA)(H2O)]2- and very similar on the two monomeric complexes (8.9 and 8.3 x 10(6) s-1 for [Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-, respectively), while it is decreased on the dendrimeric conjugate (5.0 x 10(6) s-1). The Gd(III) complex of the dendrimer conjugate has a relaxivity of 26.8 mM-1 s-1 at 37 degrees C and 0.47 T (corresponding to 1H Larmor frequency of 20 MHz). Given the contribution of the second sphere water molecules to the overall relaxivity, this value is slightly higher than those reported for similar size dendrimers. The experimental 17O and 1H NMR data were fitted to the Solomon-Bloembergen-Morgan equations extended with a contribution from second coordination sphere water molecules. The rotational dynamics of the dendrimeric conjugate was described in terms of global and local motions with the Lipari-Szabo approach.

Targeted conjugation of breast anticancer drug tamoxifen and its metabolites with synthetic polymers.

PubMed

Sanyakamdhorn, S; Agudelo, D; Bekale, L; Tajmir-Riahi, H A

2016-09-01

Conjugation of antitumor drug tamoxifen and its metabolites, 4-hydroxytamxifen and ednoxifen with synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3) and polyamidoamine (PAMAM-G4) dendrimers was studied in aqueous solution at pH 7.4. Multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were used to characterize the drug binding process to synthetic polymers. Structural analysis showed that drug-polymer binding occurs via both H-bonding and hydrophobic contacts. The order of binding is PAMAM-G4>mPEG-PAMAM-G3>PEG-6000 with 4-hydroxttamoxifen forming more stable conjugate than tamoxifen and endoxifen. Transmission electron microscopy showed significant changes in carrier morphology with major changes in the shape of the polymer aggregate as drug encapsulation occurred. Modeling also showed that drug is located in the surface and in the internal cavities of PAMAM with the free binding energy of -3.79 for tamoxifen, -3.70 for 4-hydroxytamoxifen and -3.69kcal/mol for endoxifen, indicating of spontaneous drug-polymer interaction at room temperature. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis and Catalytic Evaluation of Dendrimer-Encapsulated Cu Nanoparticles: An Undergraduate Experiment Exploring Catalytic Nanomaterials

ERIC Educational Resources Information Center

Feng, Z. Vivian; Lyon, Jennifer L.; Croley, J. Sawyer; Crooks, Richard M.; Vanden Bout, David A.; Stevenson, Keith J.

2009-01-01

Copper nanoparticles were synthesized using generation 4 hydroxyl-terminated (G4-OH) poly(amidoamine) (PAMAM) dendrimers as templates. The synthesis is conducted by coordinating copper ions with the interior amines of the dendrimer, followed by chemical reduction to form dendrimer-encapsulated copper nanoparticles (Cu-DEN). The catalytic…

Analysing generator matrices G of similar state but varying minimum determinants

NASA Astrophysics Data System (ADS)

Harun, H.; Razali, M. F.; Rahman, N. A. Abdul

2016-10-01

Since Tarokh discovered Space-Time Trellis Code (STTC) in 1998, a considerable effort has been done to improve the performance of the original STTC. One way of achieving enhancement is by focusing on the generator matrix G, which represents the encoder structure for STTC. Until now, researchers have only concentrated on STTCs of different states in analyzing the performance of generator matrix G. No effort has been made on different generator matrices G of similar state. The reason being, it is difficult to produce a wide variety of generator matrices G with diverse minimum determinants. In this paper a number of generator matrices G with minimum determinant of four (4), eight (8) and sixteen (16) of the same state (i.e., 4-PSK) have been successfully produced. The performance of different generator matrices G in term of their bit error rate and signal-to-noise ratio for a Rayleigh fading environment are compared and evaluated. It is found from the MATLAB simulation that at low SNR (<8), the BER of generator matrices G with smaller minimum determinant is comparatively lower than those of higher minimum determinant. However, at high SNR (>14) there is no significant difference between the BER of these generator matrices G.

Synthesis and evaluation of gadolinium complexes based on PAMAM as MRI contrast agents.

PubMed

Yan, Guo-Ping; Hu, Bin; Liu, Mai-Li; Li, Li-Yun

2005-03-01

Diethylenetriaminepentaacetic acid (DTPA) and pyridoxamine (PM) were incorporated into the amine groups on the surface of ammonia-core poly(amidoamine) dendrimers (PAMAM, Generation 2.0-5.0) to obtain dendritic ligands. These dendritic ligands were reacted with gadolinium chloride to yield the corresponding dendritic gadolinium (Gd) complexes. The dendritic ligands and their gadolinium complexes were characterized by(1)HNMR, IR, UV and elemental analysis. Relaxivity studies showed that the dendritic gadolinium complexes possessed higher relaxation effectiveness compared with the clinically used Gd-DTPA. After administration of the dendritic gadolinium complexes (0.09 mmol kg(-1) ) to rats, magnetic resonance imaging of the liver indicated that the dendritic gadolinium complexes containing pyridoxamine groups enhanced the contrast of the MR images of the liver, provided prolonged intravascular duration and produced highly contrasted visualization of blood vessels.

Quark-lepton flavor democracy and the nonexistence of the fourth generation

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

Cvetic, G.; Kim, C.S.

1995-01-01

In the standard model with two Higgs doublets (type II), which has a consistent trend to a flavor gauge theory and its related flavor democracy in the quark and the leptonic sectors (unlike the minimal standard model) when the energy of the probes increases, we impose the mixed quark-lepton flavor democracy at high transition'' energy and assume the usual seesaw mechanism, and consequently find out that the existence of the fourth generation of fermions in this framework is practically ruled out.

Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport.

PubMed

Hong, Seungpyo; Bielinska, Anna U; Mecke, Almut; Keszler, Balazs; Beals, James L; Shi, Xiangyang; Balogh, Lajos; Orr, Bradford G; Baker, James R; Banaszak Holl, Mark M

2004-01-01

We have investigated poly(amidoamine) (PAMAM) dendrimer interactions with supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers and KB and Rat2 cell membranes using atomic force microscopy (AFM), enzyme assays, flow cell cytometry, and fluorescence microscopy. Amine-terminated generation 7 (G7) PAMAM dendrimers (10-100 nM) were observed to form holes of 15-40 nm in diameter in aqueous, supported lipid bilayers. G5 amine-terminated dendrimers did not initiate hole formation but expanded holes at existing defects. Acetamide-terminated G5 PAMAM dendrimers did not cause hole formation in this concentration range. The interactions between PAMAM dendrimers and cell membranes were studied in vitro using KB and Rat 2 cell lines. Neither G5 amine- nor acetamide-terminated PAMAM dendrimers were cytotoxic up to a 500 nM concentration. However, the dose dependent release of the cytoplasmic proteins lactate dehydrogenase (LDH) and luciferase (Luc) indicated that the presence of the amine-terminated G5 PAMAM dendrimer decreased the integrity of the cell membrane. In contrast, the presence of acetamide-terminated G5 PAMAM dendrimer had little effect on membrane integrity up to a 500 nM concentration. The induction of permeability caused by the amine-terminated dendrimers was not permanent, and leaking of cytosolic enzymes returned to normal levels upon removal of the dendrimers. The mechanism of how PAMAM dendrimers altered cells was investigated using fluorescence microscopy, LDH and Luc assays, and flow cytometry. This study revealed that (1) a hole formation mechanism is consistent with the observations of dendrimer internalization, (2) cytosolic proteins can diffuse out of the cell via these holes, and (3) dye molecules can be detected diffusing into the cell or out of the cell through the same membrane holes. Diffusion of dendrimers through holes is sufficient to explain the uptake of G5 amine-terminated PAMAM dendrimers into cells and is consistent

A low-cost municipal sewage treatment system with a combination of UASB and the "fourth-generation" downflow hanging sponge reactors.

PubMed

Tandukar, M; Uemura, S; Machdar, I; Ohashi, A; Harada, H

2005-01-01

This paper presents an evaluation of the process performance of a pilot-scale "fourth generation" downflow hanging sponge (DHS) post-treatment system combined with a UASB pretreatment unit treating municipal wastewater. After the successful operation of the second- and third-generation DHS reactors, the fourth-generation DHS reactor was developed to overcome a few shortcomings of its predecessors. This reactor was designed to further enhance the treatment efficiency and simplify the construction process in real scale, especially for the application in developing countries. Configuration of the reactor was modified to enhance the dissolution of air into the wastewater and to avert the possible clogging of the reactor especially during sudden washout from the UASB reactor. The whole system was operated at a total hydraulic retention time (HRT) of 8 h (UASB: 6 h and DHS: 2 h) for a period of over 600 days. The combined system was able to remove 96% of unfiltered BOD with only 9 mg/L remaining in the final effluent. Likewise, F. coli were removed by 3.45 log with the final count of 10(3) to 10(4) MPN/100 ml. Nutrient removal by the system was also satisfactory.

Learning Progression of Ecological System Reasoning for Lower Elementary (G1-4) Students

ERIC Educational Resources Information Center

Hokayem, Hayat Al

2012-01-01

In this study, I utilized a learning progression framework to investigate lower elementary students (G1-4) systemic reasoning in ecology and I related students reasoning to their sources of knowledge. I used semi-structured interviews with 44 students from first through fourth grade, four teachers, and eight parents. The results revealed that a…

Joint Development of a Fourth Generation Single Crystal Superalloy

NASA Technical Reports Server (NTRS)

Walston, S.; Cetel, A.; MacKay, R.; OHara, K.; Duhl, D.; Dreshfield, R.

2004-01-01

A new, fourth generation, single crystal superalloy has been jointly developed by GE Aircraft Engines, Pratt & Whitney, and NASA. The focus of the effort was to develop a turbine airfoil alloy with long-term durability for use in the High Speed Civil Transport. In order to achieve adequate long-time strength improvements at moderate temperatures and retain good microstructural stability, it was necessary to make significant composition changes from 2nd and 3rd generation single crystal superalloys. These included lower chromium levels, higher cobalt and rhenium levels and the inclusion of a new alloying element, ruthenium. It was found that higher Co levels were beneficial to reducing both TCP precipitation and SRZ formation. Ruthenium caused the refractory elements to partition more strongly to the ' phase, which resulted in better overall alloy stability. The final alloy, EPM 102, had significant creep rupture and fatigue improvements over the baseline production alloys and had acceptable microstructural stability. The alloy is currently being engine tested and evaluated for advanced engine applications.

Fourth-generation spinal instrumentation: experience with adolescent idiopathic scoliosis at a tertiary care hospital in Pakistan

PubMed Central

Fazal, Akil; Lakdawala, Riaz H

2012-01-01

Objective To evaluate the radiological and functional outcome of surgical treatment of adolescent idiopathic scoliosis using fourth-generation posterior spinal instrumentation at The Aga Khan University, Karachi, Pakistan. Design Case series. Place and duration of study The Aga Khan University Hospital after a minimum of 2 years postoperatively. Patients and methods A total of 20 patients with adolescent idiopathic scoliosis were recruited into the study and evaluated for radiological and functional outcome. The study period was from 2000 to 2005. Radiological outcome was assessed using Cobb angle measurement pre and postoperatively, hence assessing percentage correction. The lower instrumented vertebra was taken as the neutral vertebra and the level was recorded. Functional outcome was determined using the Scoliosis Research Society patient administered questionnaire. All patients were called to the clinic and asked to fill in the form. Those patients who were out of the city were mailed the forms and requested via telephone to complete and return. Results Of the 20 patients operated on, twelve were female and eight were male. The average age at operation was 12.7 years. The mean Cobb angle was 69° preoperatively and 20° postoperatively, representing a percentage correction of 71%. The average duration of follow-up was 3.6 years. There was one major complication involving neurological injury post-op and two minor complications involving wound infection. The average Scoliosis Research Society score (on a scale of 1–5, with 5 being best) for pain was 4.5, self-image was 4.2, functional status was 4.1, mental status was 3.8, and satisfaction was 4.4. There was no relationship between the percentage correction of scoliosis and the functional outcome. Those patients with a high preoperative Cobb angle tended to have a better outcome for functional and mental status postoperatively. There was no relation between the lower instrumented vertebra and functional outcome

Fourth-generation spinal instrumentation: experience with adolescent idiopathic scoliosis at a tertiary care hospital in Pakistan.

PubMed

Fazal, Akil; Lakdawala, Riaz H

2012-01-01

To evaluate the radiological and functional outcome of surgical treatment of adolescent idiopathic scoliosis using fourth-generation posterior spinal instrumentation at The Aga Khan University, Karachi, Pakistan. Case series. The Aga Khan University Hospital after a minimum of 2 years postoperatively. A total of 20 patients with adolescent idiopathic scoliosis were recruited into the study and evaluated for radiological and functional outcome. The study period was from 2000 to 2005. Radiological outcome was assessed using Cobb angle measurement pre and postoperatively, hence assessing percentage correction. The lower instrumented vertebra was taken as the neutral vertebra and the level was recorded. Functional outcome was determined using the Scoliosis Research Society patient administered questionnaire. All patients were called to the clinic and asked to fill in the form. Those patients who were out of the city were mailed the forms and requested via telephone to complete and return. Of the 20 patients operated on, twelve were female and eight were male. The average age at operation was 12.7 years. The mean Cobb angle was 69° preoperatively and 20° postoperatively, representing a percentage correction of 71%. The average duration of follow-up was 3.6 years. There was one major complication involving neurological injury post-op and two minor complications involving wound infection. The average Scoliosis Research Society score (on a scale of 1-5, with 5 being best) for pain was 4.5, self-image was 4.2, functional status was 4.1, mental status was 3.8, and satisfaction was 4.4. There was no relationship between the percentage correction of scoliosis and the functional outcome. Those patients with a high preoperative Cobb angle tended to have a better outcome for functional and mental status postoperatively. There was no relation between the lower instrumented vertebra and functional outcome. In the correct indications, fourth-generation posterior instrumentation

Dendrimers for Drug Delivery.

PubMed

Chauhan, Abhay Singh

2018-04-18

Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine) (PAMAM) dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i) formulation and (ii) nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

Direct detection of OTA by impedimetric aptasensor based on modified polypyrrole-dendrimers.

PubMed

Mejri-Omrani, Nawel; Miodek, Anna; Zribi, Becem; Marrakchi, Mouna; Hamdi, Moktar; Marty, Jean-Louis; Korri-Youssoufi, Hafsa

2016-05-12

Ochratoxin A (OTA) is a carcinogenic mycotoxin that contaminates food such as cereals, wine and beer; therefore it represents a risk for human health. Consequently, the allowed concentration of OTA in food is regulated by governmental organizations and its detection is of major agronomical interest. In the current study we report the development of an electrochemical aptasensor able to directly detect trace OTA without any amplification procedure. This aptasensor was constructed by coating the surface of a gold electrode with a film layer of modified polypyrrole (PPy), which was thereafter covalently bound to polyamidoamine dendrimers of the fourth generation (PAMAM G4). Finally, DNA aptamers that specifically binds OTA were covalently bound to the PAMAM G4 providing the aptasensor, which was characterized by using both Atomic Force Microscopy (AFM) and Surface Plasmon Resonance (SPR) techniques. The study of OTA detection by the constructed electrochemical aptasensor was performed using Electrochemical Impedance Spectroscopy (EIS) and revealed that the presence of OTA led to the modification of the electrical properties of the PPy layer. These modifications could be assigned to conformational changes in the folding of the aptamers upon specific binding of OTA. The aptasensor had a dynamic range of up to 5 μg L(-1) of OTA and a detection limit of 2 ng L(-1) of OTA, which is below the OTA concentration allowed in food by the European regulations. The efficient detection of OTA by this electrochemical aptasensor provides an unforeseen platform that could be used for the detection of various small molecules through specific aptamer association. Copyright © 2016 Elsevier B.V. All rights reserved.

Non-critical phase-matching fourth harmonic generation of a 1053-nm laser in an ADP crystal

PubMed Central

Ji, Shaohua; Wang, Fang; Zhu, Lili; Xu, Xinguang; Wang, Zhengping; Sun, Xun

2013-01-01

In current inertial confinement fusion (ICF) facilities, KDP and DKDP crystals are the second harmonic generation (SHG) and third harmonic generation (THG) materials for the Nd:glass laser (1053 nm). Based on the trend for the development of short wavelengths for ICF driving lasers, technical solutions for fourth harmonic generation (FHG) will undoubtedly attract more and more attention. In this paper, the rapid growth of an ADP crystal and non-critical phase-matching (NCPM) FHG of a 1053-nm laser using an ADP crystal are reported. The NCPM temperature is 33.7°C. The conversion efficiency from 526 to 263 nm is 70%, and the angular acceptance range is 55.4 mrad; these results are superior to those for the DKDP crystals. This research has shown that ADP crystals will be a competitive candidate in future ICF facilities when the utilisation of high-energy, high-efficiency UV lasers at wavelengths shorter than the present 351 nm is of interest. PMID:23549389

Non-critical phase-matching fourth harmonic generation of a 1053-nm laser in an ADP crystal.

PubMed

Ji, Shaohua; Wang, Fang; Zhu, Lili; Xu, Xinguang; Wang, Zhengping; Sun, Xun

2013-01-01

In current inertial confinement fusion (ICF) facilities, KDP and DKDP crystals are the second harmonic generation (SHG) and third harmonic generation (THG) materials for the Nd:glass laser (1053 nm). Based on the trend for the development of short wavelengths for ICF driving lasers, technical solutions for fourth harmonic generation (FHG) will undoubtedly attract more and more attention. In this paper, the rapid growth of an ADP crystal and non-critical phase-matching (NCPM) FHG of a 1053-nm laser using an ADP crystal are reported. The NCPM temperature is 33.7°C. The conversion efficiency from 526 to 263 nm is 70%, and the angular acceptance range is 55.4 mrad; these results are superior to those for the DKDP crystals. This research has shown that ADP crystals will be a competitive candidate in future ICF facilities when the utilisation of high-energy, high-efficiency UV lasers at wavelengths shorter than the present 351 nm is of interest.

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization.

PubMed

Igartúa, Daniela E; Martinez, Carolina S; Temprana, C Facundo; Alonso, Silvia Del V; Prieto, M Jimena

2018-06-10

Carbamazepine (CBZ) is an antiepileptic drug, which also could be used in the treatment of neurodegenerative diseases, such as the Alzheimer's disease. However, its use has been limited due to its low solubility, inefficient pharmacokinetic profiles, and multiple side effects. PAMAM dendrimers, ethylenediamine core, generation 4.0 (amine terminal groups) and 4.5 (carboxylate terminal groups) (DG4.0 and DG4.5 respectively) are polymers that can increase drug solubility through complexation. Thus, the aim of this work was to obtain and characterize complexes between CBZ and dendrimers. Both DG4.0 and DG4.5 allowed the incorporation of ∼20 molecules of CBZ per dendrimer, into their hydrophobic pockets. DG4.0-CBZ and DG4.5-CBZ complexes were found to be stable for 90 days at 37 °C and resistant to a lyophilization process, presenting controlled drug release. Also, the complexes nanotoxicity was tested ex vivo (human red blood cells), in vitro (N2a cell line), and in vivo (zebrafish). No hemolytic effect was observed in the ex vivo model. As regards in vitro toxicity, the DG4.5-CBZ complexes significantly reduced the toxicity caused by the free drug. Moreover, the DG4.5-CBZ did not cause neurotoxicity or cardiotoxicity in zebrafish larvae. In conclusion, a stable and biocompatible drug delivery system based on the DG4.5 capable of complex the CBZ has been developed. This achievement highlights the advantages of using negatively charged dendrimers for nanomedicine. Copyright © 2018 Elsevier B.V. All rights reserved.

Toward a Fourth Generation of Disparities Research to Achieve Health Equity

PubMed Central

Thomas, Stephen B.; Quinn, Sandra Crouse; Butler, James; Fryer, Craig S.; Garza, Mary A.

2011-01-01

Achieving health equity, driven by the elimination of health disparities, is a goal of Healthy People 2020. In recent decades, the improvement in health status has been remarkable for the U.S. population as a whole. However, racial and ethnic minority populations continue to lag behind whites with a quality of life diminished by illness from preventable chronic diseases and a life span cut short by premature death. We examine a conceptual framework of three generations of health disparities research to understand (a) data trends, (b) factors driving disparities, and (c) solutions for closing the gap. We propose a new, fourth generation of research grounded in public health critical race praxis, utilizing comprehensive interventions to address race, racism, and structural inequalities and advancing evaluation methods to foster our ability to eliminate disparities. This new generation demands that we address the researcher’s own biases as part of the research process. PMID:21219164

Fourth Generation War: Paradigm for Change

DTIC Science & Technology

2005-06-01

efficiency has suffered. An example is the Waffen SS who were in essence specialized troops. They were formed in 1940 as 110 specialized bodyguards or to...the later part of World War II, the Waffen SS had in essence become much like the U.S. Marine Corps; they were a fourth service with their own

Thinking beyond Measurement, Description and Judgment: Fourth Generation Evaluation in Family-Centered Pediatric Healthcare Organizations

ERIC Educational Resources Information Center

Moreau, Katherine Ann; Clarkin, Chantalle Louise

2012-01-01

Background: Although pediatric healthcare organizations have widely implemented the philosophy of family-centered care (FCC), evaluators and health professionals have not explored how to preserve the philosophy of FCC in evaluation processes. Purpose: To illustrate how fourth generation evaluation, in theory, could facilitate collaboration between…

Efficient 2(nd) and 4(th) harmonic generation of a single-frequency, continuous-wave fiber amplifier.

PubMed

Sudmeyer, Thomas; Imai, Yutaka; Masuda, Hisashi; Eguchi, Naoya; Saito, Masaki; Kubota, Shigeo

2008-02-04

We demonstrate efficient cavity-enhanced second and fourth harmonic generation of an air-cooled, continuous-wave (cw), single-frequency 1064 nm fiber-amplifier system. The second harmonic generator achieves up to 88% total external conversion efficiency, generating more than 20-W power at 532 nm wavelength in a diffraction-limited beam (M(2) < 1.05). The nonlinear medium is a critically phase-matched, 20-mm long, anti-reflection (AR) coated LBO crystal operated at 25 degrees C. The fourth harmonic generator is based on an AR-coated, Czochralski-grown beta-BaB(2)O(4) (BBO) crystal optimized for low loss and high damage threshold. Up to 12.2 W of 266-nm deep-UV (DUV) output is obtained using a 6-mm long critically phase-matched BBO operated at 40 degrees C. This power level is more than two times higher than previously reported for cw 266-nm generation. The total external conversion efficiency from the fundamental at 1064 nm to the fourth harmonic at 266 nm is >50%.

Surface Engineering of PAMAM-SDB Chelating Resin with Diglycolamic Acid (DGA) Functional Group for Efficient Sorption of U(VI) and Th(IV) from Aqueous Medium.

PubMed

Ilaiyaraja, P; Deb, A K Singha; Ponraju, D; Ali, Sk Musharaf; Venkatraman, B

2017-04-15

A novel chelating resin obtained via growth of PAMAM dendron on surface of styrene divinyl benzene resin beads, followed by diglycolamic acid functionalization of the dendrimer terminal. Batch experiments were conducted to study the effects of pH, nitric acid concentration, amount of adsorbent, shaking time, initial metal ion concentration and temperature on U(VI) and Th(IV) adsorption efficiency. Diglycolamic acid terminated PAMAM dendrimer functionalized styrene divinylbenzene chelating resin (DGA-PAMAM-SDB) is found to be an efficient candidate for the removal of U(VI) and Th(IV) ions from aqueous (pH >4) and nitric acid media (>3M). The sorption equilibrium could be reached within 60min, and the experimental data fits with pseudo-second-order model. Langmuir sorption isotherm model correlates well with sorption equilibrium data. The maximum U(VI) and Th(IV) sorption capacity onto DGA-PAMAMG 5 -SDB was estimated to be about 682 and 544.2mgg -1 respectively at 25°C. The interaction of actinides and chelating resin is reversible and hence, the resin can be regenerated and reused. DFT calculation on the interaction of U(VI) and Th(IV) ions with chelating resin validates the experimental findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Size, Surface Charge, and Hydrophobicity of Poly(amidoamine) Dendrimers on Their Skin Penetration

PubMed Central

Yang, Yang; Sunoqrot, Suhair; Stowell, Chelsea; Ji, Jingli; Lee, Chan-Woo; Kim, Jin Woong; Khan, Seema A.; Hong, Seungpyo

2012-01-01

The barrier functions of the stratum corneum (SC) and the epidermal layers present a tremendous challenge in achieving effective transdermal delivery of drug molecules. Although a few reports have shown that poly(amidoamine) (PAMAM) dendrimers are effective skin penetration enhancers, little is known regarding the fundamental mechanisms behind the dendrimer-skin interactions. In this paper, we have performed a systematic study to better elucidate how dendrimers interact with skin layers depending on their size and surface groups. Franz diffusion cells and confocal microscopy were employed to observe dendrimer interactions with full-thickness porcine skin samples. We have found that smaller PAMAM dendrimers (generation 2 (G2)) penetrate the skin layers more efficiently than the larger ones (G4). We have also found that G2 PAMAM dendrimers that are surface modified by either acetylation or carboxylation exhibit increased skin permeation and likely diffuse through an extracellular pathway. In contrast, amine-terminated dendrimers show enhanced cell internalization and skin retention but reduced skin permeation. In addition, conjugation of oleic acid (OA) to G2 dendrimers increases their 1-octanol/PBS partition coefficient, resulting in increased skin absorption and retention. Here we report that size, surface charge, and hydrophobicity directly dictate the permeation route and efficiency of dendrimer translocation across the skin layers, providing a design guideline for engineering PAMAM dendrimers as a potential transdermal delivery vector. PMID:22621160

Intramedullary nailing: evolutions of femoral intramedullary nailing: first to fourth generations.

PubMed

Russell, Thomas A

2011-12-01

Intramedullary femoral nailing is the gold standard for femoral shaft fixation but only in the past 27 years. This rapid replacement of closed traction and cast techniques in North America was a controversial and contentious evolution in surgery. As we enter the fourth generation of implant design, capabilities, and surgical technique, it is important to understand the driving forces for this technology. These forces included changes in radiographic imaging capabilities, biomaterial design and computer-assisted manufacturing, and the recognition of the importance of mobilization of the trauma patient to avoid systemic complications and optimize functional recovery.

MECHANICAL PROPERTIES OF BLENDS OF PAMAM DENDRIMERS WITH POLY(VINYL CHLORIDE) AND POLY(VINYL ACETATE)

EPA Science Inventory

Hybrid blends of poly(amidoamine) PAMAM dendrimers with two linear high polymers, poly(vinyl chloride), PVC, and poly(vinyl acetate), PVAc, are reported. The interaction between the blend components was studied using dynamic mechanical analysis, xenon nuclear magnetic resonacne ...

Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations.

PubMed

Jain, Vaibhav; Maiti, Prabal K; Bharatam, Prasad V

2016-09-28

Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH 2 ) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH 2 ) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH 2 ) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations

NASA Astrophysics Data System (ADS)

Jain, Vaibhav; Maiti, Prabal K.; Bharatam, Prasad V.

2016-09-01

Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH2) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH2) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH2) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

PubMed

Özcan, Hakkı Mevlüt; Sezgintürk, Mustafa Kemal

2015-01-01

This paper presents a novel hormone-based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12-mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti-PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) couple, self-assembled monolayer structure from one of the other NH2 sites. The immobilization of anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC-NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10-60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples. © 2015 American Institute of Chemical Engineers.

Synthetic PAMAM-RGD conjugates target and bind to odontoblast-like MDPC 23 cells and the predentin in tooth organ cultures.

PubMed

Hill, Elliott; Shukla, Rameshwer; Park, Steve S; Baker, James R

2007-01-01

Screening techniques now allow for the identification of small peptides that bind specifically to molecules like cells. However, despite the enthusiasm for this approach, single peptides often lack the binding affinity to target in vivo and regulate cell function. We took peptides containing the Arg-Gly Asp(RGD) motif that bind to the alpha Vbeta 3 integrin and have shown potential as therapeutics. To improve their binding affinity, we synthesized polyamidoamine (PAMAM) dendrimer-RGD conjugates that that contain 12-13 copies of the peptide. When cultured with human dermal microvessel endothelial cells (HDMEC), human vascular endothelial cells (HUVEC), or odontoblast-like MDPC-23 cells, the PAMAM dendrimer conjugate targets this receptor in a manner that is both time- and dose-dependent. Finally, this conjugate selectively targets RGD binding sites in the predentin of human tooth organ cultures. Taken together, these studies provide proof of principle that synthetic PAMAM-RGD conjugates could prove useful as carriers for the tissue-specific delivery of integrin-targeted therapeutics or imaging agents and could be used to engineer tissue regeneration.

Picosecond x-ray diagnostics for third and fourth generation synchrotron sources

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

DeCamp, Matthew

2016-03-30

In the DOE-EPSCoR State/National Laboratory partnership grant ``Picosecond x-ray diagnostics for third and fourth generation synchrotron sources'' Dr. DeCamp set forth a partnership between the University of Delaware and Argonne National Laboratory. This proposal aimed to design and implement a series of experiments utilizing, or improving upon, existing time-domain hard x-ray spectroscopies at a third generation synchrotron source. Specifically, the PI put forth three experimental projects to be explored in the grant cycle: 1) implementing a picosecond ``x-ray Bragg switch'' using a laser excited nano-structured metallic film, 2) designing a robust x-ray optical delay stage for x-ray pump-probe studies atmore » a hard x-ray synchrotron source, and 3) building/installing a laser based x-ray source at the Advanced Photon Source for two-color x-ray pump-probe studies.« less

Stopped-flow kinetic studies of poly(amidoamine) dendrimer-calf thymus DNA to form dendriplexes.

PubMed

Dey, Debabrata; Kumar, Santosh; Maiti, Souvik; Dhara, Dibakar

2013-11-07

Poly(amidoamine) (PAMAM) dendrimers are known to be highly efficient nonviral carriers in gene delivery. Dendrimer-mediated transfection is known to be a function of the dendrimer to DNA charge ratio as well as the size of the dendrimer. In the present study, the binding kinetics of four PAMAM dendrimers (G1, G2, G3, and G4) with calf thymus DNA (CT-DNA) has been studied using stopped-flow fluorescence spectroscopy. The effect of dendrimer-to-DNA charge ratio and dendrimer generation on the binding kinetics was investigated. In most cases, the results of dendrimer-CT-DNA binding can be explained by a two-step reaction mechanism: a rapid electrostatic binding between the dendrimer and DNA, followed by a conformational change of the dendrimer-DNA complex that ultimately leads to DNA condensation. It was observed that the charge ratio on the dendrimer and the DNA phosphate groups, as well as the dendrimer generation (size), has a marked effect on the kinetics of binding between the DNA and the dendrimers. The rate constant (k'1) of the first step was much higher compared to that of the second step (k'2), and both were found to increase with an increase in dendrimer concentration. Among the four generations of dendrimers, G4 exhibited significantly faster binding kinetics compared to the three smaller generation dendrimers.

Direct mass limits for chiral fourth-generation quarks in all mixing scenarios.

PubMed

Flacco, Christian J; Whiteson, Daniel; Tait, Tim M P; Bar-Shalom, Shaouly

2010-09-10

Present limits on chiral fourth-generation quark masses mb' and mt' are broadly generalized and strengthened by combining both t' and b' decays and considering a full range of t' and b' flavor-mixing scenarios with the lighter generations (to 1-‖V44‖2≈10(-13)). Various characteristic mass-splitting choices are considered. With mt'>mb' we find that CDF Collaboration limits on the b' mass vary by no more than 10%-20% with any choice of flavor mixing, while for the t' mass, we typically find stronger bounds, in some cases up to mt'>430  GeV. For mb'>mt', we find mb'>380-430  GeV, depending on the flavor mixing and the size of the mt'-mb' mass splitting.

Performances of fourth generation HIV antigen/antibody assays on filter paper for detection of early HIV infections.

PubMed

Kania, Dramane; Truong, Tam Nguyen; Montoya, Ana; Nagot, Nicolas; Van de Perre, Philippe; Tuaillon, Edouard

2015-01-01

Point-of-care testing and diagnosis of HIV acute infections play important roles in preventing transmission, but HIV rapid diagnosis tests have poor capacity to detect early infections. Filter paper can be used for capillary blood collection and HIV testing using 4th generation immunoassays. Antigen/antibody combined immunoassays were evaluated for their capacity to identify early HIV infections using filter paper in comparison with rapid test. Thirty nine serum samples collected from HIV seroconverters were spotted onto filter paper and tested by the Roche Elecsys(®) HIV Combi PT test and the DiaSorin Liaison XL Murex HIV Ab/Ag assay. Fourth generation immunoassays identified 34 out of 39 HIV early infections using dried serum spot, whereas the Determine™ HIV-1/2 rapid test detected 24 out of 39 HIV positive serum (87.2% vs 61.5% respectively, p = 0.009). p24 antigen was detected by the Liaison XL in 19 dried serum samples (48.7%). In the group characterized by a negative western blot, 7 out of 8 (87.5%) and 6 out of 8 (75.0%) samples were found positive for HIV using the Elecsys and the Liaison XL, respectively. None of these eight samples classified in this group of early acute infections were found positive by the rapid test. Fourth generation Ag/Ab immunoassays performed on dried serum spot had good performance for HIV testing during the early phases of HIV infection. This method may be useful to detect HIV early infections in hard-to-reach populations and individuals living in remote areas before rapid tests become positive. Copyright © 2014 Elsevier B.V. All rights reserved.

Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection.

PubMed

Ganda, Ingrid S; Zhong, Qian; Hali, Mirabela; Albuquerque, Ricardo L C; Padilha, Francine F; da Rocha, Sandro R P; Whittum-Hudson, Judith A

2017-07-15

Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen-Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance. Copyright © 2017 Elsevier B.V. All

Effect and Stability of Poly(Amido Amine)-Induced Biomineralization on Dentinal Tubule Occlusion

PubMed Central

Gao, Yuan; Liang, Kunneng; Li, Jianshu; Yuan, He; Liu, Hongling; Duan, Xiaolei; Li, Jiyao

2017-01-01

In recent years, scientists have developed various biomaterials to remineralize human teeth to treat dentine hypersensitivity. Poly(amido amine) (PAMAM) dendrimers have become a research focus in this field. It has been demonstrated that PAMAM is able to create precipitates both on the surface of and within the dentinal tubules, however, there is little information about its effect on reducing dentine permeability in vitro. This study aimed to evaluate the in vitro effectiveness and stability of the fourth generation amine-terminated PAMAM on dentinal tubule occlusion, especially on dentine permeability. Sodium fluoride (NaF), which has been widely used as a desensitizing agent, is regarded as positive control. Demineralized sensitive dentine samples were coated with PAMAM or sodium fluoride solutions and soaked in artificial saliva (AS) at 37 °C for different periods. Four weeks later, samples in each group were then equally split into two subgroups for testing using a brushing challenge and an acid challenge. Dentine permeability of each specimen was measured before and after each challenge using a fluid filtration system. Dentine morphology and surface deposits were characterized by scanning electron microscope (SEM) and analyzed with Image-Pro Plus software. Data were evaluated through multifactorial ANOVA with repeated measures and pair-wise comparisons at a level of 5%. The results showed that PAMAM and NaF significantly reduced dentine permeability to 25.1% and 20.7%. Both of them created precipitates on dentine surfaces after AS immersion for 28 days. PAMAM-induced biomineralization not only on dentine surfaces, but also deeper in dentinal tubules, significantly reduced dentine permeability. Moreover, PAMAM-induced biomineralization elicited excellent stable occlusion effects after acid challenge. In conclusion, PAMAM demonstrated a strong ability to resist acid and showed great potential to be used in the treatment of dentine hypersensitivity in future

Complexes formed between DNA and poly(amido amine) dendrimers of different generations--modelling DNA wrapping and penetration.

PubMed

Qamhieh, Khawla; Nylander, Tommy; Black, Camilla F; Attard, George S; Dias, Rita S; Ainalem, Marie-Louise

2014-07-14

This study deals with the build-up of biomaterials consisting of biopolymers, namely DNA, and soft particles, poly(amido amine) (PAMAM) dendrimers, and how to model their interactions. We adopted and applied an analytical model to provide further insight into the complexation between DNA (4331 bp) and positively charged PAMAM dendrimers of generations 1, 2, 4, 6 and 8, previously studied experimentally. The theoretical models applied describe the DNA as a semiflexible polyelectrolyte that interacts with dendrimers considered as either hard (impenetrable) spheres or as penetrable and soft spheres. We found that the number of DNA turns around one dendrimer, thus forming a complex, increases with the dendrimer size or generation. The DNA penetration required for the complex to become charge neutral depends on dendrimer generation, where lower generation dendrimers require little penetration to give charge neutral complexes. High generation dendrimers display charge inversion for all considered dendrimer sizes and degrees of penetration. Consistent with the morphologies observed experimentally for dendrimer/DNA aggregates, where highly ordered rods and toroids are found for low generation dendrimers, the DNA wraps less than one turn around the dendrimer. Disordered globular structures appear for high generation dendrimers, where the DNA wraps several turns around the dendrimer. Particularly noteworthy is that the dendrimer generation 4 complexes, where the DNA wraps about one turn around the dendrimers, are borderline cases and can form all types of morphologies. The net-charges of the aggregate have been estimated using zeta potential measurements and are discussed within the theoretical framework.

The formation of shocks and fundamental solution of a fourth-order quasilinear Boussinesq-type equation

NASA Astrophysics Data System (ADS)

Galaktionov, Victor A.

2009-02-01

As a basic higher-order model, the fourth-order Boussinesq-type quasilinear wave equation (the QWE-4) \\[ \\begin{equation*}\\fl u_{tt} = -(|u|^n u)_{xxxx} \\tqs in\\ \\mathbb{R} \\times \\mathbb{R}_+, \\quad with\\ exponent\\ n > 0,\\end{equation*} \\] is considered. Self-similar blow-up solutions \\[ \\begin{eqnarray*}\\tqs\\tqs u_-(x,t)=g(z), \\quad\\, z=\\frac x{\\sqrt{T-t}},\\\\ where\\ g\\ solved\\ the\\ ODE\\ \\frac 14 g'' z^2 + \\frac 34 g'z = -(|g|^n g)^{(4)},\\end{eqnarray*} \\] are shown to exist that generate as t → T- discontinuous shock waves. The QWE-4 is also shown to admit a smooth (for t > 0) global 'fundamental solution' \\[ \\begin{eqnarray*}\\fl b_n(x,t)= t^{\\frac{2}{n+4}} F_n(y),\\ y = x/t^{\\frac{n+2}{n+4}},\\ such\\ that\\ b_{n}(x,0)= 0,\\ b_{nt}(x,0)= {\\delta}(x),\\end{eqnarray*} \\] i.e. having a measure as initial data. A 'homotopic' limit n → 0 is used to get b_0(x,t)= \\sqrt t \\, F_0(x/\\sqrt t) being the classic fundamental solution of the 1D linear beam equation \\[ \\begin{equation*}u_{tt} = -u_{xxxx} \\tqs in\\ \\mathbb{R} \\times \\mathbb{R}_+.\\end{equation*} \\

Assessment of the cost-effectiveness and clinical outcomes of a fourth-generation synchronous telehealth program for the management of chronic cardiovascular disease.

PubMed

Ho, Yi-Lwun; Yu, Jiun-Yu; Lin, Yen-Hung; Chen, Ying-Hsien; Huang, Ching-Chang; Hsu, Tse-Pin; Chuang, Pao-Yu; Hung, Chi-Sheng; Chen, Ming-Fong

2014-06-10

Telehealth programs are a growing field in the care of patients. The evolution of information technology has resulted in telehealth becoming a fourth-generation synchronous program. However, long-term outcomes and cost-effectiveness analysis of fourth-generation telehealth programs have not been reported in patients with chronic cardiovascular diseases. We conducted this study to assess the clinical outcomes and cost-effectiveness of a fourth-generation synchronous telehealth program for patients with chronic cardiovascular diseases. We retrospectively analyzed 575 patients who had joined a telehealth program and compared them with 1178 patients matched for sex, age, and Charlson comorbidity index. The program included: (1) instant transmission of biometric data, (2) daily telephone interview, and (3) continuous decision-making support. Data on hospitalization, emergency department (ED) visits, and medical costs were collected from the hospital's database and were adjusted to the follow-up months. The mean age was 64.5 years (SD 16.0). The mean number of monthly ED visits (mean 0.06 SD 0.13 vs mean 0.09 SD 0.23, P<.001), hospitalizations (mean 0.05 SD 0.12 vs mean 0.11 SD 0.21, P<.001), length of hospitalization (mean 0.77 days SD 2.78 vs mean 1.4 SD 3.6, P<.001), and intensive care unit admissions (mean 0.01 SD 0.07 vs mean 0.036 SD 0.14, P<.001) were lower in the telehealth group. The monthly mean costs of ED visits (mean US$20.90 SD 66.60 vs mean US$37.30 SD 126.20, P<.001), hospitalizations (mean US$386.30 SD 1424.30 vs mean US$878.20 SD 2697.20, P<.001), and all medical costs (mean US$587.60 SD 1497.80 vs mean US$1163.60 SD 3036.60, P<.001) were lower in the telehealth group. The intervention costs per patient were US$224.80 per month. Multivariate analyses revealed that age, telehealth care, and Charlson index were the independent factors for ED visits, hospitalizations, and length of hospitalization. A bootstrap method revealed the dominant cost

Four-Quadrant Analog Multipliers Using G4-FETs

NASA Technical Reports Server (NTRS)

Mojarradi, Mohammad; Blalock, Benjamin; Christoloveanu, Sorin; Chen, Suheng; Akarvardar, Kerem

2006-01-01

Theoretical analysis and some experiments have shown that the silicon-on-insulator (SOI) 4-gate transistors known as G4-FETs can be used as building blocks of four-quadrant analog voltage multiplier circuits. Whereas a typical prior analog voltage multiplier contains between six and 10 transistors, it is possible to construct a superior voltage multiplier using only four G4-FETs. A G4-FET is a combination of a junction field-effect transistor (JFET) and a metal oxide/semiconductor field-effect transistor (MOSFET). It can be regarded as a single transistor having four gates, which are parts of a structure that affords high functionality by enabling the utilization of independently biased multiple inputs. The structure of a G4-FET of the type of interest here (see Figure 1) is that of a partially-depleted SOI MOSFET with two independent body contacts, one on each side of the channel. The drain current comprises of majority charge carriers flowing from one body contact to the other that is, what would otherwise be the side body contacts of the SOI MOSFET are used here as the end contacts [the drain (D) and the source (S)] of the G4-FET. What would otherwise be the source and drain of the SOI MOSFET serve, in the G4-FET, as two junction-based extra gates (JG1 and JG2), which are used to squeeze the channel via reverse-biased junctions as in a JFET. The G4-FET also includes a polysilicon top gate (G1), which plays the same role as does the gate in an accumulation-mode MOSFET. The substrate emulates a fourth MOS gate (G2). By making proper choices of G4-FET device parameters in conjunction with bias voltages and currents, one can design a circuit in which two input gate voltages (Vin1,Vin2) control the conduction characteristics of G4-FETs such that the output voltage (Vout) closely approximates a value proportional to the product of the input voltages. Figure 2 depicts two such analog multiplier circuits. In each circuit, there is the following: The input and output

Organometallic rotaxane dendrimers with fourth-generation mechanically interlocked branches.

PubMed

Wang, Wei; Chen, Li-Jun; Wang, Xu-Qing; Sun, Bin; Li, Xiaopeng; Zhang, Yanyan; Shi, Jiameng; Yu, Yihua; Zhang, Li; Liu, Minghua; Yang, Hai-Bo

2015-05-05

Mechanically interlocked molecules, such as catenanes, rotaxanes, and knots, have applications in information storage, switching devices, and chemical catalysis. Rotaxanes are dumbbell-shaped molecules that are threaded through a large ring, and the relative motion of the two components along each other can respond to external stimuli. Multiple rotaxane units can amplify responsiveness, and repetitively branched molecules--dendrimers--can serve as vehicles for assembly of many rotaxanes on single, monodisperse compounds. Here, we report the synthesis of higher-generation rotaxane dendrimers by a divergent approach. Linkages were introduced as spacer elements to reduce crowding and to facilitate rotaxane motion, even at the congested periphery of the compounds up to the fourth generation. The structures were characterized by 1D multinuclear ((1)H, (13)C, and (31)P) and 2D NMR spectroscopy, MALDI-TOF-MS, gel permeation chromatography (GPC), and microscopy-based methods including atomic force microscopy (AFM) and transmission electron microscopy (TEM). AFM and TEM studies of rotaxane dendrimers vs. model dendrimers show that the rotaxane units enhance the rigidity and reduce the tendency of these assemblies to collapse by self-folding. Surface functionalization of the dendrimers with ferrocenes as termini produced electrochemically active assemblies. The preparation of dendrimers with a well-defined topological structure, enhanced rigidity, and diverse functional groups opens previously unidentified avenues for the application of these materials in molecular electronics and materials science.

The development of folate-PAMAM dendrimer conjugates for targeted delivery of anti-arthritic drugs and their pharmacokinetics and biodistribution in arthritic rats.

PubMed

Chandrasekar, Durairaj; Sistla, Ramakrishna; Ahmad, Farhan J; Khar, Roop K; Diwan, Prakash V

2007-01-01

The aim of this study was to synthesize folate-dendrimer conjugates as suitable vehicle for site specific delivery of anti-arthritic drug (indomethacin) to inflammatory regions and to determine its targeting efficiency, biodistribution in adjuvant induced arthritic rats. Folic acid was coupled to the surface amino groups of G4-PAMAM dendrimer (G4D) via a carbodiimide reaction and loaded with indomethacin. The conjugates were characterized by (1)H-NMR and IR spectroscopy. The drug content and percent encapsulation efficiency increased with increasing folate content for the dendrimer conjugates. The in vitro release rate was decreased for the folate conjugates when compared with unconjugated dendrimer (DNI). The plasma concentration profile showed a biphasic curve indicating rapid distribution followed by slow elimination. The AUC(0-infinity), half-life and residence time of indomethacin in inflamed paw was higher for folate-dendrimer conjugates. The time-averaged relative drug exposure (r(e)) of the drug in paw and overall drug targeting efficiency (T(e)) were higher for folate conjugate with 21 folate moieties (4.1 and 2.78, respectively) when compared with DNI (1.91 and 1.88, respectively). This study demonstrated the superiority of active targeting over dendrimer mediated passive targeting and also for the first time, folate-mediated targeting of an anti-arthritic drug to the inflammatory tissues.

Generation dependent cancer targeting potential of poly(propyleneimine) dendrimer.

PubMed

Kesharwani, Prashant; Tekade, Rakesh K; Jain, Narendra K

2014-07-01

Dendrimer-mediated delivery of bioactive is a successful and widely explored concept. This paper desribes comparative data pertaining to generation dependent cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut report reportsthe drug targeting and antciancer potential of different dendrimer generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were synthesized and loaded with Melphalan. Results from loading, hemolysis, hematologic, cytotoxicty and flow cytometry assay depicted that as the generation of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is increased exponentionally. However, others parameters, i.e. loading, sustained release behavior, and targeting efficacy increased negligibly. Kaplan-Meier survival curves clearly depicted comparable therapeutic potential of PPI4M with PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to be preferable nanocarrier for anticancer drug delivery owing to analogous anticancer potential. The outcomes of the investigation evidently projects 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery benefit as well as superior biocompatibility. Thus, much against the common belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers no benefit over 4.0G. Copyright © 2014 Elsevier Ltd. All rights reserved.

Design of a new integrated chitosan-PAMAM dendrimer biosorbent for heavy metals removing and study of its adsorption kinetics and thermodynamics.

PubMed

Zarghami, Zabihullah; Akbari, Ahmad; Latifi, Ali Mohammad; Amani, Mohammad Ali

2016-04-01

In this research, different generations of PAMAM-grafted chitosan as integrated biosorbents were successfully synthesized via step by step divergent growth approach of dendrimer. The synthesized products were utilized as adsorbents for heavy metals (Pb(2+) in this study) removing from aqueous solution and their reactive Pb(2+) removal potential was evaluated. The results showed that as-synthesized products with higher generations of dendrimer, have more adsorption capacity compared to products with lower generations of dendrimer and sole chitosan. Adsorption capacity of as-prepared product with generation 3 of dendrimer is 18times more than sole chitosan. Thermodynamic and kinetic studies were performed for understanding equilibrium data of the uptake capacity and kinetic rate uptake, respectively. Thermodynamic and kinetic studies showed that Langmuir isotherm model and pseudo second order kinetic model are more compatible for describing equilibrium data of the uptake capacity and kinetic rate of the Pb(2+) uptake, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Constructing polyamidoamine dendrons from poly(poly(ethylene glycol) monomethacrylate) brushes grafted from planar silicon hydride surfaces for biomedical applications

NASA Astrophysics Data System (ADS)

Liu, Xiang; Zheng, Hong-Ning; Yan, Qin; Wang, Cuie; Ma, Yin-Zhou; Tang, Yan-Chun; Xiao, Shou-Jun

2011-06-01

A facile approach was established to construct polyamidoamine (PAMAM) dendrons from polymer brushes of poly(poly(ethylene glycol) monomethacrylate) (Si-g-P(PEGMA-OH)) grafted from a planar silicon hydride surface. First the Si-g-P(PEGMA-OH) brushes were grown via surface-initiated atom transfer radical polymerization with robust Si-C links on silicon surfaces. The side-chain hydroxyl groups of Si-g-P(PEGMA-OH) were chlorinated with thionyl chloride and further chlorines were substituted with amino groups of ethylenediamine, giving terminal primary amines. Borrowing the solution synthesis approach, we constructed second and third generations of PAMAM dendrons on-chip by surface-initiated alternative growth of two monomers, methyl acrylate and ethylenediamine. Two applications of silicon-based PAMAM dendrons were shown: the dense amino groups were activated via a cross-linker, N-succinimidyl-6-maleimidylhexanoate, to capture a free-thiol-carrying peptide of oxytocin and the third generation of PAMAM dendrons was used as a platform to on-chip synthesize a three amino acid peptide of Arg-Gly-Asp (RGD). The above conclusions were mainly derived from a home-built multiple transmission-reflection infrared spectroscopy, and complemented by X-ray photoelectron spectroscopy, UV-Vis spectroscopy and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry.

Systems Prototyping with Fourth Generation Tools: One Answer to the Productivity Puzzle? AIR 1983 Annual Forum Paper.

ERIC Educational Resources Information Center

Sholtys, Phyllis A.

The development of information systems using an engineering approach employing both traditional programming techniques and nonprocedural languages is described. A fourth generation application tool is used to develop a prototype system that is revised and expanded as the user clarifies individual requirements. When fully defined, a combination of…

Hyaluronic acid-modified polyamidoamine dendrimer G5-entrapped gold nanoparticles delivering METase gene inhibits gastric tumor growth via targeting CD44+ gastric cancer cells.

PubMed

Li, Yi-Fan; Zhang, Hou-Ting; Xin, Lin

2018-06-01

Gastric cancer (GC) is the second most common leading cause of cancer-related death. Cancer stem cell (CSC) with the mark of CD44 played an important role in GC. rMETase was wildly exploited as chemotherapeutic option for GC. Polymers synthetic nanoparticle drug delivery systems have been commonly used for cancer therapy. With the decorating of Hyaluronic acid (HA), a receptor of CD44, nanoparticles exhibit with good biocompatibility and aqueous solubility. The characteristic of nanoparticles (NPs) was analyzed by TEM and DLS. The viability and proliferation of GC cells were examined by MTT assays. The levels of CD44, Cyt C, and c-caspase 3 were examined by Western blot. The level of ROS was measured by DCFH-DA assays. The morphology of tissues was detected using hematoxylin-eosin (H&E) stain. Nude mice xenograft models were used to evaluate the effect of HA-PAMAM-Au-METase on GC. The transfection of rMETase carried by HA-G5 PAMAM-Au visibly inhibited the proliferation and tumorsphere formation of GC cells through obviously enhancing METase activity. Elevation of METase activity suppressed the proliferation of CD44(+) GC cells through down-regulating MET in cellular supernatant that resulted in the increase of Cyc C and ROS levels. The number of CD44(+) GC cells in nude mice injected with G5 PAMAM-Au-METase decorated by HA was markly declined resulting in the inhibition of tumor growth. HA-G5 PAMAM-Au-METase significantly suppressed tumor growth of GC by targeted damaging the mitochondrial function of CD44(+) gastric CSCs.

Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications.

PubMed

Esfand, R; Tomalia, D A.

2001-04-01

Poly(amidoamine) (PAMAM) dendrimers are the first complete dendrimer family to be synthesized, characterized and commercialized. Based on this extensive activity, they are recognized as a unique new class of synthetic nanostructures. Dendrimers allow the precise control of size, shape and placement of functional groups that is desirable for many life science applications. From this perspective, this review focuses on crucial properties of biomimetic dendrimers that will broaden the potential for their use as macromolecular vectors in novel drug delivery and biomedical applications.

Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement.

