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Sample records for unlabeled dimeric rgd

  1. Comparison of biological properties of 111In-labeled dimeric cyclic RGD peptides

    International Nuclear Information System (INIS)

    Zheng, Yumin; Ji, Shundong; Tomaselli, Elena; Yang, Yong; Liu, Shuang

    2015-01-01

    Introduction: In this study two 111 In-labeled dimeric cyclic RGD peptides, 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ), were evaluated as radiotracers for breast tumor imaging. The objective was to evaluate the impact of SAA, PEG 2 and 1,2,3-triazole linkers as compare to PEG 4 on the tumor uptake and excretion kinetics of 111 In radiotracers. Methods: DOTA-Galacto-RGD 2 was prepared by conjugation of Galacto-RGD 2 with DOTA-OSu in the presence of diisopropylethylamine. Its integrin α v β 3 binding affinity was determined using a whole-cell displacement assay against 125 I-echistatin bound to U87MG glioma cells, and was compared with those of c(RGDfK), DOTA-3P-RGD 2 and DOTA-3P-RGK 2 (a nonsense peptide conjugate with “scrambled” RGK sequences). 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ) were prepared and evaluated for their tumor-targeting capability and biodistribution properties in athymic nude mice bearing MDA-MB-435 breast tumor xenografts. Planar imaging studies were performed to demonstrate the utility of 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ) for breast tumor imaging. Results: IC 50 values of DOTA-Galacto-RGD 2 , DOTA-3P-RGD 2 , and DOTA-3P-RGK 2 were calculated to be 27 ± 2, 29 ± 4, 596 ± 48 nM, respectively. The tumor uptake values of 111 In(DOTA-Galacto-RGD 2 ) (6.79 ± 0.98, 6.56 ± 0.56, 4.17 ± 0.61 and 1.09 ± 0.13 %ID/g at 1, 4, 24 and 72 hours p.i., respectively) were almost identical to those of 111 In(DOTA-3P-RGD 2 ) (6.17 ± 1.65, 5.94 ± 0.84, 3.40 ± 0.50 and 0.99 ± 0.20 %ID/g, respectively). 111 In(DOTA-Galacto-RGD 2 ) had a faster clearance from blood and muscle than 111 In(DOTA-3P-RGD 2 ), leading to higher tumor/blood and tumor/muscle ratios. 111 In(DOTA-3P-RGD 2 ) had lower liver uptake and better tumor/liver ratios than 111 In(DOTA-Galacto-RGD 2 ). The tumor uptake of 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ) was both integrin α v β 3 and RGD-specific. Imaging data suggest

  2. Iminodiacetic acid as bifunctional linker for dimerization of cyclic RGD peptides

    International Nuclear Information System (INIS)

    Xu, Dong; Zhao, Zuo-Quan; Chen, Shu-Ting; Yang, Yong; Fang, Wei; Liu, Shuang

    2017-01-01

    Introduction: In this study, I2P-RGD 2 was used as the example to illustrate a novel approach for dimerization of cyclic RGD peptides. The main objective of this study was to explore the impact of bifunctional linkers (glutamic acid vs. iminodiacetic acid) on tumor-targeting capability and excretion kinetics of the 99m Tc-labeled dimeric cyclic RGD peptides. Methods: HYNIC-I2P-RGD 2 was prepared by reacting I2P-RGD 2 with HYNIC-OSu in the presence of diisopropylethylamine, and was evaluated for its α v β 3 binding affinity against 125 I-echistatin bound to U87MG glioma cells. 99m Tc-I2P-RGD 2 was prepared with high specific activity (~185 GBq/μmol). The athymic nude mice bearing U87MG glioma xenografts were used to evaluate its biodistribution properties and image quality in comparison with those of 99m Tc-3P-RGD 2 . Results: The IC 50 value for HYNIC-I2P-RGD 2 was determined to be 39 ± 6 nM, which was very close to that (IC 50 = 33 ± 5 nM) of HYNIC-3P-RGD 2 . Replacing glutamic acid with iminodiacetic acid had little impact on α v β 3 binding affinity of cyclic RGD peptides. 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 shared similar tumor uptake values over the 2 h period, and its α v β 3 -specificity was demonstrated by a blocking experiment. The uptake of 99m Tc-I2P-RGD 2 was significantly lower than 99m Tc-3P-RGD 2 in the liver and kidneys. The U87MG glioma tumors were visualized by SPECT with excellent contrast using both 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 . Conclusion: Iminodiacetic acid is an excellent bifunctional linker for dimerization of cyclic RGD peptides. Bifunctional linkers have significant impact on the excretion kinetics of 99m Tc radiotracers. Because of its lower liver uptake and better tumor/liver ratios, 99m Tc-I2P-RGD 2 may have advantages over 99m Tc-3P-RGD 2 for diagnosis of tumors in chest region. -- Graphical abstract: This report presents novel approach for dimerization of cyclic RGD peptides using iminodiacetic acid as a

  3. Preparation of 177Lu-DOTA/DTPA-Bz-Cys-RGD dimer and biodistribution evaluation in normal mice

    International Nuclear Information System (INIS)

    Sheng Feng; Jia Bing; Wang Fan; He Weiwei; Liu Zhaofei; Zhao Huiyun

    2008-01-01

    177 Lu-DOTA-Bz-Cys-RGD dimer and 177 Lu-DTPA-Bz-Cys-RGD dimer were prepared, and the in vitro and in vivo properties were compared. TLC and HPLC show that the labeling yields of two radiolabeled compounds are more than 95% under optimal conditions (pH=5.0, reacting at 100 degree C for 15-20 min), and the two radiolabeled compounds show pretty good in vitro stability. HPLC analyses and lg P values reveal that lipophilicity of 177 Lu-DOTA-Bz-Cys- RGD dimer is higher than 177 Lu-DTPA-Bz-Cys-RGD dimer. The uptake of 177 Lu-DTPA-Bz-Cys- RGD dimer in other tissues is significantly higher than that of 177 Lu-DOTA-Bz-Cys-RGD dimer at 4 h postinjection, except for blood and spleen. The in vivo stability of 177 Lu-DOTA-Bz-Cys-RGD dimer is much better than 177 Lu-DTPA-Bz-Cys-RGD dimer. Bz-DOTA is an ideal bifunctional chelator for 177 Lu labeling of RGD dimer. (authors)

  4. Noninvasive imaging of tumor integrin expression using 18F-labeled RGD dimer peptide with PEG4 linkers

    International Nuclear Information System (INIS)

    Liu, Zhaofei; Liu, Shuanglong; Wang, Fan; Liu, Shuang; Chen, Xiaoyuan

    2009-01-01

    Various radiolabeled Arg-Gly-Asp (RGD) peptides have been previously investigated for tumor integrin α v β 3 imaging. To further develop RGD radiotracers with enhanced tumor-targeting efficacy and improved in vivo pharmacokinetics, we designed a new RGD homodimeric peptide with two PEG 4 spacers (PEG 4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) between the two monomeric RGD motifs and one PEG 4 linker on the glutamate α-amino group ( 18 F-labeled PEG 4 -E[PEG 4 -c(RGDfK)] 2 , P-PRGD2), as a promising agent for noninvasive imaging of integrin expression in mouse models. P-PRGD2 was labeled with 18 F via 4-nitrophenyl 2- 18 F-fluoropropionate ( 18 F-FP) prosthetic group. In vitro and in vivo characteristics of the new dimeric RGD peptide tracer 18 F-FP-P-PRGD2 were investigated and compared with those of 18 F-FP-P-RGD2 ( 18 F-labeled RGD dimer without two PEG 4 spacers between the two RGD motifs). The ability of 18 F-FP-P-PRGD2 to image tumor vascular integrin expression was evaluated in a 4T1 murine breast tumor model. With the insertion of two PEG 4 spacers between the two RGD motifs, 18 F-FP-P-PRGD2 showed enhanced integrin α v β 3 -binding affinity, increased tumor uptake and tumor-to-nontumor background ratios compared with 18 F-FP-P-RGD2 in U87MG tumors. MicroPET imaging with 18 F-FP-P-PRGD2 revealed high tumor contrast and low background in tumor-bearing nude mice. Biodistribution studies confirmed the in vivo integrin α v β 3 -binding specificity of 18 F-FP-P-RGD2. 18 F-FP-P-PRGD2 can specifically image integrin α v β 3 on the activated endothelial cells of tumor neovasculature. 18 F-FP-P-PRGD2 can provide important information on integrin expression on the tumor vasculature. The high integrin binding affinity and specificity, excellent pharmacokinetic properties and metabolic stability make the new RGD dimeric tracer 18 F-FP-P-PRGD2 a promising agent for PET imaging of tumor angiogenesis and for monitoring the efficacy of antiangiogenic

  5. Micro-PET Imaging of αvβ3-Integrin Expression with 18F-Labeled Dimeric RGD Peptide

    Directory of Open Access Journals (Sweden)

    Xiaoyuan Chen

    2004-04-01

    Full Text Available The αv integrins, which act as cell adhesion molecules, are closely involved with tumor invasion and angiogenesis. In particular, αvβ3 integrin, which is specifically expressed on proliferating endothelial cells and tumor cells, is a logical target for development of a radiotracer method to assess angiogenesis and anti-angiogenic therapy. In this study, a dimeric cyclic RGD peptide E[c(RGDyK]2 was labeled with 18F (t1/2 = 109.7 min by using a prosthetic 4-[18F]fluorobenzoyl moiety to the amino group of the glutamate. The resulting [18F]FB-E[c(RGDyK]2, with high specific activity (200–250 GBq/μmol at the end of synthesis, was administered to subcutaneous U87MG glioblastoma xenograft models for micro-PET and autoradiographic imaging as well as direct tissue sampling to assess tumor targeting efficacy and in vivo kinetics of this PET tracer. The dimeric RGD peptide demonstrated significantly higher tumor uptake and prolonged tumor retention in comparison with a monomeric RGD peptide analog [18F]FB-c(RGDyK. The dimeric RGD peptide had predominant renal excretion, whereas the monomeric analog was excreted primarily through the biliary route. Micro-PET imaging 1 hr after injection of the dimeric RGD peptide exhibited tumor to contralateral background ratio of 9.5 ± 0.8. The synergistic effect of polyvalency and improved pharmacokinetics may be responsible for the superior imaging characteristics of [18F]FB-E[c(RGDyK]2.

  6. Improving Tumor Uptake and Pharmacokinetics of 64Cu-Labeled Cyclic RGD Peptide Dimers with Gly3 and PEG4 Linkers

    OpenAIRE

    Shi, Jiyun; Kim, Young-Seung; Zhai, Shizhen; Liu, Zhaofei; Chen, Xiaoyuan; Liu, Shuang

    2009-01-01

    Radiolabeled cyclic RGD (Arg-Gly-Asp) peptides represent a new class of radiotracers with potential for the early tumor detection and non-invasive monitoring of tumor metastasis and therapeutic response in cancer patients. This report describes the synthesis of two cyclic RGD peptide dimer conjugates, DOTA-PEG4-E[PEG4-c(RGDfK)]2 (DOTA-3PEG4-dimer: DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and DOTA-G3-E[G3-c(RGDfK)]2 ...

  7. Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide-paclitaxel conjugate in mice with breast cancer

    International Nuclear Information System (INIS)

    Cao, Qizhen; Li, Zi-Bo; Chen, Kai; Wu, Zhanhong; He, Lina; Chen, Xiaoyuan; Neamati, Nouri

    2008-01-01

    Targeting drugs to receptors involved in tumor angiogenesis has been demonstrated as a novel and promising approach to improve cancer treatment. In this study, we evaluated the anti-tumor efficacy of a dimeric RGD peptide-paclitaxel conjugate (RGD2-PTX) in an orthotopic MDA-MB-435 breast cancer model. To assess the effect of conjugation and the presence of drug moiety on the MDA-MB-435 tumor and normal tissue uptake, the biodistribution of 3 H-RGD2-PTX was compared with that of 3 H-PTX. The treatment effect of RGD2-PTX and RGD2+PTX was measured by tumor size, 18 F-FDG/PET, 18 F-FLT/PET, and postmortem histopathology. By comparing the biodistribution of 3 H-RGD2-PTX and 3 H-PTX, we found that 3 H-RGD2-PTX had higher initial tumor exposure dose and prolonged tumor retention than 3 H-PTX. Metronomic low-dose treatment of breast cancer indicated that RGD2-PTX is significantly more effective than PTX+RGD2 combination and solvent control. Although in vivo 18 F-FLT/PET imaging and ex vivo Ki67 staining indicated little effect of the PTX-based drug on cell proliferation, 18 F-FDG/PET imaging showed significantly reduced tumor metabolism in the RGD2-PTX-treated mice versus those treated with RGD2+PTX and solvent control. Terminal uridine deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining also showed that RGD2-PTX treatment also had significantly higher cell apoptosis ratio than the other two groups. Moreover, the microvessel density was significantly reduced after RGD2-PTX treatment as determined by CD31 staining. Our results demonstrate that integrin-targeted delivery of paclitaxel allows preferential cytotoxicity to integrin-expressing tumor cells and tumor vasculature. The targeted delivery strategies developed in this study may also be applied to other chemotherapeutics for selective tumor killing. (orig.)

  8. Single step 18F-labeling of dimeric cycloRGD for functional PET imaging of tumors in mice

    International Nuclear Information System (INIS)

    Li, Ying; Liu, Zhibo; Lozada, Jerome; Wong, May Q.; Lin, Kuo-Shyan; Yapp, Donald; Perrin, David M.

    2013-01-01

    Introduction: Arylboronates afford rapid aqueous 18 F-labeling via the creation of a highly polar 18 F-aryltrifluoroborate anion ( 18 F-ArBF 3 − ). Hypothesis: Radiosynthesis of an 18 F-ArBF 3 − can be successfully applied to a clinically relevant peptide. To test this hypothesis, we labeled dimeric-cylcoRGD, [c(RGDfK)] 2 E because a) it is molecularly complex and provides a challenging substrate to test the application of this technique, and b) [c(RGDfK)] 2 E has already been labeled via several 18 F-labeling methods which provide for a preliminary comparison. Goal: To validate this labeling method in the context of a complex and clinically relevant tracer to show tumor-specific uptake ex vivo with representative PET images in vivo. Methods: An arylborimidine was conjugated to [c(RGDfK)] 2 E to give the precursor [c(RGDfK)] 2 E-ArB(dan), which was aliquoted and stored at − 20 °C. Aliquots of 10 or 25 nmol, containing only micrograms of precursor, were labeled using relatively low levels of 18 F-activity. Following purification eight mice (pre-blocked/unblocked) with U87M xenograft tumors were injected with [c(RGDfK)] 2 E- 18 F-ArBF 3 − (n = 4) for ex vivo tissue dissection. Two sets of mice (pre-blocked/unblocked) were also imaged with PET–CT (n = 2). Results: The [c(RGDfK)] 2 E-ArB(dan) is converted within 15 min to [c(RGDfK)] 2 E- 18 F-ArBF 3 − in isolated radiochemical yields of ∼ 10% (n = 3) at a minimum effective specific activity of 0.3 Ci/μmol. Biodistribution shows rapid clearance to the bladder via the kidney resulting in high tumor-to-blood and tumor-to-muscle ratios of > 9 and > 6 respectively while pre-blocking with [c(RGDfK)] 2 E showed high tumor specificity. PET imaging showed good contrast between tumor and non-target tissues confirming the biodistribution data. Conclusion: An arylborimidine-RGD peptide is rapidly 18 F-labeled in one step, in good yield, at useful specific activity. Biodistribution studies with blocking controls

  9. Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with 177Lu for tumors therapy that expressing αβ integrin s

    International Nuclear Information System (INIS)

    Luna G, M. A.

    2014-01-01

    The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of 177 Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of 177 Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential 177 Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain 177 Lu-AuNP-c[RGDfK(C)], the 177 Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. 177 Lu-DOTA-GGC, 177 Lu- DOTA-cRGDfK and 177 Lu-DOTA-E-c(RGDfK) 2 were prepared by adding 177 LuCl 3 (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with 177 Lu-AuNP-c[RGDfK(C)], the MCF7 cell proliferation was significantly inhibited

  10. Comparison of biological properties of 99mTc-labeled cyclic RGD Peptide trimer and dimer useful as SPECT radiotracers for tumor imaging

    International Nuclear Information System (INIS)

    Zhao, Zuo-Quan; Yang, Yong; Fang, Wei; Liu, Shuang

    2016-01-01

    Introduction: This study sought to evaluate a 99m Tc-labeled trimeric cyclic RGD peptide ( 99m Tc-4P-RGD 3 ) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of 99m Tc-3P-RGD 2 in the same animal model. Methods: HYNIC-4P-RGD 3 was prepared by reacting 4P-RGD 3 with excess HYNIC-OSu in the presence of diisopropylethylamine. 99m Tc-4P-RGD 3 was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose, 99m Tc-3P-RGD 2 (a α v β 3 -targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the α v β 3 specificity of 99m Tc-4P-RGD 3 . Results: 99m Tc-4P-RGD 3 was prepared with > 95% RCP and high specific activity (~ 200 GBq/μmol). 99m Tc-4P-RGD 3 and 99m Tc-3P-RGD 2 shared almost identical tumor uptake and similar biodistribution properties. 99m Tc-4P-RGD 3 had higher uptake than 99m Tc-3P-RGD 2 in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with 99m Tc-4P-RGD 3 and 99m Tc-3P-RGD 2 . Conclusion: Increasing peptide multiplicity from 3P-RGD 2 to 4P-RGD 3 offers no advantages with respect to the tumor-targeting capability. 99m Tc-4P-RGD 3 is as good a SPECT radiotracer as 99m Tc-3P-RGD 2 for imaging α v β 3 -positive tumors. -- Graphical abstract: This report presents evaluations of a 99m Tc-labeled cyclic RGD peptide trimer ( 99m Tc-4P-RGD 3 ) as the new SPECT radiotracer for tumor imaging. It was found that 99m Tc-4P-RGD 3 was able to accumulate in the xenografted U87MG tumors with high specificity. Display Omitted

  11. Utilization of a novel electrochemical {sup 90}Sr/{sup 90}Y generator for the preparation of {sup 90}Y-labeled RGD peptide dimer in clinically relevant dose

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sudipta; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, Haladhar Dev [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

    2014-09-01

    The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dose of {sup 90}Y-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)]{sub 2} [DOTA-(RGD){sub 2}] for in vivo targeted therapy utilizing {sup 90}Y obtained from a novel electrochemical {sup 90}Sr/{sup 90}Y generator. The performance of the generator was evaluated to ensure its suitability for providing {sup 90}Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. {sup 90}Y-DOTA-(RGD){sub 2} was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∝ 3.8 GBq) of {sup 90}Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing {sup 90}Y labeled cyclic RGD peptides for targeted therapy of tumors over-expressing integrin-α{sub ν}β{sub 3} receptors. (orig.)

  12. Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with {sup 177}Lu for tumors therapy that expressing αβ integrin s; Sistema monomerico, dimerico y multimerico de peptidos de RGD radiomarcados con {sup 177}Lu para terapia de tumores que expresan integrinas αβ

    Energy Technology Data Exchange (ETDEWEB)

    Luna G, M. A.

    2014-07-01

    The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of {sup 177}Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of {sup 177}Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential {sup 177}Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain {sup 177}Lu-AuNP-c[RGDfK(C)], the {sup 177}Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. {sup 177}Lu-DOTA-GGC, {sup 177}Lu- DOTA-cRGDfK and {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} were prepared by adding {sup 177}LuCl{sub 3} (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with {sup 177}Lu

  13. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  14. Using Unlabeled Data to Improve Text Classification

    National Research Council Canada - National Science Library

    Nigam, Kamal P

    2001-01-01

    .... This dissertation demonstrates that supervised learning algorithms that use a small number of labeled examples and many inexpensive unlabeled examples can create high-accuracy text classifiers...

  15. Enhancement of breast CADx with unlabeled data.

    Science.gov (United States)

    Jamieson, Andrew R; Giger, Maryellen L; Drukker, Karen; Pesce, Lorenzo L

    2010-08-01

    Unlabeled medical image data are abundant, yet the process of converting them into a labeled ("truth-known") database is time and resource expensive and fraught with ethical and logistics issues. The authors propose a dual-stage CADx scheme in which both labeled and unlabeled (truth-known and "truth-unknown") data are used. This study is an initial exploration of the potential for leveraging unlabeled data toward enhancing breast CADx. From a labeled ultrasound image database consisting of 1126 lesions with an empirical cancer prevalence of 14%, 200 different randomly sampled subsets were selected and the truth status of a variable number of cases was masked to the algorithm to mimic different types of labeled and unlabeled data sources. The prevalence was fixed at 50% cancerous for the labeled data and 5% cancerous for the unlabeled. In the first stage of the dual-stage CADx scheme, the authors term "transductive dimension reduction regularization" (TDR-R), both labeled and unlabeled images characterized by extracted lesion features were combined using dimension reduction (DR) techniques and mapped to a lower-dimensional representation. (The first stage ignored truth status therefore was an unsupervised algorithm.) In the second stage, the labeled data from the reduced dimension embedding were used to train a classifier toward estimating the probability of malignancy. For the first CADx stage, the authors investigated three DR approaches: Laplacian eigen-maps, t-distributed stochastic neighbor embedding (t-SNE), and principal component analysis. For the TDR-R methods, the classifier in the second stage was a supervised (i.e., utilized truth) Bayesian neural net. The dual-stage CADx schemes were compared to a single-stage scheme based on manifold regularization (MR) in a semisupervised setting via the LapSVM algorithm. Performance in terms of areas under the ROC curve (AUC) of the CADx schemes was evaluated in leave-one-out and .632+ bootstrap analyses on a by

  16. One-step radiosynthesis of {sup 18}F-AlF-NOTA-RGD{sub 2} for tumor angiogenesis PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shuanglong; Liu, Hongguang; Xu, Yingding; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford, CA (United States); Jiang, Han [Stanford University, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford, CA (United States); Institute of Nuclear Medicine and Molecular Imaging, and the Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Department of Nuclear Medicine, Medical PET Center, Hangzhou, Zhejiang (China); Zhang, Hong [Institute of Nuclear Medicine and Molecular Imaging, and the Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Department of Nuclear Medicine, Medical PET Center, Hangzhou, Zhejiang (China)

    2011-09-15

    One of the major obstacles of the clinical translation of {sup 18}F-labeled arginine-glycine-aspartic acid (RGD) peptides has been the laborious multistep radiosynthesis. In order to facilitate the application of RGD-based positron emission tomography (PET) probes in the clinical setting we investigated in this study the feasibility of using the chelation reaction between Al{sup 18}F and a macrocyclic chelator-conjugated dimeric RGD peptide as a simple one-step {sup 18}F labeling strategy for development of a PET probe for tumor angiogenesis imaging. Dimeric cyclic peptide E[c(RGDyK)]{sub 2} (RGD{sub 2}) was first conjugated with a macrocyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and the resulting bioconjugate NOTA-RGD{sub 2} was then radiofluorinated via Al{sup 18}F intermediate to synthesize {sup 18}F-AlF-NOTA-RGD{sub 2}. Integrin binding affinities of the peptides were assessed by a U87MG cell-based receptor binding assay using {sup 125}I-echistatin as the radioligand. The tumor targeting efficacy and in vivo profile of {sup 18}F-AlF-NOTA-RGD{sub 2} were further evaluated in a subcutaneous U87MG glioblastoma xenograft model by microPET and biodistribution. NOTA-RGD{sub 2} was successfully {sup 18}F-fluorinated with good yield within 40 min using the Al{sup 18}F intermediate. The IC{sub 50} of {sup 19}F-AlF-NOTA-RGD{sub 2} was determined to be 46 {+-} 4.4 nM. Quantitative microPET studies demonstrated that {sup 18}F-AlF-NOTA-RGD{sub 2} showed high tumor uptake, fast clearance from the body, and good tumor to normal organ ratios. NOTA-RGD{sub 2} bioconjugate has been successfully prepared and labeled with Al{sup 18}F in one single step of radiosynthesis. The favorable in vivo performance and the short radiosynthetic route of {sup 18}F-AlF-NOTA-RGD{sub 2} warrant further optimization of the probe and the radiofluorination strategy to accelerate the clinical translation of {sup 18}F-labeled RGD peptides. (orig.)

  17. PET imaging of alphavbeta integrin expression in tumours with Ga-labelled mono-, di- and tetrameric RGD peptides

    NARCIS (Netherlands)

    Dijkgraaf, I.; Yim, C.B.; Franssen, G.M.; Schuit, R.C.; Luurtsema, G.; Liu, S.; Oyen, W.J.G.; Boerman, O.C.

    2011-01-01

    PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared

  18. Use of Unlabeled Samples for Mitigating the Hughes Phenomenon

    Science.gov (United States)

    Landgrebe, David A.; Shahshahani, Behzad M.

    1993-01-01

    The use of unlabeled samples in improving the performance of classifiers is studied. When the number of training samples is fixed and small, additional feature measurements may reduce the performance of a statistical classifier. It is shown that by using unlabeled samples, estimates of the parameters can be improved and therefore this phenomenon may be mitigated. Various methods for using unlabeled samples are reviewed and experimental results are provided.

  19. Multivalent cyclic RGD ligands: influence of linker lengths on receptor binding

    Energy Technology Data Exchange (ETDEWEB)

    Kubas, Holger; Schaefer, Martin; Bauder-Wuest, Ulrike; Eder, Matthias; Oltmanns, Doerte [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Haberkorn, Uwe; Mier, Walter [Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Eisenhut, Michael, E-mail: m.eisenhut@dkfz.d [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2010-11-15

    Peptides involving the RGD motive (arginine-glycine-aspartic acid) recognize members of the integrin receptor family. Since the receptors are located mainly on the surface of endothelial cells, structural modifications including multimers of c(RGDfE) were recently found to improve the binding avidity for {alpha}{sub v{beta}3} integrin significantly. The multivalent RGD peptides exhibited rather loose linkages partly including oligo(ethylene glycol) spacers (EG{sub n}) with different chain lengths. Therefore, the dependence of multivalent RGD systems with and without EG{sub n} linkers were investigated on their binding properties to cultured {alpha}{sub v{beta}3} integrin-expressing U87MG cells. Methods: We synthesized a series of di-, tri- and tetravalent rigid scaffolds (terephthalic acid, trimesic acid and adamantane-1,3,5,7-tetracarboxylic acid) conjugated to c(RGDyK) ligands, which were linked contiguously or separated by the oligo(ethylene glycol) spacers. The inhibition constants of these c(RGDyK) derivatives were determined by competition assays with {sup 125}I-labeled echistatin. Results: While c(RGDyK) function is a relative weak competitor against [{sup 125}I]echistatin (K{sub i}, 329{+-}18 nM) for {alpha}{sub v{beta}3} integrin-expressing U87MG cells, RGD dimers improved the competition potency considerably (K{sub i}, 64{+-}23 nM). This effect was even more pronounced with the RGD trimers (K{sub i}, 40{+-}7 nM) and tetramers (K{sub i}, 26{+-}9 nM). The introduction of EG{sub n} spacers and the increase of linker lengths proved to be detrimental since more competitors were needed to compete with [{sup 125}I]echistatin. The EG{sub 6} group, for example, reduced the inhibition constants by 29% (dimer), 57% (trimer) and 97% (tetramer). Conclusion: The binding experiments performed with the three forms of multivalent RGD ligands indicate the weakening of competitive potency against [{sup 125}I]echistatin with the introduction of EG{sub n} spacers. This effect

  20. PET imaging of alpha(v)beta(3) integrin expression in tumours with Ga-68-labelled mono-, di- and tetrameric RGD peptides

    NARCIS (Netherlands)

    Dijkgraaf, Ingrid; Yim, Cheng-Bin; Franssen, Gerben M.; Schuit, Robert C.; Luurtsema, Gert; Liu, Shuang; Oyen, Wim J. G.; Boerman, Otto C.

    Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of Ga-68-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their

  1. Active learning in the presence of unlabelable examples

    Science.gov (United States)

    Mazzoni, Dominic; Wagstaff, Kiri

    2004-01-01

    We propose a new active learning framework where the expert labeler is allowed to decline to label any example. This may be necessary because the true label is unknown or because the example belongs to a class that is not part of the real training problem. We show that within this framework, popular active learning algorithms (such as Simple) may perform worse than random selection because they make so many queries to the unlabelable class. We present a method by which any active learning algorithm can be modified to avoid unlabelable examples by training a second classifier to distinguish between the labelable and unlabelable classes. We also demonstrate the effectiveness of the method on two benchmark data sets and a real-world problem.

  2. Enhancement of breast CADx with unlabeled data1

    Science.gov (United States)

    Jamieson, Andrew R.; Giger, Maryellen L.; Drukker, Karen; Pesce, Lorenzo L.

    2010-01-01

    Purpose: Unlabeled medical image data are abundant, yet the process of converting them into a labeled (“truth-known”) database is time and resource expensive and fraught with ethical and logistics issues. The authors propose a dual-stage CADx scheme in which both labeled and unlabeled (truth-known and “truth-unknown”) data are used. This study is an initial exploration of the potential for leveraging unlabeled data toward enhancing breast CADx. Methods: From a labeled ultrasound image database consisting of 1126 lesions with an empirical cancer prevalence of 14%, 200 different randomly sampled subsets were selected and the truth status of a variable number of cases was masked to the algorithm to mimic different types of labeled and unlabeled data sources. The prevalence was fixed at 50% cancerous for the labeled data and 5% cancerous for the unlabeled. In the first stage of the dual-stage CADx scheme, the authors term “transductive dimension reduction regularization” (TDR-R), both labeled and unlabeled images characterized by extracted lesion features were combined using dimension reduction (DR) techniques and mapped to a lower-dimensional representation. (The first stage ignored truth status therefore was an unsupervised algorithm.) In the second stage, the labeled data from the reduced dimension embedding were used to train a classifier toward estimating the probability of malignancy. For the first CADx stage, the authors investigated three DR approaches: Laplacian eigenmaps, t-distributed stochastic neighbor embedding (t-SNE), and principal component analysis. For the TDR-R methods, the classifier in the second stage was a supervised (i.e., utilized truth) Bayesian neural net. The dual-stage CADx schemes were compared to a single-stage scheme based on manifold regularization (MR) in a semisupervised setting via the LapSVM algorithm. Performance in terms of areas under the ROC curve (AUC) of the CADx schemes was evaluated in leave-one-out and .632

  3. Radiolabelled RGD peptides for imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gaertner, F.C.; Schwaiger, M.; Beer, A.J. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kessler, H. [Technische Universitaet Muenchen, Institute for Advanced Study and Center of Integrated Protein Science, Department of Chemistry, Garching (Germany); King Abdulaziz University, Chemistry Department, Faculty of Science, Jeddah (Saudi Arabia); Wester, H.-J. [Institute for Pharmaceutical Radiochemistry, Garching (Germany)

    2012-02-15

    Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin {alpha}{sub v}{beta}{sub 3}. For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of {alpha}{sub v}{beta}{sub 3} expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy. (orig.)

  4. Improvements of RGD3 TLD reader

    International Nuclear Information System (INIS)

    Zhao Jianxing; Wang Jiaqi; Li Yuanfang; Wu Furong; Xiao Wuyun

    1999-01-01

    The author summarized the main features of the improved RGD3 TLD reader. Through a large number of experiments some persuasive data are obtained, which show that an remarkable improvement has been achieved, especially in its stability to the standard illuminates, data dispersivity, and effectiveness to glow curves analysis. Working with the newly developed data processing software, the comprehensive performance of the whole system will be enhanced greatly

  5. Personalized Resource Recommendations using Learning from Positive and Unlabeled Examples

    Directory of Open Access Journals (Sweden)

    Priyank Thakkar

    2016-08-01

    Full Text Available This paper proposes a novel approach for recommending social resources using learning from positive and unlabeled examples. Bookmarks submitted on social bookmarking system delicious1 and artists on online music system last.fm2 are considered as social resources. The foremost feature of this problem is that there are no labeled negative resources/examples available for learning a recommender/classifier. The memory based collaborative filtering has served as the most widely used algorithm for social resource recommendation. However, its predictions are based on some ad hoc heuristic rules and its success depends on the availability of a critical mass of users. This paper proposes model based two-step techniques to learn a classifier using positive and unlabeled examples to address personalized resource recommendations. In the first step of these techniques, naïve Bayes classifier is employed to identify reliable negative resources. In the second step, to generate effective resource recommender, classification and regression tree and least square support vector machine (LS-SVM are exercised. A direct method based on LS-SVM is also put forward to realize the recommendation task. LS-SVM is customized for learning from positive and unlabeled data. Furthermore, the impact of feature selection on our proposed techniques is also studied. Memory based collaborative filtering as well as our proposed techniques exploit usage data to generate personalized recommendations. Experimental results show that the proposed techniques outperform existing method appreciably.

  6. Positive-Unlabeled Learning for Pupylation Sites Prediction

    Directory of Open Access Journals (Sweden)

    Ming Jiang

    2016-01-01

    Full Text Available Pupylation plays a key role in regulating various protein functions as a crucial posttranslational modification of prokaryotes. In order to understand the molecular mechanism of pupylation, it is important to identify pupylation substrates and sites accurately. Several computational methods have been developed to identify pupylation sites because the traditional experimental methods are time-consuming and labor-sensitive. With the existing computational methods, the experimentally annotated pupylation sites are used as the positive training set and the remaining nonannotated lysine residues as the negative training set to build classifiers to predict new pupylation sites from the unknown proteins. However, the remaining nonannotated lysine residues may contain pupylation sites which have not been experimentally validated yet. Unlike previous methods, in this study, the experimentally annotated pupylation sites were used as the positive training set whereas the remaining nonannotated lysine residues were used as the unlabeled training set. A novel method named PUL-PUP was proposed to predict pupylation sites by using positive-unlabeled learning technique. Our experimental results indicated that PUL-PUP outperforms the other methods significantly for the prediction of pupylation sites. As an application, PUL-PUP was also used to predict the most likely pupylation sites in nonannotated lysine sites.

  7. Synthesis and characterization of a new class of glycosylated porphyrins bearing the RGD moiety and their application in photodynamic therapy

    International Nuclear Information System (INIS)

    Chaleix, Vincent

    2003-01-01

    The use of porphyrins and analogues as photosensitisers together with visible light is a new treatment of tumors (photodynamic therapy, PDT). Carbohydrate-substituted porphyrins are in this domain very promising compounds. In addition, it is known that endothelial cells of the neo-vascularisation in tumors express αVβ3 integrin. Extracellular domains of this transmembrane glycoprotein are able to bind components of the extracellular matrix (ECM) and more precisely the sequence Arg-Gly-Asp. With the aim of their utilization in photodynamic therapy of cancers, we describe the synthesis and characterization (UV-Visible, mass, NMR) of new glucosylated porphyrins bearing the RGD moiety. The first synthesised compounds were derived from tritolyl and tri-glucosyl-aryl-porphyrins where the peptidic moiety is linked to the phenyl group by a spacer arm by means of a solid phase reaction.. The second series consists of glucosylated porphyrin derivatives bearing a cyclical unsaturated pentapeptide including RGD sequence, obtained by ring closing metathesis in solid phase. We have also synthesized a dimer in which the two glucosylated porphyrins are linked by the RGD sequence. These compounds produced 1 O 2 and photo-cyto-toxicities against K562 leukemia cell line were favourably compared to Photofrin II R . Due to their sensitising abilities, these compounds are of considerable interest for photodynamic therapy. (author) [fr

  8. Sensitive optical biosensors for unlabeled targets: A review

    International Nuclear Information System (INIS)

    Fan Xudong; White, Ian M.; Shopova, Siyka I.; Zhu Hongying; Suter, Jonathan D.; Sun Yuze

    2008-01-01

    This article reviews the recent progress in optical biosensors that use the label-free detection protocol, in which biomolecules are unlabeled or unmodified, and are detected in their natural forms. In particular, it will focus on the optical biosensors that utilize the refractive index change as the sensing transduction signal. Various optical label-free biosensing platforms will be introduced, including, but not limited to, surface plasmon resonance, interferometers, waveguides, fiber gratings, ring resonators, and photonic crystals. Emphasis will be given to the description of optical structures and their respective sensing mechanisms. Examples of detecting various types of biomolecules will be presented. Wherever possible, the sensing performance of each optical structure will be evaluated and compared in terms of sensitivity and detection limit

  9. Learning gene regulatory networks from only positive and unlabeled data

    Directory of Open Access Journals (Sweden)

    Elkan Charles

    2010-05-01

    Full Text Available Abstract Background Recently, supervised learning methods have been exploited to reconstruct gene regulatory networks from gene expression data. The reconstruction of a network is modeled as a binary classification problem for each pair of genes. A statistical classifier is trained to recognize the relationships between the activation profiles of gene pairs. This approach has been proven to outperform previous unsupervised methods. However, the supervised approach raises open questions. In particular, although known regulatory connections can safely be assumed to be positive training examples, obtaining negative examples is not straightforward, because definite knowledge is typically not available that a given pair of genes do not interact. Results A recent advance in research on data mining is a method capable of learning a classifier from only positive and unlabeled examples, that does not need labeled negative examples. Applied to the reconstruction of gene regulatory networks, we show that this method significantly outperforms the current state of the art of machine learning methods. We assess the new method using both simulated and experimental data, and obtain major performance improvement. Conclusions Compared to unsupervised methods for gene network inference, supervised methods are potentially more accurate, but for training they need a complete set of known regulatory connections. A supervised method that can be trained using only positive and unlabeled data, as presented in this paper, is especially beneficial for the task of inferring gene regulatory networks, because only an incomplete set of known regulatory connections is available in public databases such as RegulonDB, TRRD, KEGG, Transfac, and IPA.

  10. UNLABELED SELECTED SAMPLES IN FEATURE EXTRACTION FOR CLASSIFICATION OF HYPERSPECTRAL IMAGES WITH LIMITED TRAINING SAMPLES

    Directory of Open Access Journals (Sweden)

    A. Kianisarkaleh

    2015-12-01

    Full Text Available Feature extraction plays a key role in hyperspectral images classification. Using unlabeled samples, often unlimitedly available, unsupervised and semisupervised feature extraction methods show better performance when limited number of training samples exists. This paper illustrates the importance of selecting appropriate unlabeled samples that used in feature extraction methods. Also proposes a new method for unlabeled samples selection using spectral and spatial information. The proposed method has four parts including: PCA, prior classification, posterior classification and sample selection. As hyperspectral image passes these parts, selected unlabeled samples can be used in arbitrary feature extraction methods. The effectiveness of the proposed unlabeled selected samples in unsupervised and semisupervised feature extraction is demonstrated using two real hyperspectral datasets. Results show that through selecting appropriate unlabeled samples, the proposed method can improve the performance of feature extraction methods and increase classification accuracy.

  11. Galloyl-RGD as a new cosmetic ingredient

    Science.gov (United States)

    2014-01-01

    Background The cosmetics market has rapidly increased over the last years. For example, in 2011 it reached 242.8 billion US dollars, which was a 3.9% increase compared to 2010. There have been many recent trials aimed at finding the functional ingredients for new cosmetics. Gallic acid is a phytochemical derived from various herbs, and has anti-fungal, anti-viral, and antioxidant properties. Although phytochemicals are useful as cosmetic ingredients, they have a number of drawbacks, such as thermal stability, residence time in the skin, and permeability through the dermal layer. To overcome these problems, we considered conjugation of gallic acid with a peptide. Results We synthesized galloyl-RGD, which represents a conjugate of gallic acid and the peptide RGD, purified it by HPLC and characterized by MALDI-TOF with the aim of using it as a new cosmetic ingredient. Thermal stability of galloyl-RGD was tested at alternating temperatures (consecutive 4°C, 20°C, or 40°C for 8 h each) on days 2, 21, 41, and 61. Galloyl-RGD was relatively safe to HaCaT keratinocytes, as their viability after 48 h incubation with 500 ppm galloyl-RGD was 93.53%. In the group treated with 50 ppm galloyl-RGD, 85.0% of free radicals were removed, whereas 1000 ppm galloyl-RGD suppressed not only L-DOPA formation (43.8%) but also L-DOPA oxidation (54.4%). Conclusions Galloyl-RGD is a promising candidate for a cosmetic ingredient. PMID:25103826

  12. Unlabeled probes for the detection and typing of herpes simplex virus.

    Science.gov (United States)

    Dames, Shale; Pattison, David C; Bromley, L Kathryn; Wittwer, Carl T; Voelkerding, Karl V

    2007-10-01

    Unlabeled probe detection with a double-stranded DNA (dsDNA) binding dye is one method to detect and confirm target amplification after PCR. Unlabeled probes and amplicon melting have been used to detect small deletions and single-nucleotide polymorphisms in assays where template is in abundance. Unlabeled probes have not been applied to low-level target detection, however. Herpes simplex virus (HSV) was chosen as a model to compare the unlabeled probe method to an in-house reference assay using dual-labeled, minor groove binding probes. A saturating dsDNA dye (LCGreen Plus) was used for real-time PCR. HSV-1, HSV-2, and an internal control were differentiated by PCR amplicon and unlabeled probe melting analysis after PCR. The unlabeled probe technique displayed 98% concordance with the reference assay for the detection of HSV from a variety of archived clinical samples (n = 182). HSV typing using unlabeled probes was 99% concordant (n = 104) to sequenced clinical samples and allowed for the detection of sequence polymorphisms in the amplicon and under the probe. Unlabeled probes and amplicon melting can be used to detect and genotype as few as 10 copies of target per reaction, restricted only by stochastic limitations. The use of unlabeled probes provides an attractive alternative to conventional fluorescence-labeled, probe-based assays for genotyping and detection of HSV and might be useful for other low-copy targets where typing is informative.