PubMed

Shadrack, Daniel M; Mubofu, Egid B; Nyandoro, Stephen S

2015-11-04

The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement. The as-synthesized dendrimer and the dendrimer-TMScu complex were characterized by spectroscopic and spectrometric techniques. The encapsulation of 1 into dendrimer was achieved by a co-precipitation method with the encapsulation efficiency of 77.8% ± 0.69% and a loading capacity of 6.2% ± 0.06%. A phase solubility diagram indicated an increased water solubility of 1 as a function of dendrimer concentration at pH 4.0 and 7.2. In vitro release of 1 from its dendrimer complex indicated high percentage release at pH 4.0. The stability study of the TMScu-dendrimer at 0, 27 and 40 °C showed the formulations to be stable when stored in cool and dark conditions compared to those stored in light and warmer temperatures. Overall, PAMAM dendrimer-G4 is capable of encapsulating 1, increasing its solubility and thus could enhance its bioactivity.

Modulation of Electroosmotic Flow through Skin: Effect of Poly(Amidoamine) Dendrimers

PubMed Central

Kim, Hye Ji; Oh, Seaung Youl

2018-01-01

The objective of this work is to evaluate the effect of polyamidoamine (PAMAM) dendrimers on electroosmotic flow (EOF) through skin. The effect of size and concentration of dendrimer was studied, using generation 1, 4 and 7 dendrimer (G1, G4 and G7, respectively). As a marker molecule for the direction and magnitude of EOF, a neutral molecule, acetoaminophen (AAP) was used. The visualization of dendrimer permeation into the current conducting pore (CCP) of skin was made using G4–fluorescein isothiocyanate (FITC) conjugate and confocal microscopy. Without dendrimer, anodal flux of AAP was much higher than cathodal or passive flux. When G1 dendrimer was added, anodal flux decreased, presumably due to the decrease in EOF by the association of G1 dendrimer with net negative charge in CCP. As the generation increased, larger decrease in anodal flux was observed, and the direction of EOF was reversed. Small amount of methanol used for the preparation of dendrimer solution also contributed to the decrease in anodal flux of AAP. Cross-sectional view perpendicular to the skin surface by confocal laser scanning microscope (CLSM) study showed that G4 dendrimer-FITC conjugate (G4-FITC) can penetrate into the viable epidermis and dermis under anodal current. The permeation route seemed to be localized on hair follicle region. These results suggest that PAMAM dendrimers can permeate into CCP and change the magnitude and direction of EOF. Overall, we obtained a better understanding on the mechanistic insights into the electroosmosis phenomena and its role on flux during iontophoresis. PMID:29310428

Dark Coulomb binding of heavy neutrinos of fourth family

NASA Astrophysics Data System (ADS)

Belotsky, K. M.; Esipova, E. A.; Khlopov, M. Yu.; Laletin, M. N.

2015-11-01

Direct dark matter searches put severe constraints on the weakly interacting massive particles (WIMPs). These constraints cause serious troubles for the model of stable neutrino of fourth generation with mass around 50GeV. Though the calculations of primordial abundance of these particles make them in the charge symmetric case a sparse subdominant component of the modern dark matter, their presence in the universe would exceed the current upper limits by several orders of the magnitude. However, if quarks and leptons of fourth generation possess their own Coulomb-like y-interaction, recombination of pairs of heavy neutrinos and antineutrinos and their annihilation in the “neutrinium” atoms can play important role in their cosmological evolution, reducing their modern abundance far below the experimental upper limits. The model of stable fourth generation assumes that the dominant part of dark matter is explained by excessive Ū antiquarks, forming (ŪŪŪ)-- charged clusters, bound with primordial helium in nuclear-interacting O-helium (OHe) dark atoms. The y charge conservation implies generation of the same excess of fourth generation neutrinos, potentially dangerous WIMP component of this scenario. We show that due to y-interaction recombination of fourth neutrinos with OHe hides these WIMPs from direct WIMP searches, leaving the negligible fraction of free neutrinos, what makes their existence compatible with the experimental constraints.

Fourth - generation languages. Volume 2. Representative 4GLs

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

Martin, J.

1986-01-01

The chapters in Part II each describe one representative product marketed by a vendor other than IBM. (Volume III of this work covers IBM languages.) The chapters in Part II cover the following 4GLs: ADS/ONLINE, APPLICATION FACTORY, DATATRIEVE, FOCUS, IDEAL, INTELLECT, MANTIS, MIMER, NATURAL, NOMAD2, RAMIS II, SYSTEM W, and USE-IT. The Perspective section of Part II presents a general overview of the product and describes its role in the marketplace. The Tutorial section describes how a user employs the language in application development.

IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy.

PubMed

Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei

2015-01-01

Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.

Interactive Design Strategy for a Multi-Functional PAMAM Dendrimer-Based Nano-Therapeutic Using Computational Models and Experimental Analysis

PubMed Central

Lee, Inhan; Williams, Christopher R.; Athey, Brian D.; Baker, James R.

2010-01-01

Molecular dynamics simulations of nano-therapeutics as a final product and of all intermediates in the process of generating a multi-functional nano-therapeutic based on a poly(amidoamine) (PAMAM) dendrimer were performed along with chemical analyses of each of them. The actual structures of the dendrimers were predicted, based on potentiometric titration, gel permeation chromatography, and NMR. The chemical analyses determined the numbers of functional molecules, based on the actual structure of the dendrimer. Molecular dynamics simulations calculated the configurations of the intermediates and the radial distributions of functional molecules, based on their numbers. This interactive process between the simulation results and the chemical analyses provided a further strategy to design the next reaction steps and to gain insight into the products at each chemical reaction step. PMID:20700476

A Critical Review of the "Motor-Free Visual Perception Test-Fourth Edition" (MVPT-4)

ERIC Educational Resources Information Center

Brown, Ted; Peres, Lisa

2018-01-01

The "Motor-Free Visual Perception Test-fourth edition" (MVPT-4) is a revised version of the "Motor-Free Visual Perception Test-third edition." The MVPT-4 is used to assess the visual-perceptual ability of individuals aged 4.0 through 80+ years via a series of visual-perceptual tasks that do not require a motor response. Test…

Ligand Accessibility and Bioactivity of a Hormone-Dendrimer Conjugate Depend on pH and pH History

PubMed Central

Kim, Sung Hoon; Madak-Erdogan, Zeynep; Bae, Sung Chul; Carlson, Kathryn E.; Mayne, Christopher G.; Granick, Steve; Katzenellenbogen, Benita S.; Katzenellenbogen, John A.

2016-01-01

Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the non-genomic actions of estrogens in target cells. In response to pH changes, however, these estrogen-dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine, TMR) and two estrogens (17α-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR-PAMAM reveal high ligand shielding above pH 7 and low shielding below pH 7. Furthermore, when pH was cycled from 8.5 (conditions of ligand-PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17α-ethynylestradiol and diphenolic acid PAMAM conjugates experience a dramatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicate that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen-dendrimer conjugates appears to be metastable. This pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers. PMID:26186415

Oriented Polyaniline Nanowire Arrays Grown on Dendrimer (PAMAM) Functionalized Multiwalled Carbon Nanotubes as Supercapacitor Electrode Materials.

PubMed

Jin, Lin; Jiang, Yu; Zhang, Mengjie; Li, Honglong; Xiao, Linghan; Li, Ming; Ao, Yuhui

2018-04-19

At present, PANI/MWNT composites have been paid more attention as promising electrode materials in supercapacitors. Yet some shortcomings still limit the widely application of PANI/MWNT electrolytes. In this work, in order to improve capacitance ability and long-term stability of electrode, a multi-amino dendrimer (PAMAM) had been covalently linked onto multi-walled carbon nanotubes (MWNT) as a bridge to facilitating covalent graft of polyaniline (PANI), affording P-MWNT/PANI electrode composites for supercapacitor. Surprisingly, ordered arrays of PANI nanowires on MWNT (setaria-like morphology) had been observed by scanning electron microscopy (SEM). Electrochemical properties of P-MWNT/PANI electrode had been characterized by cyclic voltammetry (CV) and galvanostatic charge-discharge technique. The specific capacitance and long cycle life of P-MWNT-PANI electrode material were both much higher than MWNT/PANI. These interesting results indicate that multi-amino dendrimer, PAMAM, covalently linked on MWNT provides more reaction sites for in-situ polymerization of ordered PANI, which could efficiently shorten the ion diffusion length in electrolytes and lead to making fully use of conducting materials.

Bioactive compounds of fourth generation gamma-irradiated Typhoniumflagelliforme Lodd. mutants based on gas chromatography-mass spectrometry

NASA Astrophysics Data System (ADS)

Sianipar, N. F.; Purnamaningsih, R.; Rosaria

2016-08-01

Rodent tuber (Typhonium flagelliforme Lodd.) is an Indonesian anticancer medicinal plant. The natural genetic diversity of rodent tuber is low due to vegetative propagation. Plant's genetic diversity has to be increased for obtaining clones which contain a high amount of anticancer compounds. In vitro calli were irradiated with 6 Gy of gamma ray to produce in vitro mutant plantlets. Mutant plantlets were acclimated and propagated in a greenhouse. This research was aimed to identify the chemical compounds in the leaves and tubers ofthe fourth generation of rodent tuber's vegetative mutant clones (MV4) and control plantsby using GC- MS method. Leaves and tubers of MV4 each contained 2 and 5 anticancer compounds which quantities were higher compared to control plants. MV4 leaves contained 5 new anticancer compounds while its tubers contained 3 new anticancer compounds which were not found in control. The new anticancer compounds in leaves were hexadecanoic acid, stigmast-5-en-3-ol, ergost-5-en-3-ol, farnesol isomer a, and oleic acid while the new anticancer compounds in tubers were alpha tocopherol, ergost-5-en-3-ol, and beta-elemene. Rodent tuber mutant clones are very potential to be developed into anticancer drugs.

Project CHECO Southeast Asia Report. The Fourth Offensive

DTIC Science & Technology

1969-10-01

DPL .... .......... 4 (e) CSH ............ . .. 1 f. AFLC (f) DOTEC ............ 5 (g) DE .... ........... 1 (1) HEADQUARTERS(h) DM. .............. .1(a...who performed politi- cal , economic, and military functions. In support of military operations, the VCI operated a vigorous recruiting net to provide...against Allied outposts rather than areas that were heavily de - fended by friendly forces. The enemy tactics of the Fourth Offensive strongly suggested that

Infective endocarditis due to Enterobacter cloacae resistant to third- and fourth-generation cephalosporins.

PubMed

Yoshino, Yusuke; Okugawa, Shu; Kimura, Satoshi; Makita, Eiko; Seo, Kazunori; Koga, Ichiro; Matsunaga, Naohisa; Kitazawa, Takatoshi; Ota, Yasuo

2015-04-01

We report the case of using a long-term combination of meropenem and amikacin to treat infective endocarditis caused by Enterobacter cloacae resistant to third- and fourth-generation cephalosporins. Multi-drug resistant Gram-negative bacilli, such as the E. cloacae in our study, may become possible pathogens of infective endocarditis. Our experience with this case indicates that long-term use of a combination of β-lactam and aminoglycosides might represent a suitable management option for future infective endocarditis cases due to non-Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. (HACEK group) Gram-negative bacilli such as ours. Copyright © 2012. Published by Elsevier B.V.

Acute HIV infection (AHI): Trained Service Linkage Workers and fourth-generation Assay Significantly Shorten Time to Antiretroviral Therapy Initiation.

PubMed Central

Smith, Daniel; Gao, Qianmiao; Miao, Hongyu; Gutierrez, Oswaldo; Martinez, Cecilio; Vigil, Karen; Utay, Netanya S; Arduino, Roberto

2017-01-01

Abstract Background Identification and early initiation of antiretroviral therapy (ART) during acute HIV infection (AHI) can preserve the immune system, reduce HIV reservoir size, and prevent transmission. We aimed to characterize patients with symptomatic AHI and their linkage/retention to care in a county clinic. Methods Retrospective chart review of 60 patients diagnosed with AHI from 7/2012 to 4/2017 at two county hospitals emergency departments in Houston, TX. We compared the interval between diagnosis and initiation of ART before and after implementation of an AHI protocol in 11/2014 comprised of trained service linkage workers and use of the fourth-generation Ag/Ab combination assay as newly recommended by the CDC in 6/2014. AHI was defined as 1) detectable HIV RNA or reactive fourth-generation Ag/Ab combination assay with non-reactive HIV-1 antibody, 2) reactive third-generation Ab assay and negative/indeterminate Western blot (WB), or 3) positive WB that is negative for p31 band. CDC and DHHS definitions were used for linkage to and retention to care respectively. Results 10 patients were diagnosed prior to AHI protocol (25-month period) and 50 after (31-month period). 92% established care with 78% retention. Median age 34 years (IQR 25–42), with 78% men, 58% Hispanic, 36% Black non-Hispanic, 50% men having sex with men. Presenting symptoms include fever 78%, chills 47%, malaise/fatigue 47%, nausea 38%, sore throat 37%, and headache 37%. Physical exam findings include rash 20%, pharyngeal edema/erythema 14%, cervical lymphadenopathy 8%, and thrush 7%. Baseline median CD4+ T cell count was 205 cells/µL (IQR 123–350), median HIV RNA 4.75 x 106 copies/mL (IQR 1.1–10.0 x 106). 56% had leukopenia, 47% thrombocytopenia, 37% syphilis, 12% aseptic meningitis and 8% K103N mutation. Median time to ART initiation decreased from 17 days (IQR 11.75–23.5) to 7 days (IQR 4.0–13.25) after protocol implementation (P = 0.011). Conclusion Employing trained service

THE FOURTH US NAVAL OBSERVATORY CCD ASTROGRAPH CATALOG (UCAC4)

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

Zacharias, N.; Finch, C. T.; Bartlett, J. L.

2013-02-01

The fourth United States Naval Observatory (USNO) CCD Astrograph Catalog, UCAC4, was released in 2012 August (double-sided DVD and CDS data center Vizier catalog I/322). It is the final release in this series and contains over 113 million objects; over 105 million of them with proper motions (PMs). UCAC4 is an updated version of UCAC3 with about the same number of stars also covering all-sky. Bugs were fixed, Schmidt plate survey data were avoided, and precise five-band photometry was added for about half the stars. Astrograph observations have been supplemented for bright stars by FK6, Hipparcos, and Tycho-2 data tomore » compile a UCAC4 star catalog complete from the brightest stars to about magnitude R = 16. Epoch 1998-2004 positions are obtained from observations with the 20 cm aperture USNO Astrograph's 'red lens', equipped with a 4k by 4k CCD. Mean positions and PMs are derived by combining these observations with over 140 ground- and space-based catalogs, including Hipparcos/Tycho and the AC2000.2, as well as unpublished measures of over 5000 plates from other astrographs. For most of the faint stars in the southern hemisphere, the first epoch plates from the Southern Proper Motion program form the basis for PMs, while the Northern Proper Motion first epoch plates serve the same purpose for the rest of the sky. These data are supplemented by 2MASS near-IR photometry for about 110 million stars and five-band (B, V, g, r, i) APASS data for over 51 million stars. Thus the published UCAC4, as were UCAC3 and UCAC2, is a compiled catalog with the UCAC observational program being a major component. The positional accuracy of stars in UCAC4 at mean epoch is about 15-100 mas per coordinate, depending on magnitude, while the formal errors in PMs range from about 1 to 10 mas yr{sup -1} depending on magnitude and observing history. Systematic errors in PMs are estimated to be about 1-4 mas yr{sup -1}.« less

High efficiency fourth-harmonic generation from nanosecond fiber master oscillator power amplifier

NASA Astrophysics Data System (ADS)

Mu, Xiaodong; Steinvurzel, Paul; Rose, Todd S.; Lotshaw, William T.; Beck, Steven M.; Clemmons, James H.

2016-03-01

We demonstrate high power, deep ultraviolet (DUV) conversion to 266 nm through frequency quadrupling of a nanosecond pulse width 1064 nm fiber master oscillator power amplifier (MOPA). The MOPA system uses an Yb-doped double-clad polarization-maintaining large mode area tapered fiber as the final gain stage to generate 0.5-mJ, 10 W, 1.7- ns single mode pulses at a repetition rate of 20 kHz with measured spectral bandwidth of 10.6 GHz (40 pm), and beam qualities of Mx 2=1.07 and My 2=1.03, respectively. Using LBO and BBO crystals for the second-harmonic generation (SHG) and fourth-harmonic generation (FHG), we have achieved 375 μJ (7.5 W) and 92.5 μJ (1.85 W) at wavelengths of 532 nm and 266 nm, respectively. To the best of our knowledge these are the highest narrowband infrared, green and UV pulse energies obtained to date from a fully spliced fiber amplifier. We also demonstrate high efficiency SHG and FHG with walk-off compensated (WOC) crystal pairs and tightly focused pump beam. An SHG efficiency of 75%, FHG efficiency of 47%, and an overall efficiency of 35% from 1064 nm to 266 nm are obtained.

Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids

PubMed Central

Louw-du Toit, Renate; Perkins, Meghan S.; Snoep, Jacky L.; Storbeck, Karl-Heinz; Africander, Donita

2016-01-01

Progestins used in contraception and hormone replacement therapy are synthetic compounds designed to mimic the actions of the natural hormone progesterone and are classed into four consecutive generations. The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked. Although some studies have investigated the effects of select progestins on a few steroidogenic enzymes, studies comparing the effects of progestins from different generations are lacking. This study therefore explored the putative modulatory effects of progestins on de novo steroid synthesis in the adrenal by comparing the effects of select progestins from the respective generations, on endogenous steroid hormone production by the H295R human adrenocortical carcinoma cell line. Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed that the fourth-generation progestins, nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first three generations, modulate the biosynthesis of several endogenous steroids. Subsequent assays performed in COS-1 cells expressing human 3βHSD2, suggest that these progestins modulate the biosynthesis of steroid hormones by inhibiting the activity of 3βHSD2. The Ki values determined for the inhibition of human 3βHSD2 by NES (9.5 ± 0.96 nM), NoMAC (29 ± 7.1 nM) and DRSP (232 ± 38 nM) were within the reported concentration ranges for the contraceptive use of these progestins in vivo. Taken together, our results suggest that newer, fourth-generation progestins may exert both positive and negative physiological effects via the modulation of endogenous steroid hormone biosynthesis. PMID:27706226

Ligand accessibility and bioactivity of a hormone–dendrimer conjugate depend on pH and pH history

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

Kim, Sung Hoon; Madak-Erdogan, Zeynep; Bae, Sung Chul

Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the nongenomic actions of estrogens in target cells in this paper. In response to pH changes, however, these estrogen–dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine [TMR]) and two estrogens (17α-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR–PAMAM revealed high ligand shielding abovemore » pH 7 and low shielding below pH 7. Furthermore, when the pH was cycled from 8.5 (conditions of ligand–PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17α-ethynylestradiol– and diphenolic acid–PAMAM conjugates experienced a dramatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicated that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen–dendrimer conjugates appears to be metastable. Finally, this pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers.« less

Ligand accessibility and bioactivity of a hormone–dendrimer conjugate depend on pH and pH history

DOE PAGES

Kim, Sung Hoon; Madak-Erdogan, Zeynep; Bae, Sung Chul; ...

2015-07-17

Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the nongenomic actions of estrogens in target cells in this paper. In response to pH changes, however, these estrogen–dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine [TMR]) and two estrogens (17α-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR–PAMAM revealed high ligand shielding abovemore » pH 7 and low shielding below pH 7. Furthermore, when the pH was cycled from 8.5 (conditions of ligand–PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17α-ethynylestradiol– and diphenolic acid–PAMAM conjugates experienced a dramatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicated that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen–dendrimer conjugates appears to be metastable. Finally, this pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers.« less

Conformational organizations of G-quadruplexes composed of d(G(4)T(n))(3)G(4).

PubMed

Wong, Wan Chi; Zhuang, Jinyi; Ng, Selina Ling Ling; New, Lilian Li Lin; Hiew, Shuhui; Guo, Juanjuan; Yang, Zhaoqi; Li, Tianhu

2010-08-01

Structural polymorphism is one of the important issues with regard to G-quadruplexes because the structural diversity may significantly affect their biological functions in vivo and their physical property in nano-material. A series of oligonucleotides with four repeat guanines sequence [d(G(4)T(n))(3)G(4) (n=1-6)] were designed. In this study, the effects of loop length on the formation of structures of G-quadruplex were investigated through the result of CD (circular dichroism) and 20% non-denatured polyacrylamide gel electrophoresis. Our studies demonstrate that the length of loop in 100mM KCl solution could predict the conformation of G-quadruplex. Copyright 2010 Elsevier Ltd. All rights reserved.

Boronic Acid vs. Folic Acid: A Comparison of the bio-recognition performances by Impedimetric Cytosensors based on Ferrocene cored dendrimer.

PubMed

Dervisevic, Muamer; Şenel, Mehmet; Sagir, Tugba; Isik, Sevim

2017-05-15

A comparative study is reported where folic acid (FA) and boronic acid (BA) based cytosensors and their analytical performances in cancer cell detection were analyzed by using electrochemical impedance spectroscopy (EIS) method. Cytosensors were fabricated using self-assembled monolayer principle by modifying Au electrode with cysteamine (Cys) and immobilization of ferrocene cored polyamidiamine dendrimers second generation (Fc-PAMAM (G2)), after which electrodes were modified with FA and BA. Au/Fc-PAMAM(G2)/FA and Au/Fc-PAMAM(G2)/BA based cytosensors showed extremely good analytical performances in cancer cell detection with linear range of 1×10 2 to 1×10 6 cellsml -1 , detection limit of 20cellsml -1 with incubation time of 20min for FA based electrode, and for BA based electrode detection limit was 28cellsml -1 with incubation time of 10min. Next to excellent analytical performances, cytosensors showed high selectivity towards cancer cells which was demonstrated in selectivity study using human embryonic kidney 293 cells (HEK 293) as normal cells and Au/Fc-PAMAM(G2)/FA electrode showed two times better selectivity than BA modified electrode. These cytosensors are promising for future applications in cancer cell diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Covalent immobilization of invertase on PAMAM-dendrimer modified superparamagnetic iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Uzun, K.; Çevik, E.; Şenel, M.; Sözeri, H.; Baykal, A.; Abasıyanık, M. F.; Toprak, M. S.

2010-10-01

In this study, polyamidoamine (PAMAM) dendrimer was synthesized on the surface of superparamagnetite nanoparticles to enhance invertase immobilization. The amount of immobilized enzyme on the surface-hyperbranched magnetite nanoparticle was up to 2.5 times (i.e., 250%) as much as that of magnetite nanoparticle modified with only amino silane. Maximum reaction rate ( V max) and Michaelis-Menten constant ( K m) were determined for the free and immobilized enzymes. Various characteristics of immobilized invertase such as; the temperature activity, thermal stability, operational stability, and storage stability were evaluated and results revealed that stability of the enzyme is improved upon immobilization.

Effects of Polyamidoamine Dendrimers on a 3-D Neurosphere System Using Human Neural Progenitor Cells.

PubMed

Zeng, Yang; Kurokawa, Yoshika; Zeng, Qin; Win-Shwe, Tin-Tin; Nansai, Hiroko; Zhang, Zhenya; Sone, Hideko

2016-07-01

The practical application of engineered nanomaterials or nanoparticles like polyamidoamine (PAMAM) dendrimers has been promoted in medical devices or industrial uses. The safety of PAMAM dendrimers needs to be assessed when used as a drug carrier to treat brain disease. However, the effects of PAMAM on the human nervous system remain unknown. In this study, human neural progenitor cells cultured as a 3D neurosphere model were used to study the effects of PAMAM dendrimers on the nervous system. Neurospheres were exposed to different G4-PAMAM dendrimers for 72 h at concentrations of 0.3, 1, 3, and 10 μg/ml. The biodistribution was investigated using fluorescence-labeled PAMAM dendrimers, and gene expression was evaluated using microarray analysis followed by pathway and network analysis. Results showed that PAMAM dendrimer nanoparticles can penetrate into neurospheres via superficial cells on them. PAMAM-NH2 but not PAMAM-SC can inhibit neurosphere growth. A reduced number of MAP2-positive cells in flare regions were inhibited after 10 days of differentiation, indicating an inhibitory effect of PAMAM-NH2 on cell proliferation and neuronal migration. A microarray assay showed 32 dendrimer toxicity-related genes, with network analysis showing 3 independent networks of the selected gene targets. Inducible immediate early gene early growth response gene 1 (Egr1), insulin-like growth factor-binding protein 3 (IGFBP3), tissue factor pathway inhibitor (TFPI2), and adrenomedullin (ADM) were the key genes in each network, and the expression of these genes was significantly down regulated. These findings suggest that exposure of neurospheres to PAMAM-NH2 dendrimers affects cell proliferation and migration through pathways regulated by Egr1, IGFBP3, TFPI2, and ADM. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Kinetic analysis of the interaction between poly(amidoamine) dendrimers and model lipid membranes.

PubMed

Tiriveedhi, Venkataswarup; Kitchens, Kelly M; Nevels, Kerrick J; Ghandehari, Hamidreza; Butko, Peter

2011-01-01

We used fluorescence spectroscopy and surface tensiometry to study the interaction between low-generation (G1 and G4) poly(amidoamine) (PAMAM) dendrimers, potential vehicles for intracellular drug delivery, and model lipid bilayers. Membrane association of fluorescently labeled dendrimers, measured by fluorescence anisotropy, increased with increasing size of the dendrimer and with increasing negative charge density in the membrane, indicating the electrostatic nature of the interaction. When the membrane was doped with pyrene-labeled phosphatidyl glycerol (pyrene-PG), pyrene excimer fluorescence demonstrated a dendrimer-induced selective aggregation of negatively charged lipids when the membrane was in the liquid crystalline state. A nonlinear Stern-Volmer quenching of dendrimer fluorescence with cobalt bromide suggested a dendrimer-induced aggregation of lipid vesicles, which increased with the dendrimer's generation number. Surface tensiometry measurements showed that dendrimers penetrated into the lipid monolayer only at subphysiologic surface pressures (<30mN/m). We conclude that the low-generation PAMAM dendrimers associate with lipid membranes predominantly electrostatically, without significantly compromising the bilayer integrity. They bind stronger to membranes with higher fluidity and lower surface pressure, which are characteristic of rapidly dividing cells. Copyright © 2010 Elsevier B.V. All rights reserved.

A label-free electrochemical impedance immunosensor based on AuNPs/PAMAM-MWCNT-Chi nanocomposite modified glassy carbon electrode for detection of Salmonella typhimurium in milk.

PubMed

Dong, Jing; Zhao, Han; Xu, Minrong; Ma, Qiang; Ai, Shiyun

2013-12-01

A sensitive and stable label-free electrochemical impedance immunosensor for the detection of Salmonella typhimurium was developed by immobilising anti-Salmonella antibodies onto the gold nanoparticles and poly(amidoamine)-multiwalled carbon nanotubes-chitosan nanocomposite film modified glassy carbon electrode (AuNPs/PAMAM-MWCNT-Chi/GCE). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to verify the stepwise assembly of the immunosensor. Co-addition of MWCNT, PAMAM and AuNPs greatly enhanced the sensitivity of the immunosensor. The immobilisation of antibodies and the binding of Salmonella cells to the modified electrode increased the electron-transfer resistance (Ret), which was directly measured with EIS using [Fe(CN)6](3-/4-) as a redox probe. A linear relationship of Ret and Salmonella concentration was obtained in the Salmonella concentration range of 1.0×10(3) to 1.0×10(7) CFU mL(-1) with a detection limit of 5.0×10(2) CFU mL(-1). Additionally, the proposed method was successfully applied to determine S. typhimurium content in milk samples with satisfactory results. Copyright © 2013 Elsevier Ltd. All rights reserved.

IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases.

PubMed

Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Singh, Gurpreet

2015-01-01

IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.

Radiative B decays with four generations

NASA Astrophysics Data System (ADS)

Hewett, Joanne L.

1987-07-01

We study the decay b-->sγ in the four-generation model including the effects of QCD corrections. We find the fourth-generation contributions to be quite significant, extending the range of allowed branching ratios, BR(b-->sγ), to lie both above and below the three-generation standard model value. The existence of a fourth family of quarks would make a prediction for the top-quark mass difficult to obtain from this process. The author would like to thank T. Rizzo and J. Trampetic for discussions on QCD corrections, G. Eilam for introducing the author to the subject of rare B decays, and the Center for Particle Theory for its hospitality while this work was completed.

Evolution of a Fourth Generation Catalyst for the Amination and Thioetherification of Aryl Halides

PubMed Central

Hartwig, John F.

2010-01-01

Conspectus Synthetic methods to form the carbon-nitrogen bonds in aromatic amines are fundamental enough to be considered part of introductory organic courses. Arylamines are important because they are common precursors to or substructures within active pharmaceutical ingredients and herbicides produced on ton scales, as well as conducting polymers and layers of organic light-emitting diodes produced on small scale. For many years, this class of compound was prepared from classical methods, such as nitration, reduction and reductive alkylation, copper-mediated chemistry at high temperatures, addition to benzyne intermediates, or direct nucleophilic substitution on particularly electron-poor aromatic or heteroaromatic halides. During the past decade, these methods to form aromatic amines have been largely supplanted by palladium-catalyzed coupling reactions of amines with aryl halides. The scope and efficiency of the palladium-catalyzed processes has gradually improved with successive generations of catalysts to the point of being useful for the synthesis of both milligrams and kilograms of product. This Account describes the conceptual basis and utility of our latest, “fourth-generation” catalyst for the coupling of amines and related reagents with aryl halides. The introductory sections of this account describe the progression of catalyst development from the first-generation to current systems and the motivation for selection of the components of the fourth-generation catalyst. This progression began with catalysts containing palladium and sterically hindered monodentate aromatic phosphines used initially for coupling of tin amides with haloarenes in the first work on C-N coupling. A second generation of catalysts was then developed based on the combination of palladium and aromatic bisphosphines. These systems were then followed by third-generation systems catalysts on the combination of palladium and a sterically hindered alkylmonophosphine or N

Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR).

PubMed

Toomes, Carmel; Downey, Louise M; Bottomley, Helen M; Scott, Sheila; Woodruff, Geoffrey; Trembath, Richard C; Inglehearn, Chris F

2004-01-15

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous inherited blinding disorder of the retinal vascular system. To date three loci have been mapped: EVR1 on chromosome 11q, EVR2 on chromosome Xp, and EVR3 on chromosome 11p. The gene underlying EVR3 remains unidentified whilst the EVR2 gene, which encodes the Norrie disease protein (NDP), was identified over a decade ago. More recently, FZD4, the gene that encodes the Wnt receptor Frizzled-4, was identified as the mutated gene at the EVR1 locus. The purpose of this study was to screen FZD4 in a large family previously proven to be linked to the EVR1 locus. PCR products were generated using genomic DNA from affected family members with primers designed to amplify the coding sequence of FZD4. The PCR products were screened for mutations by direct sequencing. Genotyping was performed in all available family members using fluorescently labeled microsatellite markers from chromosome 11q. Sequencing of the EVR1 gene, FZD4, in this family identified no mutation. To investigate this family further we performed high-resolution genotyping with markers spanning chromosome 11q. Haplotype analysis excluded FZD4 as the mutated gene in this family and identified a candidate region approximately 10 cM centromeric to EVR1. This new FEVR locus is flanked by markers D11S1368 (centromeric) and D11S937 (telomeric) and spans approximately 15 cM. High-resolution genotyping and haplotype analysis excluded FZD4 as the defective gene in a family previously linked to the EVR1 locus. The results indicate that the gene mutated in this family lies centromeric to the EVR1 gene, FZD4, and is also genetically distinct from the EVR3 locus. This new locus has been designated EVR4 and is the fourth FEVR locus to be described.

Test Review: Wilkinson, G. S., & Robertson, G. J. (2006). Wide Range Achievement Test--Fourth Edition. Lutz, FL: Psychological Assessment Resources. WRAT4 Introductory Kit (Includes Manual, 25 Test/Response Forms [Blue and Green], and Accompanying Test Materials): $243.00

ERIC Educational Resources Information Center

Dell, Cindy Ann; Harrold, Barbara; Dell, Thomas

2008-01-01

The Wide Range Achievement Test-Fourth Edition (WRAT4) is designed to provide "a quick, simple, psychometrically sound assessment of academic skills". The test was first published in 1946 by Joseph F. Jastak, with the purpose of augmenting the cognitive performance measures of the Wechsler-Bellevue Scales, developed by David Wechsler.…

A review of football injuries on third and fourth generation artificial turfs compared with natural turf.

PubMed

Williams, Sean; Hume, Patria A; Kara, Stephen

2011-11-01

Football codes (rugby union, soccer, American football) train and play matches on natural and artificial turfs. A review of injuries on different turfs was needed to inform practitioners and sporting bodies on turf-related injury mechanisms and risk factors. Therefore, the aim of this review was to compare the incidence, nature and mechanisms of injuries sustained on newer generation artificial turfs and natural turfs. Electronic databases were searched using the keywords 'artificial turf', 'natural turf', 'grass' and 'inj*'. Delimitation of 120 articles sourced to those addressing injuries in football codes and those using third and fourth generation artificial turfs or natural turfs resulted in 11 experimental papers. These 11 papers provided 20 cohorts that could be assessed using magnitude-based inferences for injury incidence rate ratio calculations pertaining to differences between surfaces. Analysis showed that 16 of the 20 cohorts showed trivial effects for overall incidence rate ratios between surfaces. There was increased risk of ankle injury playing on artificial turf in eight cohorts, with incidence rate ratios from 0.7 to 5.2. Evidence concerning risk of knee injuries on the two surfaces was inconsistent, with incidence rate ratios from 0.4 to 2.8. Two cohorts showed beneficial inferences over the 90% likelihood value for effects of artificial surface on muscle injuries for soccer players; however, there were also two harmful, four unclear and five trivial inferences across the three football codes. Inferences relating to injury severity were inconsistent, with the exception that artificial turf was very likely to have harmful effects for minor injuries in rugby union training and severe injuries in young female soccer players. No clear differences between surfaces were evident in relation to training versus match injuries. Potential mechanisms for differing injury patterns on artificial turf compared with natural turf include increased peak torque and

Diagnostic Performance of Serum IgG4 Levels in Patients With IgG4-Related Disease

PubMed Central

Yu, Kuang-Hui; Chan, Tien-Ming; Tsai, Ping-Han; Chen, Ching-Hui; Chang, Pi-Yueh

2015-01-01

Abstract The aim of this study is to study the clinical features and diagnostic performance of IgG4 in Chinese populations with IgG4-related diseases (IgG4-RDs). The medical records of 2901 adult subjects who underwent serum IgG4 level tests conducted between December 2007 and May 2014 were reviewed. Serum concentrations of IgG4 were measured in 2901 cases, including 161 (5.6%) patients with IgG4-RD and 2740 (94.4%) patients without IgG4-RD (non-IgG4-RD group). The mean age of the IgG4-RD patients was 58.4 ± 16.1 years (range: 21–87), and 48 (29.8%) were women. The mean serum IgG4 level was significantly much higher in IgG4-RD patients than in non-IgG4-RD (1062.6 vs 104.3 mg/dL, P < 0.001) participants. For IgG4 >135 mg/dL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+, and LR− were 86%, 77%, 18%, 99%, 3.70, and 0.19, respectively. When the upper limit of normal was doubled for an IgG4 >270 mg/dL, the corresponding data were 75%, 94%, 43%, 98%, 12.79, and 0.26, respectively. For IgG4 >405 mg/dL (tripling the upper limit of normal), the corresponding data were 62%, 98%, 68%, 98%, 37.00, and 0.39, respectively. When calculated according to the manufacturer's package insert cutoff (>201 mg/dL) for the diagnosis of IgG4-RD, the corresponding sensitivity, specificity, PPV, NPV, LR+, and LR− were 80%, 89%, 29%, 99%, 7.00, and 0.23, respectively. For IgG4 >402 mg/dL (>2× the upper limit of the normal range), the corresponding data were 62%, 98%, 68%, 98%, 36.21, and 0.39, respectively. For IgG4 >603 mg/dL (>3× the upper limit of the normal range), the corresponding data were 50%, 99%, 84%, 97%, 90.77 and 0.51, respectively. The optimal cutoff value of serum IgG4 (measured by nephelometry using a Siemens BN ProSpec instrument and Siemens reagent) for the diagnosis of IgG4-RD was 248 mg/dL, the sensitivity and specificity were 77.6% and 92.8%, respectively. The present

Carbon dots on based folic acid coated with PAMAM dendrimer as platform for Pt(IV) detection.

PubMed

Campos, Bruno B; Oliva, María Moreno; Contreras-Cáceres, Rafael; Rodriguez-Castellón, Enrique; Jiménez-Jiménez, José; da Silva, Joaquim C G Esteves; Algarra, Manuel

2016-03-01

Carbon quantum dots (CQDs) coated with poly(amidoamine) (PAMAM-NH2) dendrimer are prepared from folic acid and phosphoric acid under a hydrothermal procedure. The obtained nanoparticles are successfully used as fluorescent sensor for Pt(IV) (in the form of chloroplatinate ion). CQDs possess many attractive features including uniform dispersion with average size about 13nm for unmodified particles and, ∼30nm when they are coated with PAMAM-NH2 dendrimer. The synthesized nanoparticles have been characterized by elemental analysis, attenuated total reflectance (ATR), X-ray photoelectron (XPS) and Raman spectroscopies, transmission electron microscopy (TEM), dynamic light scattering (DLS), and steady-state and life-time fluorescence. CQDs are used as fluorescent sensor of Pt(IV) ion in aqueous media showing linear quenching effect of their fluorescence. The results obtained demonstrated a limit of detection of 657nM with an accuracy of the method of 0.13% (as RSD, n=10) and sensitivity of 78nM. Moreover, with the presence of other interference species, good results are obtained when applied in real samples from platinum nanoparticles synthesis. The dissolved platinum ions can be quantified in the range 6-96μM with an accuracy of 2.5%. Copyright © 2015 Elsevier Inc. All rights reserved.

The Climate Science Special Report (CSSR) of the Fourth National Climate Assessment (NCA4)

NASA Astrophysics Data System (ADS)

Wuebbles, D. J.; Fahey, D. W.; Hibbard, K. A.

2016-12-01

The Climate Science Special Report (CSSR) will provide key input into the Fourth National Climate Assessment (NCA4). The report was initiated in 2016 under the guidance of the U.S. Global Change Research Program (USGCRP) as a new, stand-alone report of the state-of-science relating to climate change and its physical impacts. The report is undergoing peer and public review in late 2016 with the aim for final publication in the fourth quarter of 2017. CSSR will provide a comprehensive assessment of the science underlying the changes occurring in the Earth's climate system, with a special focus on the United States. CSSR will serve several purposes for NCA4, including 1) providing an updated detailed analysis of the findings of how climate change is affecting weather and climate across the United States, 2) providing an executive summary that will be used as the basis for the climate science discussion in NCA4, and 3) providing foundational information and projections for climate change, including extremes, to improve "end-to-end" consistency in sectoral, regional, and resilience analyses for NCA4. We will present a summary of the origins and development of CSSR, the writing team, the chapter topics and the relation of CSSR content to NCA4, other assessments and relevance to policy and research communities.

Interfacial Interaction between Transmembrane Ocular Mucins and Adhesive Polymers and Dendrimers Analyzed by Surface Plasmon Resonance

PubMed Central

Noiray, M.; Briand, E.; Woodward, A. M.; Argüeso, P.; Molina Martínez, I. T.; Herrero-Vanrell, R.; Ponchel, G.

2013-01-01

Purpose Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. Methods The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). Results While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH2(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)≫ CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). Conclusions The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and den-drimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability. PMID:22565639

Adaptive Antenna System for Both 4G LTE and 5G Cellular Systems

NASA Astrophysics Data System (ADS)

Henderson, Kendrick Q. T.

Given the steep increase in the use of mobile communication systems, the current 4G/LTE (Long Term Evolution), cellular system will not be able to handle the increase in data. It is estimated that by 2020 the bandwidth requirements will be 10 times greater than what LTE can sustain. A new 5th generation (5G) communication system has been proposed to meet this demand. The physical layer or the antenna is the most critical part of any wireless communication systems as it is the interface between the free space medium and an electrical circuit. It sets the margin for almost all design parameters in the system such as the system noise and bandwidth. Several interactions of antennas have been proposed over the years for cellular services. These antennas are of various geometries, bandwidths, and radiation patterns with almost all having linear polarization. This thesis attempts to solve the multiple LTE antenna problem by creating a simple antenna that covers most of the LTE bands (850-2700 MHz) as well as introducing an antenna system at the 28 GHz 5G band. This allows for a greater educated hypothesis into what 5G can offer at the physical layer. The proposed concept will provide a solution to the co-existence problem of upcoming 5G wireless systems to be interoperable with existing 4G/LTE system.

IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease.

PubMed

Geyer, Julia T; Niesvizky, Ruben; Jayabalan, David S; Mathew, Susan; Subramaniyam, Shivakumar; Geyer, Alexander I; Orazi, Attilio; Ely, Scott A

2014-03-01

IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.

Transport of dendrimer nanocarriers through epithelial cells via the transcellular route.

PubMed

Jevprasesphant, Rachaneekorn; Penny, Jeffrey; Attwood, David; D'Emanuele, Antony

2004-06-18

The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl-dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4',6-diamidino-2-phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4 degrees C. Copyright 2004 Elsevier B.V.

Immunoglobulin class switching to IgG4 in Warthin tumor and analysis of serum IgG4 levels and IgG4-positive plasma cells in the tumor.

PubMed

Aga, Mitsuharu; Kondo, Satoru; Yamada, Kazunori; Wakisaka, Naohiro; Yagi-Nakanishi, Sayaka; Tsuji, Akira; Endo, Kazuhira; Murono, Shigeyuki; Ito, Makoto; Muramatsu, Masamichi; Kawano, Mitsuhiro; Yoshizaki, Tomokazu

2014-04-01

We previously reported a case of immunoglobulin (Ig)G4-related immune inflammation in Warthin tumor. Increased serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells are characteristics of IgG4-related disease (IgG4-RD), a newly emerging clinicopathological entity. However, the relationship between IgG4-RD and Warthin tumor remains to be elucidated. We aimed to investigate the involvement of systemic and local IgG4 production and class-switch recombination in Warthin tumor. We examined serum IgG4 levels and also analyzed the involvement of IgG4-positive plasma cells in Warthin tumors (18 cases) compared with those of pleomorphic adenomas (19 cases) as controls. Furthermore, in specimens of Warthin tumors (3 cases), pleomorphic adenomas (2 cases), and IgG4-RDs (2 cases), we examined messenger RNA expression of activation-induced cytidine deaminase, IgG4 germline transcripts and productive IgG4 by reverse transcription polymerase chain reaction. Serum IgG4 levels were increased in 5 of 18 Warthin tumors and not in any of the 19 pleomorphic adenomas. Infiltration of IgG4-positive plasma cells was detected in 4 Warthin tumors and none in the pleomorphic adenomas. Moreover, activation-induced cytidine deaminase, IgG4 germline transcripts, and productive IgG4 messenger RNA were found to be expressed in 2 of 3 Warthin tumors as well as IgG4-RDs by reverse transcription polymerase chain reaction, but not in pleomorphic adenomas. In conclusion, immunoglobulin class switching to IgG4 may be involved in the pathogenesis of Warthin tumor, and it is possible that certain inflammatory background with an immune reaction is involved in the pathogenesis of Warthin tumor. © 2013.

Physiology response of fourth generation saline resistant soybean (Glycine max (L.) Merrill) with application of several types of antioxidants

NASA Astrophysics Data System (ADS)

Manurung, I. R.; Rosmayati; Rahmawati, N.

2018-02-01

Antioxidant applications are expected to reduce the adverse effects of soil saline. This research was conducted in plastic house, Plant Tissue Laboratory Faculty of Agriculture and Plant Physiology Laboratory Faculty of Mathematic and Natural Science, Universitas Sumatera Utara, Medan also in Research Centers and Industry Standardization, Medan from July-December 2016. The objective of the research was to know the effect of various antioxidant treatments with different concentrations (control, ascorbic acid 250, 500 and 750 ppm; salicylic acid 250, 500 and 750 ppm; α-tocopherol 250, 500 and 750 ppm) on fourth generation soybean physiology in saline condition (Electric Conductivity 5-6 dS/m). The results of this research showed that the antioxidant type and concentration affected not significantly to physiology of fourth generation soybean. Descriptively the highest average of superoxide dismutase and peroxide dismutase was showed on ascorbic acid 250 ppm. The highest average of ascorbate peroxidase was showed on α-tocopherol 750 ppm. The highest average of carotenoid content was showed on ascorbic acid 500 ppm. The highest average of chlorophyll content was showed on α-tocopherol 250 ppm. The highest average of ratio of K/Na was showed on salicylic acid 250 ppm.

An in situ mediator-free route to fabricate Cu2O/g-C3N4 type-II heterojunctions for enhanced visible-light photocatalytic H2 generation

NASA Astrophysics Data System (ADS)

Ji, Cong; Yin, Su-Na; Sun, Shasha; Yang, Shengyang

2018-03-01

Cu2O nanoparticles doped g-C3N4 are synthesized via an in situ method and investigated in detail by IR techniques, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, ultraviolet visible diffuse reflection spectroscopy, and photoluminescence spectroscopy. The as-prepared Cu2O/g-C3N4 hybrids demonstrate enhanced photocatalytic activity toward hydrogen generation compared to pure bulk g-C3N4, the effect of Cu2O content on the rate of visible light photocatalytic hydrogen evolution reveals the optimal hydrogen evolution rate can reach 33.2 μmol h-1 g-1, which is about 4 times higher that of pure g-C3N4. The enhanced photocatalytic activity can be attributed to the improved separation and transfer of photogenerated electron-hole pairs at the intimate interface between g-C3N4 and Cu2O. A possible photocatalytic mechanism of the Cu2O/g-C3N4 composite is also discussed. This mediator-free in situ chemical doping strategy developed in this work will contribute to the achievement of other multicomponent photocatalysts.

Hashimoto's thyroiditis with elevated serum IgG4 concentrations is not equivalent to IgG4 Hashimoto's thyroiditis.

PubMed

Yu, Yang; Yu, Nan; Lu, Guizhi; Li, Ting; Zhang, Yang; Zhang, Jing; Gao, Ying; Gao, Yanming; Guo, Xiaohui

2018-06-01

Hashimoto's thyroiditis (HT) with serum IgG4 concentrations greater than 135 mg/dL can be diagnosed as elevated serum IgG4 HT. HT can also be classified into IgG4 HT and non-IgG4 HT based on an immunohistochemistry analysis of IgG4. The aim of our study was to determine the relationship between elevated serum IgG4 HT and IgG4 HT. Both thyroid tissues and serum samples stored before pathological examination from 93 patients with HT were collected. The serum levels of IgG, IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG and TPOAb IgG4 were measured by ELISAs. The expression levels of IgG4, IgG and TGF-β1 in thyroid tissues were detected by immunohistochemistry. Patients with HT were divided into two groups: elevated serum IgG4 HT (n = 12) and nonelevated serum IgG4 HT (n = 81). Hypothyroidism was found in 5 of 12 cases (41.7%) in the elevated serum IgG4 HT group and 10 of 81 cases (12.3%) in the nonelevated serum IgG4 HT group (P = .023). Serologically, there were no significant differences in the levels of TgAb IgG, TPOAb IgG, TgAb IgG4 and TPOAb IgG4 between the two groups, and the expression of TGF-β1 in thyroid tissues was not significantly different between the groups. Most importantly, the frequency of patients who satisfied the criteria for IgG4 HT diagnosis was comparable (25% vs 20.9%, P = .756). The measurement of serum IgG4 allows the identification of patients with HT closely associated with hypothyroidism. However, our study demonstrated that elevated serum IgG4 HT is not equivalent to IgG4 HT. © 2018 John Wiley & Sons Ltd.

A study of the possible association of plasminogen activator inhibitor type 1 4G/5G insertion/deletion polymorphism with susceptibility to schizophrenia and in its subtypes.

PubMed

Yenilmez, C; Ozdemir Koroglu, Z; Kurt, H; Yanas, M; Colak, E; Degirmenci, I; Gunes, H V

2017-02-01

Inhibition of the fibrinolytic system may occur at the level of plasminogen activation, mainly by PAI-1. Mental and physical stress caused to alterations of platelet function, and also decreased to fibrinolytic activity. Furthermore, stress-induced thrombosis regulation was proposed to be by PAI-1 in schizophrenia patients. In this study, the distribution of genotypes and frequency of alleles of the plasminogen activator inhibitor type 1 (PAI-1) gene 4G/5G polymorphism in different Turkish clinical schizophrenia subtypes was investigated for its role in schizophrenia development. The clinical schizophrenia subtypes include paranoid, catatonic, disorganized, undifferentiated and residual, as diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition IV (DSM-IV). Samples of genomic DNA (250 total, including 150 schizophrenia patients and 100 healthy subjects) were analysed. PAI-1 4G/5G genotyping was performed by polymerase chain reaction-allele-specific amplification. PCR products were separated by 2% agarose gel electrophoresis and then visualized. The genotype distributions (P = 0·136) and allele frequencies (P = 0·721 for 4G, P = 0. 097 for 5G) were not significantly different between patients with schizophrenia and control subjects for the 4G/5G polymorphism. Similar results were also found for the genotype distributions (P = 0·640) and allele frequencies (P = 0·763 for 4G, P = 0·448 for 5G) in the clinical schizophrenia subtypes compared to the each other. We conclude that PAI-1 4G/5G polymorphism was not significantly associated with schizophrenia or its subtypes in the Turkish population. However, we recognize that with our sample sizes, we cannot exclude weak associations. © 2016 John Wiley & Sons Ltd.

Alcohol biosensing by polyamidoamine (PAMAM)/cysteamine/alcohol oxidase-modified gold electrode.

PubMed

Akin, Mehriban; Yuksel, Merve; Geyik, Caner; Odaci, Dilek; Bluma, Arne; Höpfner, Tim; Beutel, Sascha; Scheper, Thomas; Timur, Suna

2010-01-01

A highly stable and sensitive amperometric alcohol biosensor was developed by immobilizing alcohol oxidase (AOX) through Polyamidoamine (PAMAM) dendrimers on a cysteamine-modified gold electrode surface. Ethanol determination is based on the consumption of dissolved oxygen content due to the enzymatic reaction. The decrease in oxygen level was monitored at -0.7 V vs. Ag/AgCl and correlated with ethanol concentration. Optimization of variables affecting the system was performed. The optimized ethanol biosensor showed a wide linearity from 0.025 to 1.0 mM with 100 s response time and detection limit of (LOD) 0.016 mM. In the characterization studies, besides linearity some parameters such as operational and storage stability, reproducibility, repeatability, and substrate specificity were studied in detail. Stability studies showed a good preservation of the bioanalytical properties of the sensor, 67% of its initial sensitivity was kept after 1 month storage at 4 degrees C. The analytical characteristics of the system were also evaluated for alcohol determination in flow injection analysis (FIA) mode. Finally, proposed biosensor was applied for ethanol analysis in various alcoholic beverage as well as offline monitoring of alcohol production through the yeast cultivation. Copyright 2010 American Institute of Chemical Engineers

The Debye light scattering equation's scaling relation reveals the purity of synthetic dendrimers

NASA Astrophysics Data System (ADS)

Tseng, Hui-Yu; Chen, Hsiao-Ping; Tang, Yi-Hsuan; Chen, Hui-Ting; Kao, Chai-Lin; Wang, Shau-Chun

2016-03-01

Spherical dendrimer structures cannot be structurally modeled using conventional polymer models of random coil or rod-like configurations during the calibration of the static light scattering (LS) detectors used to determine the molecular weight (M.W.) of a dendrimer or directly assess the purity of a synthetic compound. In this paper, we used the Debye equation-based scaling relation, which predicts that the static LS intensity per unit concentration is linearly proportional to the M.W. of a synthetic dendrimer in a dilute solution, as a tool to examine the purity of high-generational compounds and to monitor the progress of dendrimer preparations. Without using expensive equipment, such as nuclear magnetic resonance or mass spectrometry, this method only required an affordable flow injection set-up with an LS detector. Solutions of the purified dendrimers, including the poly(amidoamine) (PAMAM) dendrimer and its fourth to seventh generation pyridine derivatives with size range of 5-9 nm, were used to establish the scaling relation with high linearity. The use of artificially impure mixtures of six or seven generations revealed significant deviations from linearity. The raw synthesized products of the pyridine-modified PAMAM dendrimer, which included incompletely reacted dendrimers, were also examined to gauge the reaction progress. As a reaction toward a particular generational derivative of the PAMAM dendrimers proceeded over time, deviations from the linear scaling relation decreased. The difference between the polydispersity index of the incompletely converted products and that of the pure compounds was only about 0.01. The use of the Debye equation-based scaling relation, therefore, is much more useful than the polydispersity index for monitoring conversion processes toward an indicated functionality number in a given preparation.

Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs.