  13. PET imaging of {alpha}{sub v}{beta}{sub 3} integrin expression in tumours with {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, Ingrid; Franssen, Gerben M.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Yim, Cheng-Bin [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Utrecht University, Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht (Netherlands); Schuit, Robert C. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); Luurtsema, Gert [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Hanzeplein 1, P.O. Box 30.001, Groningen (Netherlands); Liu, Shuang [Purdue University, School of Health Sciences, West Lafayette, IN (United States)

    2011-01-15

    Due to the restricted expression of {alpha}{sub v}{beta}{sub 3} in tumours, {alpha}{sub v}{beta}{sub 3} is considered a suitable receptor for tumour targeting. In this study the {alpha}{sub v}{beta}{sub 3}-binding characteristics of {sup 68}Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their {sup 111}In-labelled counterparts. A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)]{sub 2}) and a tetrameric (E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2}) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with {sup 68}Ga. In vitro {alpha}{sub v}{beta}{sub 3}-binding characteristics were determined in a competitive binding assay. In vivo {alpha}{sub v}{beta}{sub 3}-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. The IC{sub 50} values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)]{sub 2} and DOTA-E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2} were 23.9 {+-} 1.22, 8.99 {+-} 1.20 and 1.74 {+-} 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 {+-} 1.15, 3.34 {+-} 1.16 and 1.80 {+-} 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 {+-} 0.30, 5.24 {+-} 0.27 and 7.11 {+-} 0.67%ID/g, respectively) was comparable to that of their {sup 111}In-labelled counterparts (2.70 {+-} 0.29, 5.61 {+-} 0.85 and 7.32 {+-} 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The {sup 68}Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of {alpha}{sub v} {beta}{sub 3} expression with PET. (orig.)

  14. Status and Advances of RGD Molecular Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning YUE

    2014-12-01

    Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  15. Efficient use of unlabeled data for protein sequence classification: a comparative study.

    Science.gov (United States)

    Kuksa, Pavel; Huang, Pai-Hsi; Pavlovic, Vladimir

    2009-04-29

    Recent studies in computational primary protein sequence analysis have leveraged the power of unlabeled data. For example, predictive models based on string kernels trained on sequences known to belong to particular folds or superfamilies, the so-called labeled data set, can attain significantly improved accuracy if this data is supplemented with protein sequences that lack any class tags-the unlabeled data. In this study, we present a principled and biologically motivated computational framework that more effectively exploits the unlabeled data by only using the sequence regions that are more likely to be biologically relevant for better prediction accuracy. As overly-represented sequences in large uncurated databases may bias the estimation of computational models that rely on unlabeled data, we also propose a method to remove this bias and improve performance of the resulting classifiers. Combined with state-of-the-art string kernels, our proposed computational framework achieves very accurate semi-supervised protein remote fold and homology detection on three large unlabeled databases. It outperforms current state-of-the-art methods and exhibits significant reduction in running time. The unlabeled sequences used under the semi-supervised setting resemble the unpolished gemstones; when used as-is, they may carry unnecessary features and hence compromise the classification accuracy but once cut and polished, they improve the accuracy of the classifiers considerably.

  16. Synthesis, analysis and biological evaluation of new RGD mimetics

    Czech Academy of Sciences Publication Activity Database

    Balacheva, A. A.; Lambev, M. K.; Pashov, I.; Detcheva, R. L.; Sázelová, Petra; Momekov, G. Ts.; Kašička, Václav; Pajpanova, T. I.; Golovinsky, E. V.

    2017-01-01

    Roč. 49, SI E (2017), s. 7-10 ISSN 0324-1130. [Bulgarian Peptide Symposium /7./. Blagoevgrad, 10.06.2016-12.06.2016] Institutional support: RVO:61388963 Keywords : RGD * biological ly active peptides * cytotoxicity Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 0.238, year: 2016

  17. Liquid crystal dimers

    CERN Document Server

    Kumar Pal, Santanu

    2017-01-01

    This book covers in-depth discussion of design principles, synthesis and thermal behavior of all types of liquid crystal (LC) dimers. The text presents recent advances in the field of LC dimers consisting of different mesogenic units such as calamitic, discotic and bent-core molecules. It starts with a chapter on the introduction of liquid crystal dimers, including their odd-even behavior, basic classification of dimers and common mesophases in dimers. The text shows how the molecular architectures are being used to develop new materials to study a range of interesting phenomena such as the biaxial nematic phase containing rod-like and disc-like mesogenic units. Finally, the text presents perspectives related to technological relevance of these dimers such as dopants in LC display mixtures exhibiting faster relaxation time, strong flexoelectric coupling and others to effect control over the properties of these materials.

  18. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide

    International Nuclear Information System (INIS)

    Dijkgraaf, Ingrid; Liu, Shuang; Kruijtzer, John A.W.; Soede, Annemieke C.; Oyen, Wim J.G.; Liskamp, Rob M.J.; Corstens, Frans H.M.; Boerman, Otto C.

    2007-01-01

    Introduction: Due to the selective expression of the α v β 3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study, we systematically investigated the effects of linker modification between two cyclic RGD sequences and DOTA (1,4,7,10-tetraazadodecane-N,N',N ' ,N'''-tetraacetic acid) on the in vitro and in vivo characteristics of the tracer. Methods: A dimeric RGD peptide was synthesized and conjugated either directly with DOTA or via different linkers: PEG 4 (polyethylene glycol), glutamic acid or lysine. The RGD peptides were radiolabeled with 111 In, and their in vitro and in vivo α v β 3 -binding characteristics were determined. Results: LogP values varied between -2.82±0.06 and -3.95±0.33. The IC 50 values for DOTA-E-[c(RGDfK)] 2 , DOTA-PEG 4 -E-[c(RGDfK)] 2 , DOTA-E-E-[c(RGDfK)] 2 and DOTA-K-E-[c(RGDfK)] 2 were comparable. Two hours after injection, the tumor uptakes of the 111 In-labeled compounds were not significantly different. The kidney accumulation of [ 111 In]-DOTA-K-E-[c(RGDfK)] 2 [4.05±0.20% of the injected dose per gram (ID/g)] was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (2.63±0.19% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.16±0.21% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.12±0.09% ID/g) was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (1.64±0.1% ID/g; P 111 In]-DOTA-K-E-[c(RGDfK)] 2 (1.52±0.04% ID/g; P v β 3 and tumor uptake. Insertion of lysine caused enhanced kidney retention; that of glutamic acid also resulted in enhanced retention in the kidneys. PEG 4 appeared to be the most suitable linker as compared with glutamic acid and lysine because it has the highest tumor-to-blood ratio and the lowest uptake in the kidney and liver

  19. Study of lignin biotransformation by Aspergillus fumigatus and white-rot fungi using 14C-labeled and unlabeled kraft lignins

    International Nuclear Information System (INIS)

    Kadam, K.K.; Drew, S.W.

    1986-01-01

    The biodegradation of lignin by fungi was studied in shake flasks using 14 C-labeled kraft lignin and in a deep-tank fermentor using unlabeled kraft lignin. Among the fungi screened, A. fumigatus - isolated in our laboratories - was most potent in lignin biotransformation. Dialysis-type fermentation, designed to study possible accumulation of low MW lignin-derived products, showed no such accumulation. Recalcitrant carbohydrates like microcrystalline cellulose supported higher lignolytic activity than easily metabolized carbohydrates like cellobiose. An assay developed to distinguish between CO 2 evolved from lignin and carbohydrate substrates demonstrated no stoichiometric correlation between the metabolism of the two cosubstrates. The submerged fermentations with unlabeled liqnin are difficult to monitor since chemical assays do not give accurate and true results. Lignolytic efficiencies that allowed monitoring of such fermentations were defined. Degraded lignins were clearly superior to C. versicolor in all aspects of lignin degradation; A fumigatus brought about substantial demethoxylation and dehydroxylation, whereas C. versicolor degraded lignins closely resembled undegraded kraft lignin. There was a good agreement among the different indices of lignin degradation, namely, 14 CO evolution, OCH 3 loss, OH loss, and monomer and dimer yield after permanganate oxidation

  20. Reproducibility study of [{sup 18}F]FPP(RGD){sub 2} uptake in murine models of human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Edwin; Liu, Shuangdong; Chin, Frederick; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Gowrishankar, Gayatri; Yaghoubi, Shahriar [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Wedgeworth, James Patrick [Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Berndorff, Dietmar; Gekeler, Volker [Bayer Schering Pharma AG, Global Drug Discovery, Berlin (Germany); Gambhir, Sanjiv S. [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Canary Center at Stanford for Cancer Early Detection, Nuclear Medicine, Departments of Radiology and Bioengineering, Molecular Imaging Program at Stanford, Stanford, CA (United States)

    2011-04-15

    An {sup 18}F-labeled PEGylated arginine-glycine-aspartic acid (RGD) dimer [{sup 18}F]FPP(RGD){sub 2} has been used to image tumor {alpha}{sub v}{beta}{sub 3} integrin levels in preclinical and clinical studies. Serial positron emission tomography (PET) studies may be useful for monitoring antiangiogenic therapy response or for drug screening; however, the reproducibility of serial scans has not been determined for this PET probe. The purpose of this study was to determine the reproducibility of the integrin {alpha}{sub v}{beta}{sub 3}-targeted PET probe, [{sup 18}F ]FPP(RGD){sub 2} using small animal PET. Human HCT116 colon cancer xenografts were implanted into nude mice (n = 12) in the breast and scapular region and grown to mean diameters of 5-15 mm for approximately 2.5 weeks. A 3-min acquisition was performed on a small animal PET scanner approximately 1 h after administration of [{sup 18}F]FPP(RGD){sub 2} (1.9-3.8 MBq, 50-100 {mu}Ci) via the tail vein. A second small animal PET scan was performed approximately 6 h later after reinjection of the probe to assess for reproducibility. Images were analyzed by drawing an ellipsoidal region of interest (ROI) around the tumor xenograft activity. Percentage injected dose per gram (%ID/g) values were calculated from the mean or maximum activity in the ROIs. Coefficients of variation and differences in %ID/g values between studies from the same day were calculated to determine the reproducibility. The coefficient of variation (mean {+-}SD) for %ID{sub mean}/g and %ID{sub max}/g values between [{sup 18}F]FPP(RGD){sub 2} small animal PET scans performed 6 h apart on the same day were 11.1 {+-} 7.6% and 10.4 {+-} 9.3%, respectively. The corresponding differences in %ID{sub mean}/g and %ID{sub max}/g values between scans were -0.025 {+-} 0.067 and -0.039 {+-} 0.426. Immunofluorescence studies revealed a direct relationship between extent of {alpha}{sub {nu}}{beta}{sub 3} integrin expression in tumors and tumor vasculature

  1. Statistical-mechanics analysis of Gaussian labeled-unlabeled classification problems

    International Nuclear Information System (INIS)

    Tanaka, Toshiyuki

    2013-01-01

    The labeled-unlabeled classification problem in semi-supervised learning is studied via statistical-mechanics approach. We analytically investigate performance of a learner with an equal-weight mixture of two symmetrically-located Gaussians, performing posterior mean estimation of the parameter vector on the basis of a dataset consisting of labeled and unlabeled data generated from the same probability model as that assumed by the learner. Under the assumption of replica symmetry, we have analytically obtained a set of saddle-point equations, which allows us to numerically evaluate performance of the learner. On the basis of the analytical result we have observed interesting phenomena, in particular the coexistence of good and bad solutions, which may happen when the number of unlabeled data is relatively large compared with that of labeled data

  2. Bidirectional Active Learning: A Two-Way Exploration Into Unlabeled and Labeled Data Set.

    Science.gov (United States)

    Zhang, Xiao-Yu; Wang, Shupeng; Yun, Xiaochun

    2015-12-01

    In practical machine learning applications, human instruction is indispensable for model construction. To utilize the precious labeling effort effectively, active learning queries the user with selective sampling in an interactive way. Traditional active learning techniques merely focus on the unlabeled data set under a unidirectional exploration framework and suffer from model deterioration in the presence of noise. To address this problem, this paper proposes a novel bidirectional active learning algorithm that explores into both unlabeled and labeled data sets simultaneously in a two-way process. For the acquisition of new knowledge, forward learning queries the most informative instances from unlabeled data set. For the introspection of learned knowledge, backward learning detects the most suspiciously unreliable instances within the labeled data set. Under the two-way exploration framework, the generalization ability of the learning model can be greatly improved, which is demonstrated by the encouraging experimental results.

  3. Mixed dimers, ch. 7

    International Nuclear Information System (INIS)

    Deursen, A.P.J. van; Reuss, J.

    1976-01-01

    An attempt has been made to detect mixed dimers in nozzle beams of mixtures; NeAr and HeNe dimers were observed with sufficient intensity to determine the total collision cross section. A similar attempt for H 2 Ar was partially hampered by the circumstance that the corresponding HAr + ion must be detected on the wing of the thousand times larger Ar + peak. The search for H 2 He, H 2 Ne and HeAr dimers was not successful, due to masking ion peaks, H 5 + for HHe + , 21 Ne + for H 20 Ne + , and CO 2 + for HeAr + . (Auth.)

  4. 2-Ethynylpyridine dimers

    DEFF Research Database (Denmark)

    Bakarić, Danijela; Spanget-Larsen, Jens

    2018-01-01

    are used to study possible 2-EP dimer structures as well as their distribution in an inert solvent such as tetrachloroethene. Experimentally, the ≡C–H stretching vibration of the 2-EPmonomer absorbs close to 3300 cm−1, whereas a broad band withmaximum around 3215 cm−1 emerges as the concentration rises...... model with counterpoise correction predict that the two most stable dimers are of the pi-stacked variety, closely followed by dimers with intermolecular ≡C–H···N hydrogen bonding; the predicted red shifts of the ≡C–H stretching wavenumbers due to hydrogen bonding are in the range 54 – 120 cm–1...

  5. Toward realization of 'mix-and-use' approach in ⁶⁸Ga radiopharmacy: preparation, evaluation and preliminary clinical utilization of ⁶⁸Ga-labeled NODAGA-coupled RGD peptide derivative.

    Science.gov (United States)

    Chakraborty, Sudipta; Chakravarty, Rubel; Vatsa, Rakhee; Bhusari, Priya; Sarma, H D; Shukla, Jaya; Mittal, B R; Dash, Ashutosh

    2016-01-01

    The present article demonstrates a 'mix-and-use' approach for radiolabeling RGD peptide derivative with (68)Ga, which is easily adaptable in hospital radiopharmacy practice. The radiotracer thus formulated was successfully used for positron emission tomography (PET) imaging of breast cancer in human patients. The conditions for radiolabeling NODAGA-coupled dimeric cyclic RGD peptide derivative [NODAGA-(RGD)2] with (68)Ga were optimized using (68)Ga obtained from a (68)Ge/(68)Ga generator developed in-house with CeO2-PAN composite sorbent as well as from a commercial (68)Ge/(68)Ga generator obtained from ITG, Germany. Preclinical studies were carried out in C57BL/6 mice bearing melanoma tumors. The radiotracer was prepared in a hospital radiopharmacy using (68)Ga obtained from ITG generator and used for monitoring breast cancer patients by positron emission tomography (PET) imaging. (68)Ga-NODAGA-(RGD)2 could be prepared with high radiolabeling yield (>98%) and specific activity (~50 GBq/μmol) within 10 min at room temperature by mixing (68)Ga with the solution of the peptide conjugate. In vivo biodistribution studies showed significant uptake (5.24±0.39% ID/g) in melanoma tumor at 30 min post-injection, with high tumor-to-background contrast. The integrin αvβ3 specificity of the tracer was corroborated by blocking study. Preliminary clinical studies in locally advanced breast cancer (LABC) patients indicated specifically high tumor uptake (SUVmax 10-15) with good contrast. This is one of the very few reports which presents preliminary clinical data on use of (68)Ga-NODAGA-(RGD)2 and the developed 'mix-and-use' holds tremendous prospect in clinical PET imaging using (68)Ga. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. D-dimer Test

    Science.gov (United States)

    ... 1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pagana, Kathleen D. & Pagana, ... www.itxm.org . Titus, K. (2003 January). Identity crisis persists: which D-dimer? CAP Today , In the ...

  7. Dimers in nucleating vapors

    Science.gov (United States)

    Lushnikov, A. A.; Kulmala, M.

    1998-09-01

    The dimer stage of nucleation may affect considerably the rate of the nucleation process at high supersaturation of the nucleating vapor. Assuming that the dimer formation limits the nucleation rate, the kinetics of the particle formation-growth process is studied starting with the definition of dimers as bound states of two associating molecules. The partition function of dimer states is calculated by summing the Boltzmann factor over all classical bound states, and the equilibrium population of dimers is found for two types of intermolecular forces: the Lennard-Jones (LJ) and rectangular well+hard core (RW) potentials. The principle of detailed balance is used for calculating the evaporation rate of dimers. The kinetics of the particle formation-growth process is then investigated under the assumption that the trimers are stable with respect to evaporation and that the condensation rate is a power function of the particle mass. If the power exponent λ=n/(n+1) (n is a non-negative integer), the kinetics of the process is described by a finite set of moments of particle mass distribution. When the characteristic time of the particle formation by nucleation is much shorter than that of the condensational growth, n+2 universal functions of a nondimensional time define the kinetic process. These functions are calculated for λ=2/3 (gas-to-particle conversion in the free molecular regime) and λ=1/2 (formation of islands on surfaces).

  8. Unlabelled and radioactive labelled derivatives of butylamino propiophenone and their preparation

    International Nuclear Information System (INIS)

    Findlay, J.W.A.; Butz, R.F.; Welch, R.M.

    1986-01-01

    This invention relates to new unlabelled and radioactive labelled derivatives of butylamino propiophenone and their preparation. This invention is primarily directed to a radioimmunoassay for clinical or experimental testing for the presence of and quantitation of bupropion, a pharmacologically active antidepressant compound, in biological fluids

  9. Discrimination of bromodeoxyuridine labelled and unlabelled mitotic cells in flow cytometric bromodeoxyuridine/DNA analysis

    DEFF Research Database (Denmark)

    Jensen, P O; Larsen, J K; Christensen, I J

    1994-01-01

    Bromodeoxyuridine (BrdUrd) labelled and unlabelled mitotic cells, respectively, can be discriminated from interphase cells using a new method, based on immunocytochemical staining of BrdUrd and flow cytometric four-parameter analysis of DNA content, BrdUrd incorporation, and forward and orthogona...

  10. High affinity recognition of a Phytophthora protein by Arabidopsis via an RGD motif

    NARCIS (Netherlands)

    Senchou, V.; Weide, R.L.; Carrasco, A.; Bouyssou, H.; Pont-Lezica, R.; Govers, F.; Canut, H.

    2004-01-01

    The RGD tripeptide sequence, a cell adhesion motif present in several extracellular matrix proteins of mammalians, is involved in numerous plant processes. In plant-pathogen interactions, the RGD motif is believed to reduce plant defence responses by disrupting adhesions between the cell wall and

  11. Enhanced transduction and replication of RGD-fiber modified adenovirus in primary T cells.

    Directory of Open Access Journals (Sweden)

    Sadhak Sengupta

    2011-03-01

    Full Text Available Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR. T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD.A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replication-competent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35-45% of splenic T cells were transduced by Ad-RGD.Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary T cells of both murine and human origin.

  12. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

  13. Accelerated healing of cardiovascular textiles promoted by an RGD peptide.

    Science.gov (United States)

    Tweden, K S; Harasaki, H; Jones, M; Blevitt, J M; Craig, W S; Pierschbacher, M; Helmus, M N

    1995-07-01

    Polytetrafluoroethylene (PTFE) and polyethylene terephthalate (Dacron polyester) fabrics are used extensively in cardiovascular devices, e.g. heart valve sewing cuffs and vascular prostheses. While devices containing these fabrics are generally successful, it is recognized that fabrics cause complications prior to tissue ingrowth due to their thrombogenic nature. A surface active synthetic peptide, called PepTite Coating (PepTite), which was modeled after the cell attachment domain of human fibronectin has been marketed as a biocompatible coating. This peptide stimulates cell attachment through the arginine-glycine-aspartic acid (RGD) sequence. Modification of medical implants with PepTite has been shown to promote ingrowth of surrounding cells into the material leading to better tissue integration, reduced inflammation and reduced fibrotic encapsulation. In this study, polyester and PTFE textiles were modified with PepTite. The effectiveness of this coating in enhancing wound healing was investigated in a simple vascular and cardiac valve model. Our results indicate that the RGD-containing peptide, PepTite, promoted the formation of an endothelial-like cell layer on both polyester and PTFE vascular patches in the dog model. PepTite was also found to promote the formation of a significantly thinner neointima (pannus) on polyester as compared to that on its uncoated control. These results were corroborated in the cardiac valve model in which a greater amount of thin pannus and less thrombus were seen on coated polyester sewing cuffs than on control uncoated cuffs. This research shows the promising tissue response to RGD coated textiles and the potential role of this peptide in material passivation via accelerated healing.

  14. Photoionization of helium dimers

    International Nuclear Information System (INIS)

    Havermeier, Tilo

    2010-01-01

    The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

  15. Pyrimidine dimer sites associated with the daughter DNA strands in uv-irradiated human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Lehmann, A R; Kirk-Bell, S [Sussex Univ., Brighton (UK)

    1978-03-01

    Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in uv-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing uv-specific endonuclease activity. In DNA synthesized immediately after irradiation, the frequency of these daughter strand dimer sites was 7 to 20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between uv irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following uv irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed.

  16. Pyrimidine dimer sites associated with the daughter DNA strands in UV-irradiated human fibroblasts

    International Nuclear Information System (INIS)

    Lehmann, A.R.; Kirk-Bell, S.

    1978-01-01

    Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in UV-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing UV-specific endonuclease activity. In DNA synthesized immediately after irradiation the frequency of these daughter strand dimer sites was 7-20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between UV-irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following UV-irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed. (author)

  17. Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice.

    Science.gov (United States)

    Simsekyilmaz, Sakine; Liehn, Elisa A; Weinandy, Stefan; Schreiber, Fabian; Megens, Remco T A; Theelen, Wendy; Smeets, Ralf; Jockenhövel, Stefan; Gries, Thomas; Möller, Martin; Klee, Doris; Weber, Christian; Zernecke, Alma

    2016-01-01

    Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.

  18. Poisoning following exposure to chemicals stored in mislabelled or unlabelled containers: a recipe for potential disaster.

    Science.gov (United States)

    Millard, Yvette C; Slaughter, Robin J; Shieffelbien, Lucy M; Schep, Leo J

    2014-09-26

    To investigate poisoning exposures to chemicals that were unlabelled, mislabelled or not in their original containers in New Zealand over the last 10 years, based on calls to the New Zealand National Poisons Centre (NZNPC). Call data from the NZNPC between 2003 and 2012 were analysed retrospectively. Parameters reviewed included patient age, route and site of exposure, product classification and recommended intervention. Of the 324,411 calls received between 2003 and 2012, 100,465 calls were associated with acute human exposure to chemicals. There were 757 inquiries related to human exposure to mislabelled or unlabelled chemicals consisting of 0.75% of chemical exposures. Adults were involved in 51% of incidents, children, containers is a problem for all age groups. Although it represents a small proportion of total calls to the NZNPC it remains a potential risk for serious poisoning. It is important that chemicals are stored securely, in their original containers, and never stored in drinking vessels.

  19. Quantification of isotope-labelled and unlabelled folates in plasma, ileostomy and food samples.

    Science.gov (United States)

    Büttner, Barbara E; Öhrvik, Veronica E; Witthöft, Cornelia M; Rychlik, Michael

    2011-01-01

    New stable isotope dilution assays were developed for the simultaneous quantitation of [(13)C(5)]-labelled and unlabelled 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid, folic acid along with unlabelled tetrahydrofolic acid and 10-formylfolic acid in clinical samples deriving from human bioavailability studies, i.e. plasma, ileostomy samples, and food. The methods were based on clean-up by strong anion exchange followed by LC-MS/MS detection. Deuterated analogues of the folates were applied as the internal standards in the stable isotope dilution assays. Assay sensitivity was sufficient to detect all relevant folates in the respective samples as their limits of detection were below 0.62 nmol/L in plasma and below 0.73 μg/100 g in food or ileostomy samples. Quantification of the [(13)C(5)]-label in clinical samples offers the possibility to differentiate between folate from endogenous body pools and the administered dose when executing bioavailability trials.

  20. Enhancing deep convolutional neural network scheme for breast cancer diagnosis with unlabeled data.

    Science.gov (United States)

    Sun, Wenqing; Tseng, Tzu-Liang Bill; Zhang, Jianying; Qian, Wei

    2017-04-01

    In this study we developed a graph based semi-supervised learning (SSL) scheme using deep convolutional neural network (CNN) for breast cancer diagnosis. CNN usually needs a large amount of labeled data for training and fine tuning the parameters, and our proposed scheme only requires a small portion of labeled data in training set. Four modules were included in the diagnosis system: data weighing, feature selection, dividing co-training data labeling, and CNN. 3158 region of interests (ROIs) with each containing a mass extracted from 1874 pairs of mammogram images were used for this study. Among them 100 ROIs were treated as labeled data while the rest were treated as unlabeled. The area under the curve (AUC) observed in our study was 0.8818, and the accuracy of CNN is 0.8243 using the mixed labeled and unlabeled data. Copyright © 2016. Published by Elsevier Ltd.

  1. Positive-unlabeled learning for the prediction of conformational B-cell epitopes

    Science.gov (United States)

    2015-01-01

    Background The incomplete ground truth of training data of B-cell epitopes is a demanding issue in computational epitope prediction. The challenge is that only a small fraction of the surface residues of an antigen are confirmed as antigenic residues (positive training data); the remaining residues are unlabeled. As some of these uncertain residues can possibly be grouped to form novel but currently unknown epitopes, it is misguided to unanimously classify all the unlabeled residues as negative training data following the traditional supervised learning scheme. Results We propose a positive-unlabeled learning algorithm to address this problem. The key idea is to distinguish between epitope-likely residues and reliable negative residues in unlabeled data. The method has two steps: (1) identify reliable negative residues using a weighted SVM with a high recall; and (2) construct a classification model on the positive residues and the reliable negative residues. Complex-based 10-fold cross-validation was conducted to show that this method outperforms those commonly used predictors DiscoTope 2.0, ElliPro and SEPPA 2.0 in every aspect. We conducted four case studies, in which the approach was tested on antigens of West Nile virus, dihydrofolate reductase, beta-lactamase, and two Ebola antigens whose epitopes are currently unknown. All the results were assessed on a newly-established data set of antigen structures not bound by antibodies, instead of on antibody-bound antigen structures. These bound structures may contain unfair binding information such as bound-state B-factors and protrusion index which could exaggerate the epitope prediction performance. Source codes are available on request. PMID:26681157

  2. Effects of RGD immobilization on light-induced cell sheet detachment from TiO{sub 2} nanodots films

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kui; Wang, Tiantian [School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027 (China); Yu, Mengliu [The Affiliated Stomatologic Hospital, Zhejiang University, Hangzhou 310003 (China); The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, 310003 (China); Wan, Hongping [School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027 (China); Lin, Jun [The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, 310003 (China); Weng, Wenjian, E-mail: wengwj@zju.edu.cn [School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027 (China); The Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050 (China); Wang, Huiming, E-mail: hmwang1960@hotmail.com [The Affiliated Stomatologic Hospital, Zhejiang University, Hangzhou 310003 (China); The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, 310003 (China)

    2016-06-01

    Light-induced cell detachment is reported to be a safe and effective cell sheet harvest method. In the present study, the effects of arginine–glycine–aspartic acid (RGD) immobilization on cell growth, cell sheet construction and cell harvest through light illumination are investigated. RGD was first immobilized on TiO{sub 2} nanodots films through simple physical adsorption, and then mouse pre-osteoblastic MC3T3-E1 cells were seeded on the films. It was found that RGD immobilization promoted cell adhesion and proliferation. It was also observed that cells cultured on RGD immobilized films showed relatively high level of pan-cadherin. Cells harvested with ultraviolet illumination (365 nm) showed good viability on both RGD immobilized and unmodified TiO{sub 2} nanodot films. Single cell detachment assay showed that cells detached more quickly on RGD immobilized TiO{sub 2} nanodot films. That could be ascribed to the RGD release after UV365 illumination. The current study demonstrated that RGD immobilization could effectively improve both the cellular responses and light-induced cell harvest. - Highlights: • RGD immobilization on TiO{sub 2} nanodots film favors light-induced cell sheet detachment. • Physically adsorbed RGD detaches from the film through ultraviolet illumination. • RGD detachment promotes cells and cell sheets detachment.

  3. Novel Approach to Prepare {sup 99m}Tc-Based Multivalent RGD Peptides

    Energy Technology Data Exchange (ETDEWEB)

    Shuang Liu

    2012-10-24

    This project presents a novel approach to prepare the {sup 99m}Tc-bridged multivalent RGD (arginine-glycine-aspartate) peptides. This project will focus on fundamentals of {sup 99m}Tc radiochemistry. The main objective of this project is to demonstrate the proof-of-principle for the proposed radiotracers. Once a kit formulation is developed for preparation of the {sup 99m}Tc-bridged multivalent RGD peptides, various tumor-bearing animal models will be used to evaluate their potential for SPECT (single photon-emission computed tomography) imaging of cancer. We have demonstrated that (1) multimerization of cyclic RGD peptides enhances the integrin {alpha}{sub v}{beta}{sub 3} bonding affinity and radiotracer tumor uptake; (2) addition of G{sub 3} or PEG{sub 4} linkers makes it possible for two RGD motifs in 3P-RGD{sub 2} and 3G-RGD{sub 2} to achieve simultaneous integrin {alpha}{sub v}{beta}{sub 3} binding; and (3) multimers are actually bivalent (not multivalent), the presence of extra RGD motifs can enhance the tumor retention time of the radiotracer.

  4. Effectively identifying compound-protein interactions by learning from positive and unlabeled examples.

    Science.gov (United States)

    Cheng, Zhanzhan; Zhou, Shuigeng; Wang, Yang; Liu, Hui; Guan, Jihong; Chen, Yi-Ping Phoebe

    2016-05-18

    Prediction of compound-protein interactions (CPIs) is to find new compound-protein pairs where a protein is targeted by at least a compound, which is a crucial step in new drug design. Currently, a number of machine learning based methods have been developed to predict new CPIs in the literature. However, as there is not yet any publicly available set of validated negative CPIs, most existing machine learning based approaches use the unknown interactions (not validated CPIs) selected randomly as the negative examples to train classifiers for predicting new CPIs. Obviously, this is not quite reasonable and unavoidably impacts the CPI prediction performance. In this paper, we simply take the unknown CPIs as unlabeled examples, and propose a new method called PUCPI (the abbreviation of PU learning for Compound-Protein Interaction identification) that employs biased-SVM (Support Vector Machine) to predict CPIs using only positive and unlabeled examples. PU learning is a class of learning methods that leans from positive and unlabeled (PU) samples. To the best of our knowledge, this is the first work that identifies CPIs using only positive and unlabeled examples. We first collect known CPIs as positive examples and then randomly select compound-protein pairs not in the positive set as unlabeled examples. For each CPI/compound-protein pair, we extract protein domains as protein features and compound substructures as chemical features, then take the tensor product of the corresponding compound features and protein features as the feature vector of the CPI/compound-protein pair. After that, biased-SVM is employed to train classifiers on different datasets of CPIs and compound-protein pairs. Experiments over various datasets show that our method outperforms six typical classifiers, including random forest, L1- and L2-regularized logistic regression, naive Bayes, SVM and k-nearest neighbor (kNN), and three types of existing CPI prediction models. Source code, datasets and

  5. Immobilisation of linear and cyclic RGD-peptides on titanium surfaces and their impact on endothelial cell adhesion and proliferation

    Directory of Open Access Journals (Sweden)

    PW Kämmerer

    2011-04-01

    Full Text Available Functional coatings on titanium vascular stents and endosseous dental implants could probably enhance endothelial cell (EC adhesion and activity with a shortening of the wound healing time and an increase of peri-implant angiogenesis during early bone formation. Therefore, the role of the structure of linear and cyclic cell adhesive peptides Arg-Gly-Asp (l-RGD and c-RGD on differently pre-treated titanium (Ti surfaces (untreated, silanised vs. functionalised with l- and c-RGD peptides on EC cell coverage and proliferation was evaluated. After 24 h and after 3 d, surface coverage of adherent cells was quantified and an alamarBlue® proliferation assay was conducted. After 24 h, l-RGD modified surfaces showed a significantly better coverage of adhered cells than untreated titanium (p=0.01. Differences between l-RGD surfaces and silanised Ti (p=0.066 as well as between l-RGD and c-RGD surfaces (p=0.191 were not significant. After 3 d, c-RGD surfaces showed a significantly higher cell coverage than untreated Ti, silanised and l-RGD titanium surfaces (all p<0.0001. After 24 h, c-RGD modified surfaces showed significant higher cell proliferation compared to untreated Ti (p=0.003. However, there were no differences in proliferation between c-RGD and l-RGD (p=0.126 or c-RGD and silanised titanium (p=0.196. After 3 d, proliferation on c-RGD surfaces outranged significantly untreated titanium (p=0.004, silanised (p=0.001 and l-RGD surfaces (p=0.023, whereas no significant difference could be found between untreated Ti and l-RGD surfaces (p=0.54. According to these results, the biomimetic coating of c-RGD peptides on conventional titanium surfaces showed a positive effect on EC cell coverage and proliferation. We were able to show that modifications of titanium surfaces with c-RGD are a promising approach in promoting endothelial cell growth.

  6. Discrimination of bromodeoxyuridine labelled and unlabelled mitotic cells in flow cytometric bromodeoxyuridine/DNA analysis

    DEFF Research Database (Denmark)

    Jensen, P O; Larsen, J K; Christensen, I J

    1994-01-01

    Bromodeoxyuridine (BrdUrd) labelled and unlabelled mitotic cells, respectively, can be discriminated from interphase cells using a new method, based on immunocytochemical staining of BrdUrd and flow cytometric four-parameter analysis of DNA content, BrdUrd incorporation, and forward and orthogonal...... light scatter. The method was optimized using the human leukemia cell lines HL-60 and K-562. Samples of 10(5) ethanol-fixed cells were treated with pepsin/HCl and stained as a nuclear suspension with anti-BrdUrd antibody, FITC-conjugated secondary antibody, and propidium iodide. Labelled mitoses could...

  7. On the asymptotic improvement of supervised learning by utilizing additional unlabeled samples - Normal mixture density case

    Science.gov (United States)

    Shahshahani, Behzad M.; Landgrebe, David A.

    1992-01-01

    The effect of additional unlabeled samples in improving the supervised learning process is studied in this paper. Three learning processes. supervised, unsupervised, and combined supervised-unsupervised, are compared by studying the asymptotic behavior of the estimates obtained under each process. Upper and lower bounds on the asymptotic covariance matrices are derived. It is shown that under a normal mixture density assumption for the probability density function of the feature space, the combined supervised-unsupervised learning is always superior to the supervised learning in achieving better estimates. Experimental results are provided to verify the theoretical concepts.

  8. Characterization of bioactive RGD peptide immobilized onto poly(acrylic acid) thin films by plasma polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hyun Suk; Ko, Yeong Mu; Shim, Jae Won [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, Gwangju (Korea, Republic of); Lim, Yun Kyong; Kook, Joong-Ki [Department of Oral Biochemistry, School of Dentistry, Chosun University, Gwangju (Korea, Republic of); Cho, Dong-Lyun [School of Applied Chemical Engineering and Center for Functional Nano Fine Chemicals, Chonnam National University, Gwangju (Korea, Republic of); Kim, Byung Hoon, E-mail: kim5055@chosun.ac.kr [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, Gwangju (Korea, Republic of)

    2010-11-01

    Plasma surface modification can be used to improve the surface properties of commercial pure Ti by creating functional groups to produce bioactive materials with different surface topography. In this study, a titanium surface was modified with acrylic acid (AA) using a plasma treatment and immobilized with bioactive arginine-glycine-aspartic acid (RGD) peptide, which may accelerate the tissue integration of bone implants. Both terminals containing the -NH{sub 2} of RGD peptide sequence and -COOH of poly(acrylic acid) (PAA) thin film were combined with a covalent bond in the presence of 1-ethyl-3-3-dimethylaminopropyl carbodiimide (EDC). The chemical structure and morphology of AA film and RGD immobilized surface were investigated by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), atomic force microscopy (AFM), and scanning electron microscopy (SEM). All chemical analysis showed full coverage of the Ti substrate with the PAA thin film containing COOH groups and the RGD peptide. The MC3T3-E1 cells were cultured on each specimen, and the cell alkaline phosphatase (ALP) activity were examined. The surface-immobilized RGD peptide has a significantly increased the ALP activity of MC3T3-E1 cells. These results suggest that the RGD peptide immobilization on the titanium surface has an effect on osteoblastic differentiation of MC3T3-E1 cells and potential use in osteo-conductive bone implants.

  9. RGD-modified poly(D,L-lactic acid nanoparticles enhance tumor targeting of oridonin

    Directory of Open Access Journals (Sweden)

    Xu J

    2012-01-01

    Full Text Available Jie Xu, Ji-Hui Zhao, Ying Liu, Nian-Ping Feng, Yong-Tai ZhangSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of ChinaObjective: The purpose of this study was to develop an active targeting strategy to improve the therapeutic antitumor efficacy of oridonin (ORI, the main active ingredient in the medicinal herb Rabdosia rubescens.Methods: A modified spontaneous emulsification solvent diffusion method was used to prepare the ORI-loaded atactic poly(D,L-lactic acid nanoparticles (ORI-PLA-NPs. Surface cross-linking with the peptide Arg-Gly-Asp (RGD further modified the ORI-PLA-NPs, generating ORI-PLA-RGD-NPs. The NPs were characterized and release experiments were performed in vitro. The pharmacokinetics, tissue distribution, and antitumor activity of the NPs were studied in mice bearing hepatocarcinoma 22 (H22-derived tumors.Results: The ORI-PLA-NPs and ORI-PLA-RGD-NPs were smooth, sphere-like, and relatively uniform in size. The RGD surface modification slightly increased the mean particle size (95.8 nm for ORI-PLA-NPs versus 105.2 nm for ORI-PLA-RGD-NPs and considerably altered the surface electrical property (-10.19 mV for ORI-PLA-NPs versus -21.95 mV for ORI-PLA-RGD-NPs, but it had no obvious influence on ORI loading (8.23% ± 0.35% for ORI-PLA-NPs versus 8.02% ± 0.38% for ORI-PLA-RGD-NPs, entrapment efficiency (28.86% ± 0.93% for ORI-PLA-NPs versus 28.24% ± 0.81% for ORI-PLA-RGD-NPs, or the release of ORI. The pharmacokinetic properties of free ORI were improved by encapsulation in NPs, as shown by increased area under the concentration-time curve (11.89 ± 0.35 µg·mL-1 · h for ORI solution versus 22.03 ± 0.01 µg · mL-1 · h for ORI-PLA-RGD-NPs and prolonged mean retention time (2.03 ± 0.09 hours for ORI solution versus 8.68 ± 0.66 hours for ORI-PLA-RGD-NPs. In the tissue distribution study, more ORI targeted tumor tissue in the mice treated with ORI-PLA-RGD-NPs than with ORI

  10. Alkane dimers interaction

    DEFF Research Database (Denmark)

    Ferrighi, Lara; Madsen, Georg Kent Hellerup; Hammer, Bjørk

    2010-01-01

    The interaction energies of a series of n-alkane dimers, from methane to decane, have been investigated with Density Functional Theory (DFT), using the MGGA-M06-L density functional. The results are compared both to the available wavefunction-based values as well as to dispersion corrected DFT...... values. The MGGA-M06-L density functional is a semi-local functional designed and has proven to provide accurate estimates of dispersion interactions for several systems at moderate computational cost. In the present application, it reproduces the trends obtained by the more expensive wavefunction...

  11. Inhibitory effect of unlabeled iodothyronines on the deiodination of labeled thyroid hormones by cultured hepatocarcinoma cells

    International Nuclear Information System (INIS)

    Sorimachi, Kenji

    1980-01-01

    Inhibitory effects of unlabeled iodothyronines on the metabolism of thyroxine (T 4 ), 3,3',5-triiodothyronine (T 3 ) and 3,3',5'-triiodothyronine (reverse T 3 , rT 3 ) were investigated in continuously cultured monkey hepatocarcinoma cells which showed a rapid metabolism of the thyroid hormones. Nonphenolic ring deiodination of [3',5'- 125 I]-T 4 and [3'- 125 I]-T 3 was strongly inhibited by excess T 3 , 3,5-diiodothyronine (3,5-T 2 ) and T 4 , whereas rT 3 was the least effective inhibitor. Phenolic ring deiodination of [3',5'- 125 I]-rT 3 was strongly affected by excess unlabeled rT 3 . However, the inhibitory effect of T 4 , T 3 and 3,5-T 3 was much weaker than that of rT 3 . It was concluded that rT 3 is apparently the most effective inhibitor of phenolic ring deiodination but the least effective inhibitor of nonphenolic ring deiodination. (author)

  12. Unlabelled advertorials in Slovenian life-style press: a study of the promotion of health products.

    Science.gov (United States)

    Kovacic, Melita Poler; Erjavec, Karmen; Stular, Katarina

    2011-01-01

    The paper analyses unlabelled advertorials about health products in four life-style magazines and three daily newspapers' life-style supplements in Slovenia. Based on 250 hours of observing the production practice, 20 in-depth interviews with the main participants and a textual analysis of 247 advertorials, supported by three detailed case studies, the process of unlabelled advertorial production was unveiled, reasons for their production explained and their discursive elements of promotion uncovered. Despite their typical news-like appearance, advertorials focus on a product's positive characteristics only and represent an oversimplified viewpoint on health, primarily oriented towards the interest of the pharmaceutical industry. In advertorials, readers are instructed in healthy living and caring about their health through buying the promoted product. No particular differences were found between the magazines and quality dailies' supplements, indicating that the advertorial practice has become a common part of the Slovenian press media scene. The outburst of advertorials in Slovenia is outstanding due to the lack of historical democracy, problems with the supervision of legal transgressions, the small media and advertising market, economic downturns and the financial weakness of the media.