PubMed

Nguyen, Thi Tram Chau; Nguyen, Cuu Khoa; Nguyen, Thi Hiep; Tran, Ngoc Quyen

2017-01-01

In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, 1 H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15-377.14kDa and around 60-180nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4.0-P123) exhibiting a higher drug loading efficiency (up to 76.25%) in comparison with another pluronics. Live/dead fibroblast cell staining assay mentioned that all conjugated nanocarriers are highly biocompatible. The drug-loaded nanocarriers also indicated a highly anti-proliferative activity against MCF-7 breast cancer cell. The obtained results demonstrated a great potential of the highly lipophilic pluronics-conjugated nanocarriers in hydrophobic drugs delivery for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of early HIV infections using the fourth generation Abbott ARCHITECT HIV Ag/Ab Combo chemiluminescent microparticle immunoassay (CIA) in San Diego County.

PubMed

Manlutac, Anna Liza M; Giesick, Jill S; McVay, Patricia A

2013-12-01

HIV screening assays have gone through several generations of development in an effort to narrow the "window period" of detection. Utilizing a fourth generation HIV screening assay has the potential to detect earlier HIV infection, thus reducing HIV-1 transmission. To identify acute infections to decrease HIV transmission in San Diego County. Serum specimens were collected from clients seen by multiple submitters in San Diego County. All acceptable specimens were screened using the 4th Gen Combo Assay. Initially reactive specimens were repeated in duplicate and if repeatedly reactive, were confirmed by HIV-1 Immunofluorescent Antibody Assay (IFA). IFA negative/inconclusive specimens were sent for HIV-1 NAT and HIV-2 antibody testing to referral laboratories. BioRad Multispot HIV-1/HIV-2 Rapid Test was also performed on a subset of specimens. Of 14,559 specimens received in 20 months, 14,517 specimens were tested. Of the 14,517 specimens that were tested, a total of 279 (1.9%) specimens were CIA repeatedly reactive and 240 of the 279 confirmed by HIV-1 IFA. Thirty-nine gave IFA negative/inconclusive result and 30 were further tested for HIV-1 NAT and 36 for HIV-2 antibody. Thirteen specimens were considered false positives by CIA and 17 specimens were classified as acute infections. Eleven of 39 IFA negative/inconclusive specimens were further tested by Multispot. Five of the 11 were positive by Multispot. The fourth generation Abbott ARCHITECT HIV Ag/Ab Combo Assay identified 17 patients who may have been missed by the prior HIV-1 screening assay used at San Diego County Public Health Laboratory. Copyright © 2013 Elsevier B.V. All rights reserved.

Self-Assembly of Amphiphilic Dendrimers: The Role of Generation and Alkyl Chain Length in siRNA Interaction

PubMed Central

Márquez-Miranda, Valeria; Araya-Durán, Ingrid; Camarada, María Belén; Comer, Jeffrey; Valencia-Gallegos, Jesús A.; González-Nilo, Fernando Danilo

2016-01-01

An ideal nucleic-acid transfection system should combine the physical and chemical characteristics of cationic lipids and linear polymers to decrease cytotoxicity and uptake limitations. Previous research described new types of carriers termed amphiphilic dendrimers (ADs), which are based on polyamidoamine dendrimers (PAMAM). These ADs display the cell membrane affinity advantage of lipids and preserve the high affinity for DNA possessed by cationic dendrimers. These lipid/dendrimer hybrids consist of a low-generation, hydrophilic dendron (G2, G1, or G0) bonded to a hydrophobic tail. The G2-18C AD was reported to be an efficient siRNA vector with significant gene silencing. However, shorter tail ADs (G2-15C and G2-13C) and lower generation (G0 and G1) dendrimers failed as transfection carriers. To date, the self-assembly phenomenon of this class of amphiphilic dendrimers has not been molecularly explored using molecular simulation methods. To gain insight into these systems, the present study used coarse-grained molecular dynamics simulations to describe how ADs are able to self-assemble into an aggregate, and, specifically, how tail length and generation play a key role in this event. Finally, explanations are given for the better efficiency of G2/18-C as gene carrier in terms of binding of siRNA. This knowledge could be relevant for the design of novel, safer ADs with well-optimized affinity for siRNA. PMID:27377641

The potential of FBMC over OFDM for the future 5G mobile communication technology

NASA Astrophysics Data System (ADS)

Ibrahim, A. N.; Abdullah, M. F. L.

2017-09-01

Fifth Generation (5G) is the new evolution of mobile communication technology and will be launched soon in many countries. The researchers and designers of mobile communication technology have been facing the increasing demand of the mobile consumers, high data rates and mobility requirements needed by new wireless applications. Most of the countries have started research on 5G mobile communication technology that is predictable to be launched on 2020 in conjunction with the Olympic Games in Tokyo. Filterbank Multicarrier (FBMC) is one of the modulation techniques for the future 5G mobile communication technology. It uses the multicarrier techniques that are immune to fading caused by transmission of more than one path at a time and also immune to intersymbol interference besides able to function effectively compared to Orthogonal Frequency Division Multiplexing (OFDM) which is used in Fourth Generation (4G) mobile communications technology. This paper discusses the performance of FBMC over OFDM based on the previous journals that were investigated by researchers.

G5G2.5 core-shell tecto-dendrimer specifically targets reactive glia in brain ischemia.

PubMed

Murta, Veronica; Schilrreff, Priscila; Rosciszewski, Gerardo; Morilla, Maria Jose; Ramos, Alberto Javier

2018-03-01

Secondary neuronal death is a serious stroke complication. This process is facilitated by the conversion of glial cells to the reactive pro-inflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke. However, drugs have difficulties to access the CNS, and to specifically target glial cells. In the present work, we explored the use core-shell polyamidoamine tecto-dendrimer (G5G2.5 PAMAM) and studied its ability to target distinct populations of stroke-activated glial cells. We found that G5G2.5 tecto-dendrimer is actively engulfed by primary glial cells in a time- and dose-dependent manner showing high cellular selectivity and lysosomal localization. In addition, oxygen-glucose deprivation or lipopolysaccharides exposure in vitro and brain ischemia in vivo increase glial G5G2.5 uptake; not being incorporated by neurons or other cell types. We conclude that G5G2.5 tecto-dendrimer is a highly suitable carrier for targeted drug delivery to reactive glial cells in vitro and in vivo after brain ischemia. © 2017 International Society for Neurochemistry.

Reduced carriership of 4G allele of plasminogen activator inhibitor-1 4G/5G polymorphism in very young survivors of myocardial infarction.

PubMed

Rallidis, Loukianos S; Gialeraki, Argyri; Merkouri, Efrosyni; Liakos, George; Dagres, Nikolaos; Sionis, Dimitrios; Travlou, Anthi; Lekakis, John; Kremastinos, Dimitrios T

2010-05-01

There are limited and controversial data regarding the impact of 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene in the pathogenesis of premature myocardial infarction (MI). We explored whether 4G/5G polymorphism of the PAI-1 gene is associated with the development of MI 4 years). The control group consisted of 140 healthy individuals matched with cases for age and sex, without a family history of premature coronary heart disease. 4G/5G polymorphism of PAI-1 was tested with polymerase chain reaction and reverse hybridization. 4G allele carriers (4G/4G and 4G/5G genotypes) of PAI-1 were less frequent in patients than in controls (69.6 vs. 83.6%, P = 0.007). 4G carriership of the polymorphism of PAI-1 was associated with lower risk for acute MI (odds ratio 0.45, 95% confidence interval 0.23-0.88, P = 0.02) after adjusting for major cardiovascular risk factors. Patients possessing the 4G allele had higher PAI-1 plasma levels (32.2 +/- 25 vs. 22.2 +/- 11.3 ng/ml, P = 0.006) but lower lipoprotein(a) levels (10.1 [2.1-29.9] vs. 15.3 [8.2-57.1] mg/dl, P = 0.03) compared to 5G/5G homozygotes. Our data indicate that the 4G allele of the PAI-1 4G/5G polymorphism is less frequent among survivors of MI at very young age compared with matched controls.

Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

PubMed

Alibolandi, Mona; Taghdisi, Seyed Mohammad; Ramezani, Pouria; Hosseini Shamili, Fazileh; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

2017-03-15

In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line. Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydrophilic acrylic intraocular lens as a drug-delivery system for fourth-generation fluoroquinolones.

PubMed

Kleinmann, Guy; Apple, David J; Chew, Jesse; Hunter, Brian; Stevens, Scott; Larson, Scott; Mamalis, Nick; Olson, Randall J

2006-10-01

To evaluate the ability and safety of a hydrophilic acrylic intraocular lens (IOL) as a drug-delivery system for commercially available gatifloxacin and moxifloxacin. David J. Apple, MD, Laboratories for Ophthalmic Research, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah, USA. Thirty rabbits were divided into 2 similar groups. In Group A (15 rabbits, 30 eyes), hydrophilic acrylic IOLs (C-flex, Rayner Intraocular Lenses, Ltd.) presoaked for 24 hours in commercially available solutions of gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL were implanted after evacuation of the crystalline lens. Group B (15 rabbits, 30 eyes) had topical preoperative and postoperative cataract prophylaxis with gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL; IOLs that were not presoaked were also implanted after evacuation of the crystalline lenses. In both groups, aqueous humor samples were taken 4, 8, or 12 hours after IOL implantation (5 eyes at each time point) to determine the antibiotic concentrations. Clinical examinations were performed 24 hours postoperatively. The antibiotic concentrations in Group A (presoaked IOLs) were statistically significantly higher than those in Group B (topical) for both antibiotics in all postoperative samples except moxifloxacin at 12 hours. In both groups, there was no statistically significant difference between the concentrations of the 2 antibiotics. No eye showed signs of clinical toxicity. Results show the C-flex IOL is a safe and effective drug-delivery system for fourth-generation fluoroquinolones.

Dendrimeric Antigens for Drug Allergy Diagnosis: A New Approach for Basophil Activation Tests.

PubMed

Molina, Noemi; Martin-Serrano, Angela; Fernandez, Tahia D; Tesfaye, Amene; Najera, Francisco; Torres, María J; Mayorga, Cristobalina; Vida, Yolanda; Montañez, Maria I; Perez-Inestrosa, Ezequiel

2018-04-24

Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients. Here we propose a new diagnostic approach using DeAns in cellular tests, in which recognition occurs through IgE bound to the basophil surface. Both IgE molecular recognition and subsequent cell activation may be influenced by the tridimensional architecture and size of the immunogens. Structural features of benzylpenicilloyl-DeAn and amoxicilloyl-DeAn (G2 and G4 PAMAM) were studied by diffusion Nuclear Magnetic Resonance (NMR) experiments and are discussed in relation to molecular dynamics simulation (MDS) observations. IgE recognition was clinically evaluated using the basophil activation test (BAT) for allergic patients and tolerant subjects. Diffusion NMR experiments, MDS and cellular studies provide evidence that the size of the DeAn, its antigen composition and tridimensional distribution play key roles in IgE-antigen recognition at the effector cell surface. These results indicate that the fourth generation DeAns induce a higher level of basophil activation in allergic patients. This approach can be considered as a potential complementary diagnostic method for evaluating penicillin allergy.

1 MVA HTS-2G Generator for Wind Turbines

NASA Astrophysics Data System (ADS)

Kovalev, K. L.; Poltavets, V. N.; Ilyasov, R. I.; Verzhbitsky, L. G.; Kozub, S. S.

2017-10-01

The calculation, design simulations and design performance of 1 MVA HTS-2G (second-generation high-temperature superconductor) Generator for Wind Turbines were done in 2013-2014 [1]. The results of manufacturing and testing of 1 MVA generator are presented in the article. HTS-2G field coils for the rotor were redesigned, fabricated and tested. The tests have shown critical current of the coils, 41-45 A (self field within the ferromagnetic core, T = 77 K), which corresponds to the current of short samples at self field. Application of the copper inner frame on the pole has improved internal cooling conditions of HTS coil windings and reduced the magnetic field in the area, thereby increased the critical current value. The original construction of the rotor with a rotating cryostat was developed, which decreases the thermal in-flow to the rotor. The stator of 1 MW HTS-2G generator has been manufactured. In order to improve the specific weight of the generator, the wave (harmonic drive) multiplier was used, which provides increasing RPM from 15 RPM up to 600 RPM. The total mass of the multiplier and generator is significantly smaller compared to traditional direct-drive wind turbines generators [2-7]. Parameters of the multiplier and generator were chosen based on the actual parameters of wind turbines, namely: 15 RPM, power is 1 MVA. The final test of the assembled synchronous generator with HTS-2G field coils for Wind Turbines with output power 1 MVA was completed during 2015.

Integration of g4tools in Geant4

NASA Astrophysics Data System (ADS)

Hřivnáčová, Ivana

2014-06-01

g4tools, that is originally part of the inlib and exlib packages, provides a very light and easy to install set of C++ classes that can be used to perform analysis in a Geant4 batch program. It allows to create and manipulate histograms and ntuples, and write them in supported file formats (ROOT, AIDA XML, CSV and HBOOK). It is integrated in Geant4 through analysis manager classes, thus providing a uniform interface to the g4tools objects and also hiding the differences between the classes for different supported output formats. Moreover, additional features, such as for example histogram activation or support for Geant4 units, are implemented in the analysis classes following users requests. A set of Geant4 user interface commands allows the user to create histograms and set their properties interactively or in Geant4 macros. g4tools was first introduced in the Geant4 9.5 release where its use was demonstrated in one basic example, and it is already used in a majority of the Geant4 examples within the Geant4 9.6 release. In this paper, we will give an overview and the present status of the integration of g4tools in Geant4 and report on upcoming new features.

Dendrimer-based nanocarriers demonstrating a high efficiency for loading and releasing anticancer drugs against cancer cells in vitro and in vivo

NASA Astrophysics Data System (ADS)

Quyen Tran, Ngoc; Khoa Nguyen, Cuu; Phuong Nguyen, Thi

2013-12-01

Dendrimer, a new class of hyper-branched polymer with predetermined molecular weight and well-controlled size, has received much attention in nanobiomedical applications such as drug carrier, gene therapy, disease diagnosis, etc. In this study, pegylated polyamidoamine (PAMAM) dendrimer at generation 3.0 (G 3.0) and carboxylated PAMAM dendrimer G 2.5 were prepared for loading anticancer drugs. For loading cisplatin, carboxylated dendrimer could carry 26.64 wt/wt% of cisplatin. The nanocomplexes have size ranging from 10 to 30 nm in diameter. The drug nanocarrier showed activity against NCI-H460 lung cancer cell line with half maximal inhibitory (IC50) of 23.11 ± 2.08 μg ml-1. Pegylated PAMAM dendrimers (G 3.0) were synthesized below 40 nm in diameter for carrying 5-fluorouracil (5-FU). For 5-FU encapsulation, pegylated dendrimer showed a high drug-loading efficiency of the drug and a slow release profile of 5-FU. The drug nanocarrier system exhibited an antiproliferative activity against MCF-7 cells (breast cancer cell) with a half maximal inhibitory (IC50) of 9.92 ± 0.19 μg ml-1. In vivo tumor xenograft study showed that the 5-FU encapsulated pegylation of dendrimer exhibited a significant decrement in volume of tumor which was generated by MCF-7 cancer cells. These positive results from our studies could pave the ways for further research of drugs dendrimer nanocarriers toward cancer chemotherapy.

A New Approach in the Preparation of Dendrimer-Based Bifunctional Diethylenetriaminepentaacetic Acid MR Contrast Agent Derivatives

PubMed Central

Nwe, Kido; Xu, Heng; Regino, Celeste Aida S.; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J.; Brechbiel, Martin W.

2009-01-01

In this paper we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves pre-forming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex® G-25 column and characterized by elemental analysis. The analysis and SEHPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the post-metal incorporation method (r1 = 26.9 vs. 13.9 mM-1s-1 at 3T and 22°C). This is hypothesized to be due to the higher hydrophobicity of this conjugate, and the lack of available charged carboxylate groups from non-complexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the post-metal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t1/2 = 24 min) suggesting a viable agent for use in clinical application. PMID:19555072

A new approach in the preparation of dendrimer-based bifunctional diethylenetriaminepentaacetic acid MR contrast agent derivatives.

PubMed

Nwe, Kido; Xu, Heng; Regino, Celeste Aida S; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J; Brechbiel, Martin W

2009-07-01

In this paper, we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves preforming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex G-25 column and characterized by elemental analysis. The analysis and SE-HPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the postmetal incorporation method (r(1) = 26.9 vs 13.9 mM(-1) s(-1) at 3 T and 22 degrees C). This is hypothesized to be due to the higher hydrophobicity of this conjugate and the lack of available charged carboxylate groups from noncomplexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the postmetal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t(1/2) = 24 min) suggesting a viable agent for use in clinical application.

A case of non-lacrimal immunoglobulin G4 (IgG4)-related orbital disease with mastitis.

PubMed

Farooq, Tahir Ali; Mudhar, Hardeep; Sandramouli, S

2016-01-01

IgG4-related orbital disease is a recognised cause for orbital inflammation. As its awareness increases and diagnostic accuracy improves there will be an increased number of cases being identified. This unique case demonstrates for the first time, with histological evidence, a case of a non-lacrimal IgG4-related orbital disease with concurrent IgG4-related mastitis. We describe a 47 year old who presented with a supraorbital swelling and mass. This was initially successfully treated with oral steroids and was later excised on recurrence. Immunohistochemical and blood serum analysis confirmed IgG4-related orbital disease. On systemic enquiry she was found to have a mass of the breast, which was shown to be IgG4-related mastitis. She is currently asymptomatic with no sign of recurrence and is under long-term surveillance. This case highlights the importance of systemic work up in patients presenting with orbital foci of IgG4 disease.

PAMAM dendrimer-baculovirus nanocomplex for microencapsulated adipose stem cell-gene therapy: in vitro and in vivo functional assessment.

PubMed

Paul, Arghya; Shao, Wei; Abbasi, Sana; Shum-Tim, Dominique; Prakash, Satya

2012-09-04

The present study aims to develop a new stem cell based gene delivery system consisting of human adipose tissue derived stem cells (hASCs) genetically modified with self-assembled nanocomplex of recombinant baculovirus and PAMAM dendrimer (Bac-PAMAM) to overexpress the vascular endothelial growth factor (VEGF). Cells were enveloped into branched PEG surface functionalized polymeric microcapsules for efficient transplantation. In vitro analysis confirmed efficient transduction of hASCs expressing 7.65 ± 0.86 ng functionally active VEGF per 10(6) microencapsulated hASCs (ASC-VEGF). To determine the potential of the developed system, chronically infarcted rat hearts were treated with either empty microcapsules (MC), microencapsulated hASCs expressing MGFP reporter protein (MC+ASC-MGFP), or MC+ASC-VEGF, and analyzed for 10 weeks. Post-transplantation data confirmed higher myocardial VEGF expressions with significantly enhanced neovasculature in the MC+ASC-VEGF group. In addition, the cardiac performance, as measured by percentage ejection fraction, also improved significantly in the MC+ASC-VEGF group (48.6 ± 6.1%) compared to that in MC+ASC-MGFP (38.8 ± 5.3%) and MC groups (31.5 ± 3.3%). Collectively, these data demonstrate the feasibility of this system for improved stem cell therapy applications.

Serum levels of IgG and IgG4 in Hashimoto thyroiditis.

PubMed

Kawashima, Sachiko-Tsukamoto; Tagami, Tetsuya; Nakao, Kanako; Nanba, Kazutaka; Tamanaha, Tamiko; Usui, Takeshi; Naruse, Mitsuhide; Minamiguchi, Sachiko; Mori, Yusuke; Tsuji, Jun; Tanaka, Issei; Shimatsu, Akira

2014-03-01

Although IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and lymphocytes of various organs, the details of this systemic disease are still unclear. We screened serum total IgG levels in the patients with Hashimoto thyroiditis (HT) to illustrate the prevalence of IgG4-related thyroiditis in HT. Twenty-four of 94 patients with HT (25.5%) had elevated serum IgG levels and their serum IgG4 was measured. Five of the 24 cases had more than 135 mg/dL of IgG4, which is the serum criterion of IgG4-related disease. One was a female patient who was initially treated as Graves' disease and rapidly developed a firm goiter and hypothyroidism. The biopsy of her thyroid gland revealed that follicular cells were atrophic with squamous metaplasia, replaced with fibrosis, which was compatible with the fibrous variant of HT. Immunohistochemical examination revealed diffuse infiltration of IgG4-positive plasma cells, and the serum IgG4 level was 179 mg/dL. The levels of IgG and IgG4 were positively correlated with the titers of anti-thyroglobulin antibody or anti-thyroid peroxidase antibody. In conclusion, at least a small portion of patients with HT with high titers of anti-thyroid antibodies may overlap the IgG4-related thyroiditis.

Wetting and layering transitions in a nano-dendrimer PAMAM structure: Monte Carlo study

NASA Astrophysics Data System (ADS)

Aouini, S.; Ziti, S.; Labrim, H.; Bahmad, L.

2016-10-01

This study is based on a nano-model of the dendrimer polyamidoamine (PAMAM). The idea is to examine the magnetic properties of such models in the context of wetting and the layering transitions. The studied system consists of spins σ ={1/2} Ising ferromagnetic in real nanostructure found in different scientific domains. To study this system, we perform Monte Carlo simulations leading to interesting results recapitulated in two classes. The former is the ground state phase diagrams study. The latter is the magnetic properties at non null temperatures. Also, we analyzed the effect of the terms present in the Hamiltonian governing our system such as the external magnetic field and the exchange couplings interactions.

Nanostructured glycan architecture is important in the inhibition of influenza A virus infection

NASA Astrophysics Data System (ADS)

Kwon, Seok-Joon; Na, Dong Hee; Kwak, Jong Hwan; Douaisi, Marc; Zhang, Fuming; Park, Eun Ji; Park, Jong-Hwan; Youn, Hana; Song, Chang-Seon; Kane, Ravi S.; Dordick, Jonathan S.; Lee, Kyung Bok; Linhardt, Robert J.

2017-01-01

Rapid change and zoonotic transmission to humans have enhanced the virulence of the influenza A virus (IAV). Neutralizing antibodies fail to provide lasting protection from seasonal epidemics. Furthermore, the effectiveness of anti-influenza neuraminidase inhibitors has declined because of drug resistance. Drugs that can block viral attachment and cell entry independent of antigenic evolution or drug resistance might address these problems. We show that multivalent 6‧-sialyllactose-polyamidoamine (6SL-PAMAM) conjugates, when designed to have well-defined ligand valencies and spacings, can effectively inhibit IAV infection. Generation 4 (G4) 6SL-PAMAM conjugates with a spacing of around 3 nm between 6SL ligands (S3-G4) showed the strongest binding to a hemagglutinin trimer (dissociation constant of 1.6 × 10-7 M) and afforded the best inhibition of H1N1 infection. S3-G4 conjugates were resistant to hydrolysis by H1N1 neuraminidase. These conjugates protected 75% of mice from a lethal challenge with H1N1 and prevented weight loss in infected animals. The structure-based design of multivalent nanomaterials, involving modulation of nanoscale backbone structures and number and spacing between ligands, resulted in optimal inhibition of IAV infection. This approach may be broadly applicable for designing effective and enduring therapeutic protection against human or avian influenza viruses.

pH-activatable nanoparticles for tumor-specific drug delivery

NASA Astrophysics Data System (ADS)

Liu, Karen C.

To address the need for a tumor-specific drug delivery system that can achieve both prolonged circulation and cellular retention at the tumor site, nanocomplexes of Zwitterionic Chitosan (ZWC) and Polyamidoamine (PAMAM) generation 5 were designed. Polyamidoamine (PAMAM) dendrimers have been widely explored as carriers of therapeutics and imaging agents, however, amine-terminated PAMAM dendrimers are rarely utilized in systemic applications due to its cytotoxicity and risk of opsonization, caused by its cationic charge. Such undesirable effects may be mitigated by shielding the PAMAM dendrimer surface with polymers that reduce the charges. However, this shielding may also interfere with PAMAM dendrimers' ability to interact with target cells, thus reducing cellular uptake and overall efficacy of the delivery system. ZWC, a new chitosan derivative, has a unique pH-sensitive charge profile and can shield the cationic surface of PAMAM dendrimers and block adsorption of serum proteins to allow for prolonged circulation. The hypothesis of this approach is that ZWC is anionic and able to coat PAMAM in neutral pH but becomes positive in the acidic tumor microenvironment, revealing the polycationic drug carrier. We expect that ZWC will provide (i) stealth coating for PAMAM drug carrier during circulation (pH 7.4) and (ii) be removed from the PAMAM drug carrier at acidic pH (pH ~6.3), allowing for cellular interaction. The cationic charge of PAMAM has been demonstrated to facilitate uptake and drug delivery to tumor cells via interactions with the negatively charged cell surface. Stable electrostatic complexes of ZWC and PAMAM dendrimers were formed at pH 7.4, as demonstrated by fluorescence spectroscopy and transmission electron microscopy. The presence of ZWC coating protected red blood cells and fibroblast cells from hemolytic and cytotoxic activities of PAMAM dendrimers, respectively. Confocal microscopy showed that the protective effect of ZWC disappeared at low pH as

4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

PubMed

Fernandes, Karla S; Sandrim, Valéria C

2012-05-01

The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

Investigating free radical generation in HepG2 cells using immuno-spin trapping.

PubMed

Horinouchi, Yuya; Summers, Fiona A; Ehrenshaft, Marilyn; Kawazoe, Kazuyoshi; Tsuchiya, Koichiro; Tamaki, Toshiaki; Mason, Ronald P

2014-10-01

Oxidative stress can induce the generation of free radicals, which are believed to play an important role in both physiological and pathological processes and a number of diseases such as cancer. Therefore, it is important to identify chemicals which are capable of inducing oxidative stress. In this study, we evaluated the ability of four environmental chemicals, aniline, nitrosobenzene (NB), N,N-dimethylaniline (DMA) and N,N-dimethyl-4-nitrosoaniline (DMNA), to induce free radicals and cellular damage in the hepatoma cell line HepG2. Cytotoxicity was assessed using lactate dehydrogenase (LDH) assays and morphological changes were observed using phase contrast microscopy. Free radicals were detected by immuno-spin trapping (IST) in in-cell western experiments or in confocal microscopy experiments to determine the subcellular localization of free radical generation. DMNA induced free radical generation, LDH release and morphological changes in HepG2 cells whereas aniline, NB and DMA did not. Confocal microscopy showed that DMNA induced free radical generation mainly in the cytosol. Preincubation of HepG2 cells with N-acetylcysteine and 2,2'-dipyridyl significantly prevented free radical generation upon subsequent incubation with DMNA, whereas preincubation with apocynin and dimethyl sulfoxide did not. These results suggest that DMNA induces oxidative stress and that reactive oxygen species, metals and free radical generation play a critical role in DMNA-induced cytotoxicity. Copyright © 2014. Published by Elsevier Inc.