  13. Inhibitory effect of unlabeled iodothyronines on the deiodination of labeled thyroid hormones by cultured hepatocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Sorimachi, K [Dokkyo Univ. Tochigi (Japan). School of Medicine

    1980-04-01

    Inhibitory effects of unlabeled iodothyronines on the metabolism of thyroxine (T/sub 4/), 3,3',5-triiodothyronine (T/sub 3/) and 3,3',5'-triiodothyronine (reverse T/sub 3/, rT/sub 3/) were investigated in continuously cultured monkey hepatocarcinoma cells which showed a rapid metabolism of the thyroid hormones. Nonphenolic ring deiodination of (3',5'-/sup 125/I)-T/sub 4/ and (3'-/sup 125/I)-T/sub 3/ was strongly inhibited by excess T/sub 3/, 3,5-diiodothyronine (3,5-T/sub 2/) and T/sub 4/, whereas rT/sub 3/ was the least effective inhibitor. Phenolic ring deiodination of (3',5'-/sup 125/I)-rT/sub 3/ was strongly affected by excess unlabeled rT/sub 3/. However, the inhibitory effect of T/sub 4/, T/sub 3/ and 3,5-T/sub 3/ was much weaker than that of rT/sub 3/. It was concluded that rT/sub 3/ is apparently the most effective inhibitor of phenolic ring deiodination but the least effective inhibitor of nonphenolic ring deiodination.

  14. New derivative of staphylokinase SAK-RGD-K2-Hirul exerts thrombolytic effects in the arterial thrombosis model in rats.

    Science.gov (United States)

    Szemraj, Janusz; Zakrzeska, Agnieszka; Brown, George; Stankiewicz, Adrian; Gromotowicz, Anna; Grędziński, Tomasz; Chabielska, Ewa

    2011-01-01

    SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul are recombinant proteins that are derivatives of r-SAK (recombinant staphylokinase). They are characterized by their fibrin-specific plasminogen activation properties and their antithrombin and antiplatelet activities. The difference between these proteins is the presence of the antithrombotic fragment (hirudin or hirulog) in the C-terminal portion of the r-SAK. The aim of the present study was to examine the thrombolytic potentials of SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul in an electrically induced carotid artery thrombosis model in rats and to compare the potentials to that of r-SAK. We determined that a bolus injection of SAK-RGD-K2-Hirul was more effective than one of r-SAK in the improvement and maintenance of carotid patency and in arterial thrombus weight reduction; however, it had the same potency as SAK-RGD-K2-Hir. The bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in the animals that were treated with either dose (1.5 or 3.0 mg/kg) of SAK-RGD-K2-Hir or SAK-RGD-K2-Hirul, whereas no changes were observed in the plasma fibrinogen concentration or the α2 plasmin inhibitor level. r-SAK alone did not change the bleeding time or coagulation parameters. In conclusion, our findings demonstrate the thrombolytic activity of intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hirul in rats. Although this protein compares favorably with r-SAK, we were unable to show the presence of any beneficial effects of SAK-RGD-K2-Hirul over those of SAK-RGD-K2-Hir. Furthermore, our results suggest that high doses of SAK-RGD-K2-Hirul bear the risk of bleeding.

  15. Discovery and in vivo evaluation of novel RGD-modified lipid-polymer hybrid nanoparticles for targeted drug delivery.

    Science.gov (United States)

    Zhao, Yinbo; Lin, Dayong; Wu, Fengbo; Guo, Li; He, Gu; Ouyang, Liang; Song, Xiangrong; Huang, Wei; Li, Xiang

    2014-09-29

    In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg-Gly-Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD-lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))-mPEG (methoxyl poly(ethylene- glycol)), RGD-polyethylene glycol (PEG)-cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD-lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD-lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD-lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD-lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD-lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD-lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD-lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.

  16. Reductive nanocomplex encapsulation of cRGD-siRNA conjugates for enhanced targeting to cancer cells

    Directory of Open Access Journals (Sweden)

    Zhou Z

    2017-10-01

    Full Text Available Zhaoxiu Zhou,* Shuang Liu,* Yanfen Zhang, Xiantao Yang, Yuan Ma, Zhu Guan, Yun Wu, Lihe Zhang, Zhenjun Yang State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: In this study, through covalent conjugation and lipid material entrapment, a combined modification strategy was established for effective delivery of small interfering RNA (siRNA. Single strands of siRNA targeting to BRAFV600E gene (siMB3 conjugated with cRGD peptide at 3'-terminus or 5'-terminus via cleavable disulfide bond was synthesized and then annealed with corresponding strands to obtain single and bis-cRGD-siRNA conjugates. A cationic lipid material (CLD developed by our laboratory was mixed with the conjugates to generate nanocomplexes; their uniformity and electrical property were revealed by particle size and zeta potential measurement. Compared with CLD/siBraf, CLD/cRGD-siBraf achieved higher cell uptake and more excellent tumor-targeting ability, especially 21 (sense-5′/antisense-3″-cRGD-congjugate nanocomplex. Moreover, they can regulate multiple pathways to varying degree and reduce acidification of endosome. Compared with the gene silencing of different conjugates, single or bis-cRGD-conjugated siRNA showed little differences except 22 (5/5 which cRGD was conjugated at 5'-terminus of antisense strand and sense strand. However bis-cRGD conjugate 21 nanocomplex exhibited better specific target gene silencing at multiple time points. Furthermore, the serum stabilities of the bis-cRGD conjugates were higher than those of the single-cRGD conjugates. In conclusion, all these data suggested that CLD/bis-conjugates, especially CLD/21, can be an effective system for delivery of siRNA to target BRAFV600E gene for therapy of melanoma. Keywords: cRGD-siRNA conjugates, cationic lipids, targeting, silencing, intracellular pathways

  17. 99mTcO(MAG2-3G3-dimer): a new integrin αvβ3-targeted SPECT radiotracer with high tumor uptake and favorable pharmacokinetics

    International Nuclear Information System (INIS)

    Shi, Jiyun; Wang, Lijun; Kim, Young-Seung; Zhai, Shizhen; Liu, Shuang; Jia, Bing; Wang, Fan

    2009-01-01

    This report presents the synthesis of a cyclic RGD dimer conjugate, MAG 2 -G 3 -E[G 3 -c(RGDfK)] 2 (MAG 2 -3G 3 -dimer, G 3 = Gly-Gly-Gly, MAG 2 = S-benzoyl mercaptoacetylglycylglycyl), and evaluation of its 99m Tc complex, 99m TcO(MAG 2 -3G 3 -dimer), as a new radiotracer for imaging the tumor integrin α v β 3 expression. An in vitro displacement assay was used to determine the integrin α v β 3 binding affinity of MAG 2 -3G 3 -dimer against 125 I-c(RGDyK) bound to U87MG human glioma cells. The athymic nude mice bearing U87MG glioma xenografts were used for biodistribution and planar imaging studies. We found that (1) MAG 2 is such a highly effective bifunctional chelator that 99m TcO(MAG 2 -3G 3 -dimer) can be prepared in high yield (radiochemical purity >95%) and with high specific activity (∝5 Ci/μmol) using a kit formulation; (2) 99m TcO(MAG 2 -3G 3 -dimer) has very high solution stability in the kit matrix; and (3) 99m TcO(MAG 2 -3G 3 -dimer) has very fast clearance kinetics from the intestine, liver, and kidneys. Among the 99m Tc-labeled cyclic RGD peptides evaluated in the xenografted U87MG glioma models, 99m TcO(MAG 2 -3G 3 -dimer) has the best pharmacokinetics and tumor to background ratios (tumor/liver = 4.29 ± 1.00 at 30 min postinjection and 8.29 ± 1.50 at 120 min postinjection; tumor/kidney = 1.16 ± 0.19 at 30 min postinjection and 2.49 ± 0.25 at 120 min postinjection). Planar imaging studies showed that tumors in the glioma-bearing mice administered with 99m TcO(MAG 2 -3G 3 -dimer) can be visualized with excellent contrast as early as 15 min postinjection. 99m TcO(MAG 2 -3G 3 -dimer) was able to maintain its chemical integrity in kidneys (>80% intact) and liver (>95% intact) over the 2-h period. However, there was significant metabolism (>50% of the injected radioactivity) detected in both urine and feces samples. 99m TcO(MAG 2 -3G 3 -dimer) is a very attractive radiotracer for early detection of integrin α v β 3 -positive tumors and has

  18. The relative importance of topography and RGD ligand density for endothelial cell adhesion.

    Directory of Open Access Journals (Sweden)

    Guillaume Le Saux

    Full Text Available The morphology and function of endothelial cells depends on the physical and chemical characteristics of the extracellular environment. Here, we designed silicon surfaces on which topographical features and surface densities of the integrin binding peptide arginine-glycine-aspartic acid (RGD could be independently controlled. We used these surfaces to investigate the relative importance of the surface chemistry of ligand presentation versus surface topography in endothelial cell adhesion. We compared cell adhesion, spreading and migration on surfaces with nano- to micro-scaled pyramids and average densities of 6×10(2-6×10(11 RGD/mm(2. We found that fewer cells adhered onto rough than flat surfaces and that the optimal average RGD density for cell adhesion was 6×10(5 RGD/mm(2 on flat surfaces and substrata with nano-scaled roughness. Only on surfaces with micro-scaled pyramids did the topography hinder cell migration and a lower average RGD density was optimal for adhesion. In contrast, cell spreading was greatest on surfaces with 6×10(8 RGD/mm(2 irrespectively of presence of feature and their size. In summary, our data suggest that the size of pyramids predominately control the number of endothelial cells that adhere to the substratum but the average RGD density governs the degree of cell spreading and length of focal adhesion within adherent cells. The data points towards a two-step model of cell adhesion: the initial contact of cells with a substratum may be guided by the topography while the engagement of cell surface receptors is predominately controlled by the surface chemistry.

  19. {sup 68}Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    Energy Technology Data Exchange (ETDEWEB)

    Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Iveson, Peter; Wilson, Ian [Medical Diagnostics, GE Healthcare Biosciences, London (United Kingdom); Karlsen, Hege; Cuthbertson, Alan [GE Healthcare MDx Research, Oslo (Norway); Laine, Jukka [Turku University Hospital, Department of Pathology, Turku (Finland); Leppaenen, Pia; Ylae-Herttula, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland); Roivainen, Anne [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Turku Centre for Disease Modelling, Turku (Finland)

    2009-12-15

    Increased expression of {alpha}v{beta}3/{alpha}v{beta}5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel {sup 68}Ga-DOTA-RGD peptide binds with high affinity to {alpha}v{beta}3/{alpha}v{beta}5 integrin. The aim of this study was to investigate the uptake of the {sup 68}Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered {sup 68}Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR{sup -/-}ApoB{sup 100/100} atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced {sup 68}Ga. The tracer had reasonably good specific radioactivity (8.7 {+-} 1.1 GBq/{mu}mol) and was quite stable in vivo. According to ex vivo biodistribution results, {sup 68}Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of {sup 68}Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio {+-} SD 1.4 {+-} 0.1, p = 0.0004). We observed that {sup 68}Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  20. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    International Nuclear Information System (INIS)

    Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani; Iveson, Peter; Wilson, Ian; Karlsen, Hege; Cuthbertson, Alan; Laine, Jukka; Leppaenen, Pia; Ylae-Herttula, Seppo; Roivainen, Anne

    2009-01-01

    Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68 Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68 Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered 68 Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR -/- ApoB 100/100 atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced 68 Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68 Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68 Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004). We observed that 68 Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  1. Wortmannin efficiently suppresses the recovery from radiation-induced damage in pimonidazole-unlabeled quiescent tumor cell population

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Ono, Koji; Sakurai, Yoshinori; Tanaka, Hiroki; Maruhashi, Akira

    2013-01-01

    Labeling of proliferating (P) cells in mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2'-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after pimonidazole administration followed by caffeine or wortmannin treatment. Twenty-four hours later, assessment of the responses of quiescent (Q) and total (=P+Q) cell populations were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. The pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using an assay performed 24 hours after irradiation, was more clearly observed in Q cells than total cells. In both the pimonidazole-unlabeled and the whole cell fractions, wortmannin efficiently suppressed the reduction in sensitivity due to delayed assay. Wortmannin combined with γ-ray irradiation is useful for suppressing the recovery from radiation-induced damage especially in the pimonidazole-unlabeled cell fraction within the total and Q tumor cell populations. (author)

  2. Selective amine catalysed steroidal dimerization

    Indian Academy of Sciences (India)

    of cholesterol is the formation of a green colour in concentrated sulphuric acid, and this was shown to be due to a polyenyl steroidal dimer carbocation.7–9 Many dimeric and oligomeric steroids exhibit interesting micellular, detergent and liquid crystal behaviour.10,11. Most of the steroidal dimmers are also well-known.

  3. Development of a new anti-cancer agent for targeted radionuclide therapy: β- radiolabeled RAFT-RGD

    International Nuclear Information System (INIS)

    Petitprin, A.

    2013-01-01

    β-emitters radiolabeled RAFT-RGD as new agents for internal targeted radiotherapy. The αvβ3 integrin is known to play an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. Because of its overexpression on neo-endothelial cells such as those present in growing tumors, as well as on tumor cells of various origins, αvβ3 integrin is an attractive molecular target for diagnosis and therapy of the rapidly growing and metastatic tumors. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin αvβ3 in vitro and in vivo. RAFT-RGD has been used for tumor imaging and drug targeting. This study is the first to evaluate the therapeutic potential of the β-emitters radiolabeled tetrameric RGD peptide RAFT-RGD in a Nude mouse model of αvβ3 -expressing tumors. An injection of 37 MBq of 90 Y-RAFT-RGD or 177 Lu-RAFT-RGD in mice with αvβ3 -positive tumors caused a significant growth delay as compared with mice treated with 37 MBq of 90 Y-RAFT-RAD or 177 Lu-RAFT-RAD or untreated mice. In comparison, an injection of 30 MBq of 90 Y-RAFT-RGD had no efficacy for the treatment of αvβ3 -negative tumors. 90 Y-RAFT-RGD and 177 Lu-RAFT-RGD are potent αvβ3 -expressing tumor targeting agents for internal targeted radiotherapy. (author)

  4. How Well Does BODIPY-Cholesteryl Ester Mimic Unlabeled Cholesteryl Esters in High Density Lipoprotein Particles?

    DEFF Research Database (Denmark)

    Karilainen, Topi; Vuorela, Timo; Vattulainen, Ilpo

    2015-01-01

    We compare the behavior of unlabeled and BODIPY-labeled cholesteryl ester (CE) in high density lipoprotein by atomistic molecular dynamics simulations. We find through replica exchange umbrella sampling and unbiased molecular dynamics simulations that BODIPY labeling has no significant effect...... on the partitioning of CE between HDL and the water phase. However, BODIPY-CE was observed to diffuse more slowly and locate itself closer to the HDL-water interface than CE due to the BODIPY probe that is constrained to the surface region, and because the CE body in BODIPY-CE prefers to align itself away from...... the HDL surface. The implications as to the suitability of BODIPY to explore lipoprotein properties are discussed....

  5. Autonomic intrusion detection: Adaptively detecting anomalies over unlabeled audit data streams in computer networks

    KAUST Repository

    Wang, Wei; Guyet, Thomas; Quiniou, René ; Cordier, Marie-Odile; Masseglia, Florent; Zhang, Xiangliang

    2014-01-01

    In this work, we propose a novel framework of autonomic intrusion detection that fulfills online and adaptive intrusion detection over unlabeled HTTP traffic streams in computer networks. The framework holds potential for self-managing: self-labeling, self-updating and self-adapting. Our framework employs the Affinity Propagation (AP) algorithm to learn a subject’s behaviors through dynamical clustering of the streaming data. It automatically labels the data and adapts to normal behavior changes while identifies anomalies. Two large real HTTP traffic streams collected in our institute as well as a set of benchmark KDD’99 data are used to validate the framework and the method. The test results show that the autonomic model achieves better results in terms of effectiveness and efficiency compared to adaptive Sequential Karhunen–Loeve method and static AP as well as three other static anomaly detection methods, namely, k-NN, PCA and SVM.

  6. Autonomic intrusion detection: Adaptively detecting anomalies over unlabeled audit data streams in computer networks

    KAUST Repository

    Wang, Wei

    2014-06-22

    In this work, we propose a novel framework of autonomic intrusion detection that fulfills online and adaptive intrusion detection over unlabeled HTTP traffic streams in computer networks. The framework holds potential for self-managing: self-labeling, self-updating and self-adapting. Our framework employs the Affinity Propagation (AP) algorithm to learn a subject’s behaviors through dynamical clustering of the streaming data. It automatically labels the data and adapts to normal behavior changes while identifies anomalies. Two large real HTTP traffic streams collected in our institute as well as a set of benchmark KDD’99 data are used to validate the framework and the method. The test results show that the autonomic model achieves better results in terms of effectiveness and efficiency compared to adaptive Sequential Karhunen–Loeve method and static AP as well as three other static anomaly detection methods, namely, k-NN, PCA and SVM.

  7. Exploiting the potential of unlabeled endoscopic video data with self-supervised learning.

    Science.gov (United States)

    Ross, Tobias; Zimmerer, David; Vemuri, Anant; Isensee, Fabian; Wiesenfarth, Manuel; Bodenstedt, Sebastian; Both, Fabian; Kessler, Philip; Wagner, Martin; Müller, Beat; Kenngott, Hannes; Speidel, Stefanie; Kopp-Schneider, Annette; Maier-Hein, Klaus; Maier-Hein, Lena

    2018-04-27

    Surgical data science is a new research field that aims to observe all aspects of the patient treatment process in order to provide the right assistance at the right time. Due to the breakthrough successes of deep learning-based solutions for automatic image annotation, the availability of reference annotations for algorithm training is becoming a major bottleneck in the field. The purpose of this paper was to investigate the concept of self-supervised learning to address this issue. Our approach is guided by the hypothesis that unlabeled video data can be used to learn a representation of the target domain that boosts the performance of state-of-the-art machine learning algorithms when used for pre-training. Core of the method is an auxiliary task based on raw endoscopic video data of the target domain that is used to initialize the convolutional neural network (CNN) for the target task. In this paper, we propose the re-colorization of medical images with a conditional generative adversarial network (cGAN)-based architecture as auxiliary task. A variant of the method involves a second pre-training step based on labeled data for the target task from a related domain. We validate both variants using medical instrument segmentation as target task. The proposed approach can be used to radically reduce the manual annotation effort involved in training CNNs. Compared to the baseline approach of generating annotated data from scratch, our method decreases exploratively the number of labeled images by up to 75% without sacrificing performance. Our method also outperforms alternative methods for CNN pre-training, such as pre-training on publicly available non-medical (COCO) or medical data (MICCAI EndoVis2017 challenge) using the target task (in this instance: segmentation). As it makes efficient use of available (non-)public and (un-)labeled data, the approach has the potential to become a valuable tool for CNN (pre-)training.

  8. Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells.

    Science.gov (United States)

    Bianchini, Francesca; Peppicelli, Silvia; Fabbrizzi, Pierangelo; Biagioni, Alessio; Mazzanti, Benedetta; Menchi, Gloria; Calorini, Lido; Pupi, Alberto; Trabocchi, Andrea

    2017-01-01

    Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident. In this study, we present a class of triazole-derived RGD antagonists that interact with αvβ3 integrin. Above different compounds, the RGD-2 specifically interferes with integrin-dependent TGFβ1 EndoMT in Endothelial Colony-Forming Cells (ECPCs) derived from circulating Endothelial Precursor Cells (ECPCs). The RGD-2 decreases the amount of membrane-associated TGFβ1, and reduces both ALK5/TGFβ1 type I receptor expression and Smad2 phosphorylation in ECPCs. We found that RGD-2 antagonist reverts EndoMT, reducing α-smooth muscle actin (α-SMA) and vimentin expression in differentiated ECPCs. Our results outline the critical role of integrin in fibrosis progression and account for the opportunity of using integrins as target for anti-fibrotic therapeutic treatment.

  9. Body distributioin of RGD-mediated liposome in brain-targeting drug delivery.

    Science.gov (United States)

    Qin, Jing; Chen, DaWei; Hu, Haiyang; Qiao, MingXi; Zhao, XiuLi; Chen, Baoyu

    2007-09-01

    RGD conjugation liposomes (RGD-liposomes) were evaluated for brain-targeting drug delivery. The flow cytometric in vitro study demonstrated that RGD-liposomes could bind to monocytes and neutrophils effectively. Ferulic acid (4-hydroxy-3-methoxycinnamic, FA) was loaded into liposomes. Rats were subjected to intrastriatal microinjections of 100 units of human recombinant IL-1beta to produce brain inflammation and caudal vein injection of three formulations (FA solution, FA liposome and RGD-coated FA liposome). Animals were sacrificed 15, 30, 60 and 120 min after administration to study the body distribution of the FA in the three formulations. HPLC was used to determine the concentration of FA in vivo with salicylic acid as internal standard. The results of body distribution indicated that RGD-coated liposomes could be mediated into the brain with a 6-fold FA concentration compared to FA solution and 3-fold in comparison to uncoated liposome. Brain targeted delivery was achieved and a reduction in dosage might be allowed.

  10. Impact of RGD amount in dextran-based hydrogels for cell delivery.

    Science.gov (United States)

    Riahi, Nesrine; Liberelle, Benoît; Henry, Olivier; De Crescenzo, Gregory

    2017-04-01

    Dextran is one of the hydrophilic polymers that is used for hydrogel preparation. As any polysaccharide, it presents a high density of hydroxyl groups, which make possible several types of derivatization and crosslinking reactions. Furthermore, dextran is an excellent candidate for hydrogel fabrication with controlled cell/scaffold interactions as it is resistant to protein adsorption and cell adhesion. RGD peptide can be grafted to the dextran in order to promote selected cell adhesion and proliferation. Altogether, we have developed a novel strategy to graft the RGD peptide sequence to dextran-based hydrogel using divinyl sulfone as a linker. The resulting RGD functionalized dextran-based hydrogels were transparent, presented a smooth surface and were easy to handle. The impact of varying RGD peptide amounts, hydrogel porosity and topology upon human umbilical vein endothelial cell (HUVEC) adhesion, proliferation and infiltration was investigated. Our results demonstrated that 0.1% of RGD-modified dextran within the gel was sufficient to support HUVEC cells adhesion to the hydrogel surface. Sodium chloride was added (i) to the original hydrogel mix in order to form a macroporous structure presenting interconnected pores and (ii) to the hydrogel surface to create small orifices essential for cells migration inside the matrix. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

    Science.gov (United States)

    Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2015-10-01

    Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy.

  12. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    International Nuclear Information System (INIS)

    Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

    2014-01-01

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images

  13. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  14. {sup 18}F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xiaoyuan; Park, Ryan; Shahinian, Anthony H.; Tohme, Michel; Khankaldyyan, Vazgen; Bozorgzadeh, Mohammed H.; Bading, James R.; Moats, Rex; Laug, Walter E.; Conti, Peter S. E-mail: pconti@usc.edu

    2004-02-01

    Brain tumors are highly angiogenesis dependent. The cell adhesion receptor integrin {alpha}{sub v}{beta}{sub 3} is overexpressed in glioma and activated endothelial cells and plays an important role in brain tumor growth, spread and angiogenesis. Suitably labeled {alpha}{sub v}{beta}{sub 3}-integrin antagonists may therefore be useful for imaging brain tumor associated angiogenesis. Cyclic RGD peptide c(RGDyK) was labeled with {sup 18}F via N-succinimidyl-4-[{sup 18}F]fluorobenzoate through the side-chain {epsilon}-amino group of the lysine residue. The radiotracer was evaluated in vivo for its tumor targeting efficacy and pharmacokinetics in subcutaneously implanted U87MG and orthotopically implanted U251T glioblastoma nude mouse models by means of microPET, quantitative autoradiography and direct tissue sampling. The N-4-[{sup 18}F]fluorobenzoyl-RGD ([{sup 18}F]FB-RGD) was produced in less than 2 h with 20-25% decay-corrected yields and specific activity of 230 GBq/{mu}mol at end of synthesis. The tracer showed very rapid blood clearance and both hepatobiliary and renal excretion. Tumor-to-muscle uptake ratio at 30 min was approximately 5 in the subcutaneous U87MG tumor model. MicroPET imaging with the orthotopic U251T brain tumor model revealed very high tumor-to-brain ratio, with virtually no uptake in the normal brain. Successful blocking of tumor uptake of [{sup 18}F]FB-RGD in the presence of excess amount of c(RGDyK) revealed receptor specific activity accumulation. Hence, N-4-[{sup 18}F]fluorobenzoyl labeled cyclic RGD peptide [{sup 18}F]FB-RGD is a potential tracer for imaging {alpha}{sub v}{beta}{sub 3}-integrin positive tumors in brain and other anatomic locations.

  15. RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells.

    Science.gov (United States)

    He, Xuedan; Alves, Carla S; Oliveira, Nilsa; Rodrigues, João; Zhu, Jingyi; Bányai, István; Tomás, Helena; Shi, Xiangyang

    2015-01-01

    Development of multifunctional nanoscale drug-delivery systems for targeted cancer therapy still remains a great challenge. Here, we report the synthesis of cyclic arginine-glycine-aspartic acid (RGD) peptide-conjugated generation 5 (G5) poly(amidoamine) dendrimers for anticancer drug encapsulation and targeted therapy of cancer cells overexpressing αvβ3 integrins. In this study, amine-terminated G5 dendrimers were used as a platform to be sequentially modified with fluorescein isothiocyanate (FI) via a thiourea linkage and RGD peptide via a polyethylene glycol (PEG) spacer, followed by acetylation of the remaining dendrimer terminal amines. The developed multifunctional dendrimer platform (G5.NHAc-FI-PEG-RGD) was then used to encapsulate an anticancer drug doxorubicin (DOX). We show that approximately six DOX molecules are able to be encapsulated within each dendrimer platform. The formed complexes are water-soluble, stable, and able to release DOX in a sustained manner. One- and two-dimensional NMR techniques were applied to investigate the interaction between dendrimers and DOX, and the impact of the environmental pH on the release rate of DOX from the dendrimer/DOX complexes was also explored. Furthermore, cell biological studies demonstrate that the encapsulation of DOX within the G5.NHAc-FI-PEG-RGD dendrimers does not compromise the anticancer activity of DOX and that the therapeutic efficacy of the dendrimer/DOX complexes is solely related to the encapsulated DOX drug. Importantly, thanks to the role played by RGD-mediated targeting, the developed dendrimer/drug complexes are able to specifically target αvβ3 integrin-overexpressing cancer cells and display specific therapeutic efficacy to the target cells. The developed RGD peptide-targeted multifunctional dendrimers may thus be used as a versatile platform for targeted therapy of different types of αvβ3 integrin-overexpressing cancer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Collisional properties of weakly bound heteronuclear dimers

    NARCIS (Netherlands)

    Marcelis, B.; Kokkelmans, S.J.J.M.F.; Shlyapnikov, G.V.; Petrov, D.S.

    2008-01-01

    We consider collisional properties of weakly bound heteronuclear molecules (dimers) formed in a two-species mixture of atoms with a large mass difference. We focus on dimers containing light fermionic atoms as they manifest collisional stability due to an effective dimer-dimer repulsion originating

  17. An exploratory study on 99mTc-RGD-BBN peptide scintimammography in the assessment of breast malignant lesions compared to 99mTc-3P4-RGD2.

    Directory of Open Access Journals (Sweden)

    Qianqian Chen

    Full Text Available This study aimed to explore the diagnostic performance of single photon emission computed tomography / computerized tomography (SPECT/CT using a new radiotracer 99mTc-RGD-BBN for breast malignant tumor compared with 99mTc-3P4-RGD2.6 female patients with breast malignant tumors diagnosed by fine needle aspiration cytology biopsy (FNAB who were scheduled to undergo surgery were included in the study. 99mTc-3P4-RGD2 and 99mTc-RGD-BBN were performed with single photon emission computed tomography (SPECT at 1 hour after intravenous injection of 299 ± 30 MBq and 293 ± 32 MBq of radiotracers respectively at separate day. The results were evaluated by the Tumor to non-Tumor ratios (T/NT. 99mTc-RGD-BBN and 99mTc-3P4-RGD2 SPECT/CT images were interpreted independently by 3 experienced nuclear medicine physicians using a 3-point scale system. All of the samples were analyzed immunohistochemically to evaluate the integrin αvβ3 and gastrin-releasing peptide receptor (GRPR expression. The safety, biodistribution and radiation dosimetry of 99mTc-RGD-BBN were also evaluated in the healthy volunteers.No serious adverse events were reported in any of the patients during the study. The effective radiation dose entirely conformed to the relevant standards. A total of 6 palpable malignant lesions were detected using 99mTc-RGD-BBN SPECT/CT with clear uptake. All malignant lesions were also detected using 99mTc-3P4-RGD2 SPECT/CT. The results showed that five malignant lesions were with clear uptake and the other one with barely an uptake. 4 malignant cases were found with both αvβ3 and GRPR expression, 1 case with only GRPR positive expression (integrin αvβ3 negative and 1 case with only integrin αvβ3 positive expression (GRPR negative.99mTc-RGD-BBN is a safe agent for detecting breast cancer. 99mTc-RGD-BBN may have the potential to make up for the deficiency of 99mTc-3P4-RGD2 in the detection of breast cancer with only GRPR positive expression (integrin

  18. Improvement of Roller Bearing Diagnosis with Unlabeled Data Using Cut Edge Weight Confidence Based Tritraining

    Directory of Open Access Journals (Sweden)

    Wei-Li Qin

    2016-01-01

    Full Text Available Roller bearings are one of the most commonly used components in rotational machines. The fault diagnosis of roller bearings thus plays an important role in ensuring the safe functioning of the mechanical systems. However, in most cases of bearing fault diagnosis, there are limited number of labeled data to achieve a proper fault diagnosis. Therefore, exploiting unlabeled data plus few labeled data, this paper proposed a roller bearing fault diagnosis method based on tritraining to improve roller bearing diagnosis performance. To overcome the noise brought by wrong labeling into the classifiers training process, the cut edge weight confidence is introduced into the diagnosis framework. Besides a small trick called suspect principle is adopted to avoid overfitting problem. The proposed method is validated in two independent roller bearing fault experiment vibrational signals that both include three types of faults: inner-ring fault, outer-ring fault, and rolling element fault. The results demonstrate the desirable diagnostic performance improvement by the proposed method in the extreme situation where there is only limited number of labeled data.

  19. Intraperitoneal delivery of monoclonal antibodies: enhanced regional delivery advantage using intravenous unlabeled anti-mouse antibody

    International Nuclear Information System (INIS)

    Wahl, R.L.; Fisher, S.

    1987-01-01

    Radiolabeled monoclonal antibodies (MAb) delivered intraperitoneally expose cells in contact with peritoneal fluid to considerably higher levels of MAb than if the MAb dose were given intravenously. This regional delivery advantage for intact MAb is present mainly due to the relatively slow exit of MAb from the peritoneal fluid to the blood. Eventually, following i.p. injection, blood levels of MAb rise resulting in exposure of the animal to high systemic MAb levels and potential toxicity. In this series of experiments, systemic exposure was minimized by the administration of unlabeled goat polyclonal anti-mouse antibody intravenously from 1 1/2 to 6 h following i.p. MAb injection. This maneuver results in the formation of immune complexes with their subsequent clearance and dehalogenation by the reticuloendothelial system, thus minimizing systemic MAb exposure. This approach, of increasing systemic clearance of MAb, did not alter intraperitoneal MAb levels and thus significantly increased the regional delivery advantage to the peritoneal cavity by 70-100%. This approach provides an immunologic rationale for the further enhancement of MAb delivery to i.p. foci of malignant disease and may have diagnostic and therapeutic utility. (author)

  20. Bystander responses in three-dimensional cultures containing radiolabelled and unlabelled human cells

    International Nuclear Information System (INIS)

    Pinto, M.; Azzam, E. I.; Howell, R. W.

    2006-01-01

    Research on the radiation-induced bystander effect has been carried out mainly in 2-D tissue culture systems. This study uses a 3-D model, wherein apparently normal human diploid fibroblasts (AG1522) are grown in a carbon scaffold, to investigate the induction of a G 1 checkpoint in bystander cells present alongside radiolabelled cells. Cultures were simultaneously pulse-labelled with 3 H-deoxycytidine ( 3 HdC) to selectively irradiate a minor fraction of cells, and bromodeoxyuridine (BrdU) to identify the radiolabelled cells. After thorough washing of cultures, iododeoxyuridine (IdU) was administered to detect proliferating bystander cells. The cultures were harvested at various times thereafter, and cells were reacted with two monoclonal antibodies specific to IdU/BrdU or BrdU, respectively, stained with propidium iodide, and subjected to multi-parameter flow cytometry. Cell-cycle progression was followed in radiolabelled cells (BrdU + ) that were chronically irradiated by low energy beta particles emitted by DNA-incorporated 3 H, and in unlabelled bystander cells (BrdU - ) by a flow cytometry based cumulative labelling index assay. As expected, radiolabelled cells were delayed, in a dose-dependent manner, in G 2 and subsequently G 1 . No delay occurred in progression of bystander cells through G 1 , when the labelled cells were irradiated at dose rates up to 0.32 Gy h -1 . (authors)

  1. A 35-year comparison of children labelled as gifted, unlabelled as gifted and average-ability

    Directory of Open Access Journals (Sweden)

    Joan Freeman

    2014-09-01

    Full Text Available http://dx.doi.org/10.5902/1984686X14273Why are some children seen as gifted while others of identical ability are not?  To find out why and what the consequences might be, in 1974 I began in England with 70 children labelled as gifted.  Each one was matched for age, sex and socio-economic level with two comparison children in the same school class. The first comparison child had an identical gift, and the second taken at random.  Investigation was by a battery of tests and deep questioning of pupils, teachers and parents in their schools and homes which went on for 35 years. A major significant difference was that those labelled gifted had significantly more emotional problems than either the unlabelled but identically gifted or the random controls.  The vital aspects of success for the entire sample, whether gifted or not, have been hard work, emotional support and a positive personal outlook.  But in general, the higher the individual’s intelligence the better their chances in life. 

  2. Dissociation of nucleosomal particles by chemical modification. Equivalence of the two binding sites for H2A.H2B dimers

    International Nuclear Information System (INIS)

    Jordano, J.; Nieto, M.A.; Palacian, E.

    1985-01-01

    Treatment of nucleosomal particles with dimethylmaleic anhydride, a reagent for protein amino groups, is accompanied by a biphasic release of histones H2A plus H2B; one H2A.H2B dimer is more easily released than the other. This behavior allows the preparation of nucleosomal particles containing only one H2A.H2B dimer, which were complemented with 125 I-labeled H2A.H2B. These reconstituted particles, which contain one labeled and one unlabeled H2A.H2B dimer, were treated with the amount of reagent needed to release one of the two H2A.H2B dimers. Radioactivity was equally distributed between residual particles and released proteins, which is consistent with equivalent binding sites in the nucleosomal particle for H2A.H2B dimers, rather than with intrinsically different sites. The asymmetric release of H2A.H2B dimers would be caused by a change in the binding site of one dimer following the release of the other. This behavior might be related to the structural dynamics of nucleosomes

  3. Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically.

    Science.gov (United States)

    Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

    2017-02-10

    The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity.

  4. Scanning electron microscopy and swelling test of shrimp shell chitosan and chitosan-RGD scaffolds

    Science.gov (United States)

    Mandacan, M. C.; Yuniastuti, M.; Amir, L. R.; Idrus, E.; Suniarti, D. F.

    2017-08-01

    Shrimp shell chitosan and chitosan-RGD scaffold membranes are produced to be biocompatible with tissue engineering. Nonetheless, their architectural properties have not yet been studied. Analyze the architectural properties of chitosan and chitosan-RGD scaffolds. Analyze pore count and size, interpore distance, and porosity (using SEM testing and ImageJ analysis) and water absorption (using a swelling test). The properties of the chitosan and chitosan-RGD scaffolds were as follows, respectively. The pore counts were 225 and 153; pore size, 171.4 μam and 180.2 μam interpore distance, 105.7 μam and 101.4 μam porosity, 22% and 10.2%; and water absorption, 9.1 mgH2O/mgScaffold and 19.3 mgH2O/mgScaffold. The shrimp shell chitosan-RGD membrane scaffold was found to have architectural properties that make it more conducive to use in tissue engineering.

  5. Bio-compatibility of ion beam-modified and RGD-grafted polyethylene

    Czech Academy of Sciences Publication Activity Database

    Ročková-Hlaváčková, K.; Švorčík, V.; Bačáková, L.; Dvořánková, B.; Heitz, J.; Hnatowicz, Vladimír

    2004-01-01

    Roč. 225, č. 3 (2004), s. 275-282 ISSN 0168-583X R&D Projects: GA AV ČR IAA5011301 Institutional research plan: CEZ:AV0Z1048901 Keywords : modified polyethylene * ion beam * RGD grafting Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 0.997, year: 2004

  6. Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines

    NARCIS (Netherlands)

    Kunjachan, Sijumon; Pola, Robert; Gremse, Felix; Theek, Benjamin; Ehling, Josef; Moeckel, Diana; Hermanns-Sachweh, Benita; Pechar, Michal; Ulbrich, Karel; Hennink, Wim E.; Storm, Gert; Lederle, Wiltrud; Kiessling, Fabian; Lammers, Twan

    2014-01-01

    Enhanced permeability and retention (EPR) and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) based active tumor targeting have received considerable attention

  7. Radiolabeled antibodies and RGD-peptides for the treatment of ovarian cancer.

    NARCIS (Netherlands)

    Janssen, M.L.H.

    2004-01-01

    In this thesis, preclinical studies on new treatment modalities for ovarian cancer are descibed, applying radiolabeled antibodies and radiolabeled RGD-peptides. In chapter 2 a study is described comparing the therapeutic efficacy of the antibody HMFG1 radiolabeled with several beta-emitting

  8. Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

    International Nuclear Information System (INIS)

    Kawamura, Wataru; Nomoto, Takahiro; Sueyoshi, Daiki; Kataoka, Kazunori; Miura, Yutaka; Toh, Kazuko; Yamada, Naoki; Matsumoto, Yu; Liu, Xueying; Kokuryo, Daisuke; Aoki, Ichio; Saga, Tsuneo; Kano, Mitsunobu R; Nishiyama, Nobuhiro; Kishimura, Akihiro

    2015-01-01

    Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by α V β 3 and α v β 5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress α V β 3 integrins. (paper)

  9. Rat Strain Ontology: structured controlled vocabulary designed to facilitate access to strain data at RGD.

    Science.gov (United States)

    Nigam, Rajni; Munzenmaier, Diane H; Worthey, Elizabeth A; Dwinell, Melinda R; Shimoyama, Mary; Jacob, Howard J

    2013-11-22

    The Rat Genome Database (RGD) ( http://rgd.mcw.edu/) is the premier site for comprehensive data on the different strains of the laboratory rat (Rattus norvegicus). The strain data are collected from various publications, direct submissions from individual researchers, and rat providers worldwide. Rat strain, substrain designation and nomenclature follow the Guidelines for Nomenclature of Mouse and Rat Strains, instituted by the International Committee on Standardized Genetic Nomenclature for Mice. While symbols and names aid in identifying strains correctly, the flat nature of this information prohibits easy search and retrieval, as well as other data mining functions. In order to improve these functionalities, particularly in ontology-based tools, the Rat Strain Ontology (RS) was developed. The Rat Strain Ontology (RS) reflects the breeding history, parental background, and genetic manipulation of rat strains. This controlled vocabulary organizes strains by type: inbred, outbred, chromosome altered, congenic, mutant and so on. In addition, under the chromosome altered category, strains are organized by chromosome, and further by type of manipulations, such as mutant or congenic. This allows users to easily retrieve strains of interest with modifications in specific genomic regions. The ontology was developed using the Open Biological and Biomedical Ontology (OBO) file format, and is organized on the Directed Acyclic Graph (DAG) structure. Rat Strain Ontology IDs are included as part of the strain report (RS: ######). As rat researchers are often unaware of the number of substrains or altered strains within a breeding line, this vocabulary now provides an easy way to retrieve all substrains and accompanying information. Its usefulness is particularly evident in tools such as the PhenoMiner at RGD, where users can now easily retrieve phenotype measurement data for related strains, strains with similar backgrounds or those with similar introgressed regions. This

  10. Inter-heterogeneity and intra-heterogeneity of α{sub v}β{sub 3} in non-small cell lung cancer and small cell lung cancer patients as revealed by {sup 68}Ga-RGD{sub 2} PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Fei; Li, Guoquan; Wang, Shengjun; Liu, Daliang; Zhang, Mingru; Zhao, Mingxuan; Yang, Weidong; Wang, Jing [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Wang, Zhe [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Fourth Military Medical University, Department of Pathology, Xijing Hospital, Xi' an (China)

    2017-08-15

    Integrin α{sub v}β{sub 3} is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare α{sub v}β{sub 3} levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer {sup 68}Ga-labeled dimerized-RGD ({sup 68}Ga-RGD{sub 2}). Thirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using {sup 68}Ga-RGD{sub 2}.{sup 18}F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker α{sub v}β{sub 3} in NSCLC and SCLC lesions was analyzed by immunohistochemistry. The {sup 18}F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The {sup 68}Ga-RGD{sub 2} uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of {sup 68}Ga-RGD{sub 2} SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that α{sub v}β{sub 3} integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression. The uptake of {sup 68}Ga-RGD{sub 2} in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower α{sub v}β{sub 3} target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of α{sub v}β{sub 3} also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of α{sub v}β{sub 3} may potentially improve current applications of α{sub v}β{sub 3}-targeted therapy

  11. Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

    Directory of Open Access Journals (Sweden)

    Chu YC

    2017-02-01

    Full Text Available Yongchao Chu,1,* Ning Chen,2,* Huajun Yu,2,* Hongjie Mu,1 Bin He,1 Hongchen Hua,1 Aiping Wang,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: A nanoparticle (NP was developed to target choroidal neovascularization (CNV via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC and transactivated transcription (TAT (RKKRRQRRRC peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol–poly(lactic-co-glycolic acid. The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs

  12. Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe

    OpenAIRE

    Zhu, Lei; Guo, Ning; Li, Quanzheng; Ma, Ying; Jacboson, Orit; Lee, Seulki; Choi, Hak Soo; Mansfield, James R.; Niu, Gang; Chen, Xiaoyuan

    2012-01-01

    Purpose: The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/64Cu dual-labeled cyclic RGD peptide. Methods: The integrin αvβ3 binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)...

  13. UV-Visible Spectroscopy-Based Quantification of Unlabeled DNA Bound to Gold Nanoparticles.

    Science.gov (United States)

    Baldock, Brandi L; Hutchison, James E

    2016-12-20

    DNA-functionalized gold nanoparticles have been increasingly applied as sensitive and selective analytical probes and biosensors. The DNA ligands bound to a nanoparticle dictate its reactivity, making it essential to know the type and number of DNA strands bound to the nanoparticle surface. Existing methods used to determine the number of DNA strands per gold nanoparticle (AuNP) require that the sequences be fluorophore-labeled, which may affect the DNA surface coverage and reactivity of the nanoparticle and/or require specialized equipment and other fluorophore-containing reagents. We report a UV-visible-based method to conveniently and inexpensively determine the number of DNA strands attached to AuNPs of different core sizes. When this method is used in tandem with a fluorescence dye assay, it is possible to determine the ratio of two unlabeled sequences of different lengths bound to AuNPs. Two sizes of citrate-stabilized AuNPs (5 and 12 nm) were functionalized with mixtures of short (5 base) and long (32 base) disulfide-terminated DNA sequences, and the ratios of sequences bound to the AuNPs were determined using the new method. The long DNA sequence was present as a lower proportion of the ligand shell than in the ligand exchange mixture, suggesting it had a lower propensity to bind the AuNPs than the short DNA sequence. The ratio of DNA sequences bound to the AuNPs was not the same for the large and small AuNPs, which suggests that the radius of curvature had a significant influence on the assembly of DNA strands onto the AuNPs.

  14. Adventures in holographic dimer models

    International Nuclear Information System (INIS)

    Kachru, Shamit; Karch, Andreas; Yaida, Sho

    2011-01-01

    We abstract the essential features of holographic dimer models, and develop several new applications of these models. Firstly, semi-holographically coupling free band fermions to holographic dimers, we uncover novel phase transitions between conventional Fermi liquids and non-Fermi liquids, accompanied by a change in the structure of the Fermi surface. Secondly, we make dimer vibrations propagate through the whole crystal by way of double trace deformations, obtaining nontrivial band structure. In a simple toy model, the topology of the band structure experiences an interesting reorganization as we vary the strength of the double trace deformations. Finally, we develop tools that would allow one to build, in a bottom-up fashion, a holographic avatar of the Hubbard model.

  15. Study of DNA Origami Dimerization and Dimer Dissociation Dynamics and of the Factors that Limit Dimerization.

    Science.gov (United States)

    Liber, Miran; Tomov, Toma E; Tsukanov, Roman; Berger, Yaron; Popov, Mary; Khara, Dinesh C; Nir, Eyal

    2018-06-01

    Organizing DNA origami building blocks into higher order structures is essential for fabrication of large structurally and functionally diverse devices and molecular machines. Unfortunately, the yields of origami building block attachment reactions are typically not sufficient to allow programed assembly of DNA devices made from more than a few origami building blocks. To investigate possible reasons for these low yields, a detailed single-molecule fluorescence study of the dynamics of rectangular origami dimerization and origami dimer dissociation reactions is conducted. Reactions kinetics and yields are investigated at different origami and ion concentrations, for different ion types, for different lengths of bridging strands, and for the "sticky end" and "weaving welding" attachment techniques. Dimerization yields are never higher than 86%, which is typical for such systems. Analysis of the dynamic data shows that the low yield cannot be explained by thermodynamic instability or structural imperfections of the origami constructs. Atomic force microscopy and gel electrophoresis evidence reveal self-dimerization of the origami monomers, likely via blunt-end interactions made possible by the presence of bridging strands. It is suggested that this mechanism is the major factor that inhibits correct dimerization and means to overcome it are discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Determination, at equilibrium, of association constants of labelled or unlabelled ligands by a non-graphical method

    International Nuclear Information System (INIS)

    Goertz, G.; Longchampt, J.; Crepy, O.; Judas, O.; Jayle, M.-F.

    1976-01-01

    Determination, at equilibrium of association constants of labelled or unlabelled ligands by a non-graphical method are described. This work deals with the determination of association constants at equilibrium by a non-graphical method in binding systems containing one specific receptor. Equations have been derived from that originally described by Lea (Biochim. Biophys. Acta, 322, 68-74), the terms of which are obtained from the data of simple displacement curves of a bound radioactive ligand by unlabelled competitors identical or different in nature. By knowing the function relating the variations of the bound ligand (B) to the affinity constant (Ksub(i)) and the quantity (Msub(i)) of competitor for a given system, it is possible to calculate any of these parameters when the two others are measured. Thus, it becomes easy to compare the relative affinities of different receptors for the same ligand or that of one receptor for various labelled or unlabelled ligands. Furthermore, theoretical displacement curves can be drawn and compared to experimental data, only when knowing the affinity constant of a specific binding system in given conditions. These modes of calculation have been tested in a study of interactions between various steroids and a fraction of human serum proteins precipitated by ammonium sulfate (30-45%) and containing the sex hormone-binding globulin. Association constants thus obtained agree well with those reported in the literature and determined by graphical procedures

  17. Dual integrin and gastrin-releasing peptide receptor targeted tumor imaging using 18F-labeled PEGylated RGD-bombesin heterodimer 18F-FB-PEG3-Glu-RGD-BBN.

    Science.gov (United States)

    Liu, Zhaofei; Yan, Yongjun; Chin, Frederic T; Wang, Fan; Chen, Xiaoyuan

    2009-01-22

    Radiolabeled RGD and bombesin peptides have been extensively investigated for tumor integrin alpha(v)beta(3) and GRPR imaging, respectively. Due to the fact that many tumors are both integrin and GRPR positive, we designed and synthesized a heterodimeric peptide Glu-RGD-BBN, which is expected to be advantageous over the monomeric peptides for dual-receptor targeting. A PEG(3) spacer was attached to the glutamate alpha-amino group of Glu-RGD-BBN to enhance the (18)F labeling yield and to improve the in vivo kinetics. PEG(3)-Glu-RGD-BBN possesses the comparable GRPR and integrin alpha(v)beta(3) receptor-binding affinities as the corresponding monomers, respectively. The dual-receptor targeting properties of (18)F-FB-PEG(3)-Glu-RGD-BBN were observed in PC-3 tumor model. (18)F-FB-PEG(3)-Glu-RGD-BBN with high tumor contrast and favorable pharmacokinetics is a promising PET tracer for dual integrin and GRPR positive tumor imaging. This heterodimer strategy may also be an applicable method to develop other molecules with improved in vitro and in vivo characterizations for tumor diagnosis and therapy.

  18. Kinetics of DNA tile dimerization.

    Science.gov (United States)

    Jiang, Shuoxing; Yan, Hao; Liu, Yan

    2014-06-24

    Investigating how individual molecular components interact with one another within DNA nanoarchitectures, both in terms of their spatial and temporal interactions, is fundamentally important for a better understanding of their physical behaviors. This will provide researchers with valuable insight for designing more complex higher-order structures that can be assembled more efficiently. In this report, we examined several spatial factors that affect the kinetics of bivalent, double-helical (DH) tile dimerization, including the orientation and number of sticky ends (SEs), the flexibility of the double helical domains, and the size of the tiles. The rate constants we obtained confirm our hypothesis that increased nucleation opportunities and well-aligned SEs accelerate tile-tile dimerization. Increased flexibility in the tiles causes slower dimerization rates, an effect that can be reversed by introducing restrictions to the tile flexibility. The higher dimerization rates of more rigid tiles results from the opposing effects of higher activation energies and higher pre-exponential factors from the Arrhenius equation, where the pre-exponential factor dominates. We believe that the results presented here will assist in improved implementation of DNA tile based algorithmic self-assembly, DNA based molecular robotics, and other specific nucleic acid systems, and will provide guidance to design and assembly processes to improve overall yield and efficiency.

  19. Dimers in Piecewise Temperleyan Domains

    Science.gov (United States)

    Russkikh, Marianna

    2018-03-01

    We study the large-scale behavior of the height function in the dimer model on the square lattice. Richard Kenyon has shown that the fluctuations of the height function on Temperleyan discretizations of a planar domain converge in the scaling limit (as the mesh size tends to zero) to the Gaussian Free Field with Dirichlet boundary conditions. We extend Kenyon's result to a more general class of discretizations. Moreover, we introduce a new factorization of the coupling function of the double-dimer model into two discrete holomorphic functions, which are similar to discrete fermions defined in Smirnov (Proceedings of the international congress of mathematicians (ICM), Madrid, Spain, 2006; Ann Math (2) 172:1435-1467, 2010). For Temperleyan discretizations with appropriate boundary modifications, the results of Kenyon imply that the expectation of the double-dimer height function converges to a harmonic function in the scaling limit. We use the above factorization to extend this result to the class of all polygonal discretizations, that are not necessarily Temperleyan. Furthermore, we show that, quite surprisingly, the expectation of the double-dimer height function in the Temperleyan case is exactly discrete harmonic (for an appropriate choice of Laplacian) even before taking the scaling limit.

  20. 99mTc-Labeled Cyclic RGD Peptides for Noninvasive Monitoring of Tumor Integrin αvβ3 Expression

    Directory of Open Access Journals (Sweden)

    Yang Zhou

    2011-09-01

    Full Text Available This report describes the biologic evaluations of [99mTc(HYNIC-3P-RGD2(tricine(TPPTS] (99mTc-3P-RGD2: 6-hydrazinonicotinyl; 3P-RGD2 = PEG4-E[PEG4-c(RGDfK]2; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid; and TPPTS = trisodium triphenylpho-sphine-3,3′,3“-trisulfonate, [99mTc(HYNIC-3G-RGD2(tricine(TPPTS] (99mTc-3G-RGD2: 3G-RGD2 = G3-E[G3-c(RGDfK]2 and G3 = Gly-Gly-Gly, and 99mTcO(MAG2−3G-RGD2 (MAG2 = mercaptoacetylglycylglycyl as radiotracers for noninvasive imaging of tumor integrin αvβ3 expression in five xenografted tumor-bearing models. Biodistribution and imaging studies were performed in athymic nude mice bearing U87MG, MDA-MB-435, A549, HT29, or PC-3 tumor xenografts. Immunochemistry was performed using the cultured primary tumor cells and xenografted tumor tissues. It was found that the radiotracer tumor uptake followed the trend U87MG > MDA-MB-435 ≈ HT29 ≈ A549 > PC-3. The total integrin β3 expression levels followed the general trend: U87MG > MDA-MB-435 ≈ A549~HT29 > PC-3. There is a linear relationship between the radiotracer injected dose per gram tumor uptake and the total integrin β3 expression levels. On the basis of these, it was concluded that radiotracer tumor uptake is contributed by integrin αVβ3 expressed on tumor cells and activated endothelial cells of the tumor neovasculature. 99mTc-3P-RGD2 has the capability to monitor integrin αvβ3 expression in a noninvasive fashion.

  1. Enhanced tumor targeting of cRGD peptide-conjugated albumin nanoparticles in the BxPC-3 cell line.

    Science.gov (United States)

    Yu, Xinzhe; Song, Yunlong; Di, Yang; He, Hang; Fu, Deliang; Jin, Chen

    2016-08-12

    The emerging albumin nanoparticle brings new hope for the delivery of antitumor drugs. However, a lack of robust tumor targeting greatly limits its application. In this paper, cyclic arginine-glycine-aspartic-conjugated, gemcitabine-loaded human serum albumin nanoparticles (cRGD-Gem-HSA-NPs) were successfully prepared, characterized, and tested in vitro in the BxPC-3 cell line. Initially, 4-N-myristoyl-gemcitabine (Gem-C14) was formed by conjugating myristoyl to the 4-amino group of gemcitabine. Then, cRGD-HSA was synthesized using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC) cross-linkers. Finally, cRGD-Gem-HSA-NPs were formulated based on the nanoparticle albumin-bound (nab) technology. The resulting NPs were characterized for particle size, zeta potential, morphology, encapsulation efficiency, and drug loading efficiency. In vitro cellular uptake and inhibition studies were conducted to compare Gem-HSA-NPs and cRGD-Gem-HSA-NPs in a human pancreatic cancer cell line (BxPC-3). The cRGD-Gem-HSA-NPs exhibited an average particle size of 160 ± 23 nm. The encapsulation rate and drug loading rate were approximately 83 ± 5.6% and 11 ± 4.2%, respectively. In vitro, the cRGD-anchored NPs exhibited a significantly greater affinity for the BxPC-3 cells compared to non-targeted NPs and free drug. The cRGD-Gem-HSA-NPs also showed the strongest inhibitory effect in the BxPC-3 cells among all the analyzed groups. The improved efficacy of cRGD-Gem-HSA-NPs in the BxPC-3 cell line warrants further in vivo investigations.

  2. Enhanced {sup 18}F-FDG uptake in activated neutrophils is unaffected by respiratory burst inhibition with RGD

    Energy Technology Data Exchange (ETDEWEB)

    Paik, J. Y.; Lee, K. H.; Go, B. H.; Jeong, K. H.; Kim, H. K.; Choi, J. S.; Choi, Y.; Kim, P. T [Samsung Medical Center, Seoul (Korea, Republic of)

    2004-07-01

    Respiratory burst generation is an important response of activated neutrophils and is associated with enhanced glucose metabolism. Since such activation in dependent on adhesion through integrins, we investigated how integrin occupation with RGD influences respiratory burst response and {sup 18}F-FDG uptake in neutrophils. Human neutrophils separated from healthy volunteers were incubated in RPMI media. For RGD peptide inhibitory experiments, neutrophils were preincubated with 200 {mu} g/ml of cRGD peptides ad 37.deg. for 2 hr prior. Respiratory burst generation and uptake of {sup 18}F-FDG was then measured with or without PMA stimulation. Cellular total hexokinase levels were assayed with a colorimetric method. Treatment with RGD in the basal state resulted in a significant but relatively small increase in neutrophil superoxide release to 1.5{+-}0.25 fold o control levels (p<0.005). Whereas PMA stimulation caused a marked increase in superoxide generation, pretreatment with RGD caused a significant attenuation of this response to 35.6{+-}0.2% (p<0.005). PMA stimulation resulted in a significant increase in {sup 18}F-FDG uptake. However, unlike the attenution of superoxide generation, neutrophils pretreated with RGD before PMA stimulation showed an identical magnitude of enhanced {sup 18}F-FDG uptake (201.8{+-}20.5 of controls, p=0.0001). In addition, hexokinase levels were increased to comparable levels of approximately 1.5 fold for PMA stimulated neutrophils irrespective of RGD pretreatment. In conclusion, soluble RGD blocks stimulation of respiratory burst activation in neutrophils but does not inhibit stimulation of cellular glucose metabolism. This dissociation may contribute to maximally enhanced neutrophil FDG uptake in inflammatory lesions regardless of the occupancy of their integrin receptors.

  3. Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA

    Directory of Open Access Journals (Sweden)

    Jing Hu

    2016-05-01

    Full Text Available To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD and a bifunctional R11 (RGD-NLS, which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100–280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18. More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector.

  4. The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is mediated by tumor-specific immunity.

    Directory of Open Access Journals (Sweden)

    Anne Kleijn

    Full Text Available The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy.

  5. RGD Peptide-Grafted Graphene Oxide as a New Biomimetic Nano interface for Impedance-Monitoring Cell Behaviors

    International Nuclear Information System (INIS)

    Li, J.; Zheng, L.; Zeng, L.; Zhang, Y.; Jiang, L.; Song, J.; Li, J.; Zheng, L.; Song, J.; Li, J.; Zheng, L.; Song, J.

    2016-01-01

    A new biomimetic nano interface was constructed by facile grafting the bioactive arginylglycylaspartic acid (RGD) peptide on the graphene oxide (GO) surface through carbodiimide and N-hydroxysuccinimide coupling amidation reaction. The formed RGD-GO nano composites own unique two-dimensional structure and desirable electrochemical performance. The linked RGD peptides could improve GO∼s biocompatibility and support the adhesion and proliferation of human periodontal ligament fibroblasts (HPLFs) on RGD-GO biofilm surface. Furthermore the biologically active RGD-GO nano composites were demonstrated as a potential biomimetic nano interface for monitoring cell bio behaviors by electrochemical impedance spectroscopy (EIS). By analysis of the data obtained from equivalent circuit-fitting impedance spectroscopy, the information related to cell membrane capacitance, cell-cell gap resistance, and cell-electrode interface gap resistance in the process of cell adhesion and proliferation could be obtained. Besides, this proposed impedance-based cell sensor could be used to assess the inhibition effect of the lipopolysaccharide (LPS) on the HPLFs proliferation. Findings from this work suggested that RGD peptide functionalized GO nano materials may be not only applied in dental tissue engineering but also used as a sensor interface for electrochemical detection and analysis of cell behaviors in vitro.

  6. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang Seok; Hong, Suck Won; Han, Dong Wook; Kim, Chun Tae; Oh, Jin Woo [Pusan National University, Busan (Korea, Republic of)

    2015-01-15

    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic-co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

  7. Imaging of 99Tcm-labeled new cyclic RGDfK Dimer in nude mice bearing U87MG human glioma xenografts

    International Nuclear Information System (INIS)

    Jin Xiao'an; Shi Jiyun; Liu Yan; Zhu Zhaohui; Jia Bing; Liu Zhaofei; Shi Ximin; Wang Fan; Li Fang

    2010-01-01

    Objective: (1) To evaluate the effect of insertion of two 15-amino-4, 7, 10, 13-tetraoxapentadecanoic (2 PEG 4 ) linkers into cyclic Arg-Gly-Asp (RGD) Dimer E [c(RGDfK)] 2 on receptor binding in vitro, (2) to assess its biodistribution in vivo and (3) to investigate the value of 99 Tc m labeled 2PEG 4 -Dimer for integrin α v β 3 -positive tumors imaging. Methods: The expression of U87 human glioma cells and integrin α v β 3 was determined by immunofluorescence staining. The half-inhibition concentrations (IC 50 ) for 125 I-cyclo (Arg-Gly-Asp-D-Tyr-Lys) (c(RGDyK)) of c (RGDyK), hydrazinonictinamide (HYNIC)-Dimer and HYNIC-2PEG 4 -Dimer binding to integrin α v β 3 were measured. 99 Tc m -HYNIC-Dimer and 99 Tc m -HYNIC-2PEG 4 -Dimer were synthesized using non-SnCl 2 formulation. Biodistribution and imaging studies were performed in nude mice bearing human glioma xenografts. The unpaired t test was used for statistical analysis. Results: The labeling yield of the two radiotracers was more than 95%, and the radiochemical purity was more than 99% through Sep-Pek C18 cartridge. HYNIC-2PEG 4 -Dimer had significantly higher binding affinity of integrin α v β 3 than c(RGDyK) and HYNIC-Dimer (IC 50 =0.8 nmol/L, 27 nmol/L and 2.4 nmol/L, respectively). Biodistribution study showed that 99 Tc m -HYNIC-2PEG 4 -Dimer was mainly excreted via the kidney. The tumor uptake of 99 Tc m -HYNIC-2PEG 4 -Dimer was higher than that of 99 Tc m -HYNIC-Dimer at 2 h post injection ((5.71±0.96) and (2.10±0.50) % ID/g, t =4.80, P 99 Tc m -HYNIC-2PEG 4 -Dimer is a promising radiotracer for integrin α v β 3 -positive tumor imaging. (authors)

  8. Covalent Grafting of the RGD-Peptide onto Polyetheretherketone Surfaces via Schiff Base Formation

    Directory of Open Access Journals (Sweden)

    Marc Becker

    2013-01-01

    Full Text Available In recent years, the synthetic polymer polyetheretherketone (PEEK has increasingly been used in a number of orthopedic implementations, due to its excellent mechanical properties, bioinertness, and chemical resistance. For in vivo applications, the surface of PEEK, which does not naturally support cell adhesion, has to be modified to improve tissue integration. In the present work we demonstrate a novel wet-chemical modification of PEEK to modify the surface, enabling the covalent grafting of the cell-adhesive RGD-peptide. Modification of the polymer surface was achieved via Schiff base formation using an aliphatic diamine and subsequent crosslinker-mediated immobilization of the peptide. In cell culture experiments with primary osteoblasts it was shown that the RGD-modified PEEK not only significantly promoted cellular adhesion but also strongly enhanced the proliferation of osteoblasts on the modified polymer surface.

  9. The Adenovirus Type 3 Dodecahedron's RGD Loop Comprises an HSPG Binding Site That Influences Integrin Binding

    Directory of Open Access Journals (Sweden)

    E. Gout

    2010-01-01

    Full Text Available Human type 3 adenovirus dodecahedron (a virus like particle made of twelve penton bases features the ability to enter cells through Heparan Sulphate Proteoglycans (HSPGs and integrins interaction and is used as a versatile vector to deliver DNA or proteins. Cryo-EM reconstruction of the pseudoviral particle with Heparan Sulphate (HS oligosaccharide shows an extradensity on the RGD loop. A set of mutants was designed to study the respective roles of the RGD sequence (RGE mutant and of a basic sequence located just downstream. Results showed that the RGE mutant binding to the HS deficient CHO-2241 cells was abolished and unexpectedly, mutation of the basic sequence (KQKR to AQAS dramatically decreased integrin recognition by the viral pseudoparticle. This basic sequence is thus involved in integrin docking, showing a close interplay between HSPGs and integrin receptors.

  10. An iRGD Based Strategy to Study Electrochemically the Species Inside a Cell

    Directory of Open Access Journals (Sweden)

    Genxi Li

    2012-08-01

    Full Text Available This paper reports a method for electrical communication between the inner part of cells and an electrode with the help of iRGD peptide. Due to the enhancement of the cell penetration caused by iRGD peptide, DNA molecules, previously modified on a gold electrode surface, can be easily transfected into the cells. At the same time, doxorubicin, an anticancer drug, can also be transfected into cells with high penetration. Consequently, doxorubicin binds to DNA chains through electrostatic interaction, and the redox reaction is transferred out of the cell across the cell membrane. As a result, this work may provide a novel way to get information from inside of cells.

  11. Rubidium dimers in paraffin-coated cells

    International Nuclear Information System (INIS)

    Acosta, V M; Windes, D; Corsini, E; Ledbetter, M P; Karaulanov, T; Budker, D; Jarmola, A; Auzinsh, M; Rangwala, S A; Jackson Kimball, D F

    2010-01-01

    Measurements were made to determine the density of rubidium dimer vapor in paraffin-coated cells. The number density of dimers and atoms in similar paraffin-coated and uncoated cells was measured by optical spectroscopy. Due to the relatively low melting point of paraffin, a limited temperature range of 43-80 0 C was explored, with the lower end corresponding to a dimer density of less than 10 7 cm -3 . With 1 min integration time, a sensitivity to dimer number density of better than 10 6 cm -3 was achieved. No significant difference in dimer density between the cells was observed.

  12. Bio-compatibility of ion beam-modified and RGD-grafted polyethylene

    Czech Academy of Sciences Publication Activity Database

    Ročková-Hlaváčková, K.; Švorčík, V.; Bačáková, Lucie; Dvořánková, B.; Heitz, J.; Hnatowicz, Vladimír

    2004-01-01

    Roč. 225, č. 3 (2004), s. 275-282 ISSN 0168-583X R&D Projects: GA AV ČR IAA5011301; GA ČR GA106/03/0514 Grant - others:CZ-AT(CZ) Aktion 2002-7 Institutional research plan: CEZ:AV0Z5011922 Keywords : modified polyethylene * ion beam * RGD grafting Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.997, year: 2004

  13. Fiber optic D dimer biosensor

    Science.gov (United States)

    Glass, Robert S.; Grant, Sheila A.

    1999-01-01

    A fiber optic sensor for D dimer (a fibrinolytic product) can be used in vivo (e.g., in catheter-based procedures) for the diagnosis and treatment of stroke-related conditions in humans. Stroke is the third leading cause of death in the United States. It has been estimated that strokes and stroke-related disorders cost Americans between $15-30 billion annually. Relatively recently, new medical procedures have been developed for the treatment of stroke. These endovascular procedures rely upon the use of microcatheters. These procedures could be facilitated with this sensor for D dimer integrated with a microcatheter for the diagnosis of clot type, and as an indicator of the effectiveness, or end-point of thrombolytic therapy.

  14. Singlet fission in pentacene dimers

    Science.gov (United States)

    Zirzlmeier, Johannes; Lehnherr, Dan; Coto, Pedro B.; Chernick, Erin T.; Casillas, Rubén; Basel, Bettina S.; Thoss, Michael; Tykwinski, Rik R.; Guldi, Dirk M.

    2015-01-01

    Singlet fission (SF) has the potential to supersede the traditional solar energy conversion scheme by means of boosting the photon-to-current conversion efficiencies beyond the 30% Shockley–Queisser limit. Here, we show unambiguous and compelling evidence for unprecedented intramolecular SF within regioisomeric pentacene dimers in room-temperature solutions, with observed triplet quantum yields reaching as high as 156 ± 5%. Whereas previous studies have shown that the collision of a photoexcited chromophore with a ground-state chromophore can give rise to SF, here we demonstrate that the proximity and sufficient coupling through bond or space in pentacene dimers is enough to induce intramolecular SF where two triplets are generated on one molecule. PMID:25858954

  15. [The Influence of New Medium with RGD on Cell Growth,Cell Fusion and Expression of Exogenous Gene].

    Science.gov (United States)

    Wang, Pei-Pei; Wei, Da-Peng; Zhu, Tong-Bo

    2018-03-01

    To investigate the influence of a new culture medium added with RGD on cell growth,cell fusion and expression of exogenous gene. A new medium was prepared by adding different concentrations of RGD to ordinary culture medium. The optimum concentration of RGD was determined by observation of the growth of human pancreatic epithelial cell line HPDE6-C7. After determining the optimum concentration of RGD,different concentrations of cells HPDE6-C7 (5×10 4 ,10 5 ,5×10 5 mL -1 ) were inoculated in the two mediums. The morphology,adherence,growth and density of the cells were observed by inverted microscope; The ratio of clone formation and the positive rate of cloning were compared between the two cultures after fusion; The fluorescence intensity after the transfection of plasmid with green fluorescent protein ( GFP ) and the protein expression after transfection of plasmid with KRAS were observed to campare the expression of exogenous genes between the new medium with ordinary medium. Firstly,the optimal concentration of RGD was 10 ng/mL. Compared with the normal medium,the cultured cells with RGD had better morphology,adhesion and faster proliferation. In addition,both of the number and positive rate of clones formed in the new medium were significantly higher than that in the ordinary medium ( P exogenous gene GFP in the new medium was significantly higher than that in normal medium ( P exogenous gene KRAS of the new medium was also significantly higher than that in normal medium. The new culture medium has highlighted advantages in cell growth,cell fusion and expression of exogenous genes. RGD peptide has widely prospect and potential value in the cell culture. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

  16. Integrin specificity and enhanced cellular activities associated with surfaces presenting a recombinant fibronectin fragment compared to RGD supports.

    Science.gov (United States)

    Petrie, Timothy A; Capadona, Jeffrey R; Reyes, Catherine D; García, Andrés J

    2006-11-01

    Biomimetic strategies focusing on presenting short bioadhesive oligopeptides, including the arginine-glycine-aspartic acid (RGD) motif present in numerous adhesive proteins, on a non-fouling support have emerged as promising approaches to improve cellular activities and healing responses. Nevertheless, these bio-inspired strategies are limited by low activity of the oligopeptides compared to the native ligand due to the absence of complementary or modulatory domains. In the present analysis, we generated well-defined biointerfaces presenting RGD-based ligands of increasing complexity to directly compare their biological activities in terms of cell adhesion strength, integrin binding and signaling. Mixed self-assembled monolayers of alkanethiols on gold were optimized to engineer robust supports that present anchoring groups for ligand tethering within a non-fouling, protein adsorption-resistant background. Controlled bioadhesive interfaces were generated by tethering adhesive ligands via standard peptide chemistry. On a molar basis, biointerfaces functionalized with the FNIII7-10 recombinant fragment presenting the RGD and PHSRN adhesive motifs in the correct structural context exhibited significantly higher adhesion strength, FAK activation, and cell proliferation rate than supports presenting RGD ligand or RGD-PHSRN, an oligopeptide presenting these two sites separated by a polyglycine linker. Moreover, FNIII7-10-functionalized surfaces displayed specificity for alpha5beta1 integrin, while cell adhesion to supports presenting RGD or RGD-PHSRN was primarily mediated by alphavbeta3 integrin. These results are significant to the rational engineering of bioactive materials that convey integrin binding specificity for directed cellular and tissue responses in biomedical and biotechnological applications.

  17. Fetal muscle gene transfer is not enhanced by an RGD capsid modification to high-capacity adenoviral vectors.

    Science.gov (United States)

    Bilbao, R; Reay, D P; Hughes, T; Biermann, V; Volpers, C; Goldberg, L; Bergelson, J; Kochanek, S; Clemens, P R

    2003-10-01

    High levels of alpha(v) integrin expression by fetal muscle suggested that vector re-targeting to integrins could enhance adenoviral vector-mediated transduction, thereby increasing safety and efficacy of muscle gene transfer in utero. High-capacity adenoviral (HC-Ad) vectors modified by an Arg-Gly-Asp (RGD) peptide motif in the HI loop of the adenoviral fiber (RGD-HC-Ad) have demonstrated efficient gene transfer through binding to alpha(v) integrins. To test integrin targeting of HC-Ad vectors for fetal muscle gene transfer, we compared unmodified and RGD-modified HC-Ad vectors. In vivo, unmodified HC-Ad vector transduced fetal mouse muscle with four-fold higher efficiency compared to RGD-HC-Ad vector. Confirming that the difference was due to muscle cell autonomous factors and not mechanical barriers, transduction of primary myogenic cells isolated from murine fetal muscle in vitro demonstrated a three-fold better transduction by HC-Ad vector than by RGD-HC-Ad vector. We hypothesized that the high expression level of coxsackievirus and adenovirus receptor (CAR), demonstrated in fetal muscle cells both in vitro and in vivo, was the crucial variable influencing the relative transduction efficiencies of HC-Ad and RGD-HC-Ad vectors. To explore this further, we studied transduction by HC-Ad and RGD-HC-Ad vectors in paired cell lines that expressed alpha(v) integrins and differed only by the presence or absence of CAR expression. The results increase our understanding of factors that will be important for retargeting HC-Ad vectors to enhance gene transfer to fetal muscle.

  18. A direct radiolabeling of 99Tcm cyclic RGD peptide, an antagonist of αvβ3 receptor

    International Nuclear Information System (INIS)

    Li Qianwei; Liu Guangyuan; Liu Kaiyuan; Huang Dingde; Xie Ganfeng

    2007-01-01

    Objective: It has been reported that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Lys-Cys (RGD) peptides, as integrin α v β 3 receptor antagonists, might inhibit angiogenesis of tumor. The aim of the present study was to investigate the feasibility of direct labeling of 99 Tc m to a cyclic nine peptide containing RGD sequence (RGD-4CK), to observe the effects of different conditions on labeling efficiency, and to evaluate the radiochemical property of 99 Tc m -RGD-4CK. Methods: The peptide RGD-4CK contained the sequence of Cys-Asp-Cys-Arg-Gly-Asp-Cys-Lys-Cys. It was labeled directly by 99 Tc m with 'pretinning' method. The Rf value of 99 Tc m -RGD-4CK and 99 Tc m O 4 were determined in 3 MM paper chromatography. The labeling efficiency and specific activity were calculated. The influences of various conditions to the labeling rate were studied. High performance liquid chromatography (HPLC) analysis and Sep-Pak C18 chromatography were used to assess the property of radiolabeled 99 Tc m -RGD-4CK. The stability in vitro, the cysteine replacement and the serum protein combination were also tested. Results: The Rf values of 99 Tc m -RGD-4CK were 0 and 0.8-0.9 respectively in mobile phase of acetone and V(NH 4 OH): V(ethanol): V(water) = 1: 2: 5. The radiochemical yield was (97.8±0.4)% and the specific activity (11.90±0.05) TBq/mmol in the basic condition of labeling. The labeling efficiency remained over 95% under the condition of 150-300 μg stannous tartrate, pH value 2.0-3.5, temperature 60 degree C and incubation time over 6 h in the process of pretinning reaction, the activity of 99 Tc m O 4 - was 37-185 MBq within volume of 200 μl. With the labeling temperature of 95 degree C in 30 min, the retention of 99 Tc m -RGD-4CK was in accordance with the major peak of time-activity curve from the analytical HPLC. The radiochemical purity of 99 Tc m -RGD-4CK remained above 95% after 6 h at room temperature. The amount of 99 Tc m O 4 - ; increased only by 0.5% as measured with Sep

  19. Crowd-Sourced Mobility Mapping for Location Tracking Using Unlabeled Wi-Fi Simultaneous Localization and Mapping

    Directory of Open Access Journals (Sweden)

    Mu Zhou

    2015-01-01

    Full Text Available Due to the increasing requirements of the seamless and round-the-clock Location-based services (LBSs, a growing interest in Wi-Fi network aided location tracking is witnessed in the past decade. One of the significant problems of the conventional Wi-Fi location tracking approaches based on received signal strength (RSS fingerprinting is the time-consuming and labor intensive work involved in location fingerprint calibration. To solve this problem, a novel unlabeled Wi-Fi simultaneous localization and mapping (SLAM approach is developed to avoid the location fingerprinting and additional inertial or vision sensors. In this approach, an unlabeled mobility map of the coverage area is first constructed by using the crowd-sourcing from a batch of sporadically recorded Wi-Fi RSS sequences based on the spectral cluster assembling. Then, the sequence alignment algorithm is applied to conduct location tracking and mobility map updating. Finally, the effectiveness of this approach is verified by the extensive experiments carried out in a campus-wide area.

  20. Effect of unlabelled monoclonal antibody (MoAb) on biodistribution of /sup 111/Indium labelled (MoAb)

    Energy Technology Data Exchange (ETDEWEB)

    Lamki, L M; Murray, J L; Rosenblum, M G; Patt, Y Z; Babaian, Richard; Unger, M W

    1988-08-01

    We have evaluated immunoscintigraphy in cancer patients using four /sup 111/In-labelled murine monoclonal antibodies (MoAb): 96.5 (anti-P97 of melanoma), ZME-018 (anti-high molecular weight antibody of melanoma), ZCE-025 (anti-CEA for colon cancer) and PAY-276 (anti-prostatic acid phosphatase for prostatic cancer). The effect of increasing the doses of unlabelled MoAb (co-infused with 1 mg labelled MoAb) on the relative body distribution of each labelled MoAb was assessed. Localization in the liver decreased significantly in all cases, with increasing MoAb dose, except for ZME-018. Localization in other organs increased significantly as the liver activity decreased. The spleen activity, however, fell in the case of MoAb ZME-018. Blood-pool activity increased with MoAb dose in all four MoAbs. These findings correlated with the rise in the detection rate of metastases, the plasma half-life, and other pharmacokinetic parameters. However, the dose level at which this correlation occurred varied with each antibody. These data demonstrate the co-infusion of unlabelled MoAb with /sup 111/In-labelled MoAb could alter the organ distribution, pharmacokinetics and tumour uptake in a favourable manner, though the degree to which this occurs depends on the antibody in question.

  1. Identification of TNIP1 Polymorphisms by High Resolution Melting Analysis with Unlabelled Probe: Association with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2012-01-01

    Full Text Available Background. TNFα-induced protein 3 (TNFAIP3 interacting with protein 1 (TNIP1 acts as a negative regulator of NF-κB and plays an important role in maintaining the homeostasis of immune system. A recent genome-wide association study (GWAS showed that the polymorphism of TNIP1 was associated with the disease risk of SLE in Caucasian. In this study, we investigated whether the association of TNIP1 with SLE was replicated in Chinese population. Methods. The association of TNIP1 SNP rs7708392 (G/C was determined by high resolution melting (HRM analysis with unlabeled probe in 285 SLE patients and 336 healthy controls. Results. A new SNP rs79937737 located on 5 bp upstream of rs7708392 was discovered during the HRM analysis. No association of rs7708392 or rs79937737 with the disease risk of SLE was found. Furthermore, rs7708392 and rs79937737 were in weak linkage disequilibrium (LD. Hypotypes analysis of the two SNPs also showed no association with SLE in Chinese population. Conclusions. High resolution melting analysis with unlabeled probes proves to be a powerful and efficient genotyping method for identifying and screening SNPs. No association of rs7708392 or rs79937737 with the disease risk of SLE was observed in Chinese population.

  2. Effect of linkers on the αvβ3 integrin targeting efficiency of cyclic RGD-conjugates

    Science.gov (United States)

    Karmakar, Partha; Grabowska, Dorota; Sudlow, Gail; Ziabrev, Kostiantyn; Sanyal, Nibedita; Achilefu, Samuel

    2018-02-01

    Cyclic arginine-glycine-aspartic acid (cRGD) peptides are well known to target ανβ3 integrin expressed on cancer cells and neovasculature. Conjugation of these peptides with dyes, drugs, antibodies and other biomolecules through covalent linkers provides a facile way to deliver these products to tumor cells for targeted cancer therapy and diagnosis. Click chemistry and acid-amine couplings are widely used conjugation strategies. However, the effects of different linkers and the distance between the cRGD and the conjugates on the binding of cRGD ligand with ανβ3 has been underexplored. In this present study, we prepared cRGD-conjugates using different linkers and determined how they altered the tumor targeting efficiency in vitro and in vivo. The results demonstrate that different linkers significantly altered the pharmacokinetics of the cRGD conjugates and the tumor uptake kinetics. Unlike large antibodies, this preliminary finding shows that linkers used to attach drugs and fluorescent molecular probes to small peptides play a major role in the accuracy of tumor targeting and treatment outcomes. As a result, considerable attention should be paid to the nature of linkers used in the design of molecular probes and targeted therapeutics.

  3. Evaluation of RGD-targeted albumin carriers for specific delivery of auristatin E to tumor blood vessels.

    Science.gov (United States)

    Temming, Kai; Meyer, Damon L; Zabinski, Roger; Dijkers, Eli C F; Poelstra, Klaas; Molema, Grietje; Kok, Robbert J

    2006-01-01

    Induction of apoptosis in endothelial cells is considered an attractive strategy to therapeutically interfere with a solid tumor's blood supply. In the present paper, we constructed cytotoxic conjugates that specifically target angiogenic endothelial cells, thus preventing typical side effects of apoptosis-inducing drugs. For this purpose, we conjugated the potent antimitotic agent monomethyl-auristatin-E (MMAE) via a lysosomal cleavable linker to human serum albumin (HSA) and further equipped this drug-albumin conjugate with cyclic c(RGDfK) peptides for multivalent interaction with alphavbeta3-integrin. The RGD-peptides were conjugated via either an extended poly(ethylene glycol) linker or a short alkyl linker. The resulting drug-targeting conjugates RGDPEG-MMAE-HSA and RGD-MMAE-HSA demonstrated high binding affinity and specificity for alphavbeta3-integrin expressing human umbilical vein endothelial cells (HUVEC). Both types of conjugates were internalized by endothelial cells and killed the target cells at low nM concentrations. Furthermore, we observed RGD-dependent binding of the conjugates to C26 carcinoma. Upon i.v. administration to C26-tumor bearing mice, both drug-targeting conjugates displayed excellent tumor homing properties. Our results demonstrate that RGD-modified albumins are suitable carriers for cell selective intracellular delivery of cytotoxic compounds, and further studies will be conducted to assess the antivascular and tumor inhibitory potential of RGDPEG-MMAE-HSA and RGD-MMAE-HSA.

  4. Fabrication and in vitro evaluation of the collagen/hyaluronic acid PEM coating crosslinked with functionalized RGD peptide on titanium.

    Science.gov (United States)

    Huang, Ying; Luo, Qiaojie; Li, Xiaodong; Zhang, Feng; Zhao, Shifang

    2012-02-01

    Surface modification of titanium (Ti) using biomolecules has attracted much attention recently. In this study, a new strategy has been employed to construct a stable and bioactive coating on Ti. To this end, a derivative of hyaluronic acid (HA), i.e. HA-GRGDSPC-(SH), was synthesized. The disulfide-crosslinked Arg-Gly-Asp (RGD)-containing collagen/hyaluronic acid polyelectrolyte membrane (PEM) coating was then fabricated on Ti through the alternate deposition of collagen and HA-GRGDSPC-(SH) with five assembly cycles and subsequent crosslinking via converting free sulphydryl groups into disulfide linkages (RGD-CHC-Ti group). The assembly processes for PEM coating and the physicochemical properties of the coating were carefully characterized. The stability of PEM coating in phosphate-buffered saline solution could be adjusted by the crosslinking degree, while its degradation behaviors in the presence of glutathione were glutathione concentration dependent. The adhesion and proliferation of MC3T3-E1 cells were significantly enhanced in the RGD-CHC-Ti group. Up-regulated bone specific genes, enhanced alkaline phosphatase activity and osteocalcin production, the increased areas of mineralization were also observed in the RGD-CHC-Ti group. These results indicate that the strategy employed herein may function as an effective way to construct stable, RGD-containing bioactive coatings on Ti. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Strain mediated interaction of adatom dimers

    OpenAIRE

    Kappus, Wolfgang

    2013-01-01

    An earlier model for substrate strain mediated interactions between monomer adatoms is extended to the interaction of monomers with dimers and the interaction of dimers. While monomers (sitting on high symmetric sites) are supposed to create isotropic stress on the substrate, dimers would create anisotropic stress caused by stretching their bond. Resulting interactions are strongly angle dependent and also reflect the elastic anisotropy of the substrate. The applicability of a continuum elast...

  6. Formic acid dimers in a nitrogen matrix

    Science.gov (United States)

    Lopes, Susy; Fausto, Rui; Khriachtchev, Leonid

    2018-01-01

    Formic acid (HCOOH) dimers are studied by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. We benefit from the use of a nitrogen matrix where the lifetime of the higher-energy (cis) conformer is very long (˜11 h vs. 7 min in an argon matrix). As a result, in a nitrogen matrix, a large proportion of the cis conformer can be produced by vibrational excitation of the lower-energy (trans) conformer. Three trans-trans, four trans-cis, and three cis-cis dimers are found in the experiments. The spectroscopic information on most of these dimers is enriched compared to the previous studies in an argon matrix. The cis-cis dimers of ordinary formic acid (without deuteration) are reported here for the first time. Several conformational processes are obtained using selective excitation by infrared light, some of them also for the first time. In particular, we report on the formation of cis-cis dimers upon vibrational excitation of trans-cis dimers. Tunneling decays of several dimers have been detected in the dark. The tunneling decay of cis-cis dimers of formic acid as well as the stabilization of cis units in cis-cis dimers is also observed for the first time.