Qualitative and quantitative analysis of poly(amidoamine) dendrimers in an aqueous matrix by liquid chromatography-electrospray ionization-hybrid quadrupole/time-of-flight mass spectrometry (LC-ESI-QTOF-MS).

PubMed

Uclés, A; Ulaszewska, M M; Hernando, M D; Ramos, M J; Herrera, S; García, E; Fernández-Alba, A R

2013-07-01

This work introduces a liquid chromatography-electrospray ionization-hybrid quadrupole/time-of-flight mass spectrometry (LC-ESI-QTOF-MS)-based method for qualitative and quantitative analysis of poly(amidoamine) (PAMAM) dendrimers of generations 0 to 3 in an aqueous matrix. The multiple charging of PAMAM dendrimers generated by means of ESI has provided key advantages in dendrimer identification by assignation of charge state through high resolution of isotopic clusters. Isotopic distribution in function of abundance of isotopes (12)C and (13)C yielded valuable and complementarity data for confident characterization. A mass accuracy below 3.8 ppm for the most abundant isotopes (diagnostic ions) provided unambiguous identification of PAMAM dendrimers. Validation of the LC-ESI-QTOF-MS method and matrix effect evaluation enabled reliable and reproducible quantification. The validation parameters, limits of quantification in the range of 0.012 to 1.73 μM, depending on the generation, good linear range (R > 0.996), repeatability (RSD < 13.4%), and reproducibility (RSD < 10.9%) demonstrated the suitability of the method for the quantification of dendrimers in aqueous matrices (water and wastewater). The added selectivity, achieved by multicharge phenomena, represents a clear advantage in screening aqueous mixtures due to the fact that the matrix had no significant effect on ionization, with what is evidenced by an absence of sensitivity loss in most generations of PAMAM dendrimers. Fig Liquid chromatography-electrospray ionization-hybrid quadrupole/time of flight mass spectrometry (LC-ESI-QTOF-MS) based method for qualitative and quantitative analysis of PAMAM dendrimers in aqueous matrix.

Towards a "fourth generation" of approaches to HIV/AIDS management: creating contexts for effective community mobilisation.

PubMed

Campbell, Catherine; Cornish, Flora

2010-01-01

Many biomedical and behavioural HIV/AIDS programmes aimed at prevention, care and treatment have disappointing outcomes because of a lack of effective community mobilisation. But community mobilisation is notoriously difficult to bring about. We present a conceptual framework that maps out those dimensions of social context that are likely to support or undermine community mobilisation efforts, proposing that attention should be given to three dimensions of social context: the material, symbolic and relational. This paper has four parts. We begin by outlining why community mobilisation is regarded as a core dimension of effective HIV/AIDS management: it increases the "reach" and sustainability of programmes; it is a vital component of the wider "task shifting" agenda given the scarcity of health professionals in many HIV/AIDS-vulnerable contexts. Most importantly it facilitates those social psychological processes that we argue are vital preconditions for effective prevention, care and treatment. Secondly we map out three generations of approaches to behaviour change within the HIV/AIDS field: HIV-awareness, peer education and community mobilisation. We critically evaluate each approach's underlying assumptions about the drivers of behaviour change, to frame our understandings of the pathways between mobilisation and health, drawing on the concepts of social capital, dialogue and empowerment. Thirdly we refer to two well-documented case studies of community mobilisation in India and South Africa to illustrate our claim that community mobilisation is unlikely to succeed in the absence of supportive material, symbolic and relational contexts. Fourthly we provide a brief overview of how the papers in this special issue help us flesh out our conceptualisation of the "health enabling social environment". We conclude by arguing for the urgent need for a 'fourth generation' of approaches in the theory and practice of HIV/AIDS management, one which pays far greater

Bismuth ferrite dielectric nanoparticles excited at telecom wavelengths as multicolor sources by second, third, and fourth harmonic generation.

PubMed

Riporto, Jérémy; Demierre, Alexis; Kilin, Vasyl; Balciunas, Tadas; Schmidt, Cédric; Campargue, Gabriel; Urbain, Mathias; Baltuska, Andrius; Le Dantec, Ronan; Wolf, Jean-Pierre; Mugnier, Yannick; Bonacina, Luigi

2018-05-03

We demonstrate the simultaneous generation of second, third, and fourth harmonics from a single dielectric bismuth ferrite nanoparticle excited using a telecom fiber laser at 1560 nm. We first characterize the signals associated with different nonlinear orders in terms of spectrum, excitation intensity dependence, and relative signal strengths. Successively, on the basis of the polarization-resolved emission curves of the three harmonics, we discuss the interplay of susceptibility tensor components at different orders and show how polarization can be used as an optical handle to control the relative frequency conversion properties.

Endocytosis and interaction of poly (amidoamine) dendrimers with Caco-2 cells.

PubMed

Kitchens, Kelly M; Foraker, Amy B; Kolhatkar, Rohit B; Swaan, Peter W; Ghandehari, Hamidreza

2007-11-01

To investigate the internalization and subcellular trafficking of fluorescently labeled poly (amidoamine) (PAMAM) dendrimers in intestinal cell monolayers. PAMAM dendrimers with positive or negative surface charge were conjugated to fluorescein isothiocyanate (FITC) and visualized for colocalization with endocytosis markers using confocal microscopy. Effect of concentration, generation and charge on the morphology of microvilli was observed using transmission electron microscopy. Both cationic and anionic PAMAM dendrimers internalized within 20 min, and differentially colocalized with endocytosis markers clathrin, EEA-1, and LAMP-1. Transmission electron microscopy analysis showed a concentration-, generation- and surface charge-dependent effect on microvilli morphology. These studies provide visual evidence that endocytic mechanism(s) contribute to the internalization and subcellular trafficking of PAMAM dendrimers across the intestinal cells, and that appropriate selection of PAMAM dendrimers based on surface charge, concentration and generation number allows the application of these polymers for oral drug delivery.

Fourth Computational Aeroacoustics (CAA) Workshop on Benchmark Problems

NASA Technical Reports Server (NTRS)

Dahl, Milo D. (Editor)

2004-01-01

This publication contains the proceedings of the Fourth Computational Aeroacoustics (CAA) Workshop on Benchmark Problems. In this workshop, as in previous workshops, the problems were devised to gauge the technological advancement of computational techniques to calculate all aspects of sound generation and propagation in air directly from the fundamental governing equations. A variety of benchmark problems have been previously solved ranging from simple geometries with idealized acoustic conditions to test the accuracy and effectiveness of computational algorithms and numerical boundary conditions; to sound radiation from a duct; to gust interaction with a cascade of airfoils; to the sound generated by a separating, turbulent viscous flow. By solving these and similar problems, workshop participants have shown the technical progress from the basic challenges to accurate CAA calculations to the solution of CAA problems of increasing complexity and difficulty. The fourth CAA workshop emphasized the application of CAA methods to the solution of realistic problems. The workshop was held at the Ohio Aerospace Institute in Cleveland, Ohio, on October 20 to 22, 2003. At that time, workshop participants presented their solutions to problems in one or more of five categories. Their solutions are presented in this proceedings along with the comparisons of their solutions to the benchmark solutions or experimental data. The five categories for the benchmark problems were as follows: Category 1:Basic Methods. The numerical computation of sound is affected by, among other issues, the choice of grid used and by the boundary conditions. Category 2:Complex Geometry. The ability to compute the sound in the presence of complex geometric surfaces is important in practical applications of CAA. Category 3:Sound Generation by Interacting With a Gust. The practical application of CAA for computing noise generated by turbomachinery involves the modeling of the noise source mechanism as a

Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model.

PubMed

Sharma, Anjali; Porterfield, Joshua E; Smith, Elizabeth; Sharma, Rishi; Kannan, Sujatha; Kannan, Rangaramanujam M

2018-06-05

Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer

Reflection paper on the use of third and fourth generation cephalosporins in food producing animals in the European Union: development of resistance and impact on human and animal health.

PubMed

2009-12-01

Resistance to third and fourth generation cephalosporins is rapidly increasing in bacteria infecting humans. Although many of these problems are linked to human to human transmission and to use of antimicrobials in human medicine, the potential role of community reservoirs such as food producing animals needs to be scrutinized. Resistance to third and fourth generation cephalosporins is emerging in enteric bacteria of food producing animals and also in food of animal origin. The genes encoding resistance to these cephalosporins are transferrable and often linked to other resistance genes. Systemic use of third and fourth cephalosporins selects for resistance, but co-selection by other antimicrobials is also likely to influence prevalence of resistance. Although there are many uncertainties, the potential consequences of a further increase of resistance to this critically important class of antimicrobials in bacteria colonising animals are serious. Measures to counter a further increase and spread of resistance among animals should therefore be considered.

[IgG4 immunohistochemistry in Riedle thyroiditis].

PubMed

Wang, S; Luo, Y F; Cao, J L; Zhang, H; Shi, X H; Liang, Z Y; Feng, R E

2017-03-08

Objective: To observe the histopathological changes and immunohistochemical expression of IgG4 in Riedle thyroiditis (RT) and to study the relationship between RT and IgG4-related diseases (IgG4-RD). Methods: A total of 5 RT patients were collected from the Department of Pathology, Peking Union Medical College Hospital during April 2012 to August 2014. The clinical and immunohistochemical features were analyzed in the 5 patients. Histopathologic analysis was performed on hematoxylin and eosin-stained sections. Results: There were one male and four female patients, aged 52 to 78 years (median 59 years). Five cases were characterized by multiple nodules of thyroid, which increased year by year. All patients were found to have surrounding tissue compression symptoms and signs. Two female patients were found to have hypothyroidism. The serum concentration of IgG was elevated in 2 cases, and the serum concentration of IgG was not tested before operation in the remaining patients. By ultrasound, all presented as low echo or medium low echo. Strong echo occasionally appeared in hypoechoic nodules. Microscopically, fibrous tissue hyperplasia was infiltrated with varying numbers of lymphocytes and plasma cells. The occlusion of phlebitis was found in 4 cases and eosinophils were found in 3 cases. IgG4 counts and IgG4/IgG ratios in 5 cases were 20/HPF, 16%; 60/HPF, 82%; 22/HPF, 28%; 400/HPF, 266% and 33/HPF, 71%, respectively. Conclusions: With the similar pathological manifestations between RT and IgG4-RD, immunohistochemical staining shows that the number of IgG4 positive plasma cells and IgG4/IgG ratio of RT are increased in varying degrees. Some cases meet the diagnostic criteria of IgG4-RD, and speculate that some cases of RT belong to IgG4-RD.

Mission Control Center (MCC) - Apollo 13 - Fourth (4th) Television Signal - MSC

NASA Image and Video Library

1970-04-13

S70-35139 (13 April 1970) --- Overall view of the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC) at Manned Spacecraft Center (MSC), during the fourth television transmission from the Apollo 13 mission in space. Eugene F. Kranz (foreground, back to camera), one of four Apollo 13 flight directors, views the large screen at front of MOCR, astronaut Fred W. Haise Jr., lunar module pilot, is seen on the screen. The fourth TV transmission from the Apollo 13 mission was on the evening of April 13, 1970.

Performance of the fourth-generation Bio-Rad GS HIV Combo Ag/Ab enzyme immunoassay for diagnosis of HIV infection in Southern Africa

PubMed Central

Piwowar-Manning, Estelle; Fogel, Jessica M.; Richardson, Paul; Wolf, Shauna; Clarke, William; Marzinke, Mark A.; Fiamma, Agnès; Donnell, Deborah; Kulich, Michal; Mbwambo, Jessie K.K.; Richter, Linda; Gray, Glenda; Sweat, Michael; Coates, Thomas J.; Eshleman, Susan H.

2015-01-01

Background Fourth-generation HIV assays detect both antigen and antibody, facilitating detection of acute/early HIV infection. The Bio-Rad GS HIV Combo Ag/Ab assay (Bio-Rad Combo) is an enzyme immunoassay that simultaneously detects HIV p24 antigen and antibodies to HIV-1 and HIV-2 in serum or plasma. Objective To evaluate the performance of the Bio-Rad Combo assay for detection of HIV infection in adults from Southern Africa. Study design Samples were obtained from adults in Soweto and Vulindlela, South Africa and Dar es Salaam, Tanzania (300 HIV-positive samples; 300 HIV-negative samples; 12 samples from individuals previously classified as having acute/early HIV infection). The samples were tested with the Bio-Rad Combo assay. Additional testing was performed to characterize the 12 acute/early samples. Results All 300 HIV-positive samples were reactive using the Bio-Rad Combo assay; false positive test results were obtained for 10 (3.3%) of the HIV-negative samples (sensitivity: 100%, 95% confidence interval [CI]: 98.8–100%); specificity: 96.7%, 95% CI: 94.0–98.4%). The assay detected 10 of the 12 infections classified as acute/early. The two infections that were not detected had viral loads < 400 copies/mL; one of those samples contained antiretroviral drugs consistent with antiretroviral therapy. Conclusions The Bio-Rad Combo assay correctly classified the majority of study specimens. The specificity reported here may be higher than that seen in other settings, since HIV-negative samples were pre-screened using a different fourth-generation test. The assay also had high sensitivity for detection of acute/early infection. False-negative test results may be obtained in individuals who are virally suppressed. PMID:25542477

Plasminogen activator inhibitor 1 4G/5G and -844G/A variants in idiopathic recurrent pregnancy loss.

PubMed

Magdoud, Kalthoum; Herbepin, Viviana G; Touraine, Renaud; Almawi, Wassim Y; Mahjoub, Touhami

2013-09-01

Plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis, and the common promoter region variants -675G/A (4G/5G) and -844G/A are associated with increased thrombotic risk. Despite evidence linking altered fibrinolysis with adverse pregnancy events, including idiopathic recurrent pregnancy loss (RPL), the contribution of PAI-1 variants to RPL risk remains controversial. We investigated the association between the PAI-1 -844G/A and 4G/5G (-675G/A) variants with altered risk of RPL. This was a case-control study involving 304 women with confirmed RPL and 371 age- and ethnically matched control women. PAI-1 genotyping was performed by PCR single-specific primer -675 (G/A) and real-time PCR (-844G/A) analysis. Minor allele frequency (MAF) of 4G/5G (P < 0.001), but not -844G/A (P = 0.507), was higher in RPL cases. PAI-1 4G/5G single-nucleotide polymorphism (SNP) was significantly associated with RPL under additive, dominant, and recessive genetic models; no association of -844G/A with RPL was seen irrespective of the genetic model tested. Taking common -844G/5G haplotype as reference (OR = 1.00), multivariate analysis confirmed the association of 4G-containing -844A/4G (P < 0.001) and -844G/4G (P = 0.011) haplotypes with increased RPL risk. 4G/5G, but not -844G/A, PAI-1 variant is associated with an increased risk of RPL. © 2013 John Wiley & Sons Ltd.

Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

PubMed

Armangil, Didem; Yurdakök, Murat; Okur, Hamza; Gürgey, Aytemiz

2011-08-01

Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.

Diffusion of flexible, charged, nanoscopic molecules in solution: Size and pH dependence for PAMAM dendrimer

NASA Astrophysics Data System (ADS)

Maiti, Prabal K.; Bagchi, Biman

2009-12-01

In order to understand self-diffusion (D) of a charged, flexible, and porous nanoscopic molecule in water, we carry out very long, fully atomistic molecular dynamics simulation of PAMAM dendrimer up to eight generations in explicit salt water under varying pH. We find that while the radius of gyration (Rg) varies as N1/3, the self-diffusion constant (D ) scales, surprisingly, as N-α, with α =0.39 at high pH and 0.5 at neutral pH, indicating a dramatic breakdown of Stokes-Einstein relation for diffusion of charged nanoscopic molecules. The variation in D as a function of radius of gyration demonstrates the importance of treating water and ions explicitly in the diffusion process of a flexible nanoscopic molecule. In agreement with recent experiments, the self-diffusion constant increases with pH, revealing the importance of dielectric friction in the diffusion process. The shape of a dendrimer is found to fluctuate on a nanosecond time scale. We argue that this flexibility (and also the porosity) of the dendrimer may play an important role in determining the mean square displacement of the dendrimer and the breakdown of the Stokes-Einstein relation between diffusion constant and the radius.

Poly(amidoamine) dendrimer-enabled simultaneous stabilization and functionalization of electrospun poly(γ-glutamic acid) nanofibers.

PubMed

Wang, Shige; Zhu, Jingyi; Shen, Mingwu; Zhu, Meifang; Shi, Xiangyang

2014-02-12

We report a facile and general approach to using generation 2 (G2) poly(amidoamine) (PAMAM) dendrimers for simultaneous stabilization and functionalization of electrospun poly(γ-glutamic acid) nanofibers (γ-PGA NFs). In this study, uniform γ-PGA NFs with a smooth morphology were generated using electrospinning technology. In order to endow the NFs with good water stability, amine-terminated G2.NH2 PAMAM dendrimers were utilized to crosslink the γ-PGA NFs via 1-ethyl-3-(3-dimethylami-nopropyl) carbodiimide coupling chemistry. Under the optimized crosslinking conditions, G2.NH2 dendrimers partially modified with fluorescein isothiocyanate (FI) or folic acid (FA) were used to crosslink γ-PGA NFs. Our results reveal that G2.NH2-FI is able to simultaneously render the NFs with good water stability and fluorescence property, while G2.NH2-FA is able to simultaneously endow the NFs with water stability and the ability to capture FA receptor-overexpressing cancer cells in vitro via ligand-receptor interaction. With the tunable dendrimer surface chemistry, multifunctional water-stable γ-PGA-based NFs may be generated via a dendrimer crosslinking approach, thereby providing diverse applications in the areas of biosensing, tissue engineering, drug delivery, and environmental sciences.

Enhanced visible-light-driven photocatalytic bacteria disinfection by g-C3N4-AgBr.

PubMed

Deng, Jun; Liang, Jialiang; Li, Mian; Tong, Meiping

2017-04-01

g-C 3 N 4 -AgBr was synthesized by depositing AgBr nanoparticles onto g-C 3 N 4 . Scanning electron microscopy (SEM), Transmission electron microscope (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectra (DRS) and Photoluminescence (PL) spectra were employed to characterize the as-synthesized photocatalysts. The disinfection activities towards representative Gram-negative strain E. coli and Gram-positive strain S. aureus were examined under visible light irradiation. Complete inactivation of 3×10 6 CFU/mL viable cell density was reached in 60min for E. coli and 150min for S. aureus, respectively. Ag + released from the photocatalysts did not contribute to the photocatalytic disinfection process. Direct contact of g-C 3 N 4 -AgBr composites and bacterial cells, as well as the presence of O 2 was indispensable for the cell inactivation. Photo-generated holes, surface bounded OH, and indirect generation of intracellular active species played important roles in disinfection process of g-C 3 N 4 -AgBr under visible light irradiation. The disruption of outside structure of cells as well as inner cell injury led to the inactivation. High pH condition led to increasing the cell disinfection due to the generation of surface bounded OH. Copyright © 2017 Elsevier B.V. All rights reserved.

Imaging Potential Evaluation of Fab Derived from the Anti-EGFRvIII Monoclonal Antibody 4G1.

PubMed

Jing, Shen; He, Yujia; He, Yanqiong; Wang, Liang; Jia, Jianhua; Shan, Xiaomin; Liu, Shuang; Tang, Min; Peng, Zhiping; Liu, Xujie

2018-05-31

As one of the most crucial epidermal growth factor receptor (EGFR) variants, EGFRvIII can be detected in various tumors but rarely in normal tissues, making it an ideal target for prognosis, diagnosis or immune therapy. The recently developed anti-EGFRvIII monoclonal antibody (mAb), 4G1, has been validated as a promising molecular probe to detect EGFRvIII expression in tumors by single-photon emission computed tomography/computed tomography imaging. To overcome shortcomings associated with the whole antibody, including long-term retention, circulation and enhanced permeability and retention effects, the Fab fragment of 4G1 (Fab-4G1) was generated, labeled with 131 I and evaluated in vitro and in vivo to test its potential application in molecular imaging. Whole mAb 4G1 was first digested by immobilized ficin and then purified through a protein A column to generate the Fab fragment, Fab-4G1. Next, SDS-PAGE, Western blot, indirect fluorescence assay, flow cytometry and enzyme-linked immunosorbent assay were performed to verify molecular weight, specificity and affinity of Fab-4G1. Finally, biodistribution planar gamma imaging was performed by injection of 131 I-labeled Fab-4G1 into xenografted EGFRvIII-overexpressed tumors in nude mice. Parallel studies were also performed with intact 4G1. The molecular weight of Fab was determined to be 35-40 kDa by SDS-PAGE. In vitro tests confirmed both intact 4G1 and Fab-4G1 specifically bound EGFRvIII but not wild-type EGFR, and Fab-4G1 showed decreased affinity. Compared to 131 I-4G1, biodistribution studies showed lower tumor uptake of 131 I-Fab-4G1 at all time points, but much faster elimination in all normal organs. As for planar gamma imaging, 131 I-Fab-4G1 and 31 I-4G1 showed similar imaging effect at 2 h after injection of tracer, while 131 I-Fab-4G1 was eliminated more quickly with time, suggesting radiolabeled Fab-4G1 could be potentially used for imaging of EGFRvIII-positive tumors at early time points. Radiolabeled

Epstein-Barr virus-infected cells in IgG4-related lymphadenopathy with comparison with extranodal IgG4-related disease.

PubMed

Takeuchi, Mai; Sato, Yasuharu; Yasui, Hiroshi; Ozawa, Hiroaki; Ohno, Kyotaro; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Tachibana, Tomoyasu; Itoh, Tomoo; Asano, Naoko; Nakamura, Shigeo; Swerdlow, Steven H; Yoshino, Tadashi

2014-07-01

IgG4-related lymphadenopathy with increased numbers of Epstein-Barr virus (EBV)-infected cells has been reported but not fully described. We analyzed 31 cases of IgG4-related lymphadenopathy and 24 cases of extranodal IgG4-related diseases for their possible relationship with EBV. Other types of reactive lymph nodes (22) and angioimmunoblastic T-cell lymphoma (AITL) (10) were also studied for comparison. EBV-encoded RNA (EBER) in situ hybridization revealed EBER(+) cells in 18 of 31 cases (58%) of IgG4-related lymphadenopathy. Increased EBER(+) cells were found in only 4 of 22 (18.1%) non-IgG4-related reactive lymphoid hyperplasia in patients of a similar age (P=0.002) and in only 5 of 24 (21%) extranodal IgG4-related biopsies (P=0.006). Interestingly, all patients with EBER(+) progressively transformed germinal center-type IgG4-related lymphadenopathy had systemic lymphadenopathy and/or extranodal involvement. AITL also is associated with EBV, and IgG4-related lymphadenopathy sometimes mimics the morphology of AITL; however, the number of IgG4(+) cells in AITL was significantly less than that in IgG4-related lymphadenopathy (P<0.001). Increased numbers of regulatory T cells are seen in IgG4-related disease; however, there was not a significant difference between the EBER(+) and EBER(-) cases. In conclusion, the presence of increased numbers of EBV-infected cells in IgG4-related lymphadenopathy, compared with other reactive lymphadenopathy or extranodal IgG4-related disease, suggests that there may be a relationship at least between nodal IgG4-related disease and EBV. It is important to avoid overdiagnosing these cases as malignant lymphomas or EBV-related lymphoproliferative disorders.

[PAL-1 5G/4G polymorphism in patients with systemic lupus erythematosus].

PubMed

Savov, A; Andonova, S; Tanev, D; Robeva, R; Marincheva, Ts; Tomova, A; Kumanov, Ph; Rashkov, R; Kolarov, Zl

2014-01-01

Systemic lupus erythematosus (SLE) is a connective tissue disease affecting predominantly women that has been widely associated with obstetric complications. Inherited thrombophilias are significant risk factors for pregnancy loss, but their role in patients with SLE, and especially in those without concomitant secondary antiphospholipid syndrome (APS) has not been clarified. The aim of the present study was to study PAI-1 5G/4G polymorphism in women with lupus. A total of 103 SLE patients as well as 69 healthy volunteers were genotyped for PAI-1 5G/4G (rs1799889). No significant differences in the PAI-1 5G/4G genotype prevalence between patients and controls were found. After exclusion of the women with secondary APS, the frequency of pregnancies and spontaneous abortions, as well as the number of live births were similar in the studied patients with different PAI-1 genotype (p> 0.05). PAI-1 5G/4G polymorphism was not significantly related to any of the lupus ACR criteria or disease activity (p > 0.05), but it could influence the platelet number in the studied patients (263.52 ± 91.10 [5G/5G genotype] versus 210.12 ± 71.79 [4G/4G genotype], p = 0.023). In conclusion, our results showed that PAI-1 4G/5G polymorphism did not worsen the reproductive outcome in SLE women without secondary APS.

Mod-5A wind turbine generator program design report. Volume 4: Drawings and specifications, book 4

NASA Technical Reports Server (NTRS)

1984-01-01

The design, development and analysis of the 7.3 MW MOD-5A wind turbine generator are documented. There are four volumes. This volume contains the drawings and specifications that were developed in preparation for building the MOD-5A wind turbine generator. This volume contains 5 books of which this is the fourth, providing drawings 47A380128 through 47A387125. In addition to the parts listing and where-used list, the logic design of the controller software and the code listing of the controller software are provided. Also given are the aerodynamic profile coordinates.

Isoguanine quartets formed by d(T4isoG4T4): tetraplex identification and stability.

PubMed Central

Seela, F; Wei, C; Melenewski, A

1996-01-01

The self-aggregation of the oligonucleotide d(T4isoG4T4) (1) is investigated. Based on ion exchange HPLC experiments and CD spectroscopy, a tetrameric structure is identified. This structure was formed in the presence of sodium ions and shows almost the same chromatographic mobility on ion exchange HPLC as d(T4G4T4) (2). The ratio of aggregate versus monomer is temperature dependent and the tetraplex of [d(T4isoG4T4)]4 is more stable than that of [d(T4G4T4)]4. A mixture of d(T4isoG4T4) and d(T4G4T4) forms mixed tetraplexes containing strands of d(T4isoG4T4) and d(T4G4T4). PMID:9016664

Self-assembled novel multi-porphyrin micro-crystals as a photocatalyst for 2,4,6-trinitrotoluene degradation

NASA Astrophysics Data System (ADS)

Hikal, Walid M.

In this thesis I have presented the findings of my research pursued during my Ph.D. study. Following the findings that 2,4,6-trinitrotoluene binds to porphyrins at room temperature and could be photoctalytically degraded using porphyrin solutions and visible light, the purpose of this work was to determine the nature of the binding between the two species and develop a solid porphyrin-based photocatalyst for TNT degradation. C1TPP porphyrin is found to be able to bind to TNT via 1.94 kcal/mole hydrogen bonds at room temperature and hydrophobic bonds at higher temperatures. Photocatalytic solid porphyrin crystalline structures have been developed using two oppositely charged, commercially available, and low cost porphyrins in presence and absence of PAMAM generation 4 (G4) dendrimer, by self-assembly at room temperature without acidification. Solid porphyrin crystals were characterized by means of optical microscopy, UV-visible spectroscopy, fluorescence spectroscopy, and powder X-ray diffraction. A hypothetical model for the structure of the crystals is proposed. The porphyrin crystals show photocatalytic capabilities; illumination of the crystals in a 2,4,6-trinitrotoluene solution by visible light results in degradation of TNT and the intermediates have been determined using high pressure liquid chromatography (HPLC) and gas chromatography (GC).

Proceedings of the Fourth Social Aspects and Recreation Research Symposium: February 4-6, 2004, San Francisco, California

Treesearch

Patrick T. Tierney; Deborah J. (Tech. coords.) Chavez

2004-01-01

The Fourth Social Aspects and Recreation Research (SARR) Symposium was held February 4-6, 2004 in San Francisco, California at the Presidio of San Francisco, a component of Golden Gate National Recreation Area and at San Francisco State University. The theme was: Linking People to the Outdoors: Connections for Healthy Lands, People and Communities.

Occurrence of IgG4-related hypophysitis lacking IgG4-bearing plasma cell infiltration during steroid therapy.

PubMed

Ohkubo, Yohsuke; Sekido, Takashi; Takeshige, Keiko; Ishi, Hiroaki; Takei, Masahiro; Nishio, Shin-ichi; Yamazaki, Masanori; Komatsu, Mitsuhisa; Kawa, Shigeyuki; Suzuki, Satoru

2014-01-01

Eight years after an episode of multiple IgG4-related disease, a pituitary mass with panhypopituitarism and a visual disturbance developed in a 70-year-old man under low-dose steroid therapy. A pituitary biopsy revealed findings of lymphocytic hypophysitis with the absence of IgG4-positive plasma cell infiltration. The serum IgG4 level was unremarkable. Although performing a pituitary biopsy and measuring the serum IgG4 level is crucial for making a diagnosis of IgG4-related hypophysitis, it is occasionally difficult to diagnose the disease in patients treated with steroid therapy, as observed in the present case. Based on a review of the diagnosis, conducting a careful assessment is required, especially in men and elderly patients thought to have solitary hypophysitis.

PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

PubMed

Wang, Shangqian; Cao, Qiang; Wang, Xiaoxiang; Li, Bingjie; Tang, Min; Yuan, Wanqing; Fang, Jianzheng; Qian, Jian; Qin, Chao; Zhang, Wei

2013-01-01

The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results. A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I(2) test. Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03-1.18, I(2) = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06-1.39, I(2) = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04-1.18, I(2) = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09-1.59, I(2) = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04-1.21, I(2) = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05-1.21, I(2) = 25.3%). The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.

Electrogenerated chemiluminescence reactions between the [Ru(bpy)3](2+) complex and PAMAM GX.0 dendrimers in an aqueous medium.

PubMed

Jimenez-Ruiz, A; Grueso, E; Perez-Tejeda, P

2015-10-01

Electrogenerated chemiluminescence, ECL, reactions between tris(2,2'-bipyridine)ruthenium(II), [Ru(bpy)3](2+), and PAMAM GX.0 (X=1 and 2) dendrimers in an aqueous medium were carried out at pH10 (fully deprotonated dendrimer surface). ECL was detected in the presence of GX.0 dendrimers without addition of any known coreactant. Atomic force microscopy, AFM, measurements for GX.0 dendrimers in the presence of the [Ru(bpy)3](2+) complex were also done. AFM images showed the existence of aggregates (pillars) of globular shape, as well as interdendrimer networks forming fibers in the x-y direction for dendrimer aqueous solutions. ECL and AFM results in cooperation suggest that the coreactant effect of the end amine groups is improved by both the dendritic branched shells and the globular z-type aggregates. The ECL efficiency trends as a function of [GX.0] (whole range) can be interpreted taking into account the coreactant effect modulated by the presence of the z and x-y type aggregates. Importantly, ECL efficiency values can be taken as a measure of the change induced on the dendrimer aggregation in aqueous solutions when their concentrations rise. Redox potentials of the [Ru(bpy)3](3+/2+) couple in the presence of the G1.0 and G2.0 dendrimers were also determined. Copyright © 2015 Elsevier Inc. All rights reserved.

A coarse grained molecular dynamics simulation study on the structural properties of carbon nanotube-dendrimer composites.

PubMed

Kavyani, Sajjad; Dadvar, Mitra; Modarress, Hamid; Amjad-Iranagh, Sepideh

2018-04-25

By employing coarse grained (CG) molecular dynamics (MD) simulation, the effect of the size and hydrophilic/hydrophobic properties of the interior/exterior structures of the dendrimers in carbon nanotube (CNT)-dendrimer composites has been studied, to find a stable composite with high solubility in water and the capability to be used in drug delivery applications. For this purpose, composites consisting of core-shell dendrimer complexes including: [PPI{core}-PAMAM{shell}], [PAMAM{core}-polyethyleneglycol (PEG){shell}] and [PAMAM{core}-fattyacid (FTA){shell}] were constructed. A new CG model for the fatty acid (FTA) molecules as functionalized to the dendrimer was developed, which, unlike the previous models, could generate the structural conformations of the FTA properly. The obtained results indicated that the dendrimer complexes with short FTA chains can form stable composites with the CNT. Also, it was found that the pristine PAMAM and PPI-PAMAM with small PPI, and PAMAM-PEG dendrimers with short PEG chains, can distribute their chains into the water medium and interact with the CNT efficiently, to form a stable water-soluble CNT-dendrimer composite. The results demonstrated that the structural difference between the interior and exterior of a core-shell dendrimer complex can prevent the core and the interior layers of the dendrimer complex from interacting with the CNT. An overall analysis of the results manifested that the CNT-PAMAM:4-PEG:4 is the most stable composite, due to strong binding of the dendrimer with the CNT while also having high solubility in water, and its core retains its structure properly and unchanged, suitable for encapsulating drugs in the targeted delivery applications.

Expansion of blood IgG4+ B, TH2, and regulatory T cells in patients with IgG4-related disease.

PubMed

Heeringa, Jorn J; Karim, A Faiz; van Laar, Jan A M; Verdijk, Robert M; Paridaens, Dion; van Hagen, P Martin; van Zelm, Menno C

2018-05-01

IgG 4 -related disease (IgG 4 -RD) is a systemic fibroinflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG 4 + plasma cells in tissue are hallmarks of the disease, and IgG 4 -RD is associated with increased IgG 4 serum levels. However, disease pathogenesis is still unclear, and these cellular and molecular parameters are neither sensitive nor specific for the diagnosis of IgG 4 -RD. Here we sought to develop a flow cytometric gating strategy to reliably identify blood IgG 4 + B cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis. Sixteen patients with histologically confirmed IgG 4 -RD, 11 patients with sarcoidosis, and 30 healthy subjects were included for 11-color flow cytometric analysis of peripheral blood for IgG 4 -expressing B cells and T H subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG 4 -expressing B cells, and IgG 4 transcripts were analyzed for somatic hypermutations. Cellular and molecular analyses revealed increased numbers of blood IgG 4 + memory B cells in patients with IgG 4 -RD. These cells showed reduced expression of CD27 and CXCR5 and increased signs of antibody maturation. Furthermore, patients with IgG 4 -RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21 low B cells, as well as T H 2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG 4 -RD. These results provide new insights into the dysregulated IgG 4 response in patients with IgG 4 -RD. A specific "peripheral lymphocyte signature" observed in patients with IgG 4 -RD, could support diagnosis and treatment monitoring. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

GUN4-Protoporphyrin IX Is a Singlet Oxygen Generator with Consequences for Plastid Retrograde Signaling*

PubMed Central

Tarahi Tabrizi, Shabnam; Sawicki, Artur; Zhou, Shuaixiang; Luo, Meizhong; Willows, Robert D.

2016-01-01

The genomes uncoupled 4 (GUN4) protein is a nuclear-encoded, chloroplast-localized, porphyrin-binding protein implicated in retrograde signaling between the chloroplast and nucleus, although its exact role in this process is still unclear. Functionally, it enhances Mg-chelatase activity in the chlorophyll biosynthesis pathway. Because GUN4 is present only in organisms that carry out oxygenic photosynthesis and because it binds protoporphyrin IX (PPIX) and Mg-PPIX, it has been suggested that it prevents production of light- and PPIX- or Mg-PPIX-dependent reactive oxygen species. A chld-1/GUN4 mutant with elevated PPIX has a light-dependent up-regulation of GUN4, implicating this protein in light-dependent sensing of PPIX, with the suggestion that GUN4 reduces PPIX-generated singlet oxygen, O2(a1Δg), and subsequent oxidative damage (Brzezowski, P., Schlicke, H., Richter, A., Dent, R. M., Niyogi, K. K., and Grimm, B. (2014) Plant J. 79, 285–298). In direct contrast, our results show that purified GUN4 and oxidatively damaged ChlH increase the rate of PPIX-generated singlet oxygen production in the light, by a factor of 5 and 10, respectively, when compared with PPIX alone. Additionally, the functional GUN4-PPIX-ChlH complex and ChlH-PPIX complexes generate O2(a1Δg) at a reduced rate when compared with GUN4-PPIX. As O2(a1Δg) is a potential plastid-to-nucleus signal, possibly through second messengers, light-dependent O2(a1Δg) generation by GUN4-PPIX is proposed to be part of a signal transduction pathway from the chloroplast to the nucleus. GUN4 thus senses the availability and flux of PPIX through the chlorophyll biosynthetic pathway and also modulates Mg-chelatase activity. The light-dependent O2(a1Δg) generation from GUN4-PPIX is thus proposed as the first step in retrograde signaling from the chloroplast to the nucleus. PMID:26969164

Next Generation Hydrogen Station Composite Data Products: Retail Stations, Data through Quarter 4 of 2016

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

Sprik, Sam; Kurtz, Jennifer; Ainscough, Chris

This publication includes 86 composite data products (CDPs) produced for next generation hydrogen stations, with data through the fourth quarter of 2016. These CDPs include data from retail stations only.

Next Generation Hydrogen Station Composite Data Products: Retail Stations, Data through Quarter 4 of 2017

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

Sprik, Samuel; Kurtz, Jennifer M; Saur, Genevieve

This publication includes 98 composite data products (CDPs) produced for next generation hydrogen stations, with data through the fourth quarter of 2017. These CDPs include data from retail stations only.

Fourth Workshop on Sustainable Software for Science: Practice and Experiences (WSSSPE4)

NASA Astrophysics Data System (ADS)

Katz, Daniel S.; Niemeyer, Kyle E.; Gesing, Sandra; Hwang, Lorraine; Bangerth, Wolfgang; Hettrick, Simon; Idaszak, Ray; Salac, Jean; Hong, Neil Chue; Núñez-Corrales, Santiago; Allen, Alice; Geiger, R. Stuart; Miller, Jonah; Chen, Emily; Dubey, Anshu; Lago, Patricia

This article summarizes motivations, organization, and activities of the Fourth Workshop on Sustainable Software for Science: Practice and Experiences (WSSSPE4). The WSSSPE series promotes sustainable research software by positively impacting principles and best practices, careers, learning, and credit. This article discusses the code of conduct; the mission and vision statements that were drafted at the workshop and finalized shortly after it; the keynote and idea papers, position papers, experience papers, demos, and lightning talks presented during the workshop; and a panel discussion on best practices. The main part of the article discusses the set of working groups that formed during the meeting, along with contact information for readers who may want to join a group. Finally, it discusses a survey of the workshop attendees.

A selective glucose sensor: the cooperative effect of monoboronic acid-modified poly(amidoamine) dendrimers.

PubMed

Tsai, Ching-Hua; Tang, Yi-Hsuan; Chen, Hui-Ting; Yao, Yi-Wen; Chien, Tun-Cheng; Kao, Chai-Lin

2018-05-01

Selective glucose binding was identified through five generations of monoboronic acid-functionalized PAMAM dendrimers. The best selectivity obtained when using G3 dendrimers (1b) generated 71.1, 94.9, and 1309 times stronger binding than when using galactose, fructose, and lactose, respectively. Further experiments using dendrimer analogues and glucose derivatives suggested that two nearby monoboronic acids cooperatively bound one glucose.

PAI-1 4G/5G Polymorphism Contributes to Cancer Susceptibility: Evidence from Meta-Analysis

PubMed Central

Li, Bingjie; Tang, Min; Yuan, Wanqing; Fang, Jianzheng; Qian, Jian; Qin, Chao; Zhang, Wei

2013-01-01

Background The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results. Methods A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I2 test. Results Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03–1.18, I2 = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06–1.39, I2 = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04–1.18, I2 = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09–1.59, I2 = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04–1.21, I2 = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05–1.21, I2 = 25.3%). Conclusions The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer. PMID:23437240

TriG: Next Generation Scalable Spaceborne GNSS Receiver

NASA Technical Reports Server (NTRS)

Tien, Jeffrey Y.; Okihiro, Brian Bachman; Esterhuizen, Stephan X.; Franklin, Garth W.; Meehan, Thomas K.; Munson, Timothy N.; Robison, David E.; Turbiner, Dmitry; Young, Lawrence E.

2012-01-01

TriG is the next generation NASA scalable space GNSS Science Receiver. It will track all GNSS and additional signals (i.e. GPS, GLONASS, Galileo, Compass and Doris). Scalable 3U architecture and fully software and firmware recofigurable, enabling optimization to meet specific mission requirements. TriG GNSS EM is currently undergoing testing and is expected to complete full performance testing later this year.

Towards 5G: A Photonic Based Millimeter Wave Signal Generation for Applying in 5G Access Fronthaul.

PubMed

Alavi, S E; Soltanian, M R K; Amiri, I S; Khalily, M; Supa'at, A S M; Ahmad, H

2016-01-27

5G communications require a multi Gb/s data transmission in its small cells. For this purpose millimeter wave (mm-wave) RF signals are the best solutions to be utilized for high speed data transmission. Generation of these high frequency RF signals is challenging in electrical domain therefore photonic generation of these signals is more studied. In this work, a photonic based simple and robust method for generating millimeter waves applicable in 5G access fronthaul is presented. Besides generating of the mm-wave signal in the 60 GHz frequency band the radio over fiber (RoF) system for transmission of orthogonal frequency division multiplexing (OFDM) with 5 GHz bandwidth is presented. For the purpose of wireless transmission for 5G application the required antenna is designed and developed. The total system performance in one small cell was studied and the error vector magnitude (EVM) of the system was evaluated.

Towards 5G: A Photonic Based Millimeter Wave Signal Generation for Applying in 5G Access Fronthaul

PubMed Central

Alavi, S. E.; Soltanian, M. R. K.; Amiri, I. S.; Khalily, M.; Supa’at, A. S. M.; Ahmad, H.

2016-01-01

5G communications require a multi Gb/s data transmission in its small cells. For this purpose millimeter wave (mm-wave) RF signals are the best solutions to be utilized for high speed data transmission. Generation of these high frequency RF signals is challenging in electrical domain therefore photonic generation of these signals is more studied. In this work, a photonic based simple and robust method for generating millimeter waves applicable in 5G access fronthaul is presented. Besides generating of the mm-wave signal in the 60 GHz frequency band the radio over fiber (RoF) system for transmission of orthogonal frequency division multiplexing (OFDM) with 5 GHz bandwidth is presented. For the purpose of wireless transmission for 5G application the required antenna is designed and developed. The total system performance in one small cell was studied and the error vector magnitude (EVM) of the system was evaluated. PMID:26814621

Towards 5G: A Photonic Based Millimeter Wave Signal Generation for Applying in 5G Access Fronthaul

NASA Astrophysics Data System (ADS)

Alavi, S. E.; Soltanian, M. R. K.; Amiri, I. S.; Khalily, M.; Supa'At, A. S. M.; Ahmad, H.

2016-01-01

5G communications require a multi Gb/s data transmission in its small cells. For this purpose millimeter wave (mm-wave) RF signals are the best solutions to be utilized for high speed data transmission. Generation of these high frequency RF signals is challenging in electrical domain therefore photonic generation of these signals is more studied. In this work, a photonic based simple and robust method for generating millimeter waves applicable in 5G access fronthaul is presented. Besides generating of the mm-wave signal in the 60 GHz frequency band the radio over fiber (RoF) system for transmission of orthogonal frequency division multiplexing (OFDM) with 5 GHz bandwidth is presented. For the purpose of wireless transmission for 5G application the required antenna is designed and developed. The total system performance in one small cell was studied and the error vector magnitude (EVM) of the system was evaluated.

Preparation and characterization of conjugated polyamidoamine-MPEG-methotrexate for potential drug delivery system

NASA Astrophysics Data System (ADS)

Mohd Sabri, Siti Noorzidah bt; Abu, Norhidayah; Mastor, Azreena; Hisham, Siti Farhana; Noorsal, Kartini

2012-07-01

Star polymers have unique characteristics due to their well-defined size and tailor ability which makes these polymers attractive candidates as carriers in drug delivery system applications. This work focuses on attaching a drug to the star polymer (polyamidoamine). The conjugation of polyamidoamine (PAMAM, generation 4) with methotrexate (MTX) (model drug) was studied in which monomethyl polyethylene glycol (MPEG) was used as a linker to reduce the toxicity of dendrimer. Conjugation starts with attaching the drug to the linker and followed by further conjugation with the polyamidoamine (PAMAM) dendrimer. The conjugation of PAMAM-PEG-MTX was confirmed through UV-Vis, FTIR, 1H NMR and DSC. The loading capacities and release profile of this conjugate were determined using 1H NMR and UV spectrometer.

Cationic poly(amidoamine) dendrimers induced cyto-protective autophagy in hepatocellular carcinoma cells

NASA Astrophysics Data System (ADS)

Li, Yubin; Wang, Shaofei; Wang, Ziyu; Qian, Xiaolu; Fan, Jiajun; Zeng, Xian; Sun, Yun; Song, Ping; Feng, Meiqing; Ju, Dianwen

2014-09-01

Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising nanomaterials for biomedical applications because of their unique tree-like structure, monodispersity and tunable properties. In this study, we found that PAMAM dendrimers could induce the formation of autophagosomes and the conversion of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM dendrimers. We also investigated the suppression of autophagy with the obviously enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive oxygen species (ROS) could enhance the growth inhibition and apoptosis of hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing autophagic effects. Taken together, these findings explored the role and mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new insight into the effect of autophagy on drug delivery nanomaterials and tumor cells and contributed to the use of a drug delivery vehicle for hepatocellular carcinoma treatment.

Fourth standard model family neutrino at future linear colliders

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

Ciftci, A.K.; Ciftci, R.; Sultansoy, S.

2005-09-01

It is known that flavor democracy favors the existence of the fourth standard model (SM) family. In order to give nonzero masses for the first three-family fermions flavor democracy has to be slightly broken. A parametrization for democracy breaking, which gives the correct values for fundamental fermion masses and, at the same time, predicts quark and lepton Cabibbo-Kobayashi-Maskawa (CKM) matrices in a good agreement with the experimental data, is proposed. The pair productions of the fourth SM family Dirac ({nu}{sub 4}) and Majorana (N{sub 1}) neutrinos at future linear colliders with {radical}(s)=500 GeV, 1 TeV, and 3 TeV are considered.more » The cross section for the process e{sup +}e{sup -}{yields}{nu}{sub 4}{nu}{sub 4}(N{sub 1}N{sub 1}) and the branching ratios for possible decay modes of the both neutrinos are determined. The decays of the fourth family neutrinos into muon channels ({nu}{sub 4}(N{sub 1}){yields}{mu}{sup {+-}}W{sup {+-}}) provide cleanest signature at e{sup +}e{sup -} colliders. Meanwhile, in our parametrization this channel is dominant. W bosons produced in decays of the fourth family neutrinos will be seen in detector as either di-jets or isolated leptons. As an example, we consider the production of 200 GeV mass fourth family neutrinos at {radical}(s)=500 GeV linear colliders by taking into account di-muon plus four jet events as signatures.« less

Poly (N-isopropylacrylamide)-functionalized dendrimer as a thermosensitive nanoplatform for delivering malloapelta B against HepG2 cancer cell proliferation

NASA Astrophysics Data System (ADS)

Ngan Le, Phung; Chuong Pham, Dinh; Hai Nguyen, Dai; Quyen Tran, Ngoc; Dimitrov, Vladimir; Ivanov, Petko; Nguyen Xuan, Cuong; Nguyen, Hoai Nam; Khoa Nguyen, Cuu

2017-06-01

In recent years, nanocarriers have emerged as effective platforms for delivering several kinds of herbal medicine and naturally bioactive compounds. In this study we developed an outstanding thermosensitive dendritic nanocarrier to efficiently deliver malloapelta B (Mall B), which is a water insoluble bioactive compound isolated from leaves of Mallotus apelta—Vietnamese medicinal plant. The thermosensitive poly(N-isopropylacrylamide) (PNIPAM) polymer-conjugated polyamidoamine (PAMAM) dendrimer copolymer was prepared via Michael reaction. The copolymer structures were confirmed by proton nuclear magnectic resonance (1H NMR). Morphology of the nanocarrier was observered around 70-120 nm by transmission electron microscopy (TEM). Size distributions were measured by dynamic light scattering (DLS) of the nanocarrier and its Mall B-loaded performed at 146.8 nm and 194.5 nm, respectively. The PNIPAM-g-PAMAM-based nanocarrier exhibited higher Mall B loading efficiency (DL  =  59.93  ±  0.19%) and entrapment efficiency (EE  =  89.98  ±  2.06%) as compared to PNIPAM (DL  =  52.54  ±  0.45% and EE  =  66.45  ±  2.78%). In vitro release indicated that approximately 30% amount of the loaded Mall B released at pH 5.5 after 54 h tracking. At the same time, 12.5% amount of the molecules released at pH 7.4.Cytotoxicity assay results showed that the Mall B-loaded nanocarrier significantly inhibited HepG2 cancer cell proliferation. These obtained results indicated that the nanocarrier could solve hydrophobic property of Mall B for further medicine applications.

A review on g-C3N4 for photocatalytic water splitting and CO2 reduction

NASA Astrophysics Data System (ADS)

Ye, Sheng; Wang, Rong; Wu, Ming-Zai; Yuan, Yu-Peng

2015-12-01

Solar fuel generation through water splitting and CO2 photoreduction is an ideal route to provide the renewable energy sources and mitigate global warming. The main challenge in photocatalysis is finding a low-cost photocatalyst that can work efficiently to split water into hydrogen and reduce CO2 to hydrocarbon fuels. Metal-free g-C3N4 photocatalyst shows great potentials for solar fuel production. In this mini review, we summarize the most current advances on novel design idea and new synthesis strategy for g-C3N4 preparation, insightful ideas on extending optical absorption of pristine g-C3N4, overall water splitting and CO2 photoreduction over g-C3N4 based systems. The research challenges and perspectives on g-C3N4 based photocatalysts were also suggested.

Relationship between post-SARS osteonecrosis and PAI-1 4G/5G gene polymorphisms.

PubMed

Sun, Wei; Li, Zirong; Shi, Zhengcai; Wang, Bailiang; Gao, Fuqiang; Yang, Yurun; Guo, Wanshou

2014-05-01

To explore the correlation between post-severe acute respiratory symptom (SARS) patients with osteonecrosis, investigate the etiology of post-SARS osteonecrosis and select the sensitive molecular symbols for early diagnosis and distinguish the high-risk population. The studied subjects were divided into two groups. Sixty-two post-SARS patients with osteonecrosis were one group, and 52 age- and sex-matched healthy people were as normal controlled group. Empty stomach blood samples from cubital veins were collected from both groups. Plasminogen activator inhibitor (PAI) by means of enzyme-linked immunosorbent assay and PAI-1 4G/5G polymorphism was detected by polymerase chain reaction and solid phase oligonucleotide assay. The blood agents of post-SARS patients changed obviously with 15.64 ± 13.85 U/ml while the control group 7.96 ± 4.27 U/ml; 4G/4G genotype for the PAI-1 polymorphism detected in post-SARS group was more than that of the control group, but had no statistical significance. The plasma PAI activity was related to homozygote 4G/4G genotype. This reveals that homozygote 4G/4G genotype may be a susceptible gene mark to Chinese osteonecrosis patients. Plasminogen activator inhibitor-1 is sensitive blood symbol for screening high-risk susceptible population; 4G/4G PAI-1 genotype may be an etiological factor in osteonecrosis.

Superconducting ECR ion source: From 24-28 GHz SECRAL to 45 GHz fourth generation ECR

NASA Astrophysics Data System (ADS)

Zhao, H. W.; Sun, L. T.; Guo, J. W.; Zhang, W. H.; Lu, W.; Wu, W.; Wu, B. M.; Sabbi, G.; Juchno, M.; Hafalia, A.; Ravaioli, E.; Xie, D. Z.

2018-05-01

The development of superconducting ECR source with higher magnetic fields and higher microwave frequency is the most straight forward path to achieve higher beam intensity and higher charge state performance. SECRAL, a superconducting third generation ECR ion source, is designed for 24-28 GHz microwave frequency operation with an innovative magnet configuration of sextupole coils located outside the three solenoids. SECRAL at 24 GHz has already produced a number of record beam intensities, such as 40Ar12+ 1.4 emA, 129Xe26+ 1.1 emA, 129Xe30+ 0.36 emA, and 209Bi31+ 0.68 emA. SECRAL-II, an upgraded version of SECRAL, was built successfully in less than 3 years and has recently been commissioned at full power of a 28 GHz gyrotron and three-frequency heating (28 + 45 + 18 GHz). New record beam intensities for highly charged ion production have been achieved, such as 620 eμA 40Ar16+, 15 eμA 40Ar18+, 146 eμA 86Kr28+, 0.5 eμA 86Kr33+, 53 eμA 129Xe38+, and 17 eμA 129Xe42+. Recent beam test results at SECRAL and SECRAL II have demonstrated that the production of more intense highly charged heavy ion beams needs higher microwave power and higher frequency, as the scaling law predicted. A 45 GHz superconducting ECR ion source FECR (a first fourth generation ECR ion source) is being built at IMP. FECR will be the world's first Nb3Sn superconducting-magnet-based ECR ion source with 6.5 T axial mirror field, 3.5 T sextupole field on the plasma chamber inner wall, and 20 kW at a 45 GHz microwave coupling system. This paper will focus on SECRAL performance studies at 24-28 GHz and technical design of 45 GHz FECR, which demonstrates a technical path for highly charged ion beam production from 24 to 28 GHz SECRAL to 45 GHz FECR.