  7. The anti-tumor effects of the recombinant toxin protein rLj-RGD3 from Lampetra japonica on pancreatic carcinoma Panc-1 cells in nude mice.

    Science.gov (United States)

    Wang, Yue; Zheng, Yuanyuan; Tu, Zuoyu; Dai, Yongguo; Xu, Hong; Lv, Li; Wang, Jihong

    2017-02-01

    Recombinant Lampetra japonica RGD peptide (rLj-RGD3) is a soluble toxin protein with three RGD (Arg-Gly-Asp) motifs and a molecular weight of 13.5kDa. The aim of this study was to investigate the effects and mechanisms of rLj-RGD3 on tumor growth and survival in pancreatic carcinoma Panc-1 cell-bearing mice. A Panc-1 human pancreatic carcinoma-bearing nude mouse model was successfully generated, and the animals were treated with different doses of rLj-RGD3 for 3 weeks. The volume and weight of the subcutaneous tumors, the survival of the nude mice, histopathological changes, the intratumoral MVD, the number of apoptotic Panc-1 cells, and apoptosis-related proteins and gene expressions were determined. rLj-RGD3 significantly decreased the tumor volumes and weights, and the maximum tumor volume and weight IR values were 53.2% (pPanc-1-bearing nude mice treated with rLj-RGD3 was increased by 56.3% (pPanc-1 cells in a nude mouse model, implying that rLj-RGD3 may serve as a potent clinical therapeutic agent for human pancreatic carcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 68Ga- and 111In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

    International Nuclear Information System (INIS)

    Decristoforo, Clemens; Hernandez Gonzalez, Ignacio; Rupprich, Marco; Virgolini, Irene; Carlsen, Janette; Huisman, Marc; Wester, Hans-Juergen; Haubner, Roland

    2008-01-01

    αvβ3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [ 18 F]Galacto-RGD that monitoring of αvβ3 expression is feasible. Here, we introduce 68 Ga- and 111 In-labelled derivatives and compare them with [ 18 F]Galacto-RGD. For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, αvβ3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (αvβ3 positive) and M21-L (αvβ3 negative) cells were used. Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [ 68 Ga]DOTA-RGD and only up to 1.4% for [ 111 In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in αvβ3-positive tumours was 2.9 ± 0.3%ID/g and in αvβ3-negative tumours 0.8 ± 0.1%ID/g for [ 68 Ga]DOTA-RGD ([ 111 In]DOTA-RGD: 1.9 ± 0.3%ID/g and 0.5 ± 0.2%ID/g; [ 18 F]Galacto-RGD: 1.6 ± 0.2%ID/g and 0.4 ± 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [ 68 Ga]DOTA-RGD, tumour/blood ratios were higher for [ 111 In]DOTA-RGD and [ 18 F]Galacto-RGD. However, microPET studies demonstrated that visualisation of αvβ3-positive tumours using [ 68 Ga]DOTA-RGD is possible. Our data indicate that [ 68 Ga]DOTA-RGD allows monitoring of αvβ3 expression. Especially, the much easier radiosynthesis compared to [ 18 F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [ 18 F]Galacto-RGD remains superior for imaging αvβ3 expression. Introduction of alternative chelator

  9. cRGD-installed docetaxel-loaded mertansine prodrug micelles: redox-triggered ratiometric dual drug release and targeted synergistic treatment of B16F10 melanoma

    Science.gov (United States)

    Zhong, Ping; Qiu, Min; Zhang, Jian; Sun, Huanli; Cheng, Ru; Deng, Chao; Meng, Fenghua; Zhong, Zhiyuan

    2017-07-01

    Combinatorial chemotherapy, which has emerged as a promising treatment modality for intractable cancers, is challenged by a lack of tumor-targeting, robust and ratiometric dual drug release systems. Here, docetaxel-loaded cRGD peptide-decorated redox-activable micellar mertansine prodrug (DTX-cRGD-MMP) was developed for targeted and synergistic treatment of B16F10 melanoma-bearing C57BL/6 mice. DTX-cRGD-MMP exhibited a small size of ca. 49 nm, high DTX and DM1 loading, low drug leakage under physiological conditions, with rapid release of both DTX and DM1 under a cytoplasmic reductive environment. Notably, MTT and flow cytometry assays showed that DTX-cRGD-MMP brought about a synergistic antitumor effect to B16F10 cancer cells, with a combination index of 0.37 and an IC50 over 3- and 13-fold lower than cRGD-MMP (w/o DTX) and DTX-cRGD-Ms (w/o DM1) controls, respectively. In vivo studies revealed that DTX-cRGD-MMP had a long circulation time and a markedly improved accumulation in the B16F10 tumor compared with the non-targeting DTX-MMP control (9.15 versus 3.13% ID/g at 12 h post-injection). Interestingly, mice treated with DTX-cRGD-MMP showed almost complete growth inhibition of B16F10 melanoma, with tumor inhibition efficacy following an order of DTX-cRGD-MMP > DTX-MMP (w/o cRGD) > cRGD-MMP (w/o DTX) > DTX-cRGD-Ms (w/o DM1) > free DTX. Consequently, DTX-cRGD-MMP significantly improved the survival rates of B16F10 melanoma-bearing mice. Importantly, DTX-cRGD-MMP caused little adverse effects as revealed by mice body weights and histological analyses. The combination of two mitotic inhibitors, DTX and DM1, appears to be an interesting approach for effective cancer therapy.

  10. Libraries of RGD analogs, labeled through ReO3+ or TcO3+ coordination, targeting αVβ3 integrin: development of tracers for the early detection of tumor neo-angiogenesis

    International Nuclear Information System (INIS)

    Aufort, M.

    2008-11-01

    Integrins form a family of hetero-dimeric integral glycoproteins which play a central role in cell-cell adhesion and cell-matrix interactions. In particular, they are over expressed during tumor neo-angiogenesis. About 10 of them recognize a structured RGD (Arg-Gly-Asp) sequence. Analogs of this sequence can be used for the early detection of tumors and metastases. We developed new tracers, labeled with 99m Tc, for the molecular imaging of α V β 3 integrin. Until recently, there was no reliable ab initio structure prediction of complex molecules containing Re and Tc chelates. Therefore, we preferred a combinatorial approach to develop potential ligands of α V β 3 integrin and we attempted to identify efficient tracers by in vivo screening. This method would account for biodistribution and pharmacokinetics properties in the early steps of the study. Tracers were obtained according two strategies: i) cyclization of linear RGD analogs; ii) combinatorial assembling of independent modules through metal core coordination by the well-known NS 2 +S motif. After synthesis and labeling, the stability of the tracers was investigated in presence of glutathione and in murine plasma. In vitro screening on purified integrin showed that a cyclic rhenium coordinate binds specifically α V β 3 . A tumor model (U87-MG tumor on nude mice) was validated in the laboratory and a method was developed to analyze in vivo experiments. Biodistribution data and percentage of activity found in tumors are encouraging for cyclic compounds though identification of efficient tracers is difficult due to their instability in the conditions of analyses. (author)

  11. Computational study of the RGD-peptide interactions with perovskite-type BFO-(1 1 1) membranes under aqueous conditions

    Science.gov (United States)

    Li, Hai-long; Bian, Liang; Hou, Wen-ping; Dong, Fa-Qin; Song, Mian-Xin; Zhang, Xiao-yan; Wang, Li-sheng

    2016-07-01

    We elucidated a number of facets regarding arginine-glycine-aspartate (RGD)-bismuth ferrite (BFO)-(1 1 1) membrane interactions and reactivity that have previously remained unexplored on a molecular level. Results demonstrate the intra-molecular interaction facilitates a ;horseshoe; structure of RGD adsorbed onto the BFO-(1 1 1) membrane, through the electrostatic (Asp-cation-Fe) and water-bridge (Osbnd H2O and H2Osbnd NH2) interactions. The effect of structural and electron-transfer interactions is attributed to the cation-valences, indicating that the divalent cations are electron-acceptors and the monovalent cations as electron-donors. Notably, the strongly bound Ca2+ ion exerts a ;gluing; effect on the Asp-side-chain, indicating a tightly packed RGD-BFO configuration. Thus, modulating the biological response of BFO-(1 1 1) membrane will allow us to design more appropriate interfaces for implantable diagnostic and therapeutic perovskite-type micro-devices.

  12. Enhancing osteogenic differentiation of MC3T3-E1 cells by immobilizing RGD onto liquid crystal substrate

    International Nuclear Information System (INIS)

    Wu, Shaopeng; Yang, Xiaohui; Li, Wenqiang; Du, Lin; Zeng, Rong; Tu, Mei

    2017-01-01

    To understand the effects of GRGDF modification on MC3T3-E1 cell behavior, we cultured these cells onto a biomimetic liquid crystalline matrix modified with GRGDF peptide (OPC-GA-RGD). Successful immobilization of GRGDF on the liquid crystalline surface was verified by fluorescent labeling, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). OPC-GA-RGDs retained its liquid crystalline feature after surface modification. The RGD-immobilized OPC substrate was hardly beneficial to initial cell adhesion but could support long-term cell survival. The enhancement in cell proliferation did not correlate with RGD density. The lower GRGDF density immobilized on the liquid crystalline OPC matrix (OPC-GA-RGD3) promoted cell adhesion, proliferation, ALP expression level and mineralization, suggesting that both the viscoelasticity-based mechanical stimuli and receptor/ligand-based biochemical cue synergistically modulate MC3T3-E1 cell behavior. - Highlight: • A novel type of GRGDF-immobilized liquid crystalline matrices was fabricated and served as a substrate for the in vitro culture of MC3T3-E1 cells. • The lower RGD density might provide a better condition for initial cell adhesion and proliferation, up-regulation of ALP expression levels, and mineralization. • The intrinsic liquid crystalline feature of OPC matrix, instead of RGD efficiency, promoted initial cell adhesion. • Properties of the liquid crystalline OPC matrix together with the stable receptor-ligand binging synergistically modulated MC3T3-E1 cell behavior.

  13. Enhancing osteogenic differentiation of MC3T3-E1 cells by immobilizing RGD onto liquid crystal substrate

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Shaopeng; Yang, Xiaohui; Li, Wenqiang; Du, Lin; Zeng, Rong; Tu, Mei, E-mail: tumei@jnu.edu.cn

    2017-02-01

    To understand the effects of GRGDF modification on MC3T3-E1 cell behavior, we cultured these cells onto a biomimetic liquid crystalline matrix modified with GRGDF peptide (OPC-GA-RGD). Successful immobilization of GRGDF on the liquid crystalline surface was verified by fluorescent labeling, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). OPC-GA-RGDs retained its liquid crystalline feature after surface modification. The RGD-immobilized OPC substrate was hardly beneficial to initial cell adhesion but could support long-term cell survival. The enhancement in cell proliferation did not correlate with RGD density. The lower GRGDF density immobilized on the liquid crystalline OPC matrix (OPC-GA-RGD3) promoted cell adhesion, proliferation, ALP expression level and mineralization, suggesting that both the viscoelasticity-based mechanical stimuli and receptor/ligand-based biochemical cue synergistically modulate MC3T3-E1 cell behavior. - Highlight: • A novel type of GRGDF-immobilized liquid crystalline matrices was fabricated and served as a substrate for the in vitro culture of MC3T3-E1 cells. • The lower RGD density might provide a better condition for initial cell adhesion and proliferation, up-regulation of ALP expression levels, and mineralization. • The intrinsic liquid crystalline feature of OPC matrix, instead of RGD efficiency, promoted initial cell adhesion. • Properties of the liquid crystalline OPC matrix together with the stable receptor-ligand binging synergistically modulated MC3T3-E1 cell behavior.

  14. Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

    International Nuclear Information System (INIS)

    Escudero-Castellanos, Alondra; Universidad Autonoma del Estado de Mexico, Toluca, Estado de Mexico; Ocampo-Garcia, B.E.; Ferro-Flores, Guillermina; Santos-Cuevas, C.L.; Isaac-Olive, Keila; Olmos-Ortiz, Andrea; Garcia-Quiroz, Janice; Garcia-Becerra, Rocio; Diaz, Lorenza

    2017-01-01

    This study aimed to synthesize a new 177 Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and α(v) β(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and α(v)β(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177 Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical. (author)

  15. Synchrotron X-ray fluorescence studies of a bromine-labelled cyclic RGD peptide interacting with individual tumor cells

    International Nuclear Information System (INIS)

    Sheridan, Erin J.; Austin, Christopher J. D.; Aitken, Jade B.; Vogt, Stefan; Jolliffe, Katrina A.; Harris, Hugh H.; Rendina, Louis M.

    2013-01-01

    The first example of synchrotron X-ray fluorescence imaging of cultured mammalian cells in cyclic peptide research is reported. The study reports the first quantitative analysis of the incorporation of a bromine-labelled cyclic RGD peptide and its effects on the biodistribution of endogenous elements (for example, K and Cl) within individual tumor cells. The first example of synchrotron X-ray fluorescence imaging of cultured mammalian cells in cyclic peptide research is reported. The study reports the first quantitative analysis of the incorporation of a bromine-labelled cyclic RGD peptide and its effects on the biodistribution of endogenous elements (for example, K and Cl) within individual tumor cells

  16. RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer

    Directory of Open Access Journals (Sweden)

    Feng C

    2015-08-01

    Full Text Available Chan Feng,1,* Xiaoyan Li,2,* Chunyan Dong,1 Xuemei Zhang,1 Xie Zhang,1 Yong Gao11Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, 2Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: In this study, long-circulating Arg-Gly-Asp (RGD-modified aclacinomycin A (ACM liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was -22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4 and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0–∞ (1.54-fold, mean residence time (2.09-fold, and elimination half-life (1.2-fold when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549 cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts.Keywords: RGD, aclacinomycin A, long-circulating liposomes, pharmacokinetic, tumor

  17. Resonance assignment for a particularly challenging protein based on systematic unlabeling of amino acids to complement incomplete NMR data sets

    International Nuclear Information System (INIS)

    Bellstedt, Peter; Seiboth, Thomas; Häfner, Sabine; Kutscha, Henriette; Ramachandran, Ramadurai; Görlach, Matthias

    2013-01-01

    NMR-based structure determination of a protein requires the assignment of resonances as indispensable first step. Even though heteronuclear through-bond correlation methods are available for that purpose, challenging situations arise in cases where the protein in question only yields samples of limited concentration and/or stability. Here we present a strategy based upon specific individual unlabeling of all 20 standard amino acids to complement standard NMR experiments and to achieve unambiguous backbone assignments for the fast precipitating 23 kDa catalytic domain of human aprataxin of which only incomplete standard NMR data sets could be obtained. Together with the validation of this approach utilizing the protein GB1 as a model, a comprehensive insight into metabolic interconversion ('scrambling”) of NH and CO groups in a standard Escherichia coli expression host is provided

  18. Molecular mechanics calculations on cobalt phthalocyanine dimers

    NARCIS (Netherlands)

    Heuts, J.P.A.; Schipper, E.T.W.M.; Piet, P.; German, A.L.

    1995-01-01

    In order to obtain insight into the structure of cobalt phthalocyanine dimers, molecular mechanics calculations were performed on dimeric cobalt phthalocyanine species. Molecular mechanics calculations are first presented on monomeric cobalt(II) phthalocyanine. Using the Tripos force field for the

  19. Mahler Measure, Eisenstein Series and Dimers

    NARCIS (Netherlands)

    Stienstra, J.

    2007-01-01

    This note reveals a mysterious link between the partition function of certain dimer models on 2-dimensional tori and the L-function of their spectral curves. It also relates the partition function in certain families of dimer models to Eisenstein series. http://www.arxiv.org/abs/math.NT/0502197

  20. Statistical transmutation in doped quantum dimer models.

    Science.gov (United States)

    Lamas, C A; Ralko, A; Cabra, D C; Poilblanc, D; Pujol, P

    2012-07-06

    We prove a "statistical transmutation" symmetry of doped quantum dimer models on the square, triangular, and kagome lattices: the energy spectrum is invariant under a simultaneous change of statistics (i.e., bosonic into fermionic or vice versa) of the holes and of the signs of all the dimer resonance loops. This exact transformation enables us to define the duality equivalence between doped quantum dimer Hamiltonians and provides the analytic framework to analyze dynamical statistical transmutations. We investigate numerically the doping of the triangular quantum dimer model with special focus on the topological Z(2) dimer liquid. Doping leads to four (instead of two for the square lattice) inequivalent families of Hamiltonians. Competition between phase separation, superfluidity, supersolidity, and fermionic phases is investigated in the four families.

  1. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

  2. Directed diffusion of reconstituting dimers

    International Nuclear Information System (INIS)

    Barma, Mustansir; Grynberg, Marcelo D; Stinchcombe, Robin B

    2007-01-01

    We discuss the dynamical aspects of an asymmetric version of assisted diffusion of hard core particles on a ring studied by Menon et al (1997 J. Stat. Phys. 86 1237). The asymmetry brings in phenomena like kinematic waves and effects of the Kardar-Parisi-Zhang non-linearity, which combine with the feature of strongly broken ergodicity, a characteristic of the model. A central role is played by a single non-local invariant, the irreducible string, whose interplay with the driven motion of reconstituting dimers, arising from the assisted hopping, determines the asymptotic dynamics and scaling regimes. These are investigated both analytically and numerically through sector-dependent mappings to the asymmetric simple exclusion process

  3. Directed diffusion of reconstituting dimers

    Energy Technology Data Exchange (ETDEWEB)

    Barma, Mustansir [Department of Theoretical Physics, Tata Institute of Fundamental Research, Mumbai 400005 (India); Grynberg, Marcelo D [Departamento de Fisica, Universidad Nacional de La Plata (1900) La Plata (Argentina); Stinchcombe, Robin B [Isaac Newton Institute for Mathematical Sciences, 20 Clarkson Road, Cambridge CB3 0EH (United Kingdom)

    2007-02-14

    We discuss the dynamical aspects of an asymmetric version of assisted diffusion of hard core particles on a ring studied by Menon et al (1997 J. Stat. Phys. 86 1237). The asymmetry brings in phenomena like kinematic waves and effects of the Kardar-Parisi-Zhang non-linearity, which combine with the feature of strongly broken ergodicity, a characteristic of the model. A central role is played by a single non-local invariant, the irreducible string, whose interplay with the driven motion of reconstituting dimers, arising from the assisted hopping, determines the asymptotic dynamics and scaling regimes. These are investigated both analytically and numerically through sector-dependent mappings to the asymmetric simple exclusion process.

  4. Electronic structure, dielectric response, and surface charge distribution of RGD (1FUV) peptide.

    Science.gov (United States)

    Adhikari, Puja; Wen, Amy M; French, Roger H; Parsegian, V Adrian; Steinmetz, Nicole F; Podgornik, Rudolf; Ching, Wai-Yim

    2014-07-08

    Long and short range molecular interactions govern molecular recognition and self-assembly of biological macromolecules. Microscopic parameters in the theories of these molecular interactions are either phenomenological or need to be calculated within a microscopic theory. We report a unified methodology for the ab initio quantum mechanical (QM) calculation that yields all the microscopic parameters, namely the partial charges as well as the frequency-dependent dielectric response function, that can then be taken as input for macroscopic theories of electrostatic, polar, and van der Waals-London dispersion intermolecular forces. We apply this methodology to obtain the electronic structure of the cyclic tripeptide RGD-4C (1FUV). This ab initio unified methodology yields the relevant parameters entering the long range interactions of biological macromolecules, providing accurate data for the partial charge distribution and the frequency-dependent dielectric response function of this peptide. These microscopic parameters determine the range and strength of the intricate intermolecular interactions between potential docking sites of the RGD-4C ligand and its integrin receptor.

  5. YY-39, a tick anti-thrombosis peptide containing RGD domain.

    Science.gov (United States)

    Tang, Jing; Fang, Yaqun; Han, Yajun; Bai, Xuewei; Yan, Xiuwen; Zhang, Yun; Lai, Ren; Zhang, Zhiye

    2015-06-01

    Ticks are obligatory blood feeding ectoparasites, which continuously attach to their hosts for 1-2 weeks. There are many biologically active compounds in tick salivary glands interfering host haemostatic system and to successfully obtain blood meal. Several platelet aggregation inhibitors have been identified from ticks. A family of conserved peptides, which were identified from transcriptome analysis of many tick salivary glands, were found to contain unique primary structure including predicted mature peptides of 39-47 amino acid residues in length and a Pro/Glu(P/E)-Pro/His(P/H)-Lys-Gly-Asp(RGD) domain. Given their unique structure and RGD domain, they are considered a novel family of disintegrins that inhibit platelet aggregation. One of them (YY-39) was tested for its effects on platelets and thrombosis in vivo. YY-39 was found effectively to inhibit platelet aggregation induced by adenosine diphosphate (ADP), thrombin and thromboxane A2 (TXA2). Furthermore, YY-39 blocked platelet adhesion to soluble collagen and bound to purified GPIIb/IIIa in a dose-dependent manner. In in vivo experiments, YY-39 reduced thrombus weight effectively in a rat arteriovenous shunt model and inhibited thrombosis in a carrageenan-induced mouse tail thrombosis model. Combined with their prevalence in ticks and platelet inhibitory functions, this family of peptides might be conserved tick anti-haemostatic molecules. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide Functionalization for Cancer Theranostics.

    Science.gov (United States)

    Yang, Liye; Li, Wenying; Huang, Yanyu; Zhou, Yangliang; Chen, Tianfeng

    2015-09-01

    A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Molecular nuclear imaging of tumoral angio genesis using a rgd-containing tracer, Raft-RGD, targeted at the neo vessel-specific integrin αvβ3

    International Nuclear Information System (INIS)

    Sancey, L.

    2006-06-01

    Tumoral neo-angio genesis targeting is currently a major field of research for the diagnostic and treatment of solid tumors. Endothelial cells from neo vessels over express several specific markers such as the α v β 3 integrin, which binds RGD (-Arg-Gly-Asp-)- containing peptides. We evaluated the potential of a novel radiotracer - RAFT-RGD - for the molecular nuclear imaging of neo vessels. In vitro, the coupling of 4 c(RGDfK) to the RAFT platform resulted in an increased cellular uptake of the tracer by α v β 3 positive cells when compared to c(RGDfK). Furthermore, RAFTRGD has a higher affinity than c(RGDfK) and similar properties for angio genesis inhibition. In vivo, both α v β 3 positive and negative tumors were visible by non invasive whole body planar and tomographic imaging from 30 min to 24 h post-injection, using a gamma camera dedicated to small animal imaging. Despite a lack of significant contrast improvement compare with c(RGDfK), RAFT-RGD could represent a promising tracer for tumoral angio genesis since it could provide invaluable information about tumor development and treatment efficacy in Nuclear Medicine departments. Furthermore, thanks to its chemical structure, RAFT-RGD can be labelled with a variety of radioisotopes including γ and β - emitters, allowing interesting therapeutical applications such as internal targeted radiotherapy. (author)

  8. Comparison of new bone formation, implant integration, and biocompatibility between RGD-hydroxyapatite and pure hydroxyapatite coating for cementless joint prostheses--an experimental study in rabbits.

    Science.gov (United States)

    Bitschnau, Achim; Alt, Volker; Böhner, Felicitas; Heerich, Katharina Elisabeth; Margesin, Erika; Hartmann, Sonja; Sewing, Andreas; Meyer, Christof; Wenisch, Sabine; Schnettler, Reinhard

    2009-01-01

    This is the first work to report on additional Arginin-Glycin-Aspartat (RGD) coating on precoated hydroxyapatite (HA) surfaces regarding new bone formation, implant bone contact, and biocompatibility compared to pure HA coating and uncoated stainless K-wires. There were 39 rabbits in total with 6 animals for the RGD-HA and HA group for the 4 week time period and 9 animals for each of the 3 implant groups for the 12 week observation. A 2.0 K-wire either with RGD-HA or with pure HA coating or uncoated was placed into the intramedullary canal of the tibia. After 4 and 12 weeks, the tibiae were harvested and three different areas of the tibia were assessed for quantitative and qualitative histology for new bone formation, direct implant bone contact, and formation of multinucleated giant cells. Both RGD-HA and pure HA coating showed statistically higher new bone formation and implant bone contact after 12 weeks than the uncoated K-wire. There were no significant differences between the RGD-HA and the pure HA coating in new bone formation and direct implant bone contact after 4 and 12 weeks. The number of multinucleated giant did not differ significantly between the RGD-HA and HA group after both time points. Overall, no significant effects of an additional RGD coating on HA surfaces were detected in this model after 12 weeks. (c) 2008 Wiley Periodicals, Inc.

  9. Effect of RGD Peptide-Coated TiO2 Nanotubes on the Attachment, Proliferation, and Functionality of Bone-Related Cells

    Directory of Open Access Journals (Sweden)

    Seunghan Oh

    2013-01-01

    Full Text Available The purpose of this research was to characterize an Arg-Gly-Asp (RGD peptide immobilized on TiO2 nanotubes. In addition, we investigated the effects of the RGD peptide-coated TiO2 nanotubes on the cellular response, proliferation, and functionality of osteogenic-induced human mesenchymal stem cells (hMSCs, which are osteoclasts that have been induced by bone marrow macrophages. The RGD peptide was grafted covalently onto the surface of TiO2 nanotubes based on the results of SEM, FT-IR, and XPS. Furthermore, the RGD peptide promoted the initial attachment and proliferation of the hMSCs, regardless of the size of the TiO2 nanotubes. However, the RGD peptide did not prominently affect the osteogenic functionality of the hMSCs because the peptide suppressed hMSC motility associated with osteogenic differentiation. The result of an in vitro osteoclast test showed that the RGD peptide accelerated the initial attachment of preosteoclasts and the formation of mature osteoclasts, which could resorb the bone matrix. Therefore, we believe that an RGD coating on TiO2 nanotubes synthesized on Ti implants might not offer significant acceleration of bone formation in vivo because osteoblasts and osteoclasts reside in the same compartment.

  10. Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene (TPX with cRGD pentapeptide

    Directory of Open Access Journals (Sweden)

    Lena Möller

    2013-02-01

    Full Text Available Covalent multistep coating of poly(methylpentene, the membrane material in lung ventilators, by using a copper-free “click” approach with a modified cyclic RGD peptide, leads to a highly biocompatible poly(methylpentene surface. The resulting modified membrane preserves the required excellent gas-flow properties while being densely seeded with lung endothelial cells.

  11. Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe.

    Science.gov (United States)

    Zhu, Lei; Guo, Ning; Li, Quanzheng; Ma, Ying; Jacboson, Orit; Lee, Seulki; Choi, Hak Soo; Mansfield, James R; Niu, Gang; Chen, Xiaoyuan

    2012-01-01

    The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/(64)Cu dual-labeled cyclic RGD peptide. The integrin α(v)β(3) binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data. The dual-labeled probe (64)Cu-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 ± 0.020) is comparable to that from dynamic PET (1.752 ± 0.026). The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models.

  12. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Liu, S.; Kruijtzer, J.A.; Soede, A.C.; Oyen, W.J.G.; Liskamp, R.M.; Corstens, F.H.M.; Boerman, O.C.

    2007-01-01

    INTRODUCTION: Due to the selective expression of the alpha(v)beta3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study,

  13. Development of a strategy to functionalize a dextrin-based hydrogel for animal cell cultures using a starch-binding module fused to RGD sequence

    Directory of Open Access Journals (Sweden)

    Gama Miguel

    2008-10-01

    Full Text Available Abstract Background Several approaches can be used to functionalize biomaterials, such as hydrogels, for biomedical applications. One of the molecules often used to improve cells adhesion is the peptide Arg-Gly-Asp (RGD. The RGD sequence, present in several proteins from the extra-cellular matrix (ECM, is a ligand for integrin-mediated cell adhesion; this sequence was recognized as a major functional group responsible for cellular adhesion. In this work a bi-functional recombinant protein, containing a starch binding module (SBM and RGD sequence was used to functionalize a dextrin-based hydrogel. The SBM, which belongs to an α-amylase from Bacillus sp. TS-23, has starch (and dextrin, depolymerized starch affinity, acting as a binding molecule to adsorb the RGD sequence to the hydrogel surface. Results The recombinant proteins SBM and RGD-SBM were cloned, expressed, purified and tested in in vitro assays. The evaluation of cell attachment, spreading and proliferation on the dextrin-based hydrogel surface activated with recombinant proteins were performed using mouse embryo fibroblasts 3T3. A polystyrene cell culture plate was used as control. The results showed that the RGD-SBM recombinant protein improved, by more than 30%, the adhesion of fibroblasts to dextrin-based hydrogel. In fact, cell spreading on the hydrogel surface was observed only in the presence of the RGD-SBM. Conclusion The fusion protein RGD-SBM provides an efficient way to functionalize the dextrin-based hydrogel. Many proteins in nature that hold a RGD sequence are not cell adhesive, probably due to the conformation/accessibility of the peptide. We therefore emphasise the successful expression of a bi-functional protein with potential for different applications.

  14. RGD-conjugated gold nanorods induce radiosensitization in melanoma cancer cells by downregulating αvβ3 expression

    Directory of Open Access Journals (Sweden)

    Pang B

    2012-02-01

    Full Text Available Wencai Xu1, Teng Luo2, Ping Li1, Chuanqing Zhou2, Daxiang Cui3, Bo Pang4, Qiushi Ren4, Shen Fu11Department of Radiation Oncology, Shanghai Sixth People's Hospital, 2School of Biomedical Engineering, and 3National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 4Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, People's Republic of ChinaBackground: Melanoma is known to be radioresistant and traditional treatments have been intractable. Therefore, novel approaches are required to improve the therapeutic efficacy of melanoma treatment. In our study, gold nanorods conjugated with Arg-Gly-Asp peptides (RGD-GNRs were used as a sensitizer to enhance the response of melanoma cells to 6 mV radiation.Methods and materials: A375 melanoma cells were treated by gold nanorods or RGD-GNRs with or without irradiation. The antiproliferative impact of the treatments was measured by MTT assay. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle data were measured by flow cytometry. Integrin αvβ3expression was also investigated by flow cytometry.Results: Addition of RGD-GNRs enhanced the radiosensitivity of A375 cells with a dose-modifying factor of 1.35, and enhanced radiation-induced apoptosis. DNA flow cytometric analysis indicated that RGD-GNRs plus irradiation induced significant G2/M phase arrest in A375 cells. Both spontaneous and radiation-induced expressions of integrin αvβ3 were downregulated by RGD-GNRs.Conclusion: Our study indicated that RGD-GNRs could sensitize melanoma A375 cells to irradiation. It was hypothesized that this was mainly through downregulation of radiation-induced αvβ3, in addition to induction of a higher proportion of cells within the G2/M phase. The combination of RGD-GNRs and

  15. Targeted radionuclide therapy with RAFT-RGD radiolabelled with {sup 90}Y or {sup 177}Lu in a mouse model of αvβ3-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bozon-Petitprin, A.; Bacot, S.; Ahmadi, M.; Marti-Batlle, D.; Perret, P.; Broisat, A.; Riou, L.M. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); Gauchez, A.S.; Bourre, J.C.; Fagret, D.; Vuillez, J.P. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); CHRU Grenoble, Hopital Michallon, Service de Medecine Nucleaire, Grenoble (France); Claron, M.; Boturyn, D. [CNRS, UMR 5250, Departement de Chimie Moleculaire, Grenoble (France); Ghezzi, Catherine [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); INSERM U1039, Radiopharmaceutiques biocliniques, Batiment Jean Roget, Domaine de la Merci, Faculte de Medecine, La Tronche (France)

    2014-08-28

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK]){sub 4} (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β{sup -} emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD and {sup 90}Y-RAFT-RAD or {sup 177}Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of {sup 90}Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of {sup 177}Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of {sup 90}Y-RAFT-RAD or 37 MBq of {sup 177}Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of {sup 90}Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. {sup 90}Y-RAFT-RGD and {sup 177}Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy. (orig.)

  16. Targeted radionuclide therapy with RAFT-RGD radiolabelled with (90)Y or (177)Lu in a mouse model of αvβ3-expressing tumours.

    Science.gov (United States)

    Bozon-Petitprin, A; Bacot, S; Gauchez, A S; Ahmadi, M; Bourre, J C; Marti-Batlle, D; Perret, P; Broisat, A; Riou, L M; Claron, M; Boturyn, D; Fagret, D; Ghezzi, Catherine; Vuillez, J P

    2015-02-01

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β(-) emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD and (90)Y-RAFT-RAD or (177)Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of (90)Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of (177)Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of (90)Y-RAFT-RAD or 37 MBq of (177)Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of (90)Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. (90)Y-RAFT-RGD and (177)Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy.

  17. Development and inter-laboratory validation of unlabeled probe melting curve analysis for detection of JAK2 V617F mutation in polycythemia vera.

    Science.gov (United States)

    Wu, Zhiyuan; Yuan, Hong; Zhang, Xinju; Liu, Weiwei; Xu, Jinhua; Zhang, Wei; Guan, Ming

    2011-01-01

    JAK2 V617F, a somatic point mutation that leads to constitutive JAK2 phosphorylation and kinase activation, has been incorporated into the WHO classification and diagnostic criteria of myeloid neoplasms. Although various approaches such as restriction fragment length polymorphism, amplification refractory mutation system and real-time PCR have been developed for its detection, a generic rapid closed-tube method, which can be utilized on routine genetic testing instruments with stability and cost-efficiency, has not been described. Asymmetric PCR for detection of JAK2 V617F with a 3'-blocked unlabeled probe, saturate dye and subsequent melting curve analysis was performed on a Rotor-Gene® Q real-time cycler to establish the methodology. We compared this method to the existing amplification refractory mutation systems and direct sequencing. Hereafter, the broad applicability of this unlabeled probe melting method was also validated on three diverse real-time systems (Roche LightCycler® 480, Applied Biosystems ABI® 7500 and Eppendorf Mastercycler® ep realplex) in two different laboratories. The unlabeled probe melting analysis could genotype JAK2 V617F mutation explicitly with a 3% mutation load detecting sensitivity. At level of 5% mutation load, the intra- and inter-assay CVs of probe-DNA heteroduplex (mutation/wild type) covered 3.14%/3.55% and 1.72%/1.29% respectively. The method could equally discriminate mutant from wild type samples on the other three real-time instruments. With a high detecting sensitivity, unlabeled probe melting curve analysis is more applicable to disclose JAK2 V617F mutation than conventional methodologies. Verified with the favorable inter- and intra-assay reproducibility, unlabeled probe melting analysis provided a generic mutation detecting alternative for real-time instruments.

  18. Development and inter-laboratory validation of unlabeled probe melting curve analysis for detection of JAK2 V617F mutation in polycythemia vera.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Wu

    Full Text Available BACKGROUND: JAK2 V617F, a somatic point mutation that leads to constitutive JAK2 phosphorylation and kinase activation, has been incorporated into the WHO classification and diagnostic criteria of myeloid neoplasms. Although various approaches such as restriction fragment length polymorphism, amplification refractory mutation system and real-time PCR have been developed for its detection, a generic rapid closed-tube method, which can be utilized on routine genetic testing instruments with stability and cost-efficiency, has not been described. METHODOLOGY/PRINCIPAL FINDINGS: Asymmetric PCR for detection of JAK2 V617F with a 3'-blocked unlabeled probe, saturate dye and subsequent melting curve analysis was performed on a Rotor-Gene® Q real-time cycler to establish the methodology. We compared this method to the existing amplification refractory mutation systems and direct sequencing. Hereafter, the broad applicability of this unlabeled probe melting method was also validated on three diverse real-time systems (Roche LightCycler® 480, Applied Biosystems ABI® 7500 and Eppendorf Mastercycler® ep realplex in two different laboratories. The unlabeled probe melting analysis could genotype JAK2 V617F mutation explicitly with a 3% mutation load detecting sensitivity. At level of 5% mutation load, the intra- and inter-assay CVs of probe-DNA heteroduplex (mutation/wild type covered 3.14%/3.55% and 1.72%/1.29% respectively. The method could equally discriminate mutant from wild type samples on the other three real-time instruments. CONCLUSIONS: With a high detecting sensitivity, unlabeled probe melting curve analysis is more applicable to disclose JAK2 V617F mutation than conventional methodologies. Verified with the favorable inter- and intra-assay reproducibility, unlabeled probe melting analysis provided a generic mutation detecting alternative for real-time instruments.

  19. Dynamic interplay between adhesive and lateral E-cadherin dimers

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Laur, Oscar Y; Troyanovsky, Regina B

    2002-01-01

    M. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime...

  20. The two-state dimer receptor model: a general model for receptor dimers.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2006-06-01

    Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

  1. The water dimer II: Theoretical investigations

    Energy Technology Data Exchange (ETDEWEB)

    Mukhopadhyay, Anamika; Xantheas, Sotiris S.; Saykally, Richard J.

    2018-03-29

    As the archetype of hydrogen bonding between water molecules, the water dimer has been extensively studied by both theory and experiment for nearly seven decades. In this article, we present a detailed chronological review of the theoretical advances using electronic structure methods pertaining to the structure, hydrogen bonding and vibrational spectroscopy of the water dimer as well as the role of its potential energy surface in the development of classical force fields to describe intermolecular interaction in clusters and liquid water.

  2. PRIMAL: Page Rank-Based Indoor Mapping and Localization Using Gene-Sequenced Unlabeled WLAN Received Signal Strength

    Directory of Open Access Journals (Sweden)

    Mu Zhou

    2015-09-01

    Full Text Available Due to the wide deployment of wireless local area networks (WLAN, received signal strength (RSS-based indoor WLAN localization has attracted considerable attention in both academia and industry. In this paper, we propose a novel page rank-based indoor mapping and localization (PRIMAL by using the gene-sequenced unlabeled WLAN RSS for simultaneous localization and mapping (SLAM. Specifically, first of all, based on the observation of the motion patterns of the people in the target environment, we use the Allen logic to construct the mobility graph to characterize the connectivity among different areas of interest. Second, the concept of gene sequencing is utilized to assemble the sporadically-collected RSS sequences into a signal graph based on the transition relations among different RSS sequences. Third, we apply the graph drawing approach to exhibit both the mobility graph and signal graph in a more readable manner. Finally, the page rank (PR algorithm is proposed to construct the mapping from the signal graph into the mobility graph. The experimental results show that the proposed approach achieves satisfactory localization accuracy and meanwhile avoids the intensive time and labor cost involved in the conventional location fingerprinting-based indoor WLAN localization.

  3. PRIMAL: Page Rank-Based Indoor Mapping and Localization Using Gene-Sequenced Unlabeled WLAN Received Signal Strength.

    Science.gov (United States)

    Zhou, Mu; Zhang, Qiao; Xu, Kunjie; Tian, Zengshan; Wang, Yanmeng; He, Wei

    2015-09-25

    Due to the wide deployment of wireless local area networks (WLAN), received signal strength (RSS)-based indoor WLAN localization has attracted considerable attention in both academia and industry. In this paper, we propose a novel page rank-based indoor mapping and localization (PRIMAL) by using the gene-sequenced unlabeled WLAN RSS for simultaneous localization and mapping (SLAM). Specifically, first of all, based on the observation of the motion patterns of the people in the target environment, we use the Allen logic to construct the mobility graph to characterize the connectivity among different areas of interest. Second, the concept of gene sequencing is utilized to assemble the sporadically-collected RSS sequences into a signal graph based on the transition relations among different RSS sequences. Third, we apply the graph drawing approach to exhibit both the mobility graph and signal graph in a more readable manner. Finally, the page rank (PR) algorithm is proposed to construct the mapping from the signal graph into the mobility graph. The experimental results show that the proposed approach achieves satisfactory localization accuracy and meanwhile avoids the intensive time and labor cost involved in the conventional location fingerprinting-based indoor WLAN localization.

  4. Adsorption of dimeric surfactants in lamellar silicates

    Energy Technology Data Exchange (ETDEWEB)

    Balcerzak, Mateusz; Pietralik, Zuzanna [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Domka, Ludwik [Department of Metalorganic Chemistry, Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań (Poland); Skrzypczak, Andrzej [Institute of Chemical Technology, Poznań University of Technology, Berdychowo 4, 60-965 Poznań (Poland); Kozak, Maciej, E-mail: mkozak@amu.edu.pl [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)

    2015-12-01

    Highlights: • The intercalation of dimeric surfactants changed the morphology of MMT samples. • XRD indicated structures formed by surfactant molecules in interlayer space. • The four-step thermal decomposition of dimeric surfactant, confirms intercalation. - Abstract: The adsorption of different types of cationic surfactants in lamellar silicates changes their surface character from hydrophilic to hydrophobic. This study was undertaken to obtain lamellar silicates modified by a series of novel dimeric (gemini) surfactants of different length alkyl chains and to characterise these organophilised materials. Synthetic sodium montmorillonite SOMASIF® ME 100 (M) and enriched bentonite of natural origin (Nanoclay – hydrophilic bentonite®) were organophilised with dimeric (gemini) surfactants (1,1′-(1,4-butanediyl)bis(alkoxymethyl)imidazolium dichlorides). As a result of surfactant molecule adsorption in interlamellar space, the d-spacing (d{sub 001}) increased from 0.97 nm (for the anhydrous structure) to 2.04 nm. A Fourier transform infrared spectroscopy (FTIR) analysis of the modified systems reveals bands assigned to the stretching vibrations of the CH{sub 2} and CH{sub 3} groups and the scissoring vibrations of the NH group from the structure of the dimeric surfactants. Thermogravimetric (TG) and derivative thermogravimetric (DTG) studies imply a four-stage process of surfactant decomposition. Scanning electron microscopy (SEM) images provide information on the influence of dimeric surfactant intercalation into the silicate structures. Particles of the modified systems show a tendency toward the formation of irregularly shaped agglomerates.

  5. Retroviral RNA Dimerization: From Structure to Functions

    Directory of Open Access Journals (Sweden)

    Noé Dubois

    2018-03-01

    Full Text Available The genome of the retroviruses is a dimer composed by two homologous copies of genomic RNA (gRNA molecules of positive polarity. The dimerization process allows two gRNA molecules to be non-covalently linked together through intermolecular base-pairing. This step is critical for the viral life cycle and is highly conserved among retroviruses with the exception of spumaretroviruses. Furthermore, packaging of two gRNA copies into viral particles presents an important evolutionary advantage for immune system evasion and drug resistance. Recent studies reported RNA switches models regulating not only gRNA dimerization, but also translation and packaging, and a spatio-temporal characterization of viral gRNA dimerization within cells are now at hand. This review summarizes our current understanding on the structural features of the dimerization signals for a variety of retroviruses (HIVs, MLV, RSV, BLV, MMTV, MPMV…, the mechanisms of RNA dimer formation and functional implications in the retroviral cycle.

  6. Can single molecule localization microscopy be used to map closely spaced RGD nanodomains?

    Directory of Open Access Journals (Sweden)

    Mahdie Mollazade

    Full Text Available Cells sense and respond to nanoscale variations in the distribution of ligands to adhesion receptors. This makes single molecule localization microscopy (SMLM an attractive tool to map the distribution of ligands on nanopatterned surfaces. We explore the use of SMLM spatial cluster analysis to detect nanodomains of the cell adhesion-stimulating tripeptide arginine-glycine-aspartic acid (RGD. These domains were formed by the phase separation of block copolymers with controllable spacing on the scale of tens of nanometers. We first determined the topology of the block copolymer with atomic force microscopy (AFM and then imaged the localization of individual RGD peptides with direct stochastic optical reconstruction microscopy (dSTORM. To compare the data, we analyzed the dSTORM data with DBSCAN (density-based spatial clustering application with noise. The ligand distribution and polymer topology are not necessary identical since peptides may attach to the polymer outside the nanodomains and/or coupling and detection of peptides within the nanodomains is incomplete. We therefore performed simulations to explore the extent to which nanodomains could be mapped with dSTORM. We found that successful detection of nanodomains by dSTORM was influenced by the inter-domain spacing and the localization precision of individual fluorophores, and less by non-specific absorption of ligands to the substratum. For example, under our imaging conditions, DBSCAN identification of nanodomains spaced further than 50 nm apart was largely independent of background localisations, while nanodomains spaced closer than 50 nm required a localization precision of ~11 nm to correctly estimate the modal nearest neighbor distance (NDD between nanodomains. We therefore conclude that SMLM is a promising technique to directly map the distribution and nanoscale organization of ligands and would benefit from an improved localization precision.

  7. Construction of expressing vectors including melanoma differentiation-associated gene-7 (mda-7 fused with the RGD sequences for better tumor targeting

    Directory of Open Access Journals (Sweden)

    Mahboobeh Khodadad

    2015-08-01

    Conclusion: Theoretically RGD tagged mda-7 would be able to induce apoptosis with more specificity and stronger than the standard one, therefore, these new constructs may have the potential for further researches.

  8. Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid–paclitaxel (CLA-PTX on B16-F10 melanoma

    Directory of Open Access Journals (Sweden)

    Du R

    2014-06-01

    Full Text Available Ruo Du,1 Ting Zhong,1 Wei-Qiang Zhang,1 Ping Song,1 Wen-Ding Song,1 Yang Zhao,1 Chao-Wang,1 Yi-Qun Tang,3 Xuan Zhang,1,2 Qiang Zhang1,2 1Department of Pharmaceutics, 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 3Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In the present study, we prepared a novel delivery system of iRGD (CRGDK/RGPD/EC-modified sterically stabilized liposomes (SSLs containing conjugated linoleic acid–paclitaxel (CLA-PTX. The anti-tumor effect of iRGD-SSL-CLA-PTX was investigated on B16-F10 melanoma in vitro and in vivo. The in vitro targeting effect of iRGD-modified SSLs was investigated in a real-time confocal microscopic analysis experiment. An endocytosis-inhibition assay was used to evaluate the endocytosis pathways of the iRGD-modified SSLs. In addition, the in vitro cellular uptake and in vitro cytotoxicity of iRGD-SSL-CLA-PTX were evaluated in B16-F10 melanoma cells. In vivo biodistribution and in vivo antitumor effects of iRGD-SSL-CLA-PTX were investigated in B16-F10 tumor-bearing mice. The induction of apoptosis by iRGD-SSL-CLA-PTX was evaluated in tumor-tissue sections. Real-time confocal microscopic analysis results indicated that the iRGD-modified SSLs internalized into B16-F10 cells faster than SSLs. The identified endocytosis pathway of iRGD-modified SSLs indicated that energy- and lipid raft-mediated endocytosis played a key role in the liposomes’ cellular uptake. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-SSL-CLA-PTX-treated group was 1.9-, 2.4-, or 2.1-fold compared with that in the CLA-PTX group after a 2-, 4-, or 6-hour incubation, respectively. In the biodistribution test, the CLA-PTX level in tumor tissues from iRGD-SSL-CLA-PTX-treated mice at 1 hour (1.84±0.17 µg/g and 4 hours (1.17±0

  9. The antitumor activity of a doxorubicin loaded, iRGD-modified sterically-stabilized liposome on B16-F10 melanoma cells: in vitro and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Yu KF

    2013-07-01

    Full Text Available Ke-Fu Yu,1 Wei-Qiang Zhang,1 Li-Min Luo,1 Ping Song,1 Dan Li,1 Ruo Du,1 Wei Ren,1 Dan Huang,1 Wan-Liang Lu,1,2 Xuan Zhang,1 Qiang Zhang1,2 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China Abstract: Considering the fact that iRGD (tumor-homing peptide demonstrates tumor-targeting and tumor-penetrating activity, and that B16-F10 (murine melanoma cells overexpress both αv integrin receptor and neuropilin-1 (NRP-1, the purpose of this study was to prepare a novel doxorubicin (DOX-loaded, iRGD-modified, sterically-stabilized liposome (SSL (iRGD-SSL-DOX in order to evaluate its antitumor activity on B16-F10 melanoma cells in vitro and in vivo. The iRGD-SSL-DOX was prepared using a thin-film hydration method. The characteristics of iRGD-SSL-DOX were evaluated. The in vitro leakage of DOX from iRGD-SSL-DOX was tested. The in vitro tumor-targeting and tumor-penetrating characteristics of iRGD-modified liposomes on B16-F10 cells were investigated. The in vivo tumor-targeting and tumor-penetrating activities of iRGD-modified liposomes were performed in B16-F10 tumor-bearing nude mice. The antitumor effect of iRGD-SSL-DOX was evaluated in B16-F10 tumor-bearing C57BL/6 mice in vivo. The average particle size of the iRGD-SSL-DOX was found to be 91 nm with a polydispersity index (PDI of 0.16. The entrapment efficiency of iRGD-SSL-DOX was 98.36%. The leakage of DOX from iRGD-SSL-DOX at the 24-hour time point was only 7.5%. The results obtained from the in vitro flow cytometry and confocal microscopy, as well as in vivo biodistribution and confocal immunofluorescence microscopy experiments, indicate that the tumor-targeting and tumor-penetrating activity of the iRGD-modified SSL was higher than that of unmodified SSL. In vivo antitumor activity

  10. iRGD-modified lipid–polymer hybrid nanoparticles loaded with isoliquiritigenin to enhance anti-breast cancer effect and tumor-targeting ability

    Directory of Open Access Journals (Sweden)

    Gao F

    2017-06-01

    Full Text Available Fei Gao,1–3 Jinming Zhang,3 Chaomei Fu,3 Xiaoming Xie,4 Fu Peng,1–3 Jieshu You,1,2 Hailin Tang,1,2,4 Zhiyu Wang,5 Peng Li,6 Jianping Chen1–3 1School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, 2Shenzhen Institute of Research and Innovation, University of Hong Kong, Shenzhen, 3College of Pharmacy, Chengdu University of Chinese Medicine, Chengdu, 4Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 5Department of Mammary Disease, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 6State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China Abstract: Isoliquiritigenin (ISL, a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid–polymer hybrid nanoparticle (NP system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs. The stable lipid–polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed. Compared to free ISL and non-iRGD-modified counterparts, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against the different type of breast cancer cells. This was attributable to higher cellular accumulation mediated by the iRGD-integrin recognition and the nanoscale effect. More importantly, based on the active tumor-tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nanostructure, ISL-iRGD NPs displayed higher tumor-growth inhibition efficiency in 4T1-bearing breast-tumor mouse

  11. Molecular imaging of alpha v beta3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA.

    Science.gov (United States)

    Burtea, Carmen; Laurent, Sophie; Murariu, Oltea; Rattat, Dirk; Toubeau, Gérard; Verbruggen, Alfons; Vansthertem, David; Vander Elst, Luce; Muller, Robert N

    2008-04-01

    The integrin alpha v beta3 is highly expressed in atherosclerotic plaques by medial and intimal smooth muscle cells and by endothelial cells of angiogenic microvessels. In this study, we have assessed non-invasive molecular magnetic resonance imaging (MRI) of plaque-associated alpha v beta3 integrin expression on transgenic ApoE-/- mice with a low molecular weight peptidomimetic of Arg-Gly-Asp (mimRGD) grafted to gadolinium diethylenetriaminepentaacetate (Gd-DTPA-g-mimRGD). The analogous compound Eu-DTPA-g-mimRGD was employed for an in vivo competition experiment and to confirm the molecular targeting. The specific interaction of mimRGD conjugated to Gd-DTPA or to 99mTc-DTPA with alpha v beta3 integrin was furthermore confirmed on Jurkat T lymphocytes. The mimRGD was synthesized and conjugated to DTPA. DTPA-g-mimRGD was complexed with GdCl3.6H2O, EuCl3.6H2O, or with [99mTc(CO)3(H2O)3]+. MRI evaluation was performed on a 4.7 T Bruker imaging system. Blood pharmacokinetics of Gd-DTPA-g-mimRGD were assessed in Wistar rats and in c57bl/6j mice. The presence of angiogenic blood vessels and the expression of alpha v beta3 integrin were confirmed in aorta specimens by immunohistochemistry. Gd-DTPA-g-mimRGD produced a strong enhancement of the external structures of the aortic wall and of the more profound layers (possibly tunica media and intima). The aortic lumen seemed to be restrained and distorted. Pre-injection of Eu-DTPA-g-mimRGD diminished the Gd-DTPA-g-mimRGD binding to atherosclerotic plaque and confirmed the specific molecular targeting. A slower blood clearance was observed for Gd-DTPA-g-mimRGD, as indicated by a prolonged elimination half-life and a diminished total clearance. The new compound is potentially useful for the diagnosis of vulnerable atherosclerotic plaques and of other pathologies characterized by alpha v beta3 integrin expression, such as cancer and inflammation. The delayed blood clearance, the significant enhancement of the signal

  12. Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides

    Directory of Open Access Journals (Sweden)

    Sun J

    2017-02-01

    Full Text Available Jiawei Sun,1 Lei Jiang,2 Yi Lin,3 Ethan Michael Gerhard,4 Xuehua Jiang,1 Li Li,3 Jian Yang,4 Zhongwei Gu3 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu, 3National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Biomedical Engineering Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, USA Abstract: Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Here, multistage tumor-targeting liposomes containing two targeted peptide-modified lipids, cRGD-PEG2000-DSPE and KLA-PEG2000-DSPE, were developed for encapsulation of the anticancer drug paclitaxel (PTX, RGD-KLA/PTX-Lips. Compared with Taxol (free PTX, RGD/PTX-Lips and KLA/PTX-Lips, the half-maximal inhibitory concentration (IC50 value of RGD-KLA/PTX-Lips in vitro was 1.9-, 36.7- and 22.7-fold lower with 4T1 cells, respectively, because of higher levels of cellular uptake. Similar results were also observed with human umbilical vascular endothelial cells (HUVECs. An apoptosis assay showed that the total apoptotic ratio of RGD-KLA/PTX-Lips was the highest because of the mitochondria-targeted drug delivery and the activation of mitochondrial apoptosis pathways, as evidenced by visible mitochondrial localization, decreased mitochondrial membrane potential, release of cytochrome c and increased activities of caspase-9 and caspase-3. The strongest tumor growth inhibition (TGI; 80.6% and antiangiogenesis effects without systemic toxicity were also observed in RGD-KLA/PTX-Lip-treated 4T1 tumor xenograft BALB/c mice. In conclusion, these multistage

  13. [{sup 68}Ga]NODAGA-RGD - Metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Haubner, Roland; Rangger, Christine; Decristoforo, Clemens; Virgolini, Irene J. [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Finkenstedt, Armin; Zoller, Heinz [Medical University of Innsbruck, Department of Internal Medicine II, Innsbruck (Austria); Stegmayr, Armin [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); FH Gesundheit/University of Applied Sciences Tyrol, Innsbruck (Austria)

    2016-10-15

    This study was designed to determine safety, tolerability, and radiation burden of a [{sup 68}Ga]NODAGA-RGD-PET for imaging integrin α{sub v}β{sub 3} expression in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Moreover, metabolic stability and biokinetic data were compiled. After injection of 154-184 MBq [{sup 68}Ga]NODAGA-RGD three consecutive PET/CT scans were acquired starting 8.3 ± 2.1, 36.9 ± 2.8, and 75.1 ± 3.4 min after tracer injection. For metabolite analysis, blood and urine samples were analyzed by HPLC. For dosimetry studies, residence time VOIs were placed in the corresponding organs. The OLINDA/EXM program was used to estimate the absorbed radiation dose. The radiopharmaceutical was well tolerated and no drug-related adverse effects were observed. No metabolites could be detected in blood (30 and 60 min p.i.) and urine (60 min p.i.). [{sup 68}Ga]NODAGA-RGD showed rapid and predominantly renal elimination. Background radioactivity in blood, intestine, lung, and muscle tissue was low (%ID/l 60 min p.i. was 0.56 ± 0.43, 0.54 ± 0.39, 0.22 ± 0.05, and 0.16 ± 0.8, respectively). The calculated effective dose was 21.5 ± 5.4 μSv/MBq, and the highest absorbed radiation dose was found for the urinary bladder wall (0.26 ± 0.09 mSv/MBq). No increased uptake of the tracer was found in HCC compared with the background liver tissue. [{sup 68}Ga]NODAGA-RGD uptake in the HCCs lesions was not sufficient to use this tracer for imaging these tumors. [{sup 68}Ga]NODAGA-RGD was well tolerated and metabolically stable. Due to rapid renal excretion, background radioactivity was low in most of the body, resulting in low radiation burden and indicating the potential of [{sup 68}Ga]NODAGA-RGD PET for non-invasive determination of integrin α{sub v}β{sub 3} expression. (orig.)

  14. D-dimers (DD) in CVST.

    Science.gov (United States)

    Wang, Hui Fang; Pu, Chuan Qiang; Yin, Xi; Tian, Cheng Lin; Chen, Ting; Guo, Jun Hong; Shi, Qiang

    2017-06-01

    We were interested in further confirming whether D-dimers (DD) are indeed elevated in cerebral venous sinus thrombosis (CVST) as reported in those studies. CVST patients who had a plasma D-dimer test (139 cases) were included and divided into two groups: elevated D-dimer group (EDG) (>0.5 μg/mL; 65 cases) and normal D-dimer group (NDG) (≤0.5 μg/mL; 74 cases). The two groups were compared in terms of demographic data, clinical manifestation, laboratory and imaging data, using inferential statistical methods. The chi-squared and Fisher exact test showed that, compared to the NDG (74 cases), patients with elevated D-dimer levels were more likely to have a shorter symptom duration (SD) (30 ± 83.9 versus 90 ± 58.9 d, p = 0.003), more risk factors (75.4% versus 52.7%, p = 0.006), higher multiple venous sinus involvement (75.4% versus 59.5%, p = 0.037), increased fibrinogen (43.1% versus 18.9%, p = 0.037) and higher levels of blood glucose (18.3% versus 11%, p = 0.037). According to correlation analyses, D-dimer levels were positively correlated with number of venous sinuses involvement (NVS) (r = 0.321, p = 0.009) in the EDG. Multivariate logistic regression analysis showed that SD (OR, 0.025; 95% CI, 1.324-6.043; p = 0.000), NVS (OR, 1.573; 95% CI, 1.15-2.151; p = 0.005) and risk factors (OR, 3.321; 95% CI, 1.451-7.564; p = 0.004) were significantly different between the two groups. D-dimer is elevated in patients with acute/subacute CVST.

  15. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

    Directory of Open Access Journals (Sweden)

    Tine N Vinther

    Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

  16. Calix[4]arene supported clusters: a dimer of [Mn(III)Mn(II)] dimers

    DEFF Research Database (Denmark)

    Taylor, Stephanie M; McIntosh, Ruaraidh D; Beavers, Christine M

    2011-01-01

    Phosphinate ligands allow for the transformation of a calix[4]arene supported [Mn(III)(2)Mn(II)(2)] tetramer cluster motif into an unusual [Mn(III)Mn(II)](2) dimer of dimers; the clusters self-assemble in the crystal to form bi-layer arrays reminiscent of the typical packing of calixarene solvates....

  17. RGD-conjugated silica-coated gold nanorods on the surface of carbon nanotubes for targeted photoacoustic imaging of gastric cancer

    Science.gov (United States)

    Wang, Can; Bao, Chenchen; Liang, Shujing; Fu, Hualin; Wang, Kan; Deng, Min; Liao, Qiande; Cui, Daxiang

    2014-05-01

    Herein, we reported for the first time that RGD-conjugated silica-coated gold nanorods on the surface of multiwalled carbon nanotubes were successfully used for targeted photoacoustic imaging of in vivo gastric cancer cells. A simple strategy was used to attach covalently silica-coated gold nanorods (sGNRs) onto the surface of multiwalled carbon nanotubes (MWNTs) to fabricate a hybrid nanostructure. The cross-linked reaction occurred through the combination of carboxyl groups on the MWNTs and the amino group on the surface of sGNRs modified with a silane coupling agent. RGD peptides were conjugated with the sGNR/MWNT nanostructure; resultant RGD-conjugated sGNR/MWNT probes were investigated for their influences on viability of MGC803 and GES-1 cells. The nude mice models loaded with gastric cancer cells were prepared, the RGD-conjugated sGNR/MWNT probes were injected into gastric cancer-bearing nude mice models via the tail vein, and the nude mice were observed by an optoacoustic imaging system. Results showed that RGD-conjugated sGNR/MWNT probes showed good water solubility and low cellular toxicity, could target in vivo gastric cancer cells, and obtained strong photoacoustic imaging in the nude model. RGD-conjugated sGNR/MWNT probes will own great potential in applications such as targeted photoacoustic imaging and photothermal therapy in the near future.

  18. Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates

    International Nuclear Information System (INIS)

    Finegood, D.T.; Bergman, R.N.; Vranic, M.

    1987-01-01

    Tracer methodology has been applied extensively to the estimation of endogenous glucose production (Ra) during euglycemic glucose clamps. The accuracy of this approach has been questioned due to the observation of significantly negative estimates for Ra when insulin levels are high. We performed hyperinsulinemic (300 microU/ml)-euglycemic glucose clamps for 180 min in normal dogs and compared the standard approach, an unlabeled exogenous glucose infusate (cold GINF protocol, n = 12), to a new approach in which a tracer (D-[3- 3 H]glucose) was added to the exogenous glucose used for clamping (hot GINF protocol, n = 10). Plasma glucose, insulin and glucagon concentrations, and glucose infusion rates were similar for the two protocols. Plasma glucose specific activity was 20 +/- 1% of basal (at 120-180 min) in the cold GINF studies, and 44 +/- 3 to 187 +/- 5% of basal in the hot GINF studies. With the one-compartment, fixed pool volume model of Steele, Ra for the cold GINF studies was -2.4 +/- 0.7 mg X min-1 X kg-1 at 25 min and remained significantly negative until 110 min (P less than .05). For the hot GINF studies, Ra was never significantly less than zero (P greater than .05) and was greater than in the cold GINF studies at 20-90 min (P less than .05). There was substantially less between-(78%) and within- (40%) experiment variation for the hot GINF studies compared with the cold GINF studies. An alternate approach (regression method) to the application of the one-compartment model, which allows for a variable and estimable effective distribution volume, yielded Ra estimates that were suppressed 60-100% from basal

  19. Plasmonic nanospherical dimers for color pixels

    KAUST Repository

    Alrasheed, Salma

    2018-04-20

    Display technologies are evolving more toward higher resolution and miniaturization. Plasmonic color pixels can offer solutions to realize such technologies due to their sharp resonances and selective scattering and absorption at particular wavelengths. Metal nanosphere dimers are capable of supporting plasmon resonances that can be tuned to span the entire visible spectrum. In this article, we demonstrate numerically bright color pixels that are highly polarized and broadly tuned using periodic arrays of metal nanosphere dimers on a glass substrate. We show that it is possible to obtain RGB pixels in the reflection mode. The longitudinal plasmon resonance of nanosphere dimers along the axis of the dimer is the main contributor to the color of the pixel, while far-field diffractive coupling further enhances and tunes the plasmon resonance. The computational method used is the finite-difference time-domain method. The advantages of this approach include simplicity of the design, bright coloration, and highly polarized function. In addition, we show that it is possible to obtain different colors by varying the angle of incidence, the periodicity, the size of the dimer, the gap, and the substrate thickness.

  20. A radioisotope dilution assay for unlabelled vitamin B12-intrinsic factor complex employing the binding intrinsic factor antibody: probable evidence for two types of binding antibody

    International Nuclear Information System (INIS)

    Jacob, E.; O'Brien, H.A.W.; Mollin, D.L.

    1977-01-01

    A new radioisotope dilution assay for vitamin B 12 -intrinsic factor complex is described. The method is based on the use of the binding type intrinsic antibody (the binding reagent), which when combined with the intrinsic factor-vitamin B 12 complex (labelled ligand), is quantitatively adsorbed onto zirconium phosphate gel pH 6.25. The new assay has been shown to provide a measure of intrinsic factor comparable with other intrinsic factor assays, but it has the important advantage of being able to measure the unlabelled vitamin B 12 -intrinsic factor complex (unlabelled ligand), and will, therefore, be valuable in the study of physiological events in the gastrointestinal tract. During the study, it was found that there is some evidence for at least two types of binding intrinsic factor antibody: One which combines preferentially with the intrinsic factor-vitamin B 12 complex and one which combines equally well with this complex or with free intrinsic factor. (author)

  1. Optimization of the production process of hybrid and multivalent formulation Bombesin/RGD for the opportune detection of breast cancer

    International Nuclear Information System (INIS)

    Robles M, M.

    2013-01-01

    The radiopharmaceuticals of third generation are used in nuclear medicine to obtain images of specific molecular targets, and they are unique in their capacity to detect in vivo specific biochemical sites as receptors that are over-expressed in diverse illness. In cancer cells several types of receptors are over-expressed, as the integrin s α(v)β(3) and α(v)β(5) that specifically recognize the sequence RGD (Arginine-Glycin-Ac. Aspartic) and gastrin-releasing peptide that recognizes specifically to the peptide Lys 3 -Bombesin. The integrin s α(v)β(3) and α(v)β(5) are involved in the tumor angio genesis processes and the gastrin-releasing peptide is over-expressed in breast and prostate cancer. The molecular recognition of the specific receptors is the basis to be utilized as targets of the radiopharmaceuticals 99m Tc-HYNIC-Bombesin and 99m Tc-HYNIC-RGD. In this work was developed a lyophilized pharmaceutical formulation effective, stable and safe for the simultaneous obtaining of the radiopharmaceuticals 99m Tc-HYNIC-Bombesin ( 99m Tc-EDDA/HYNIC-Lys 3 -Bombesin) and 99m Tc-HYNIC-RGD ( 99m Tc EDDA/HYNIC-E-[c(RGDfK)] 2 ). Later on the production process of the product HYNIC-Bombesin/RGD-Sn was optimized using a factorial design and the formulation was transferred to the production plant of radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ). The optimized formulation is described in the following chart: HYNIC-[Lys 3 ]-Bombesin - 12.5 μg; HYNIC-E-c[RGDfK] 2 - 12.5 μg; Stannous chloride (SnCl 2 ) - 20 μg; Ethylenediamine diacetic acid (EDDA) - 10 mg; N-tris(hydroxymethyl)methyl glycin (Tricine) - 20 mg; Mannitol - 50 mg. The production process was validated and were carried out the stability studies under refrigeration conditions. (Author)

  2. Combination of NRP1-mediated iRGD with 5-fluorouracil suppresses proliferation, migration and invasion of gastric cancer cells.

    Science.gov (United States)

    Zhang, Li; Xing, Yanfeng; Gao, Qi; Sun, Xuejun; Zhang, Di; Cao, Gang

    2017-09-01

    Gastric cancer is one of the most of common cancers in the world. 5-Fluorouracil (5-FU) has been identified as one of the standard first-line chemotherapy drugs for locally advanced or metastatic gastric cancer. However, poor tumor penetration, bad selectivity and toxic side effects are the major limitations for the application of chemotherapy drugs in anticancer therapy. Recently, plenty of studies demonstrate that the novel tumor-homing peptide iRGD could promote the tumor-penetrating capability of chemotherapy drugs in multiple cancers, and neuropilin-1 (NRP1) protein is the critical mediator for iRGD. Here,we found that NRP1 protein expression was significantly up-regulated in gastric cancer tissues and cell lines by Immunohistochemistry and Western blot. And elevated NRP1 was notably associated with tumor differentiation (P=0.021), tumor size (P=0.004), tumor stage(P=0.028), lymph node metastasis(P=0.032), TNM tumor stage (P=0.006) and poorer prognosis. Functionally, the data of Methyl thiazolyl tetrazolium (MTT) assay, Colony formation assay and Transwell assay revealed that NRP1 could facilitate gastric cancer cells proliferation, migration and invasion. Furthermore, iRGD could strengthen the chemotherapy effect of 5-FU on gastric cancer cells through NRP1. Taken together, NPR1 might be a promising tumor target for gastric cancer, and combination of iRGD with 5-FU may be a novel and valuable approach to improving the prognosis of gastric cancer patients. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe

    Directory of Open Access Journals (Sweden)

    Lei Zhu, Ning Guo, Quanzheng Li, Ying Ma, Orit Jacboson, Seulki Lee, Hak Soo Choi, James R. Mansfield, Gang Niu, Xiaoyuan Chen

    2012-01-01

    Full Text Available Purpose: The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/64Cu dual-labeled cyclic RGD peptide.Methods: The integrin αvβ3 binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data.Results: The dual-labeled probe 64Cu-RGD-C(DOTA-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp derived from dynamic optical imaging (1.762 ± 0.020 is comparable to that from dynamic PET (1.752 ± 0.026.Conclusion: The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models.

  4. Radiation chemistry of aromatic dimer radical cations

    International Nuclear Information System (INIS)

    Okamoto, Kazumasa; Tagawa, Seiichi

    2009-01-01

    π-π Interactions of aromatic molecules are paid attention much in many fields, especially biology, chemistry, and applied physics, represented as protein, DNA, electron donor-accepter complexes, charge transfers, and self assembly molecules. Aromatic molecules including benzene rings are the simplest case to study the π-π interactions. To interpret the charge resonance (CR) structure in the dimer radical cations, spectroscopic and ESR methods have been carried out. The spectroscopic study on the dimer radical ion of molecules with two chromophores would be profitable to identify the electronic and configurational properties. In this article, dynamics of the dimer radical cation of benzenes, polystyrenes, and resist polymers is described on the basis of direct observation of CR band by the nanosecond pulse radiolysis and low temperature γ-radiolysis methods. (author)

  5. Photoionization of helium dimers; Photoionisation von Heliumdimeren

    Energy Technology Data Exchange (ETDEWEB)

    Havermeier, Tilo

    2010-06-09

    The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

  6. In vitro cell studies of technetium-99m labeled RGD-HYNIC peptide, a comparison of tricine and EDDA as co-ligands

    International Nuclear Information System (INIS)

    Su Zifen; He, Jiang; Rusckowski, Mary; Hnatowich, Donald J.

    2003-01-01

    The level of α V β 3 integrins on endothelial cells is elevated in angiogenesis. The high binding specificity to α V β 3 integrins of peptides containing Arg-Gly-Asp (RGD) residues suggests that the radiolabeled RGD peptides may be useful as tumor specific imaging agents. In this research, cyclised peptides containing Arg-Gly-Asp (RGD) and Arg-Gly-Glu (RGE, as control) residues were conjugated with HYNIC and labeled with 99m Tc. Objective: The goal was to evaluate the influence of co-ligand, either tricine or ethylenediamine-N,N'-diacetic acid (EDDA) on protein and integrin binding and on cellular uptake in culture. Methods: The n-octanol/water partition coefficient, binding to bovine serum albumin (BSA) and human umbilical vein endothelial (HUVE) cells, and cell lysate distributions of the radiolabeled peptides were evaluated. Results: The co-ligands had a significant effect on the labeling efficiency of the HYNIC conjugates and on certain properties of the 99m Tc complexes. The labeling efficiency with tricine was 10 fold higher and BSA binding was over 8 fold greater compared to EDDA. Both RGD labels showed higher (6 to 28 fold) binding to HUVE cells than that of the RGE labels, indicating binding specificity. After cell-lysis, only a small percentage of the total RGD label that accumulated in the cells was found bound to cellular proteins (9% of RGD/tricine and 5% of RGD/EDDA), implying that over 90% of the radiolabeled peptides were internalized for both radiolabeled RGDs. The number of the RGD molecules bound to proteins was estimated to be approximately three per cell, suggesting that only a small number of α V β 3 integrin proteins are expressed on the cells. Conclusions: Apart from the differences in radiolabeling, the only important effect of substituting EDDA for tricine as co-ligand on the HYNIC-peptides was the lower degree of serum protein binding. In spite of the lower serum protein binding potential, in vivo tumor accumulation of the RGD

  7. In vitro cell studies of technetium-99m labeled RGD-HYNIC peptide, a comparison of tricine and EDDA as co-ligands.

    Science.gov (United States)

    Su, Zi-Fen; He, Jiang; Rusckowski, Mary; Hnatowich, Donald J

    2003-02-01

    The level of alpha(V)beta(3) integrins on endothelial cells is elevated in angiogenesis. The high binding specificity to alpha(V)beta(3) integrins of peptides containing Arg-Gly-Asp (RGD) residues suggests that the radiolabeled RGD peptides may be useful as tumor specific imaging agents. In this research, cyclised peptides containing Arg-Gly-Asp (RGD) and Arg-Gly-Glu (RGE, as control) residues were conjugated with HYNIC and labeled with (99m)Tc. The goal was to evaluate the influence of co-ligand, either tricine or ethylenediamine-N,N'-diacetic acid (EDDA) on protein and integrin binding and on cellular uptake in culture. The n-octanol/water partition coefficient, binding to bovine serum albumin (BSA) and human umbilical vein endothelial (HUVE) cells, and cell lysate distributions of the radiolabeled peptides were evaluated. The co-ligands had a significant effect on the labeling efficiency of the HYNIC conjugates and on certain properties of the (99m)Tc complexes. The labeling efficiency with tricine was 10 fold higher and BSA binding was over 8 fold greater compared to EDDA. Both RGD labels showed higher (6 to 28 fold) binding to HUVE cells than that of the RGE labels, indicating binding specificity. After cell-lysis, only a small percentage of the total RGD label that accumulated in the cells was found bound to cellular proteins (9% of RGD/tricine and 5% of RGD/EDDA), implying that over 90% of the radiolabeled peptides were internalized for both radiolabeled RGDs. The number of the RGD molecules bound to proteins was estimated to be approximately three per cell, suggesting that only a small number of alpha(V)beta(3) integrin proteins are expressed on the cells. Apart from the differences in radiolabeling, the only important effect of substituting EDDA for tricine as co-ligand on the HYNIC-peptides was the lower degree of serum protein binding. In spite of the lower serum protein binding potential, in vivo tumor accumulation of the RGD/EDDA may not be improved

  8. Induction of Chondrogenic Differentiation of Human Mesenchymal Stem Cells by Biomimetic Gold Nanoparticles with Tunable RGD Density.

    Science.gov (United States)

    Li, Jingchao; Li, Xiaomeng; Zhang, Jing; Kawazoe, Naoki; Chen, Guoping

    2017-07-01

    Nanostructured materials have drawn a broad attention for their applications in biomedical fields. Ligand-modified nanomaterials can well mimic the dynamic extracellular matrix (ECM) microenvironments to regulate cell functions and fates. Herein, ECM mimetic gold nanoparticles (Au NPs) with tunable surface arginine-glycine-aspartate (RGD) density are designed and synthesized to induce the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The biomimetic Au NPs with an average size of 40 nm shows good biocompatibility without affecting the cell proliferation in the studied concentration range. The RGD motifs on Au NPs surface facilitate cellular uptake of NPs into monolayer hMSCs through integrin-mediated endocytosis. The biomimetic NPs have a promotive effect on cartilaginous matrix production and marker gene expression in cell pellet culture, especially for the biomimetic Au NPs with high surface RGD density. This study provides a novel strategy for fabricating biomimetic NPs to regulate cell differentiation, which holds great potentials in tissue engineering and biomedical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Photon Propagation through Linearly Active Dimers

    Directory of Open Access Journals (Sweden)

    José Delfino Huerta Morales

    2017-06-01

    Full Text Available We provide an analytic propagator for non-Hermitian dimers showing linear gain or losses in the quantum regime. In particular, we focus on experimentally feasible realizations of the PT -symmetric dimer and provide their mean photon number and second order two-point correlation. We study the propagation of vacuum, single photon spatially-separable, and two-photon spatially-entangled states. We show that each configuration produces a particular signature that might signal their possible uses as photon switches, semi-classical intensity-tunable sources, or spatially entangled sources to mention a few possible applications.

  10. On the asymptotics of dimers on tori

    OpenAIRE

    Kenyon, Richard W.; Sun, Nike; Wilson, David B.

    2013-01-01

    We study asymptotics of the dimer model on large toric graphs. Let $\\mathbb L$ be a weighted $\\mathbb{Z}^2$-periodic planar graph, and let $\\mathbb{Z}^2 E$ be a large-index sublattice of $\\mathbb{Z}^2$. For $\\mathbb L$ bipartite we show that the dimer partition function on the quotient $\\mathbb{L}/(\\mathbb{Z}^2 E)$ has the asymptotic expansion $\\exp[A f_0 + \\text{fsc} + o(1)]$, where $A$ is the area of $\\mathbb{L}/(\\mathbb{Z}^2 E)$, $f_0$ is the free energy density in the bulk, and $\\text{fsc...

  11. Sigma- versus Pi-Dimerization Modes of Triangulene.

    Science.gov (United States)

    Mou, Zhongyu; Kertesz, Miklos

    2018-04-20

    We show that the diradicaloid triangulene, a graphene nano-flake molecule, can aggregate in a variety of dimerization modes. We found by density functional theory modeling a number of triangulene dimers including six doubly bonded σ-dimers in addition to the previously reported six pancake bonded π-dimer isomers. The σ-dimers display a wide range of stabilities: the interaction energy of the most stable σ-dimer is -25.17 kcal mol -1 . Besides the doubly bonded σ-dimers with closed shell ground states, we also found an open-shell singly σ-bonded diradicaloid dimer. We found an interesting isomerization route between a doubly bonded σ-dimer, a singly bonded σ-dimer with a low-lying triplet state and two π-bonded dimers with low-lying quintet states. Derivatives of triangulene, trioxo-triangulenes (TOTs) have been previously characterized experimentally. Here, we show the reasons why so far only the π-dimer but not the σ-dimer was experimentally observed for all TOTs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. RGD(F/S/V-Dex: towards the development of novel, effective, and safe glucocorticoids

    Directory of Open Access Journals (Sweden)

    Jiang X

    2016-03-01

    Full Text Available Xueyun Jiang,1 Ming Zhao,1,2 Yuji Wang,1 Haimei Zhu,1 Shurui Zhao,1 Jianhui Wu,1 Yuanbo Song,3 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Guangxi Pusen Biotechnology Co. Ltd., Nanning, Guangxi, People’s Republic of China Abstract: Dexamethasone (Dex is an effective glucocorticoid in treating inflammation and preventing rejection reaction. However, the side effects limit its clinical application. To improve its druggable profile, the conjugates of RGD-peptide-modified Dex were presented and their enhanced anti-inflammation activity, minimized osteoporotic action, and nanoscaled assembly were explored. (RGD stands for Arg-Gly-Asp. Standard single letter biochemical abbreviations for amino acids have been used throughout this paper. In respect of the rejection reaction, the survival time of the implanted myocardium of the mice treated with 1.43 µmol/kg/d of the conjugates for 15 consecutive days was significantly longer than that of the mice treated with 2.5 µmol/kg/d of Dex, and the conjugates, but not Dex, exhibited no toxic action. At a single dose of 14.3 µmol/kg (100 times minimal effective dose, 0.143 µmol/kg, the conjugates induced no liver, kidney, or systemic toxicity. At the dose of 1.43 µmol/kg, the conjugates, but not Dex, prolonged the bleeding time of the mice, and inhibited the thrombosis of the rats. In water and rat plasma, the conjugates formed nanoparticles of 14–250 and 101–166 nm in diameter, respectively. Since the nanoparticles of ~100 nm in size cannot be entrapped by macrophages in the circulation, RGDF-Dex would particularly be worthy

  13. In-vivo study of adhesion and bone growth around implanted laser groove/RGD-functionalized Ti-6Al-4V pins in rabbit femurs

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J., E-mail: jianboc@gmail.com [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Bly, R.A. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Saad, M.M.; AlKhodary, M.A.; El-Backly, R.M. [Tissue Engineering laboratories, Faculty of Dentistry, Alexandria University, Alexandria (Egypt); Cohen, D.J.; Kattamis, N. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Fatta, M.M.; Moore, W.A. [Tissue Engineering laboratories, Faculty of Dentistry, Alexandria University, Alexandria (Egypt); Arnold, C.B. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Marei, M.K. [Tissue Engineering laboratories, Faculty of Dentistry, Alexandria University, Alexandria (Egypt); Soboyejo, W.O. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States)

    2011-07-20

    Titanium surfaces were designed, produced, and evaluated for levels of osseointegration into the femurs of rabbits. A total of 36 Ti-6Al-4V pins (15 mm length, 1.64 mm diameter) were prepared into three experimental groups. These were designed to test the effects of osseointegration on laser grooved, RGD coated, and polished control surfaces, as well as combined effects. Circumferential laser grooves were introduced onto pin surfaces (40 {mu}m spacing) using a UV laser ({lambda} = 355 nm). The tripeptide sequence, Arginine-Glycine-Aspartic acid (RGD), was functionalized onto laser grooved surfaces. Of the prepared samples, surface morphology and chemistry were analyzed using scanning electron microscopy (SEM) and Immunoflourescence (IF) spectroscopy, respectively. The experimental pin surfaces were surgically implanted into rabbit femurs. The samples were then harvested and evaluated histologically. Sections of the sample were preserved in a methylmethacralate mold, sliced via a hard microtome, and polished systematically. In the case of the RGD coated and laser grooved surfaces, histological results showed accelerated bone growth into the implant, pull-out tests were also used to compare the adhesion between bone and the titanium pins with/without laser textures and/or RGD coatings. - Research highlights: {yields} Circumferential laser grooves were introduced onto pin surfaces using a UV laser. {yields} The tripeptide sequence, RGD, was functionalized onto laser grooved surfaces. {yields} The experimental pin surfaces were surgically implanted into rabbit femurs. {yields} RGD coated laser groove surfaces accelerated bone growth into the implant. {yields} RGD coated laser grooved surfaces enhanced the adhesion between the bone and implant.

  14. In-vivo study of adhesion and bone growth around implanted laser groove/RGD-functionalized Ti-6Al-4V pins in rabbit femurs

    International Nuclear Information System (INIS)

    Chen, J.; Bly, R.A.; Saad, M.M.; AlKhodary, M.A.; El-Backly, R.M.; Cohen, D.J.; Kattamis, N.; Fatta, M.M.; Moore, W.A.; Arnold, C.B.; Marei, M.K.; Soboyejo, W.O.

    2011-01-01

    Titanium surfaces were designed, produced, and evaluated for levels of osseointegration into the femurs of rabbits. A total of 36 Ti-6Al-4V pins (15 mm length, 1.64 mm diameter) were prepared into three experimental groups. These were designed to test the effects of osseointegration on laser grooved, RGD coated, and polished control surfaces, as well as combined effects. Circumferential laser grooves were introduced onto pin surfaces (40 μm spacing) using a UV laser (λ = 355 nm). The tripeptide sequence, Arginine-Glycine-Aspartic acid (RGD), was functionalized onto laser grooved surfaces. Of the prepared samples, surface morphology and chemistry were analyzed using scanning electron microscopy (SEM) and Immunoflourescence (IF) spectroscopy, respectively. The experimental pin surfaces were surgically implanted into rabbit femurs. The samples were then harvested and evaluated histologically. Sections of the sample were preserved in a methylmethacralate mold, sliced via a hard microtome, and polished systematically. In the case of the RGD coated and laser grooved surfaces, histological results showed accelerated bone growth into the implant, pull-out tests were also used to compare the adhesion between bone and the titanium pins with/without laser textures and/or RGD coatings. - Research highlights: → Circumferential laser grooves were introduced onto pin surfaces using a UV laser. → The tripeptide sequence, RGD, was functionalized onto laser grooved surfaces. → The experimental pin surfaces were surgically implanted into rabbit femurs. → RGD coated laser groove surfaces accelerated bone growth into the implant. → RGD coated laser grooved surfaces enhanced the adhesion between the bone and implant.