G4CEP: A G4 theory modification by including pseudopotential for molecules containing first-, second- and third-row representative elements.

PubMed

Silva, Cleuton de Souza; Pereira, Douglas Henrique; Custodio, Rogério

2016-05-28

The G4CEP composite method was developed from the respective G4 all-electron version by considering the implementation of compact effective pseudopotential (CEP). The G3/05 test set was used as reference to benchmark the adaptation by treating in this work atoms and compounds from the first and second periods of the periodic table, as well as representative elements of the third period, comprising 440 thermochemical data. G4CEP has not reached a so high level of accuracy as the G4 all-electron theory. G4CEP presented a mean absolute error around 1.09 kcal mol(-1), while the original method presents a deviation corresponding to 0.83 kcal mol(-1). The similarity of the optimized molecular geometries between G4 and G4CEP indicates that the core-electron effects and basis set adjustments may be pointed out as a significant factor responsible for the large discrepancies between the pseudopotential results and the experimental data, or even that the all-electron calculations are more efficient either in its formulation or in the cancellation of errors. When the G4CEP mean absolute error (1.09 kcal mol(-1)) is compared to 1.29 kcal mol(-1) from G3CEP, it does not seem so efficient. However, while the G3CEP uncertainty is ±4.06 kcal mol(-1), the G4CEP deviation is ±2.72 kcal mol(-1). Therefore, the G4CEP theory is considerably more reliable than any previous combination of composite theory and pseudopotential, particularly for enthalpies of formation and electron affinities.

Genetic characterization of an extended-spectrum AmpC cephalosporinase with hydrolysing activity against fourth-generation cephalosporins in a clinical isolate of Enterobacter aerogenes selected in vivo.

PubMed

Rodríguez-Martínez, Jose M; Fernández-Echauri, Pedro; Fernández-Cuenca, Felipe; Diaz de Alba, Paula; Briales, Alejandra; Pascual, Alvaro

2012-01-01

Extended-spectrum AmpC cephalosporinases (ESACs) have been reported in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. Here, we characterize a new AmpC variant presenting a broadened substrate activity towards fourth-generation cephalosporins, selected in vivo following cefepime treatment for Enterobacter aerogenes. Two consecutive clonally related isolates of E. aerogenes were evaluated. Screening for ESAC production was performed using plates containing 200 mg/L cloxacillin. MICs were determined by microdilution (CLSI guidelines). bla(AmpC) genes were cloned into a pCR-Blunt II-TOPO vector and expressed in Escherichia coli. The ampC genes were cloned into vector pGEX-6P-1 for protein purification. Isolate Ea595 was resistant to two fourth-generation cephalosporins, cefepime and cefpirome; using plates containing cloxacillin, susceptibility to ceftazidime and cefepime was restored, suggesting overproduction of the ESAC β-lactamase. Sequencing identified a new AmpC β-lactamase variant presenting one amino acid substitution, Val291Gly, inside the H-10 helix. Recombinant plasmids harbouring this ESAC β-lactamase conferred a broadened resistance profile to cefepime and cefpirome, with resistance levels increasing from 16- to 32-fold in E. coli. AmpC-Ea595 hydrolysed ceftazidime, cefepime and cefpirome at high levels, presenting a lower K(m) and enabling us to classify the enzyme as an ESAC. Homology modelling suggested that the size of the active site could have increased. We characterized an ESAC β-lactamase selected in vivo and conferring a high level of resistance to fourth-generation cephalosporins in E. aerogenes. The broadened spectrum was caused by a new modification to the H-10 helix, which modified the active site.

Development of PEGylated carboxylic acid-modified polyamidoamine dendrimers as bone-targeting carriers for the treatment of bone diseases.

PubMed

Yamashita, Shugo; Katsumi, Hidemasa; Hibino, Nozomi; Isobe, Yugo; Yagi, Yumiko; Kusamori, Kosuke; Sakane, Toshiyasu; Yamamoto, Akira

2017-09-28

In this study, we aimed to develop a polyethylene glycol (PEG)-conjugated third generation polyamidoamine (PAMAM) dendrimer with multiple carboxylic acids as a bone-targeting carrier for the treatment of bone diseases. We conjugated PAMAM backbones to various carboxylic acids [aspartic acid (Asp), glutamic acid (Glu), succinic acid (Suc), or aconitic acid (Aco)] to obtain four different types of carboxylic acid-modified PAMAMs. PEG was covalently bound to carboxylic acid-modified PAMAMs to obtain PEGylated carboxylic acid-modified PAMAMs. In a tissue distribution study, the amount of 111 In-labeled unmodified PAMAM taken up by the bone after intravenous injection in mice was 11.3%. In contrast, the dose of 111 In-labeled PEG(5)-Asp-PAMAM, PEG(5)-Glu-PAMAM, PEG(5)-Suc-PAMAM, or PEG(5)-Aco-PAMAM that accumulated in the bone after injection was approximately 46.0, 15.6, 22.6, and 24.5%, respectively. The bone clearance rates of 111 In-labeled PEGylated carboxylic acid-modified PAMAMs were proportional to their affinities to hydroxyapatite and Ca 2+ . An intra-bone distribution study showed that fluorescein isothiocyanate-labeled PEG(5)-Asp-PAMAM predominantly accumulated on eroded and quiescent surfaces, a pattern associated with the pathogenesis of bone diseases, such as rheumatoid arthritis and osteoporosis. Our findings indicate that PEG(5)-Asp-PAMAM is a promising drug carrier for efficient drug targeting to the bones. Copyright © 2017 Elsevier B.V. All rights reserved.

[IgG4-related disease].

PubMed

González-Moreno, Juan; Losada López, Inés; Ortego Centeno, Norberto

2015-12-21

IgG4-related disease is a recently described clinicopathological entity showing a wide spectrum of clinical manifestations that share a common pathology. Its most characteristic feature is the formation of inflammatory tumors in different organs, which makes differentiation mainly with neoplastic diseases fundamental. The inflammatory process is typically comprised of IgG4 lymphoplasmacytic cells. The pathophysiological role of the immunoglobulin is not clear. The treatment of choice is corticosteroids. This article aims to summarize the main features of the disease. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Drug resistance reversal in ovarian cancer cells of paclitaxel and borneol combination therapy mediated by PEG-PAMAM nanoparticles.

PubMed

Zou, Liang; Wang, Di; Hu, Yichen; Fu, Chaomei; Li, Wei; Dai, Liping; Yang, Lin; Zhang, Jinming

2017-09-01

Paclitaxel (PTX) is frequently suffered from multidrug resistance (MDR), resulting in lower chemotherapeutic efficacy and even chemotherapy failure. To combine the P-glycolprotein (P-gp) inhibitor would be a useful strategy to overcome MDR. However, what is needed now is an efficient vehicle to deliver multiple drugs into tumor simultaneously. In this study, PTX and Borneol (BNL), a natural compound with P-gp inhibition effect confirmed in intestinal absorption, were co-loaded in the fabricated PEG-PAMAM nanoparticle (NPs) by a one-step nano-precipitation method with high drug loading efficiency, narrow size distribution and low hemolysis rate. Based on P-gp inhibition activity of BNL, confirmed by drug efflux test and molecular docking model, the combination of PTX and BNL could improve intracellular concentration of PTX in A2780/PTX cells. Furthermore, compared to both free PTX and PTX+BNL, PB/NPs and P/NPs plus BNL exhibited higher cellular uptake and cytotoxicity in A2780/PTX cells, as well as the decreased MMP and enhanced apoptosis rate. More importantly, although PB/NPs and P/NPs+B showed similar tumor accumulation in tumor-bearing mice, PB/NPs could significantly decrease tumor growth of A2780/PTX tumor-bearing mice, in comparison to P/NPs+B. These results indicated the advantage of PTX and BNL co-delivery NPs for MDR reversal. These findings demonstrate that the co-delivery nano-sized system comprised by PEG-PAMAM polymer with PTX and BNL co-loaded would be a promising candidate for MDR treatment.

Drug resistance reversal in ovarian cancer cells of paclitaxel and borneol combination therapy mediated by PEG-PAMAM nanoparticles

PubMed Central

Zou, Liang; Wang, Di; Hu, Yichen; Fu, Chaomei; Li, Wei; Dai, Liping; Yang, Lin; Zhang, Jinming

2017-01-01

Paclitaxel (PTX) is frequently suffered from multidrug resistance (MDR), resulting in lower chemotherapeutic efficacy and even chemotherapy failure. To combine the P-glycolprotein (P-gp) inhibitor would be a useful strategy to overcome MDR. However, what is needed now is an efficient vehicle to deliver multiple drugs into tumor simultaneously. In this study, PTX and Borneol (BNL), a natural compound with P-gp inhibition effect confirmed in intestinal absorption, were co-loaded in the fabricated PEG-PAMAM nanoparticle (NPs) by a one-step nano-precipitation method with high drug loading efficiency, narrow size distribution and low hemolysis rate. Based on P-gp inhibition activity of BNL, confirmed by drug efflux test and molecular docking model, the combination of PTX and BNL could improve intracellular concentration of PTX in A2780/PTX cells. Furthermore, compared to both free PTX and PTX+BNL, PB/NPs and P/NPs plus BNL exhibited higher cellular uptake and cytotoxicity in A2780/PTX cells, as well as the decreased MMP and enhanced apoptosis rate. More importantly, although PB/NPs and P/NPs+B showed similar tumor accumulation in tumor-bearing mice, PB/NPs could significantly decrease tumor growth of A2780/PTX tumor-bearing mice, in comparison to P/NPs+B. These results indicated the advantage of PTX and BNL co-delivery NPs for MDR reversal. These findings demonstrate that the co-delivery nano-sized system comprised by PEG-PAMAM polymer with PTX and BNL co-loaded would be a promising candidate for MDR treatment. PMID:28947984

G4CEP: A G4 theory modification by including pseudopotential for molecules containing first-, second- and third-row representative elements

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

Silva, Cleuton de Souza; Instituto de Ciências Exatas e Tecnologia, Universidade Federal do Amazonas, Campus de Itacoatiara, 69100-021 Itacoatiara, Amazonas; Pereira, Douglas Henrique

2016-05-28

The G4CEP composite method was developed from the respective G4 all-electron version by considering the implementation of compact effective pseudopotential (CEP). The G3/05 test set was used as reference to benchmark the adaptation by treating in this work atoms and compounds from the first and second periods of the periodic table, as well as representative elements of the third period, comprising 440 thermochemical data. G4CEP has not reached a so high level of accuracy as the G4 all-electron theory. G4CEP presented a mean absolute error around 1.09 kcal mol{sup −1}, while the original method presents a deviation corresponding to 0.83more » kcal mol{sup −1}. The similarity of the optimized molecular geometries between G4 and G4CEP indicates that the core-electron effects and basis set adjustments may be pointed out as a significant factor responsible for the large discrepancies between the pseudopotential results and the experimental data, or even that the all-electron calculations are more efficient either in its formulation or in the cancellation of errors. When the G4CEP mean absolute error (1.09 kcal mol{sup −1}) is compared to 1.29 kcal mol{sup −1} from G3CEP, it does not seem so efficient. However, while the G3CEP uncertainty is ±4.06 kcal mol{sup −1}, the G4CEP deviation is ±2.72 kcal mol{sup −1}. Therefore, the G4CEP theory is considerably more reliable than any previous combination of composite theory and pseudopotential, particularly for enthalpies of formation and electron affinities.« less

Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies.

PubMed

Shadrack, Daniel M; Swai, Hulda S; Munissi, Joan J E; Mubofu, Egid B; Nyandoro, Stephen S

2018-06-12

Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties. This review, therefore, compiles the recently reported applications of PAMAM dendrimers in pre-clinical and clinical uses as enhancers of solubility and other desirable properties such as sustained and controlled release, bioavailability, bio-distribution, toxicity reduction or enhancement, and targeted delivery of small molecules with emphasis on cancer treatment.

Enhanced visible light photocatalytic water reduction from a g-C 3N 4/SrTa 2O 6 heterojunction

DOE PAGES

Adhikari, Shiba P.; Hood, Zachary D.; Wang, Hui; ...

2017-06-02

In this paper, a new g-C 3N 4/SrTa 2O 6 heterojunction photocatalyst was designed and prepared by chimie douce (soft chemistry) method where carbon nitride (g-C 3N 4) was deposited over the metastable perovskite phase of SrTa 2O 6. The morphological study of the heterojunction using SEM and STEM revealed that g-C 3N 4 nanofibers are dispersed uniformly on the surface of SrTa 2O 6 plates leading to the intimate contact between them. The heterojunction could achieve a high and stable visible light photocatalytic H 2 generation of 137 mmol/h/mole of g-C 3N 4, which is much larger than themore » amount of hydrogen generated by one mole of pristine g-C 3N 4. Finally, a plausible mechanism for the observed enhanced photocatalytic activity for the heterojunction is proposed on the basis of effective charge separation of photogenerated electron-hole pairs, supported by band position calculations and photo-physical properties of g-C 3N 4 and SrTa 2O 6.« less

Enhanced visible light photocatalytic water reduction from a g-C 3N 4/SrTa 2O 6 heterojunction

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

Adhikari, Shiba P.; Hood, Zachary D.; Wang, Hui

In this paper, a new g-C 3N 4/SrTa 2O 6 heterojunction photocatalyst was designed and prepared by chimie douce (soft chemistry) method where carbon nitride (g-C 3N 4) was deposited over the metastable perovskite phase of SrTa 2O 6. The morphological study of the heterojunction using SEM and STEM revealed that g-C 3N 4 nanofibers are dispersed uniformly on the surface of SrTa 2O 6 plates leading to the intimate contact between them. The heterojunction could achieve a high and stable visible light photocatalytic H 2 generation of 137 mmol/h/mole of g-C 3N 4, which is much larger than themore » amount of hydrogen generated by one mole of pristine g-C 3N 4. Finally, a plausible mechanism for the observed enhanced photocatalytic activity for the heterojunction is proposed on the basis of effective charge separation of photogenerated electron-hole pairs, supported by band position calculations and photo-physical properties of g-C 3N 4 and SrTa 2O 6.« less

4G/5G Plasminogen Activator Inhibitor-1 Polymorphisms and Haplotypes Are Associated with Pneumonia

PubMed Central

Yende, Sachin; Angus, Derek C.; Ding, Jingzhong; Newman, Anne B.; Kellum, John A.; Li, Rongling; Ferrell, Robert E.; Zmuda, Joseph; Kritchevsky, Stephen B.; Harris, Tamara B.; Garcia, Melissa; Yaffe, Kristine; Wunderink, Richard G.

2007-01-01

Rationale: Plasminogen activator inhibitor (PAI)-1 inhibits urokinase and tissue plasminogen activator, required for host response to infection. Whether variation within the PAI-1 gene is associated with increased susceptibility to infection is unknown. Objectives: To ascertain the role of the 4G/5G polymorphism and other genetic variants within the PAI-1 gene. We hypothesized that variants associated with increased PAI-1 expression would be associated with an increased occurrence of community-acquired pneumonia (CAP). Methods: Longitudinal analysis (>12 yr) of the Health, Aging, and Body Composition cohort, aged 65–74 years at start of analysis. Measurements and Main Results: We genotyped the 4G/5G PAI-1 polymorphism and six additional single nucleotide polymorphisms. Of the 3,075 subjects, 272 (8.8%) had at least one hospitalization for CAP. Among whites, variants at the PAI4G,5G, PAI2846, and PAI7343 sites had higher risk of CAP (P = 0.018, 0.021, and 0.021, respectively). At these sites, variants associated with higher PAI-1 expression were associated with increased CAP susceptibility. Compared with the 5G/5G genotypes at PAI4G,5G site, the 4G/4G and 4G/5G genotypes were associated with a 1.98-fold increased risk of CAP (95% confidence interval, 1.2–3.2; P = 0.006). In whole blood stimulation assay, subjects with a 4G allele had 3.3- and 1.9-fold increased PAI-1 expression (P = 0.043 and 0.034, respectively). In haplotype analysis, the 4G/G/C/A haplotype at the PAI4G,5G, PAI2846, PAI4588, and PAI7343 single nucleotide polymorphisms was associated with higher CAP susceptibility, whereas the 5G/G/C/A haplotype was associated with lower CAP susceptibility. No associations were seen among blacks. Conclusions: Genotypes associated with increased expression of PAI-1 were associated with increased susceptibility to CAP in elderly whites. PMID:17761618

A New Classification System for IgG4 Autoantibodies

PubMed Central

Koneczny, Inga

2018-01-01

IgG4 autoimmune diseases are characterized by the presence of antigen-specific autoantibodies of the IgG4 subclass and contain well-characterized diseases such as muscle-specific kinase myasthenia gravis, pemphigus, and thrombotic thrombocytopenic purpura. In recent years, several new diseases were identified, and by now 14 antigens targeted by IgG4 autoantibodies have been described. The IgG4 subclass is considered immunologically inert and functionally monovalent due to structural differences compared to other IgG subclasses. IgG4 usually arises after chronic exposure to antigen and competes with other antibody species, thus “blocking” their pathogenic effector mechanisms. Accordingly, in the context of IgG4 autoimmunity, the pathogenicity of IgG4 is associated with blocking of enzymatic activity or protein–protein interactions of the target antigen. Pathogenicity of IgG4 autoantibodies has not yet been systematically analyzed in IgG4 autoimmune diseases. Here, we establish a modified classification system based on Witebsky’s postulates to determine IgG4 pathogenicity in IgG4 autoimmune diseases, review characteristics and pathogenic mechanisms of IgG4 in these disorders, and also investigate the contribution of other antibody entities to pathophysiology by additional mechanisms. As a result, three classes of IgG4 autoimmune diseases emerge: class I where IgG4 pathogenicity is validated by the use of subclass-specific autoantibodies in animal models and/or in vitro models of pathogenicity; class II where IgG4 pathogenicity is highly suspected but lack validation by the use of subclass specific antibodies in in vitro models of pathogenicity or animal models; and class III with insufficient data or a pathogenic mechanism associated with multivalent antigen binding. Five out of the 14 IgG4 antigens were validated as class I, five as class II, and four as class III. Antibodies of other IgG subclasses or immunoglobulin classes were present in several diseases

Potential of poly(amidoamine) dendrimers as drug carriers of camptothecin based on encapsulation studies.

PubMed

Cheng, Yiyun; Li, Mingzhong; Xu, Tongwen

2008-08-01

Camptothecin (CPT), a plant alkaloid isolated from Camptotheca acuminata, has an extremely low solubility in aqueous medium, which presents a major challenge during drug formulation in clinical trails. In the present study we investigated the potential of poly(amidoamine) (PAMAM) dendrimers as drug carriers of CPT through aqueous solubility studies. Results showed that the aqueous solubility of CPT was significantly increased by PAMAM dendrimers. The effect of PAMAM generation on CPT solubility was also evaluated. These studies indicated that PAMAM dendrimers might be considered as biocompatible carriers of CPT.

IgG4-related disease of the rectum

PubMed Central

Choi, Sung-Bong; Lim, Chul-Hyun; Cha, Myung-Guen

2016-01-01

IgG4-related disease is a relatively new disease entity characterized by elevated serum IgG4 levels and marked infiltration of IgG4-positive plasma cells in lesions. Organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs throughout. We encountered a patient with an inflammatory pseudotumor of the rectum, which was histopathologically confirmed to be an IgG4-related disease. The patient was a 28-year-old woman who had constipation for 3 months. The endoluminal ultrasonography showed a lesion that was heterogeneous and low echogenic in lower rectum. The result of colonoscopic biopsy findings was of chronic proctitis with lymphoid aggregates. For a confirmative diagnosis, excision was performed. Histopathological examination represented plasma cell infiltration and fibrosis. Immunohistochemistry revealed prominence of IgG4-positive plasma cells and confirmed the diagnosis of IgG4-related disease. The patient is currently under observation on low-dose oral prednisolone without relapse. PMID:27186575

CNA’s Integrated Ship Database, Fourth Quarter 2011 Update

DTIC Science & Technology

2012-09-01

AKR300 G T-AKR301 G T-AKR302 8 T-AKR303 A 8 T-AKR304 G T-AKR305 G T-AKR30S 8 T- AKR 31l R - G T- AKR 312 G T- AKR 313 8 T- AKR 314 G T- AKR 315...CNA’s Integrated Ship Database Fourth Quarter 2011 Update Gregory N. Suess, Lynette A . McClain, and Rhea Stone CNA Interactive Software DIS-2012-U...no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control

Photooxidation of d(TpG) by phthalocyanines and riboflavin. Isolation and characterization of dinucleoside monophosphates containing the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxy-guanosine.

PubMed Central

Buchko, G W; Cadet, J; Berger, M; Ravanat, J L

1992-01-01

Phthalocyanine mediated photosensitization of 2'-deoxyguanosine (dG) in oxygen saturated aqueous solution has previously been shown to result in the addition of molecular oxygen to the guanine base generating the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine (dO) (the asterisk denotes unambiguous assignment of the 4R and 4S diastereoisomers). The data presented here show that the same guanine modified bases are generated in a 1:1 ratio when thymidylyl-(3',5')-2'-deoxyguanosine (d(TpG)) is similarly photo-oxidized. These modified dinucleoside monophosphates, labelled d(TpO)-A and -B, have been isolated by high performance liquid chromatography and characterized by proton NMR spectrometry, fast atom bombardment mass spectrometry, and enzymatic digestions. Photosensitization in D2O instead of H2O leads to an increase in the rate of d(TpO) formation that is consistent with a type II (singlet oxygen) reaction mechanism. Three interesting properties of these modified dinucleoside monophosphates are: i) the rate of their digestion with spleen phosphodiesterase is greatly reduced relative to d(TpG), ii) they are not digested by snake venom phosphodiesterase, and iii) they are stable to 1.0 M piperidine at 90 degrees C for 30 min. The latter observation indicates that 4,8-dihydro-4-hydroxy-8-oxoguanine is not a base lesion responsible for the strand breaks observed following hot piperidine treatment of DNA exposed to type II photosensitizers or chemically generated singlet oxygen. PMID:1329029

Next-generation sequencing reveals low-dose effects of cationic dendrimers in primary human bronchial epithelial cells.

PubMed

Feliu, Neus; Kohonen, Pekka; Ji, Jie; Zhang, Yuning; Karlsson, Hanna L; Palmberg, Lena; Nyström, Andreas; Fadeel, Bengt

2015-01-27

Gene expression profiling has developed rapidly in recent years with the advent of deep sequencing technologies such as RNA sequencing (RNA Seq) and could be harnessed to predict and define mechanisms of toxicity of chemicals and nanomaterials. However, the full potential of these technologies in (nano)toxicology is yet to be realized. Here, we show that systems biology approaches can uncover mechanisms underlying cellular responses to nanomaterials. Using RNA Seq and computational approaches, we found that cationic poly(amidoamine) dendrimers (PAMAM-NH2) are capable of triggering down-regulation of cell-cycle-related genes in primary human bronchial epithelial cells at doses that do not elicit acute cytotoxicity, as demonstrated using conventional cell viability assays, while gene transcription was not affected by neutral PAMAM-OH dendrimers. The PAMAMs were internalized in an active manner by lung cells and localized mainly in lysosomes; amine-terminated dendrimers were internalized more efficiently when compared to the hydroxyl-terminated dendrimers. Upstream regulator analysis implicated NF-κB as a putative transcriptional regulator, and subsequent cell-based assays confirmed that PAMAM-NH2 caused NF-κB-dependent cell cycle arrest. However, PAMAM-NH2 did not affect cell cycle progression in the human A549 adenocarcinoma cell line. These results demonstrate the feasibility of applying systems biology approaches to predict cellular responses to nanomaterials and highlight the importance of using relevant (primary) cell models.

Test Review: Abidin, R. R. (2012) "Parenting Stress Index, Fourth Edition" ("PSI-4"). Lutz, Florida: Psychological Assessment Resources

ERIC Educational Resources Information Center

Johnson, Alyce O.

2015-01-01

The "Parenting Stress Index, Fourth Edition" (PSI-4) is a 120-item measure used to explore parental stress levels considering a parent's relationship with one of his or her children between the ages of 1 month and 12 years. The main purpose of the test is to define these stress levels and from where they originate in order to identify…

Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases.

PubMed

Yamamoto, Motohisa; Tabeya, Tetsuya; Naishiro, Yasuyoshi; Yajima, Hidetaka; Ishigami, Keisuke; Shimizu, Yui; Obara, Mikiko; Suzuki, Chisako; Yamashita, Kentaro; Yamamoto, Hiroyuki; Hayashi, Toshiaki; Sasaki, Shigeru; Sugaya, Toshiaki; Ishida, Tadao; Takano, Ken-Ichi; Himi, Tetsuo; Suzuki, Yasuo; Nishimoto, Norihiro; Honda, Saho; Takahashi, Hiroki; Imai, Kohzoh; Shinomura, Yasuhisa

2012-06-01

IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.

IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

PubMed

Zaydfudim, Victor M; Wang, Andrew Y; de Lange, Eduard E; Zhao, Zimin; Moskaluk, Christopher A; Bauer, Todd W; Adams, Reid B

2015-07-01

IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

The Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and the Risk of Alzheimer's Disease.

PubMed

Fekih-Mrissa, Najiba; Mansour, Malek; Sayeh, Aicha; Bedoui, Ines; Mrad, Meriem; Riahi, Anis; Mrissa, Ridha; Nsiri, Brahim

2017-09-01

The aim of this study was to determine whether plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. We analyzed the genotype and allele frequency distribution of the PAI-1 polymorphism in 60 Tunisian patients with AD and 120 healthy controls. The results show a significantly increased risk of AD in carriers of the 4G/4G and 4G/5G genotypes versus the wild-type 5G/5G genotype (4G/4G: 28.33% in patients vs 10.0% in controls; P < 10 -3 ; OR = 8.78; 4G/5G: 55.0% in patients vs 38.33% in controls; OR = 4.45; P < 10 -3 ). The 4G allele was also more frequently found in patients compared with controls; P < 10 -3 ; OR = 3.07. For all participants and by gender, homozygotic carriers (4G/4G) were at an increased risk of AD over heterozygotes and women were at an increased risk over their male genotype counterparts. The odds ratio for AD among 4G/4G carriers for any group was approximately twice that of heterozygotes in the same group. Women homozygotes ranked highest for AD risk (OR = 20.8) and, in fact, women heterozygotes (OR = 9.03) ranked higher for risk than male homozygotes (OR = 6.12). These preliminary exploratory results should be confirmed in a larger study.