  15. Molecular Magnetic Resonance Imaging of Angiogenesis In Vivo using Polyvalent Cyclic RGD-Iron Oxide Microparticle Conjugates

    Science.gov (United States)

    Melemenidis, Stavros; Jefferson, Andrew; Ruparelia, Neil; Akhtar, Asim M; Xie, Jin; Allen, Danny; Hamilton, Alastair; Larkin, James R; Perez-Balderas, Francisco; Smart, Sean C; Muschel, Ruth J; Chen, Xiaoyuan; Sibson, Nicola R; Choudhury, Robin P

    2015-01-01

    Angiogenesis is an essential component of tumour growth and, consequently, an important target both therapeutically and diagnostically. The cell adhesion molecule αvβ3 integrin is a specific marker of angiogenic vessels and the most prevalent vascular integrin that binds the amino acid sequence arginine-glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of tumour angiogenesis, have identified a number of limitations, including non-specific extravasation, long blood half-life (reducing specific contrast) and low targeting valency. The aim of this study, therefore, was to determine whether conjugation of a cyclic RGD variant [c(RGDyK)], with enhanced affinity for αvβ3, to microparticles of iron oxide (MPIO) would provide a more sensitive contrast agent for imaging of angiogenic tumour vessels. Cyclic RGD [c(RGDyK)] and RAD [c(RADyK)] based peptides were coupled to 2.8 μm MPIO, and binding efficacy tested both in vitro and in vivo. Significantly greater specific binding of c(RGDyK)-MPIO to S-nitroso-n-acetylpenicillamine (SNAP)-stimulated human umbilical vein endothelial cells in vitro than PBS-treated cells was demonstrated under both static (14-fold increase; P agent in both tumour models (melanoma P < 0.001; colorectal P < 0.0001). Correspondingly, MPIO density per tumour volume assessed immunohistochemically was significantly greater for c(RGDyK)-MPIO than c(RADyK)-MPIO injected animals, in both melanoma (P < 0.05) and colorectal (P < 0.0005) tumours. In both cases, binding of c(RGDyK)-MPIO co-localised with αvβ3 expression. Comparison of RGD-targeted and dynamic contrast enhanced (DCE) MRI assessment of tumour perfusion indicated sensitivity to different vascular features. This study demonstrates specific binding of c(RGDyK)-MPIO to αvβ3 expressing neo-vessels, with marked and quantifiable contrast and rapid clearance of unbound particles from the

  16. Structural insights into the intertwined dimer of fyn SH2.

    Science.gov (United States)

    Huculeci, Radu; Garcia-Pino, Abel; Buts, Lieven; Lenaerts, Tom; van Nuland, Nico

    2015-12-01

    Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide-bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand. © 2015 The Protein Society.

  17. Synthesis and characterization of monomeric and dimeric ...

    African Journals Online (AJOL)

    The two complexes are isostructural, with the central metal atom lying on a crystallographic 2-fold axis. Both complexes are approximately octahedral, the coordination being provided by two trans pyridine nitrogen atoms and two cis amine nitrogen atoms from the oxime ligands, and by two cis chlorides. The dimeric ...

  18. The hyperfine spectrum of hydrogen dimers

    International Nuclear Information System (INIS)

    Verberne, J.F.C.

    1979-01-01

    The authors' aim was to obtain the level scheme for the hydrogen dimers and to investigate the angle dependent interactions by analyzing the zero magnetic field hyperfine spectrum of the ortho-ortho and ortho-para species. The results were tested by several recent semi-empirical and ab initio potentials. (Auth.)

  19. What factors control dimerization of coniferyl alcohol?

    Science.gov (United States)

    Carl J. Houtman

    1999-01-01

    Data suggest that the dimerization of coniferyl alcohol is not under thermodynamic control. In this study, molecular dynamics calculations were used to estimate the effect of the solvent environment. In water, the coniferyl alcohol radicals were forced to associate by the formation of a solvent cage. In glycerol, the solvent cage effect appeared to be absent. These...

  20. Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.

    Science.gov (United States)

    De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai

    2016-07-01

    Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. © 2016 The Authors.

  1. Determination of the Tetramer-Dimer Equilibrium Constant of Rabbit ...

    African Journals Online (AJOL)

    Hemoglobin is a tetrameric protein which is able to dissociate into dimers. The dimers can in turn dissociate into tetramers. It has been found that dimers are more reactive than tetramers. The difference in the reactivity of these two species has been used to determine the tetramerdimer dissociation constant of various ...

  2. Stochastic optimization-based study of dimerization kinetics

    Indian Academy of Sciences (India)

    To this end, we study dimerization kinetics of protein as a model system. We follow the dimerization kinetics using a stochastic simulation algorithm and ... optimization; dimerization kinetics; sensitivity analysis; stochastic simulation ... tion in large molecules and clusters, or the design ..... An unbiased strategy of allocating.

  3. Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in rats

    Directory of Open Access Journals (Sweden)

    Rodriguez-Nogales A

    2016-11-01

    Full Text Available Alba Rodriguez-Nogales,1 Francesca Algieri,1 Laura De Matteis,2 A. Abel Lozano-Perez,3 Jose Garrido-Mesa,1 Teresa Vezza,1 J M. de la Fuente,2 Jose Luis Cenis,3 Julio Gálvez,1,* Maria Elena Rodriguez-Cabezas1,* 1CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada, 2Instituto de Nanociencia de Aragón, Universidad de Zaragoza, Zaragoza, 3Department of Biotechnology, Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario, Murcia, Spain *These authors contributed equally to this work Background: Current treatment of inflammatory bowel disease is based on the use of immunosuppressants or anti-inflammatory drugs, which are characterized by important side effects that can limit their use. Previous research has been performed by administering these drugs as nanoparticles that target the ulcerated intestinal regions and increase their bioavailability. It has been reported that silk fibroin can act as a drug carrier and shows anti-inflammatory properties. Purpose: This study was designed to enhance the interaction of the silk fibroin nanoparticles (SFNs with the injured intestinal tissue by functionalizing them with the peptide motif RGD (arginine–glycine–aspartic acid and to evaluate the intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin nanoparticles (RGD-SFNs in the trinitrobenzenesulfonic acid (TNBS model of rat colitis. Materials and methods: SFNs were prepared by nanoprecipitation in methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as the crosslinker. The SFNs (1 mg/rat and RGD-SFNs (1 mg/rat were administered intrarectally to TNBS-induced colitic rats for 7 days. Results: The SFN treatments ameliorated the colonic damage, reduced neutrophil infiltration, and improved the compromised oxidative status of the colon. However, only the rats treated with RGD-SFNs showed a significant reduction in the

  4. Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Cui Y

    2016-11-01

    Full Text Available Yanfen Cui,1,* Caiyuan Zhang,1,* Ran Luo,1 Huanhuan Liu,1 Zhongyang Zhang,1 Tianyong Xu,2 Yong Zhang,2 Dengbin Wang11Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 2MR Advanced Application and Research Center, GE Healthcare China, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: Arginine-glycine-aspartic acid (RGD-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA-coated ultrasmall superparamagnetic iron oxide (USPIO (referred to as RGD-PAA-USPIO in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC xenograft model by magnetic resonance imaging (MRI.Materials and methods: The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group.Results: The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05.Conclusion: This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in

  5. RGD peptide-targeted polyethylenimine-entrapped gold nanoparticles for targeted CT imaging of an orthotopic model of human hepatocellular carcinoma

    Science.gov (United States)

    Zhou, Benqing; Wang, Meng; Zhou, Feifan; Song, Jun; Qu, Junle; Chen, Wei R.

    2018-02-01

    We report the synthesis and characterization of arginine-glycine-aspartic acid (RGD) peptide-targeted polyethylenimine (PEI)-entrapped gold nanoparticles (RGD-Au PENPs) for targeted CT imaging of hepatic carcinomas in situ. In this work, PEI sequentially modified with polyethylene glycol (PEG), and RGD linked-PEG was used as a nanoplatform to prepare AuNPs, followed by complete acetylation of PEI surface amines. We showed that the designed RGD-Au PENPs were colloidally stable and biocompatible in the given concentration range, and could be specifically taken up by αvβ3 integrin-overexpressing liver cancer cells in vitro. Furthermore, in vivo CT imaging results revealed that the particles displayed a great contrast enhancement of hepatic carcinomas region, and could target to hepatic carcinomas region in situ. With the proven biodistribution and histological examinations in vivo, the synthesized RGD-Au PENPs show a great formulation to be used as a contrast agent for targeted CT imaging of different αvβ3 integrin receptoroverexpressing tumors.

  6. Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.

    Science.gov (United States)

    Richardson, Adam; Muir, Lewis; Mousdell, Sasha; Sexton, Darren; Jones, Sarah; Howl, John; Ross, Kehinde

    2018-01-30

    Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis. In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L -1 , MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes.

  7. Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold.

    Science.gov (United States)

    Moshaverinia, Alireza; Chen, Chider; Xu, Xingtian; Akiyama, Kentaro; Ansari, Sahar; Zadeh, Homayoun H; Shi, Songtao

    2014-02-01

    Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD- (arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

  8. Dual targeting strategy of magnetic nanoparticle-loaded and RGD peptide-activated stimuli-sensitive polymeric micelles for delivery of paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Meng Meng [Tsinghua University, Department of Chemical Engineering (China); Kang, Yoon Joong [Jungwon University, Department of Biomedical Science (Korea, Republic of); Sohn, Youngjoo [Kyung Hee University, Department of Anatomy, College of Korean Medicine (Korea, Republic of); Kim, Do Kyung, E-mail: eurokorean@gmail.com, E-mail: dokyung@konyang.ac.kr [Konyang University, Industry Cooperation Foundation (Korea, Republic of)

    2015-06-15

    A double targeting strategy of anti-neoplastic agent paclitaxel (PTX) was developed by incorporating magnetic nanoparticles and RGD peptide for enhanced cell cytotoxicity effect at lower dosage. A dual targeting mechanism including magnetic targeting and RGD ligand-specific targeting enhanced the overall cytotoxicity and reduced the effective dosage of PTX to achieve enhanced and sustained release of PTX in vitro. We addressed the issues of water-insolubility of oleic acid (OA)-stabilized SPIONs and low incorporation efficiency of hydrophobic PTX with SPION nanocarriers by using an amphiphilic polymer poly[(N-isopropylacrylamide-r-acrylamide)-b-l-lactic acid] (PNAL) as micelle-forming materials. A targeting moiety, GGGGRGD peptide, a RGD sequence-containing peptide with a short linker, is attached to the surface of PNAL-SPIONs via a homo-crosslinker. Confocal microscopy image analysis revealed that the cellular uptake was increased from (1.5 ± 0.5 % (PNAL) to 11.7 ± 0.8 % (RGD-PNAL-SPIONs) at 6 h incubation, once both RGD peptide and magnetic force attraction were incorporated into the carriers. Such multi-targeting nanocarriers showed promising potential in cancer-oriented diagnosis and therapy.

  9. Three-Dimensional Graphene–RGD Peptide Nanoisland Composites That Enhance the Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Ee-Seul Kang

    2018-02-01

    Full Text Available Graphene derivatives have immense potential in stem cell research. Here, we report a three-dimensional graphene/arginine-glycine-aspartic acid (RGD peptide nanoisland composite effective in guiding the osteogenesis of human adipose-derived mesenchymal stem cells (ADSCs. Amine-modified silica nanoparticles (SiNPs were uniformly coated onto an indium tin oxide electrode (ITO, followed by graphene oxide (GO encapsulation and electrochemical deposition of gold nanoparticles. A RGD–MAP–C peptide, with a triple-branched repeating RGD sequence and a terminal cysteine, was self-assembled onto the gold nanoparticles, generating the final three-dimensional graphene–RGD peptide nanoisland composite. We generated substrates with various gold nanoparticle–RGD peptide cluster densities, and found that the platform with the maximal number of clusters was most suitable for ADSC adhesion and spreading. Remarkably, the same platform was also highly efficient at guiding ADSC osteogenesis compared with other substrates, based on gene expression (alkaline phosphatase (ALP, runt-related transcription factor 2, enzyme activity (ALP, and calcium deposition. ADSCs induced to differentiate into osteoblasts showed higher calcium accumulations after 14–21 days than when grown on typical GO-SiNP complexes, suggesting that the platform can accelerate ADSC osteoblastic differentiation. The results demonstrate that a three-dimensional graphene–RGD peptide nanoisland composite can efficiently derive osteoblasts from mesenchymal stem cells.

  10. Structure of Acostatin, a Dimeric Disintegrin From Southern Copperhead (Agkistrodon Contortrix Contortrix), at 1.7 Angstrom Resolution

    Energy Technology Data Exchange (ETDEWEB)

    Moiseeva, N.; Bau, R.; Swenson, S.D.; Marklund, F.S.; Jr.; Choe, J.-Y.; Liu, Z.-J.; Allaire, M.

    2009-05-26

    Disintegrins are a family of small (4-14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an {alpha}{beta} heterodimeric disintegrin, has been isolated from the venom of Southern copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure of acostatin has been determined by macromolecular crystallography using the molecular-replacement method. The asymmetric unit of the acostatin crystals consists of two heterodimers. The structure has been refined to an R{sub work} and R{sub free} of 18.6% and 21.5%, respectively, using all data in the 20-1.7 {angstrom} resolution range. The structure of all subunits is similar and is well ordered into N-terminal and C-terminal clusters with four intramolecular disulfide bonds. The overall fold consists of short {beta}-sheets, each of which is formed by a pair of antiparallel {beta}-strands connected by {beta}-turns and flexible loops of different lengths. Conformational flexibility is found in the RGD loops and in the C-terminal segment. The interaction of two N-terminal clusters via two intermolecular disulfide bridges anchors the {alpha}{beta}chains of the acostatin dimers. The C-terminal clusters of the heterodimer project in opposite directions and form a larger angle between them in comparison with other dimeric disintegrins. Extensive interactions are observed between two heterodimers, revealing an {alpha}{beta}{beta}{alpha} acostatin tetramer. Further experiments are required to identify whether the {alpha}{beta}{beta}{alpha} acostatin complex plays a functional role in vivo.

  11. Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 Å resolution

    International Nuclear Information System (INIS)

    Moiseeva, Natalia; Bau, Robert; Swenson, Stephen D.; Markland, Francis S. Jr; Choe, Jun-Yong; Liu, Zhi-Jie; Allaire, Marc

    2008-01-01

    Two acostatin heterodimers interact together to form an αββα tetramer. Disintegrins are a family of small (4–14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an αβ heterodimeric disintegrin, has been isolated from the venom of Southern copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure of acostatin has been determined by macromolecular crystallography using the molecular-replacement method. The asymmetric unit of the acostatin crystals consists of two heterodimers. The structure has been refined to an R work and R free of 18.6% and 21.5%, respectively, using all data in the 20–1.7 Å resolution range. The structure of all subunits is similar and is well ordered into N-terminal and C-terminal clusters with four intramolecular disulfide bonds. The overall fold consists of short β-sheets, each of which is formed by a pair of antiparallel β-strands connected by β-turns and flexible loops of different lengths. Conformational flexibility is found in the RGD loops and in the C-terminal segment. The interaction of two N-terminal clusters via two intermolecular disulfide bridges anchors the αβ chains of the acostatin dimers. The C-terminal clusters of the heterodimer project in opposite directions and form a larger angle between them in comparison with other dimeric disintegrins. Extensive interactions are observed between two heterodimers, revealing an αββα acostatin tetramer. Further experiments are required to identify whether the αββα acostatin complex plays a functional role in vivo

  12. Pyrimidine dimer formation and repair in human skin

    International Nuclear Information System (INIS)

    Sutherland, B.M.; Harber, L.C.; Kochevar, I.E.

    1980-01-01

    Cyclobutyl pyrimidine dimers have been detected in the DNA of human skin following in vivo irradiation with suberythermal doses of ultraviolet (UV) radiation from FS-20 sun lamp fluorescent tubes. Dimers were assayed by treatment of extracted DNA with Micrococus luteus UV-specific endonuclease, alkaline agarose electrophoresis, and ethidum bromide staining. This technique, in contrast to conventional dimer assays, can be used with nonradioactive DNA and is optimal at low UV light doses. These data suggest that some dimer disappearance by excision repair occurs within 20 min of UV irradiation and that photoreactivation of dimers can make a contribution to the total repair process

  13. Reduction of renal uptake of 111In-DOTA-labeled and A700-labeled RAFT-RGD during integrin αvβ3 targeting using single photon emission computed tomography and optical imaging.

    Science.gov (United States)

    Briat, Arnaud; Wenk, Christiane H F; Ahmadi, Mitra; Claron, Michael; Boturyn, Didier; Josserand, Véronique; Dumy, Pascal; Fagret, Daniel; Coll, Jean-Luc; Ghezzi, Catherine; Sancey, Lucie; Vuillez, Jean-Philippe

    2012-06-01

    Integrin α(v)β(3) expression is upregulated during tumor growth and invasion in newly formed endothelial cells in tumor neovasculature and in some tumor cells. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin α(v)β(3) in vitro and in vivo. When labeled with indium-111, the RAFT-RGD is partially reabsorbed and trapped in the kidneys, limiting its use for further internal targeted radiotherapy and imaging investigations. We studied the effect of Gelofusine on RAFT-RGD renal retention in tumor-bearing mice. Mice were imaged using single photon emission computed tomography and optical imaging 1 and 24 h following tracer injection. Distribution of RAFT-RGD was further investigated by tissue removal and direct counting of the tracer. Kidney sections were analyzed by confocal microscopy. Gelofusine significantly induced a >50% reduction of the renal reabsorption of (111)In-DOTA-RAFT-RGD and A700-RAFT-RGD, without affecting tumor uptake. Injection of Gelofusine significantly reduced the renal retention of labeled RAFT-RGD, while increasing the tumor over healthy tissue ratio. These results will lead to the development of future therapeutic approaches. © 2012 Japanese Cancer Association.

  14. A pilot study imaging integrin αvβ3 with RGD PET/CT in suspected lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Song [Shandong Cancer Hospital and Institute, Department of Radiation Oncology, Jinan, Shandong (China); University of Jinan-Shandong Academy of Medical Sciences, School of Medicine and Life Sciences, Jinan, Shandong (China); Wu, Honghu [Wuyi County People' s Hospital of Hengshui City, Hengshui, Hebei Province (China); Li, Wenwu; Zhao, Shuqiang; Teng, Xuepeng; Lu, Hong [Shandong Cancer Hospital and Institute, Department of Radiology, Jinan, Shandong (China); Hu, Xudong; Wang, Suzhen; Yu, Jinming; Yuan, Shuanghu [Shandong Cancer Hospital and Institute, Department of Radiation Oncology, Jinan, Shandong (China)

    2015-12-15

    Angiogenesis is an essential step in tumour development and metastasis. Integrin αvβ3 plays a major role in angiogenesis, tumour growth and progression. A new tracer, {sup 18}F-AL-NOTA-PRGD2, denoted as {sup 18}F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin αvβ3. This is a pilot study to test the safety and diagnostic value of {sup 18}F- arginine-glycine-aspartic acid (RGD) PET/computed tomography (CT) in suspected lung cancer patients. Twenty-six patients with suspected lung cancer on enhanced CT underwent {sup 18}F-alfatide RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUVs) and the tumour-to-blood ratios were measured, and diagnoses were pathologically confirmed. RGD PET/CT with {sup 18}F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed. The {sup 18}F-alfatide RGD PET/CT analysis correctly recognized 17 patients with lung cancer, 4 patients (hamartoma) as true negative, and 5 patients (4 chronic inflammation and 1 inflammatory pseudotumour) as false positive. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of {sup 18}F-alfatide RGD PET/CT for the diagnosis of suspected lung cancer patients was 100, 44.44, 80.77, 77.27, and 100 %, respectively. The area under a receiver operating characteristic (ROC) curve was 0.75 (P = 0.038), and ROC analysis suggested an SUVmax cut-off value of 2.65 to differentiate between malignant lesions and benign lesions. The SUV for malignant lesions was 5.37 ± 2.17, significantly higher than that for hamartomas (1.60 ± 0.11; P < 0.001). The difference between the tumour-to-blood ratio for malignant lesions (4.13 ± 0.91) and tissue of interest-to-blood ratio for hamartomas (1.56 ± 0.24) was also statistically significant (P < 0.001). Neither the SUVmax nor the tumour-to-blood ratio was significantly different between malignant

  15. Fibrillar dimer formation of islet amyloid polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Chi-cheng [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); de Pablo, Juan J. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-05-08

    Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

  16. An introduction to the dimer model

    International Nuclear Information System (INIS)

    Kenyon, R.

    2004-01-01

    A perfect matching of a graph is a subset of edges which covers every vertex exactly once, that is, for every vertex there is exactly one edge in the set with that vertex as endpoint. The dimer model is the study of the set of perfect matchings of a (possibly infinite) graph. The most well-known example is when the graph is Z 2 , for which perfect matchings are equivalent (via a simple duality) to domino tilings, that is, tilings of the plane with 2 x 1 and 1 x 2 rectangles. In the first three sections we study domino tilings of the plane and of finite polygonal regions, or equivalently, perfect matchings on Z 2 and subgraphs of Z 2 . In the last two sections we study the FK-percolation model and the dimer model on a more general family of planar graphs

  17. Revisiting the Optical PT-Symmetric Dimer

    Directory of Open Access Journals (Sweden)

    José Delfino Huerta Morales

    2016-08-01

    Full Text Available Optics has proved a fertile ground for the experimental simulation of quantum mechanics. Most recently, optical realizations of PT -symmetric quantum mechanics have been shown, both theoretically and experimentally, opening the door to international efforts aiming at the design of practical optical devices exploiting this symmetry. Here, we focus on the optical PT -symmetric dimer, a two-waveguide coupler where the materials show symmetric effective gain and loss, and provide a review of the linear and nonlinear optical realizations from a symmetry-based point of view. We go beyond a simple review of the literature and show that the dimer is just the smallest of a class of planar N-waveguide couplers that are the optical realization of the Lorentz group in 2 + 1 dimensions. Furthermore, we provide a formulation to describe light propagation through waveguide couplers described by non-Hermitian mode coupling matrices based on a non-Hermitian generalization of the Ehrenfest theorem.

  18. Palmitoylated APP Forms Dimers, Cleaved by BACE1.

    Directory of Open Access Journals (Sweden)

    Raja Bhattacharyya

    Full Text Available A major rate-limiting step for Aβ generation and deposition in Alzheimer's disease brains is BACE1-mediated cleavage (β-cleavage of the amyloid precursor protein (APP. We previously reported that APP undergoes palmitoylation at two cysteine residues (Cys186 and Cys187 in the E1-ectodomain. 8-10% of total APP is palmitoylated in vitro and in vivo. Palmitoylated APP (palAPP shows greater preference for β-cleavage than total APP in detergent resistant lipid rafts. Protein palmitoylation is known to promote protein dimerization. Since dimerization of APP at its E1-ectodomain results in elevated BACE1-mediated cleavage of APP, we have now investigated whether palmitoylation of APP affects its dimerization and whether this leads to elevated β-cleavage of the protein. Here we report that over 90% of palAPP is dimerized while only ~20% of total APP forms dimers. PalAPP-dimers are predominantly cis-oriented while total APP dimerizes in both cis- and trans-orientation. PalAPP forms dimers 4.5-times more efficiently than total APP. Overexpression of the palmitoylating enzymes DHHC7 and DHHC21 that increase palAPP levels and Aβ release, also increased APP dimerization in cells. Conversely, inhibition of APP palmitoylation by pharmacological inhibitors reduced APP-dimerization in coimmunoprecipitation and FLIM/FRET assays. Finally, in vitro BACE1-activity assays demonstrate that palmitoylation-dependent dimerization of APP promotes β-cleavage of APP in lipid-rich detergent resistant cell membranes (DRMs, when compared to total APP. Most importantly, generation of sAPPβ-sAPPβ dimers is dependent on APP-palmitoylation while total sAPPβ generation is not. Since BACE1 shows preference for palAPP dimers over total APP, palAPP dimers may serve as novel targets for effective β-cleavage inhibitors of APP as opposed to BACE1 inhibitors.

  19. Oxidation of NAD dimers by horseradish peroxidase.

    OpenAIRE

    Avigliano, L; Carelli, V; Casini, A; Finazzi-Agrò, A; Liberatore, F

    1985-01-01

    Horseradish peroxidase catalyses the oxidation of NAD dimers, (NAD)2, to NAD+ in accordance with a reaction that is pH-dependent and requires 1 mol of O2 per 2 mol of (NAD)2. Horseradish peroxidase also catalyses the peroxidation of (NAD)2 to NAD+. In contrast, bacterial NADH peroxidase does not catalyse the peroxidation or the oxidation of (NAD)2. A free-radical mechanism is proposed for both horseradish-peroxidase-catalysed oxidation and peroxidation of (NAD)2.

  20. On the dimerization of linear polymers

    International Nuclear Information System (INIS)

    Aragao Carvalho, C. de.

    1988-08-01

    We use the continuum limit of the Su-Schrieffer-Heeger model for linear polymers to construct its effective potential (Gibbs free energy) both at zero and finite temperature. We study both trans and cis-polymers. Our results show that, depending on a renormalization condition to be extracted from experiment, there are several possibilities for the minima of the dimerized ground state of cis-polymers. All calculations are done in the one-loop approximation. (author). 16 refs, 3 figs

  1. Entanglement in a Dimerized Antiferromagnetic Heisenberg Chain

    OpenAIRE

    Hao, Xiang; Zhu, Shiqun

    2008-01-01

    The entanglement properties in an antiferromagnetic dimerized Heisenberg spin-1/2 chain are investigated. The entanglement gap, which is the difference between the ground-state energy and the minimal energy that any separable state can attain, is calculated to detect the entanglement. It is found that the entanglement gap can be increased by varying the alternation parameter. Through thermal energy, the witness of the entanglement can determine a characteristic temperature below that an entan...

  2. Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yinbo Zhao

    2014-09-01

    Full Text Available In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs modified by Arg–Gly–Asp(RGD peptide, loaded with curcumin (Cur, were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid–mPEG (methoxyl poly(ethylene- glycol, RGD–polyethylene glycol (PEG–cholesterol (Chol copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD–lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD–lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD–lpNPs was increased for human umbilical vein endothelial cells (HUVEC. Furthermore, Cur loaded RGD–lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD–lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD–lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD–lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.

  3. Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin alphanubeta3 receptor-expressed tumor-MR molecular imaging of angiogenesis.

    Science.gov (United States)

    Huo, Tianlong; Du, Xiangke; Zhang, Sen; Liu, Xia; Li, Xubing

    2010-02-01

    The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin alphanubeta3 receptor-expressed tumor. Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd(3+), and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin alphanubeta3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90min p.i., while the control arms do not show this tendency. Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin alphanubeta3 receptor-expressed tumor. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

  4. Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin {alpha}{nu}{beta}3 receptor-expressed tumor-MR molecular imaging of angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Huo Tianlong [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: huotianlong@bjmu.edu.cn; Du Xiangke [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: duxk@263.net; Zhang Sen [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: skagerrak_s@yahoo.com.cn; Liu Xia [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: iamliuxia@126.com; Li Xubing [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: lixb@bjmu.edu.cn

    2010-02-15

    Rationale and objective: The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin {alpha}{nu}{beta}3 receptor-expressed tumor. Materials and methods: Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd{sup 3+}, and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin {alpha}{nu}{beta}3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90 min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Results: Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90 min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90 min p.i., while the control arms do not show this tendency. Conclusion: Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin {alpha}{nu}{beta}3 receptor-expressed tumor.

  5. Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin ανβ3 receptor-expressed tumor-MR molecular imaging of angiogenesis

    International Nuclear Information System (INIS)

    Huo Tianlong; Du Xiangke; Zhang Sen; Liu Xia; Li Xubing

    2010-01-01

    Rationale and objective: The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin ανβ3 receptor-expressed tumor. Materials and methods: Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd 3+ , and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin ανβ3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90 min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Results: Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90 min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90 min p.i., while the control arms do not show this tendency. Conclusion: Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin ανβ3 receptor-expressed tumor.

  6. Genome-wide DNA polymorphism in the indica rice varieties RGD-7S and Taifeng B as revealed by whole genome re-sequencing.

    Science.gov (United States)

    Fu, Chong-Yun; Liu, Wu-Ge; Liu, Di-Lin; Li, Ji-Hua; Zhu, Man-Shan; Liao, Yi-Long; Liu, Zhen-Rong; Zeng, Xue-Qin; Wang, Feng

    2016-03-01

    Next-generation sequencing technologies provide opportunities to further understand genetic variation, even within closely related cultivars. We performed whole genome resequencing of two elite indica rice varieties, RGD-7S and Taifeng B, whose F1 progeny showed hybrid weakness and hybrid vigor when grown in the early- and late-cropping seasons, respectively. Approximately 150 million 100-bp pair-end reads were generated, which covered ∼86% of the rice (Oryza sativa L. japonica 'Nipponbare') reference genome. A total of 2,758,740 polymorphic sites including 2,408,845 SNPs and 349,895 InDels were detected in RGD-7S and Taifeng B, respectively. Applying stringent parameters, we identified 961,791 SNPs and 46,640 InDels between RGD-7S and Taifeng B (RGD-7S/Taifeng B). The density of DNA polymorphisms was 256.8 SNPs and 12.5 InDels per 100 kb for RGD-7S/Taifeng B. Copy number variations (CNVs) were also investigated. In RGD-7S, 1989 of 2727 CNVs were overlapped in 218 genes, and 1231 of 2010 CNVs were annotated in 175 genes in Taifeng B. In addition, we verified a subset of InDels in the interval of hybrid weakness genes, Hw3 and Hw4, and obtained some polymorphic InDel markers, which will provide a sound foundation for cloning hybrid weakness genes. Analysis of genomic variations will also contribute to understanding the genetic basis of hybrid weakness and heterosis.

  7. Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate

    Science.gov (United States)

    Velikyan, Irina; Lindhe, Örjan

    2018-01-01

    Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced 68Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to αvβ3 integrin receptors. The main objective of this study was to develop a method for 68Ga-labeling of RGD containing bicyclic octapeptide ([68Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [68Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full 68Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [68Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis. PMID:29531858

  8. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

    International Nuclear Information System (INIS)

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-01-01

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair

  9. The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Lotte M E Berghauser Pont

    Full Text Available A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastoma-pathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delta24-RGD. HDAC inhibitors (HDACi affect integrins and share common cell death pathways with Delta24-RGD. We studied the combination treatment effects of HDACi and Delta24-RGD in patient-derived glioblastoma stem-like cells (GSC, and we determined the most effective HDACi.SAHA, Valproic Acid, Scriptaid, MS275 and LBH589 were combined with Delta24-RGD in fourteen distinct GSCs. Synergy was determined by Chou Talalay method. Viral infection and replication were assessed using luciferase and GFP encoding vectors and hexon-titration assays. Coxsackie adenovirus receptor and αvβ3 integrin levels were determined by flow cytometry. Oncolysis and mechanisms of cell death were studied by viability, caspase-3/7, LDH and LC3B/p62, phospho-p70S6K. Toxicity was studied on normal human astrocytes. MGMT promotor methylation status, TCGA classification, Rb-pathway and integrin gene expression levels were assessed as markers of responsiveness.Scriptaid and LBH589 acted synergistically with Delta24-RGD in approximately 50% of the GSCs. Both drugs moderately increased αvβ3 integrin levels and viral infection in responding but not in non-responding GSCs. LBH589 moderately increased late viral gene expression, however, virus titration revealed diminished viral progeny production by both HDACi, Scriptaid augmented caspase-3/7 activity, LC3B conversion, p62 and phospho-p70S6K consumption, as well as LDH levels. LBH589 increased LDH and phospho-p70S6K consumption. Responsiveness correlated with expression of various Rb-pathway genes and integrins. Combination treatments induced limited toxicity to human astrocytes.LBH589 and Scriptaid combined with Delta24-RGD revealed synergistic anti

  10. In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

    Science.gov (United States)

    2011-01-01

    Background Foot-and-mouth disease virus (FMDV) uses a highly conserved Arg-Gly-Asp (RGD) triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05) and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD) or an Arg-Ser-Asp (RSD) triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals. Results Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that developed typical

  11. In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

    Directory of Open Access Journals (Sweden)

    Yin Hong

    2011-06-01

    Full Text Available Abstract Background Foot-and-mouth disease virus (FMDV uses a highly conserved Arg-Gly-Asp (RGD triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05 and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD or an Arg-Ser-Asp (RSD triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals. Results Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that

  12. A Paper-Based Sandwich Format Hybridization Assay for Unlabeled Nucleic Acid Detection Using Upconversion Nanoparticles as Energy Donors in Luminescence Resonance Energy Transfer.

    Science.gov (United States)

    Zhou, Feng; Noor, M Omair; Krull, Ulrich J

    2015-09-24

    Bioassays based on cellulose paper substrates are gaining increasing popularity for the development of field portable and low-cost diagnostic applications. Herein, we report a paper-based nucleic acid hybridization assay using immobilized upconversion nanoparticles (UCNPs) as donors in luminescence resonance energy transfer (LRET). UCNPs with intense green emission served as donors with Cy3 dye as the acceptor. The avidin functionalized UCNPs were immobilized on cellulose paper and subsequently bioconjugated to biotinylated oligonucleotide probes. Introduction of unlabeled oligonucleotide targets resulted in a formation of probe-target duplexes. A subsequent hybridization of Cy3 labeled reporter with the remaining single stranded portion of target brought the Cy3 dye in close proximity to the UCNPs to trigger a LRET-sensitized emission from the acceptor dye. The hybridization assays provided a limit of detection (LOD) of 146.0 fmol and exhibited selectivity for one base pair mismatch discrimination. The assay was functional even in undiluted serum samples. This work embodies important progress in developing DNA hybridization assays on paper. Detection of unlabeled targets is achieved using UCNPs as LRET donors, with minimization of background signal from paper substrates owing to the implementation of low energy near-infrared (NIR) excitation.

  13. Peptides Interfering 3A Protein Dimerization Decrease FMDV Multiplication.

    Directory of Open Access Journals (Sweden)

    Mónica González-Magaldi

    Full Text Available Nonstructural protein 3A is involved in relevant functions in foot-and-mouth disease virus (FMDV replication. FMDV 3A can form homodimers and preservation of the two hydrophobic α-helices (α1 and α2 that stabilize the dimer interface is essential for virus replication. In this work, small peptides mimicking residues involved in the dimer interface were used to interfere with dimerization and thus gain insight on its biological function. The dimer interface peptides α1, α2 and that spanning the two hydrophobic α-helices, α12, impaired in vitro dimer formation of a peptide containing the two α-helices, this effect being higher with peptide α12. To assess the effect of dimer inhibition in cultured cells, the interfering peptides were N-terminally fused to a heptaarginine (R7 sequence to favor their intracellular translocation. Thus, when fused to R7, interference peptides (100 μM were able to inhibit dimerization of transiently expressed 3A, the higher inhibitions being found with peptides α1 and α12. The 3A dimerization impairment exerted by the peptides correlated with significant, specific reductions in the viral yield recovered from peptide-treated FMDV infected cells. In this case, α2 was the only peptide producing significant reductions at concentrations lower than 100 μM. Thus, dimer interface peptides constitute a tool to understand the structure-function relationship of this viral protein and point to 3A dimerization as a potential antiviral target.

  14. Molecular nuclear imaging of tumoral angio genesis using a rgd-containing tracer, Raft-RGD, targeted at the neo vessel-specific integrin {alpha}{sub v}{beta}{sub 3}; Evaluation d'un radioligand de l'integrine {alpha}{sub v}{beta}{sub 3} (RAFT-RGD) pour l'imagerie moleculaire de l'angiogenese tumorale

    Energy Technology Data Exchange (ETDEWEB)

    Sancey, L

    2006-06-15

    Tumoral neo-angio genesis targeting is currently a major field of research for the diagnostic and treatment of solid tumors. Endothelial cells from neo vessels over express several specific markers such as the {alpha}{sub v}{beta}{sub 3} integrin, which binds RGD (-Arg-Gly-Asp-)- containing peptides. We evaluated the potential of a novel radiotracer - RAFT-RGD - for the molecular nuclear imaging of neo vessels. In vitro, the coupling of 4 c(RGDfK) to the RAFT platform resulted in an increased cellular uptake of the tracer by {alpha}{sub v}{beta}{sub 3} positive cells when compared to c(RGDfK). Furthermore, RAFTRGD has a higher affinity than c(RGDfK) and similar properties for angio genesis inhibition. In vivo, both {alpha}{sub v}{beta}{sub 3} positive and negative tumors were visible by non invasive whole body planar and tomographic imaging from 30 min to 24 h post-injection, using a gamma camera dedicated to small animal imaging. Despite a lack of significant contrast improvement compare with c(RGDfK), RAFT-RGD could represent a promising tracer for tumoral angio genesis since it could provide invaluable information about tumor development and treatment efficacy in Nuclear Medicine departments. Furthermore, thanks to its chemical structure, RAFT-RGD can be labelled with a variety of radioisotopes including {gamma} and {beta}{sup -} emitters, allowing interesting therapeutical applications such as internal targeted radiotherapy. (author)

  15. Analysis of a conserved RGE/RGD motif in HCV E2 in mediating entry

    Directory of Open Access Journals (Sweden)

    Rong Lijun

    2009-01-01

    Full Text Available Abstract Background Hepatitis C virus (HCV encodes two transmembrane glycoproteins E1 and E2 which form a heterodimer. E1 is believed to mediate fusion while E2 has been shown to bind cellular receptors. It is clear that HCV uses a multi-receptor complex to gain entry into susceptible cells, however key elements of this complex remain elusive. In this study, the role of a highly conserved RGE/RGD motif of HCV E2 glycoprotein in viral entry was examined. The effect of each substitution mutation in this motif was tested by challenging susceptible cell lines with mutant HCV E1E2 pseudotyped viruses generated using a lentiviral system (HCVpp. In addition to assaying infectivity, producer cell expression and HCVpp incorporation of HCV E2 proteins, CD81 binding profiles, and conformation of mutants were examined. Results Based on these characteristics, mutants either displayed wt characteristics (high infectivity [≥ 90% of wt HCVpp], CD81 binding, E1E2 expression, and incorporation into viral particles and proper conformation or very low infectivity (≤ 20% of wt HCVpp. Only amino acid substitutions of the 3rd position (D or E resulted in wt characteristics as long as the negative charge was maintained or a neutral alanine was introduced. A change in charge to a positive lysine, disrupted HCVpp infectivity at this position. Conclusion Although most amino acid substitutions within this conserved motif displayed greatly reduced HCVpp infectivity, they retained soluble CD81 binding, proper E2 conformation, and incorporation into HCVpp. Our results suggest that although RGE/D is a well-defined integrin binding motif, in this case the role of these three hyperconserved amino acids does not appear to be integrin binding. As the extent of conservation of this region extends well beyond these three amino acids, we speculate that this region may play an important role in the structure of HCV E2 or in mediating the interaction with other factor(s during

  16. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  17. Dimerization in the Grb7 Protein

    OpenAIRE

    Peterson, Tabitha A.; Benallie, Renee L.; Bradford, Andrew M.; Pias, Sally C.; Yazzie, Jaron.; Lor, Siamee N.; Haulsee, Zachary M.; Park, Chad K.; Johnson, Dennis L.; Rohrschneider, Larry R.; Spuches, Anne.; Lyons, Barbara A.

    2012-01-01

    In previous studies, we showed that the tyrosine phosphorylation state of growth factor receptor–bound protein 7 (Grb7) affects its ability to bind to the transcription regulator FHL2 and the cortactin-interacting protein, human HS-1-associated protein-1. Here, we present results describing the importance of dimerization in the Grb7–Src homology 2 (SH2) domain in terms of its structural integrity and the ability to bind phosphorylated tyrosine peptide ligands. A tyrosine phosphorylation-mimic...

  18. Dimerization and oligomerization of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte S; Ryder, L Rebekka; Steinø, Anne

    2003-01-01

    protein. Using PAGE, urea gradient gel electrophoresis, capillary electrophoresis and MS, we show that dimerization through the SH group can be induced by lowering the pH to 5-6, heating, or under conditions that favour partial unfolding such as urea concentrations above 2.6 m or SDS concentrations above...... that favour partial unfolding or an intramolecular local conformational change that allows oligomerization, resulting in a heterogeneous mixture of oligomers consisting of up to 10 calreticulin monomers. The oligomeric calreticulin was very stable, but oligomerization was partially reversed by addition of 8 m...

  19. Dimeric assembly of enterocyte brush border enzymes

    DEFF Research Database (Denmark)

    Danielsen, E M

    1994-01-01

    The noncovalent, dimeric assembly of small intestinal brush border enzymes was studied by sedimentation analysis in density gradients of extracts of pulse-labeled pig jejunal mucosal explants. Like aminopeptidase N (EC 3.4.11.2), sucrase-isomaltase (EC 3.2.1.48-10), aminopeptidase A (EC 3...... appearance of the liposome-reconstituted enzyme [Norén et al. (1986) J. Biol. Chem. 261, 12306-12309], showing only the inner, membrane-anchored domains of the monomers to be in close contact with one another while the outer domains are far apart. In contrast to the other brush border enzymes studied...

  20. Dimer pair correlations on the brick lattice

    International Nuclear Information System (INIS)

    Yokoi, C.S.O.; Nagle, J.F.; Sulinas, S.R.

    1986-01-01

    Using exact methods, pair-correlation functions are studied in the dimer model defined on a brick lattice. At long distances these functions exhibit strongly anisotropic algebraic decay and, near criticality, the length scales diverge differently in the two principal directions. The critical exponents are v /sub x/ =1/2 and v /sub y/ =1. These results are in agreement with deductions drawn from recent exact finite-size scaling calculations. We also interpret our results in the light of domain wall theories of commensurate-incommensurate transitions, and in particular we study the relation of the present model to the discrete version of the Pokrovsky-Talapov model introduced by Villain

  1. Tunneling anisotropic magnetoresistance via molecular π orbitals of Pb dimers

    Science.gov (United States)

    Schöneberg, Johannes; Ferriani, Paolo; Heinze, Stefan; Weismann, Alexander; Berndt, Richard

    2018-01-01

    Pb dimers on a ferromagnetic surface are shown to exhibit large tunneling anisotropic magnetoresistance (TAMR) due to molecular π orbitals. Dimers oriented differently with respect to the magnetization directions of a ferromagnetic Fe double layer on W(110) were made with a scanning tunneling microscope. Depending on the dimer orientations, TAMR is absent or as large as 20% at the Fermi level. General arguments and first-principles calculations show that mixing of molecular orbitals due to spin-orbit coupling, which leads to TAMR, is maximal when the magnetization is oriented parallel to the dimer axis.

  2. Pharmacokinetics of 99m Tc-EDDA/HYNIC-Lys-D-Phe-RGD in athymic mice with induced malignant tumors for integrin imaging

    International Nuclear Information System (INIS)

    Lopez D, F.A.; Pedraza L, M.; Murphy, C.A. de; Ferro F, G.; Hernandez H, E.

    2007-01-01

    Full text: Nuclear medicine imaging techniques are non-invasive and monitor the spatiotemporal distribution of molecular events. Radiolabeled RGD-peptides are currently investigated to target integrin receptors for in vivo tumor imaging. The α v β 3 integrin is a target structure involved in the angio genesis process which mediates the binding to extracellular matrix via different proteins such as vitronectin, fibronectin and von Willebrand factor. The aim of this research was to prepare [ 99m Tc]-Lys-D-Phe-RGD and to evaluate its pharmacokinetics in athymic mice with three different induced malignant tumors. Tumor uptake values of 99m Tc-Lys-D-Phe-RGD labeled via HYNIC and EDDA showed good ability to target α v β 3 integrin receptors in the three different kinds of tumors (breast, prostate and neuroendocrine). A high in vivo stability and favorable pharmacokinetic properties such as fast blood clearance, rapid renal excretion, low liver and muscle uptake and low intestinal excretion were observed. This study demonstrated that 99m Tc-EDDA/HYNIC-Lys-D-Phe-RGD is a specific and potential radiopharmaceutical to image α v β 3 integrin receptors in a variety of tumors. (Author)

  3. Preparation and biological study of 99Tcm(N) (PNP6) (Cyc-RGD) for integrin αvβ3-positive tumor imaging

    International Nuclear Information System (INIS)

    Chen Baojun; Hu Ji; Liang Jixin; Li Hongyu; Luo Lianzhe; Shen Langtao; Luo Zhifu; Chen Yang

    2007-01-01

    The Cys-RGD peptide is labelled with 99 Tc m -nitrido core combined with PNP6 lig- and (PNP6=bis (diethoxypropylphosphino ethyl) ethoxy ethylamine) to investigate the possibility of radiolabelled RGD peptides for tumor α v β 3 integrin receptor scintigraphy. The radiochemical purity is measured with HPLC, the in vitro stability is investigated at room temperature and at 37 degree C incubated in the cystein and serum solution. Biodistribution studies and gamma camera imaging are performed in normal mice and nude mice bearing FWK-1 pancreatic tumor xenografts. More than 92% radiolabelling yield is achieved under optimized condition. The high in vitro stability is found for 99 Tc m (N) (PNP6) (Cys-RGD). In vivo biodistribution studies indicate the radiolabelled peptide is cleared rapidly from blood and mainly excreted via urinary system. Tumor uptake is 2.92 ± 0.71%/g at 1 h after injection. The uptake ratios of tumor to blood and tumor to muscle (T/NT) are 11.0 and 3. 1 at 4 h after injection, respectively. Scintigraphic imaging allows contrasting visualisation of α v β 3 -expressed tumors at 1 h after injection. The results suggest 99 Tc m (N) (PNP6) (Cys- RGD) may be the potential agent for α v β 3 -positive tumor imaging. (authors)

  4. Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces

    NARCIS (Netherlands)

    Sankaran, Shrikrishnan; Cavatorta, Emanuela; Huskens, Jurriaan; Jonkheijm, Pascal

    2017-01-01

    Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form

  5. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with 177Lu and evaluation in vitro and in vivo stability

    International Nuclear Information System (INIS)

    Vilchis J, A.

    2010-01-01

    Integrin αvβ3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the αvβ3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with 177 Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of 177 LuCl 3 with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90 o C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive αvβ3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. 177 Lu-DOTA-RGD and 177 Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to □ v □ 3 receptors. (Author)

  6. Fibrillar dimer formation of islet amyloid polypeptides

    Directory of Open Access Journals (Sweden)

    Chi-cheng Chiu

    2015-09-01

    Full Text Available Amyloid deposits of human islet amyloid polypeptide (hIAPP, a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

  7. In vivo endothelization of tubular vascular grafts through in situ recruitment of endothelial and endothelial progenitor cells by RGD-fused mussel adhesive proteins

    International Nuclear Information System (INIS)

    Kang, Tae-Yun; Lee, Jung Ho; Kang, Jo-A; Rhie, Jong-Won; Kim, Bum Jin; Cha, Hyung Joon; Hong, Jung Min; Kim, Byoung Soo; Cho, Dong-Woo

    2015-01-01

    The use of tissue mimics in vivo, including patterned vascular networks, is expected to facilitate the regeneration of functional tissues and organs with large volumes. Maintaining patency of channels in contact with blood is an important issue in the development of a functional vascular network. Endothelium is the only known completely non-thrombogenic material; however, results from treatments to induce endothelialization are inconclusive. The present study was designed to evaluate the clinical applicability of in situ recruitment of endothelial cells/endothelial progenitor cells (EC/EPC) and pre-endothelization using a recombinant mussel adhesive protein fused with arginine–glycine–aspartic acid peptide (MAP-RGD) coating in a model of vascular graft implantation. Microporous polycaprolactone (PCL) scaffolds were fabricated with salt leaching methods and their surfaces were modified with collagen and MAP-RGD. We then evaluated their anti-thrombogenicity with an in vitro hemocompatibility assessment and a 4-week implantation in the rabbit carotid artery. We observed that MAP-RGD coating reduced the possibility of early in vivo graft failure and enhanced re-endothelization by in situ recruitment of EC/EPC (patency rate: 2/3), while endothelization prior to implantation aggravated the formation of thrombosis and/or IH (patency rate: 0/3). The results demonstrated that in situ recruitment of EC/EPC by MAP-RGD could be a promising strategy for vascular applications. In addition, it rules out several issues associated with pre-endothelization, such as cell source, purity, functional modulation and contamination. Further evaluation of long term performance and angiogenesis from the luminal surface may lead to the clinical use of MAP-RGD for tubular vascular grafts and regeneration of large-volume tissues with functional vascular networks. (paper)

  8. Excitonic Behavior of Rhodamine Dimers: A Single-Molecule Study

    NARCIS (Netherlands)

    Hernando Campos, J.; van der Schaaf, Martijn; van Dijk, E.M.H.P.; Sauer, Markus; Garcia Parajo, M.F.; van Hulst, N.F.

    2003-01-01

    The optical behavior of a dimer of tetramethylrhodamine-5-isothiocyanate has been investigated by means of single-molecule measurements. Bulk absorption and fluorescence spectra show the existence of two populations of the dimer molecule that exhibit distinct excitonic interactions (strong and weak

  9. Two Populations Mean-Field Monomer-Dimer Model

    Science.gov (United States)

    Alberici, Diego; Mingione, Emanuele

    2018-04-01

    A two populations mean-field monomer-dimer model including both hard-core and attractive interactions between dimers is considered. The pressure density in the thermodynamic limit is proved to satisfy a variational principle. A detailed analysis is made in the limit of one population is much smaller than the other and a ferromagnetic mean-field phase transition is found.

  10. On the diffusion and self-trapping of surface dimers

    Science.gov (United States)

    Kappus, W.

    1982-03-01

    The theory of elastic interactions between surface atoms which are caused by substrate strains is applied to the interaction of dimers on the (211) surface of tungsten. From the comparison of theoretical and experimental interactions which were derived from the diffusion behaviour of dimers, conclusions are drawn on the nature of the adatom-substrate bond.

  11. Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

    KAUST Repository

    Han, Yu; Huang, Jianfeng; Zhu, Yihan

    2016-01-01

    and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near

  12. Exact Solution of a Generalized Nonlinear Schrodinger Equation Dimer

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Maniadis, P.; Tsironis, G.P.

    1998-01-01

    We present exact solutions for a nonlinear dimer system defined throught a discrete nonlinear Schrodinger equation that contains also an integrable Ablowitz-Ladik term. The solutions are obtained throught a transformation that maps the dimer into a double Sine-Gordon like ordinary nonlinear...... differential equation....

  13. Dimers at Ge/Si(001) surfaces: Ge coverage dependent quenching, reactivation of flip-flop motion, and interaction with dimer vacancy lines

    International Nuclear Information System (INIS)

    Hirayama, H.; Mizuno, H.; Yoshida, R.

    2002-01-01

    We studied Ge coverage (θ Ge ) dependent quenching, reactivation of the flip-flop motion, and interaction with dimer vacancy lines (DVLs) of dimers on Ge/Si(001) surfaces using a scanning tunneling microscope (STM) combined with a molecular beam epitaxy apparatus. Deposition of ∼0.3 ML (monolayer) Ge quenched the flip-flop motion, making all dimers asymmetric. Further deposition introduced DVLs at θ Ge ≥∼0.5 ML, and symmetric dimer domains appeared again locally at θ≥1.5 ML. High-resolution STM images indicated that asymmetric dimer rows always invert their phase in alternation with buckled dimer's up-end at the DVLs. Low-temperature STM images indicated that the symmetric dimer domains were due to flip-flopping of asymmetric dimers activated by large θ Ge at room temperature. The symmetric dimer domains extended along the dimer rows over the DVLs due to the phase correlation

  14. Molecular Docking Characterization of a Four-Domain Segment of Human Fibronectin Encompassing the RGD Loop with Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Tailin Guo

    2013-12-01

    Full Text Available Fibronectin adsorption on biomaterial surfaces plays a key role in the biocompatibility of biomedical implants. In the current study, the adsorption behavior of the 7–10th type III modules of fibronectin (FN-III7–10 in the presence of hydroxyapatite (HAP was systematically investigated by using molecular docking approach. It was revealed that the FN-III10 is the most important module among FN-III7–10 in promoting fibronectin binding to HAP by optimizing the interaction energy; the arginine residues were observed to directly interact with the hydroxyl group of HAP through electrostatic forces and hydrogen bonding. Moreover, it was found that the HAP-binding sites on FN-III10 are mainly located at the RGD loop region, which does not affect the interaction between the fibronectin protein and its cognate receptors on the cell surface.

  15. Dualism of Sensitivity and Selectivity of Porphyrin Dimers in Electroanalysis.

    Science.gov (United States)

    Lisak, Grzegorz; Tamaki, Takashi; Ogawa, Takuji

    2017-04-04

    This work uncovers the application of porphyrin dimers for the use in electroanalysis, such as potentiometric determination of ions. It also puts in question a current perception of an occurrence of the super-Nernstian response, as a result of the possible dimerization of single porphyrins within an ion-selective membrane. To study that, four various porphyrin dimers were used as ionophores, namely, freebase-freebase, Zn-Zn, Zn-freebase, and freebase-Zn. Since the Zn-freebase and freebase-Zn porphyrin dimers carried both anion- and cation-sensitive porphyrin units, their application in ISEs was utilized in both anion- and cation-sensitive sensors. With respect to the lipophilic salt added, both porphyrins dimers were found anion- and cation-sensitive. This allowed using a single molecule as novel type of versatile ionophore (anion- and cation-selective), simply by varying the membrane composition. All anion-sensitive sensors were perchlorate-sensitive, while the cation-selective sensors were silver-sensitive. The selectivity of the sensors depended primarily on the porphyrin dimers in the ion-selective membrane. Furthermore, the selectivity of cation-sensitive dimer based sensors was found significantly superior to the ones measured for the single porphyrin unit based sensors (precursors of the porphyrin dimers). Thus, the dimerization of single porphyrins may actually be a factor to increase or modulate porphyrin selectivity. Moreover, in the case of cation-sensitive sensors, the selectivity vastly depended on the order of porphyrin units in the dimer. This opens a new approach of regulating and adjusting sensitivity and selectivity of the sensor through the application of complex porphyrin systems with more than one porphyrin units with mix sensitive porphyrins.

  16. Anti-EGFR-iRGD recombinant protein conjugated silk fibroin nanoparticles for enhanced tumor targeting and antitumor efficiency

    Directory of Open Access Journals (Sweden)

    Bian X

    2016-05-01

    Full Text Available Xinyu Bian,* Puyuan Wu,* Huizi Sha, Hanqing Qian, Qing Wang, Lei Cheng, Yang Yang, Mi Yang, Baorui LiuComprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workAbstract: In this study, we report a novel kind of targeting with paclitaxel (PTX-loaded silk fibroin nanoparticles conjugated with iRGD–EGFR nanobody recombinant protein (anti-EGFR-iRGD. The new nanoparticles (called A-PTX-SF-NPs were prepared using the carbodiimide-mediated coupling procedure and their characteristics were evaluated. The cellular cytotoxicity and cellular uptake of A-PTX-SF-NPs were also investigated. The results in vivo suggested that NPs conjugated with the recombinant protein exhibited more targeting and anti-neoplastic property in cells with high EGFR expression. In the in vivo antitumor efficacy assay, the A-PTX-SF-NPs group showed slower tumor growth and smaller tumor volumes than PTX-SF-NPs in a HeLa xenograft mouse model. A real-time near-infrared fluorescence imaging study showed that A-PTX-SF-NPs could target the tumor more effectively. These results suggest that the anticancer activity and tumor targeting of A-PTX-SF-NPs were superior to those of PTX-SF-NPs and may have the potential to be used for targeted delivery for tumor therapies. Keywords: EGFR, nanobody, iRGD, recombinant protein, targeting drug carriers, antitumor efficiency

  17. Preparation of the radiopharmaceutical 99m Tc-HYNIC-cyclo-Lys-D-Phe-RGD for In vivo image of integrines

    International Nuclear Information System (INIS)

    Hernandez H, E.

    2007-01-01

    The diagnostic of some pathological processes by means of images constitutes one of the used methods in the determination of the origin, condition and/or evolution of one illness. The use of contrast agents in conjunction with other techniques help to the obtaining and visualization of complex systems, among these we can find to those radiopharmaceuticals used in nuclear medicine to visualize diverse organs and corporal systems. At the moment it is sought to develop a radiopharmaceutical of third generation that can be used for image In vivo of integrines with the purpose of detecting angio genesis processes, that which would allow to diagnose in way it specifies a wide range of primary tumors and their metastasis. Presently work it developed the radiopharmaceutical 99m Tc-HYNIC-cycle-Lys-D-Phe-RGD, likewise the good conditions were determined for the formation of this complex. The HYNIC was employee as chelating agent, using as co ligands EDDA and Tricine for to complete the sphere of coordination of the 99m Tc. The conjugated HYNIC-RGD was synthesized, purified, characterized and radiolabelled In situ with 99m Tc using High pressure liquid chromatography as analysis method in Reverse Phase (RP-HPLC). By this way it was developed the lyophilized formulation for its instantaneous labelled to which were carried out quality control tests. The one conjugated was obtained free of impurities, showing stability at same as their complex formed with 99m Tc. The analysis method was validated turning out to be necessary, exact, lineal and specific for the quantification of the analyte of interest. The lyophilized formulation showed a radiochemical purity bigger than 95%, besides being sterile and free of pyrogens. The biodistribution tests in athymic mice with induced tumors showed that the radiopharmaceutical was united mainly to the tumor and that this it was excreted mainly for renal via. (Author)

  18. Synthesis and Bioevaluation of Iodine-131 Directly Labeled Cyclic RGD-PEGylated Gold Nanorods for Tumor-Targeted Imaging

    Directory of Open Access Journals (Sweden)

    Yingying Zhang

    2017-01-01

    Full Text Available Introduction. Radiolabeled gold nanoparticles play an important role in biomedical application. The aim of this study was to prepare iodine-131 (131I-labeled gold nanorods (GNRs conjugated with cyclic RGD and evaluate its biological characteristics for targeted imaging of integrin αvβ3-expressing tumors. Methods. HS-PEG(5000-COOH molecules were applied to replace CTAB covering the surface of bare GNRs for better biocompatibility, and c(RGDfK peptides were conjugated onto the carboxyl terminal of GNR-PEG-COOH via EDC/NHS coupling reactions. The nanoconjugate was characterized, and 131I was directly tagged on the surface of GNRs via AuI bonds for SPECT/CT imaging. We preliminarily studied the characteristics of the probe and its feasibility for tumor-targeting SPECT/CT imaging. Results. The [131I]GNR-PEG-cRGD probe was prepared in a simple and rapid manner and was stable in both PBS and fetal bovine serum. It targeted selectively and could be taken up by tumor cells mainly via integrin αvβ3-receptor-mediated endocytosis. In vivo imaging, biodistribution, and autoradiography results showed evident tumor uptake in integrin αvβ3-expressing tumors. Conclusions. These promising results showed that this smart nanoprobe can be used for angiogenesis-targeted SPECT/CT imaging. Furthermore, the nanoprobe possesses a remarkable capacity for highly efficient photothermal conversion in the near-infrared region, suggesting its potential as a multifunctional theranostic agent.

  19. rLj-RGD3, a Novel Recombinant Toxin Protein from Lampetra japonica, Protects against Cerebral Reperfusion Injury Following Middle Cerebral Artery Occlusion Involving the Integrin-PI3K/Akt Pathway in Rats.

    Directory of Open Access Journals (Sweden)

    Qian Lu

    Full Text Available The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3 and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO in a rat stroke model. We also explored the mechanism by which rLj-RGD3 acts by measuring protein and mRNA expression levels, with an emphasis on the FAK and integrin-PI3K/Akt anti-apoptosis pathways.rLj-RGD3 was obtained from the buccal secretions of Lampetra japonica using gene recombination technology. Sprague Dawley (SD rats were randomly divided into the following seven groups: a sham group; a vehicle-treated (VT group; 100.0 μg·kg-1, 50.0 μg·kg-1 and 25.0 μg·kg-1 dose rLj-RGD3 groups; and two positive controls, including 1.5 mg·kg-1 Edaravone (ED and 100.0 μg·kg-1 Eptifibatide (EP. MCAO was induced using a model consisting of 2 h of ischemia and 24 h of reperfusion. Behavioral changes were observed in the normal and operation groups after focal cerebral ischemia/reperfusion was applied. In addition, behavioral scores were evaluated at 4 and 24 h after reperfusion. Brain infarct volumes were determined based on 2,3,5-triphenyltetrazolium chloride (TTC staining. Pathological changes in brain tissues were observed using hematoxylin and eosin (H&E staining. Moreover, neuronal apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL assays. We determined the expression levels of focal adhesion kinase (FAK, phosphatidyl inositol 3-kinase (PI3K, protein kinase B

  20. Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

    KAUST Repository

    Han, Yu

    2016-03-31

    The fabrication of asymmetric monometallic nanocrystals with novel properties for plasmonics, nanophotonics and nanoelectronics. Asymmetric monometallic plasmonic nanocrystals are of both fundamental synthetic challenge and practical significance. In an example, a thiol-ligand mediated growth strategy that enables the synthesis of unprecedented Au Nanorod-Au Nanoparticle (AuNR-AuNP) dimers from pre-synthesized AuNR seeds. Using high-resolution electron microscopy and tomography, crystal structure and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near infrared regions (300 - 1300 nm). This unexpected property makes the AuNR-AuNP dimer example useful for many nanophotonic applications. In two experiments, the dimer example was tested as a surface- enhanced Raman scattering (SERS) substrate and a solar light harvester for photothermal conversion, in comparison with the mixture of AuNR and AuNP. In the SERS experiment, the dimer example showed an enhancement factor about 10 times higher than that of the mixture, when the excitation wavelength (660 nm) was off the two surface plasmon resonance (SPR) bands of the mixture. In the photothermal conversion experiment under simulated sunlight illumination, the dimer example exhibited an energy conversion efficiency about 1.4 times as high as that of the mixture.

  1. Role of cyclobutane dimers in UV-denaturation of DNA

    International Nuclear Information System (INIS)

    Zavil'gel'skij, G.B.; Zuev, A.V.

    1978-01-01

    UV irradiation of double-stranded DNA produces local denatured regions. The evidence presented indicates that these single-stranded regions arise from photoproducts other than pyrimidine dimers. The irradiation of T2 DNA at 8x10 4 erg/mm 2 (254 nm) produces 6-8% thymine dimers, amd Tsub(mel) drops by 12-14 deg C, accompanied by a significant broadening of the transition profile. The kinetics of denatured region formation and lowering Tsub(mel) corresponds to that of formation of crosslinkages and differs markedly from the kinetics of formation of cyclobutane pyrimidine dimers. Treatment of UV-irradiated DNA with light in the presence of yeast photoreactivating enzyme monomerizes almost all thymine dimers but does not change the Tsub(mel). Local denatured regions are detected in UV-irradiated DNA and are absent from AcPhM-sensibilized DNA, which contains 20-25% thymine dimers, as determined by the accridine orange fluorescence technique. S1 nuclease from Aspergillis oryzae produces single-strand breaks in UV-irradiated DNA of phage PM2 but is not active on AcPhM-treated PM2 DNA, which contains about 50 thymine dimers. It is supposed that the formation of a cyclobutane dimer only weakens the hydrogen bonds in the AT base pair rather than breaks them. Local denatured regions are thought to arise from the accumulation in UV-irradiated DNA (254 nm) of the sufficient number of photoproducts with impaired ability to base pairing

  2. Quantum dissipative dynamics and decoherence of dimers on helium droplets

    International Nuclear Information System (INIS)

    Schlesinger, Martin

    2011-01-01

    In this thesis, quantum dynamical simulations are performed in order to describe the vibrational motion of diatomic molecules in a highly quantum environment, so-called helium droplets. We aim to reproduce and explain experimental findings which were obtained from dimers on helium droplets. Nanometer-sized helium droplets contain several thousands of 4 He atoms. They serve as a host for embedded atoms or molecules and provide an ultracold ''refrigerator'' for them. Spectroscopy of molecules in or on these droplets reveals information on both the molecule and the helium environment. The droplets are known to be in the superfluid He II phase. Superfluidity in nanoscale systems is a steadily growing field of research. Spectra obtained from full quantum simulations for the unperturbed dimer show deviations from measurements with dimers on helium droplets. These deviations result from the influence of the helium environment on the dimer dynamics. In this work, a well-established quantum optical master equation is used in order to describe the dimer dynamics effectively. The master equation allows to describe damping fully quantum mechanically. By employing that equation in the quantum dynamical simulation, one can study the role of dissipation and decoherence in dimers on helium droplets. The effective description allows to explain experiments with Rb 2 dimers on helium droplets. Here, we identify vibrational damping and associated decoherence as the main explanation for the experimental results. The relation between decoherence and dissipation in Morse-like systems at zero temperature is studied in more detail. The dissipative model is also used to investigate experiments with K 2 dimers on helium droplets. However, by comparing numerical simulations with experimental data, one finds that further mechanisms are active. Here, a good agreement is obtained through accounting for rapid desorption of dimers. We find that decoherence occurs in the electronic manifold of the

  3. Subsurface dimerization in III-V semiconductor (001) surfaces

    DEFF Research Database (Denmark)

    Kumpf, C.; Marks, L.D.; Ellis, D.

    2001-01-01

    We present the atomic structure of the c(8 X 2) reconstructions of InSb-, InAs-, and GaAs-(001) surfaces as determined by surface x-ray diffraction using direct methods. Contrary to common belief, group III dimers are not prominent on the surface, instead subsurface dimerization of group m atoms ...... takes place in the second bilayer, accompanied by a major rearrangement of the surface atoms above the dimers to form linear arrays. By varying the occupancies of four surface sites the (001)-c(8 X 2) reconstructions of III-V semiconductors can be described in a unified model....

  4. Dimeric Surfactants: Promising Ingredients of Cosmetics and Toiletries

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    2013-11-01

    Full Text Available Surfactants are an essential ingredient for cosmetic, toiletries and personal care products for enhancing their performance. Dimeric surfactants demonstrate superiority compared to conventional surfactants in all areas of application. Dimeric surfactants are extremely promising for utilization in various cosmetic formulations viz. shampoo, lotions, creams, conditioners etc. These surfactants possess extremely unique surface properties viz. lower surface tension, unique micellization, low critical micelle concentration (CMC and antimicrobial activity, higher solubilization etc. Dimerics enhance the performances of cosmetics in an extraordinary manner and provide eco-friendly preparations for human epidermis.

  5. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with {sup 177}Lu and evaluation in vitro and in vivo stability; Radiomarcado del peptido c-DOTA-RGD y c-DOTA-RGDf con {sup 177}Lu y evaluacion de su estabilidad in vitro e in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2010-07-01

    Integrin {alpha}v{beta}3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the {alpha}v{beta}3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with {sup 177}Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of {sup 177}LuCl{sub 3} with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90{sup o} C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive {alpha}v{beta}3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. {sup 177}Lu-DOTA-RGD and {sup 177}Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to {open_square}{sub v}{open_square}{sub 3} receptors. (Author)

  6. Regulating the migration of smooth muscle cells by a vertically distributed poly(2-hydroxyethyl methacrylate) gradient on polymer brushes covalently immobilized with RGD peptides.

    Science.gov (United States)

    Wu, Sai; Du, Wang; Duan, Yiyuan; Zhang, Deteng; Liu, Yixiao; Wu, Bingbing; Zou, Xiaohui; Ouyang, Hongwei; Gao, Changyou

    2018-05-30

    The gradient localization of biological cues is of paramount importance to guide directional migration of cells. In this study, poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate)-block- poly(2-hydroxyethyl methacrylate) (P(HEMA-co-GMA)-b-PHEMA) brushes with a uniform underneath P(HEMA-co-GMA) layer and a gradient thickness of PHEMA blocks were prepared by using surface-initiated atom-transfer radical polymerization and a dynamically controlled polymerization process. The polymer chains were subsequently functionalized with the cell-adhesive arginine-glycine-aspartic acid (RGD) peptides by reaction with the glycidyl groups, and their structures and properties were characterized by X-ray photoelectron spectrometry (XPS), quartz crystal microbalance with dissipation (QCM-D) and air contact angle. Adhesion and migration processes of smooth muscle cells (SMCs) were then studied. Compared with those on the sufficiently exposed RGD surface, the cell adhesion and mobility were well maintained when the RGD peptides were localized at 18.9 nm depth, whereas the adhesion, spreading and migration rate of SMCs were significantly impaired when the RGD peptides were localized at a depth of 38.4 nm. On the RGD depth gradient surface, the SMCs exhibited preferential orientation and enhanced directional migration toward the direction of reduced thickness of the second PHEMA brushes. Half of the cells were oriented within ± 30° to the x-axis direction, and 72% of the cells moved directionally at the optimal conditions. Cell adhesion strength, arrangement of cytoskeleton, and gene and protein expression levels of adhesion-related proteins were studied to corroborate the mechanisms, demonstrating that the cell mobility is regulated by the complex and synergetic intracellular signals resulted from the difference in surface properties. Cell migration is of paramount importance for the processes of tissue repair and regeneration. So far, the gradient localization of

  7. Isotopic measurements (C,N,O) of detonation soot produced from labeled and unlabeled Composition B-3 indicate source of solid carbon residues

    Science.gov (United States)

    Podlesak, David; Manner, Virginia; Amato, Ronald; Dattelbaum, Dana; Gusavsen, Richard; Huber, Rachel

    2017-06-01

    Detonation of HE is an exothermic process whereby metastable complex molecules are converted to simple stable molecules such as H2 O, N2, CO, CO2, and solid carbon. The solid carbon contains various allotropes such as detonation nanodiamonds, graphite, and amorphous carbon. It is well known that certain HE formulations such as Composition B (60% RDX, 40% TNT) produce greater amounts of solid carbon than other more oxygen-balanced formulations. To develop a greater understanding of how formulation and environment influence solid carbon formation, we synthesized TNT and RDX with 13 C and 15 N at levels slightly above natural abundance levels. Synthesized RDX and TNT were mixed at a ratio of 60:40 to form Composition B and solid carbon residues were collected from detonations of isotopically-labeled as well as un-labelled Composition B. The raw HE and detonation residues were analyzed isotopically for C, N, O isotopic compositions. We will discuss differences between treatments groups as a function of formulation and environment. LA-UR - 17-21266.

  8. Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits.

    Science.gov (United States)

    Nishimichi, Norihisa; Kawashima, Nagako; Yokosaki, Yasuyuki

    2015-09-09

    Identification of epitopes for integrin-blocking monoclonal antibodies (mAbs) has aided our understanding of structure-function relationship of integrins. We mapped epitopes of chicken anti-integrin-α8-subunit-blocking mAbs by mutational analyses, examining regions that harboured all mapped epitopes recognized by mAbs against other α-subunits in the RGD-binding-integrin subfamily. Six mAbs exhibited blocking function, and these mAbs recognized residues on the same W2:41-loop on the top-face of the β-propeller. Loop-tips sufficiently close to W2:41 (face was identified as an additional component of the epitope of one antibody, clone YZ5. Binding sequences on the two loops were conserved in virtually all mammals, and that on W3:34 was also conserved in chickens. These indicate 1) YZ5 binds both top and bottom loops, and the binding to W3:34 is by interactions to conserved residues between immunogen and host species, 2) five other blocking mAbs solely bind to W2:41 and 3) the α8 mAbs would cross-react with most mammals. Comparing with the mAbs against the other α-subunits of RGD-integrins, two classes were delineated; those binding to "W3:34 and an top-loop", and "solely W2:41", accounting for 82% of published RGD-integrin-mAbs.

  9. DFT Study of dimers of dimethyl sulfoxide in gas phase

    Directory of Open Access Journals (Sweden)

    Reza Fazaeli

    2014-10-01

    Full Text Available Density functional (DFT calculations at M05-2x/aug-cc-pVDZ level were used to analyze the interactions between dimethyl sulfoxide (DMSO dimers. The structures obtained have been ana-lyzed with the Atoms in Molecules (AIMs and Natural Bond Orbital (NBO methodologies. Four minima were located on the potential energy surface of the dimers. Three types of interac-tions are observed, CH•••O, CH•••S hydrogen bonds and orthogonal interaction between the lone pair of the oxygen with the electron-deficient region of the sulfur atom. Stabilization energies of dimers including BSSE and ZPE are in the range 27–40 kJmol-1. The most stable conformers of dimers at DFT level is cyclic structure with antiparallel orientation of S=O groups pairing with three C–H∙∙∙O and a S∙∙∙O interactions.

  10. 21 CFR 176.120 - Alkyl ketene dimers.

    Science.gov (United States)

    2010-04-01

    ..., processing, preparing, treating, packaging, transporting, or holding food, subject to the provisions of this... paperboard. (c) The alkyl ketene dimers may be used in the form of an aqueous emulsion which may contain...

  11. Dimer-based model for heptaspanning membrane receptors.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferré, Sergi; Fuxe, Kjell; Cortés, Antonio; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2005-07-01

    The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dimers as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.

  12. Family C 7TM receptor dimerization and activation

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Sheikh, Søren P; Hansen, Jakob Lerche

    2006-01-01

    The family C seven transmembrane (7TM) receptors constitutes a small and especially well characterized subfamily of the large 7TM receptor superfamily. Approximately 50% of current prescription drugs target 7TM receptors, this biologically important family represents the largest class of drug...... to be fully defined. This review presents the biochemical support for family C 7TM receptor dimerization and discusses its importance for receptor biosynthesis, surface expression, ligand binding and activation, since lessons learnt here may well be applicable to the whole superfamily of 7TM receptors.......-targets today. It is well established that family C 7TM receptors form homo- or hetero-dimers on the cell surface of living cells. The large extra-cellular domains (ECD) have been crystallized as a dimer in the presence and absence of agonist. Upon agonist binding, the dimeric ECD undergoes large conformational...

  13. Dynamics of the water dimer + nitric oxide collision

    Energy Technology Data Exchange (ETDEWEB)

    Ree, Jong Baik [Dept. of Chemistry Education, Chonnam National University, Gwangju (Korea, Republic of); Kim, Yoo Hang [Dept. of Chemistry, Inha University, Incheon (Korea, Republic of); Shin, Hyung Kyu [Dept. of Chemistry, University of Nevada, Nevada (Korea, Republic of)

    2017-02-15

    Collision-induced intermolecular energy transfer and intramolecular vibrational redistribution in the collision of a water dimer and nitric oxide are studied by use of quasiclassical procedures. Intermolecular energy flow is shown to occur mainly through a direct-mode mechanism transferring relatively large amounts in strong collisions. About a quarter of the energy initially deposited in the dimer transfers to the ground state NO, while the rest redistributes among internal motions of the collision system. The main portion of initial energy deposited in the dimer redistributes in the stretches of the donor monomer through the 1:1 resonance followed by in the bend through the 1:2 resonance. Energy transfer from the excited NO to the ground-state dimer is equally efficient, transferring more than half the initial excitation to the donor monomer, the efficiency that is attributed to the internal modes operating as energy reservoirs. The hydrogen bond shares about 15% of the initial excitation stored in both dimer-to-NO and NO-to-dimer processes as a result of strong coupling of the hydrogen bond with the proton-donor OH bond of the monomer. A small fraction of collisions proceeds through a complex-mode mechanism and lead to NO dissociation, the dissociated O atom showing a propensity to form a new hydrogen bond.

  14. VUV spectroscopy of rare gas van der Waals dimers

    International Nuclear Information System (INIS)

    Dehmer, P.M.; Pratt, S.T.

    1982-01-01

    We have undertaken a systematic study of the photoionization spectra of the homonuclear and heteronuclear rare gas dimers in order to better understand the nature of the bonding in the Rydberg states adnd ions of these molecules. We have obtained results for Ar 2 , Kr 2 , Xe 2 , NeAr, NeKr, NeXe, ArKr, ArXe, and KrXe. Of the remaining dimer species (Ne 2 and the Herare gas dimers), only Ne 2 has been studied using photoionization mass spectrometry. The results of the present series of experiments provide information both on the excited states of the neutral dimers and on the ground and excited states of the dimer ions. Using the data obtained in these measurements, we are able to compile for the first time a nearly complete list of ground state dissociation energies for the homonuclear and heteronuclear rare gas dimer ions. Somewhat less complete results are obtained for the excited states of these species. The observed trends in binding energy provide an excellent example of the systematic changes that occur as a result of changes in atomic orbital energies, polarizability, and internuclear distance, and these trends can be explained qualitatively in terms of simple molecular orbital theory

  15. Optical properties of electrically connected plasmonic nanoantenna dimer arrays

    Science.gov (United States)

    Zimmerman, Darin T.; Borst, Benjamin D.; Carrick, Cassandra J.; Lent, Joseph M.; Wambold, Raymond A.; Weisel, Gary J.; Willis, Brian G.

    2018-02-01

    We fabricate electrically connected gold nanoantenna arrays of homodimers and heterodimers on silica substrates and present a systematic study of their optical properties. Electrically connected arrays of plasmonic nanoantennas make possible the realization of novel photonic devices, including optical sensors and rectifiers. Although the plasmonic response of unconnected arrays has been studied extensively, the present study shows that the inclusion of nanowire connections modifies the device response significantly. After presenting experimental measurements of optical extinction for unconnected dimer arrays, we compare these to measurements of dimers that are interconnected by gold nanowire "busbars." The connected devices show the familiar dipole response associated with the unconnected dimers but also show a second localized surface plasmon resonance (LSPR) that we refer to as the "coupled-busbar mode." Our experimental study also demonstrates that the placement of the nanowire along the antenna modifies the LSPR. Using finite-difference time-domain simulations, we confirm the experimental results and investigate the variation of dimer gap and spacing. Changing the dimer gap in connected devices has a significantly smaller effect on the dipole response than it does in unconnected devices. On the other hand, both LSPR modes respond strongly to changing the spacing between devices in the direction along the interconnecting wires. We also give results for the variation of E-field strength in the dimer gap, which will be important for any working sensor or rectenna device.

  16. Hydrodynamic Torques and Rotations of Superparamagnetic Bead Dimers

    Science.gov (United States)

    Pease, Christopher; Etheridge, J.; Wijesinghe, H. S.; Pierce, C. J.; Prikockis, M. V.; Sooryakumar, R.

    Chains of micro-magnetic particles are often rotated with external magnetic fields for many lab-on-a-chip technologies such as transporting beads or mixing fluids. These applications benefit from faster responses of the actuated particles. In a rotating magnetic field, the magnetization of superparamagnetic beads, created from embedded magnetic nano-particles within a polymer matrix, is largely characterized by induced dipoles mip along the direction of the field. In addition there is often a weak dipole mop that orients out-of-phase with the external rotating field. On a two-bead dimer, the simplest chain of beads, mop contributes a torque Γm in addition to the torque from mip. For dimers with beads unbound to each other, mop rotates individual beads which generate an additional hydrodynamic torque on the dimer. Whereas, mop directly torques bound dimers. Our results show that Γm significantly alters the average frequency-dependent dimer rotation rate for both bound and unbound monomers and, when mop exceeds a critical value, increases the maximum dimer rotation frequency. Models that include magnetic and hydrodynamics torques provide good agreement with the experimental findings over a range of field frequencies.

  17. Pair Interaction of Catalytical Sphere Dimers in Chemically Active Media

    Directory of Open Access Journals (Sweden)

    Jing-Min Shi

    2018-01-01

    Full Text Available We study the pair dynamics of two self-propelled sphere dimers in the chemically active medium in which a cubic autocatalytic chemical reaction takes place. Concentration gradient around the dimer, created by reactions occurring on the catalytic sphere surface and responsible for the self-propulsion, is greatly influenced by the chemical activities of the environment. Consequently, the pair dynamics of two dimers mediated by the concentration field are affected. In the particle-based mesoscopic simulation, we combine molecular dynamics (MD for potential interactions and reactive multiparticle collision dynamics (RMPC for solvent flow and bulk reactions. Our results indicate three different configurations between a pair of dimers after the collision, i.e., two possible scenarios of bound dimer pairs and one unbound dimer pair. A phase diagram is sketched as a function of the rate coefficients of the environment reactions. Since the pair interactions are the basic elements of larger scale systems, we believe the results may shed light on the understanding of the collective dynamics.

  18. Metal membrane with dimer slots as a universal polarizer

    Science.gov (United States)

    Zhukovsky, Sergej; Zalkovskij, Maksim; Malureanu, Radu; Kremers, Christian; Chigrin, Dmitry; Tang, Peter T.; Jepsen, Peter U.; Lavrinenko, Andrei V.

    2014-03-01

    In this work, we show theoretically and confirm experimentally that thin metal membranes patterned with an array of slot dimers (or their Babinet analogue with metal rods) can function as a versatile spectral and polarization filter. We present a detailed covariant multipole theory for the electromagnetic response of an arbitrary dimer based on the Green functions approach. The theory confirms that a great variety of polarization properties, such as birefringence, chirality and elliptical dichroism, can be achieved in a metal layer with such slot-dimer patterning (i.e. in a metasurface). Optical properties of the metasurface can be extensively tuned by varying the geometry (shape and dimensions) of the dimer, for example, by adjusting the sizes and mutual placement of the slots (e.g. inter-slot distance and alignment angle). Three basic shapes of dimers are analyzed: II-shaped (parallel slots), V-shaped, and T-shaped. These particular shapes of dimers are found to be sensitive to variations of the slots lengths and orientation of elements. Theoretical results are well supported by full-wave three-dimensional simulations. Our findings were verified experimentally on the metal membranes fabricated using UV lithography with subsequent Ni growth. Such metasurfaces were characterized using time-domain THz spectroscopy. The samples exhibit pronounced optical activity (500 degrees per wavelength) and high transmission: even though the slots cover only 4.3 % of the total membrane area the amplitude transmission reaches 0.67 at the resonance frequency 0.56 THz.

  19. Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles: preparation, cellular uptake, tissue distribution, and anticancer activity

    Directory of Open Access Journals (Sweden)

    Duan YR

    2012-07-01

    Full Text Available Peihao Yin,1,* Yan Wang,1,* YanYan Qiu,1 LiLi Hou,1 Xuan Liu,1 Jianmin Qin,1 Yourong Duan,2 Peifeng Liu,2 Ming Qiu,3 Qi Li11Department of Clinical Oncology, Putuo Hospital and Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Shanghai Cancer Institute, Jiaotong University, Shanghai, China; 3Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China *These authors contributed equally to this workBackground: Recent studies have shown that bufalin has a good antitumor effect but has high toxicity, poor water solubility, a short half-life, a narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study aimed to determine the targeting efficacy of nanoparticles (NPs made of methoxy polyethylene glycol (mPEG, polylactic-co-glycolic acid (PLGA, poly-L-lysine (PLL, and cyclic arginine-glycine-aspartic acid (cRGD loaded with bufalin, ie, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles (BNPs, in SW620 colon cancer-bearing mice.Methods: BNPs showed uniform size. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these nanoparticles were studied in vitro. The tumor targeting, cellular uptake, and growth-inhibitory effect of BNPs in vivo were tested.Results: BNPs were of uniform size with an average particle size of 164 ± 84 nm and zeta potential of 2.77 mV. The encapsulation efficiency was 81.7% ± 0.89%, and the drug load was 3.92% ± 0.16%. The results of in vitro cytotoxicity studies showed that although the blank NPs were nontoxic, they enhanced the cytotoxicity of bufalin in BNPs. Drug release experiments showed that the release of the drug was prolonged and sustained. The results of confocal laser scanning microscopy indicated that BNPs could effectively bind to human umbilical vein endothelial cells. In the SW620

  20. Synergistic retention strategy of RGD active targeting and radiofrequency-enhanced permeability for intensified RF & chemotherapy synergistic tumor treatment.

    Science.gov (United States)

    Zhang, Kun; Li, Pei; He, Yaping; Bo, Xiaowan; Li, Xiaolong; Li, Dandan; Chen, Hangrong; Xu, Huixiong

    2016-08-01

    Despite gaining increasing attention, chelation of multiple active targeting ligands greatly increase the formation probability of protein corona, disabling active targeting. To overcome it, a synergistic retention strategy of RGD-mediated active targeting and radiofrequency (RF) electromagnetic field-enhanced permeability has been proposed here. It is validated that such a special synergistic retention strategy can promote more poly lactic-co-glycolic acid (PLGA)-based capsules encapsulating camptothecin (CPT) and solid DL-menthol (DLM) to enter and retain in tumor in vitro and in vivo upon exposure to RF irradiation, receiving an above 8 fold enhancement in HeLa retention. Moreover, the PLGA-based capsules can respond RF field to trigger the entrapped DLM to generate solid-liquid-gas (SLG) tri-phase transformation for enhancing RF ablation and CPT release. Therefore, depending on the enhanced RF ablation and released CPT and the validated synergistic retention effect, the inhibitory outcome for tumor growth has gained an over 10-fold improvement, realizing RF ablation & chemotherapy synergistic treatment against HeLa solid tumor, which indicates a significant promise in clinical RF ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Dimer coverings on random multiple chains of planar honeycomb lattices

    International Nuclear Information System (INIS)

    Ren, Haizhen; Zhang, Fuji; Qian, Jianguo

    2012-01-01

    We study dimer coverings on random multiple chains. A multiple chain is a planar honeycomb lattice constructed by successively fusing copies of a ‘straight’ condensed hexagonal chain at the bottom of the previous one in two possible ways. A random multiple chain is then generated by admitting the Bernoulli distribution on the two types of fusing, which describes a zeroth-order Markov process. We determine the expectation of the number of the pure dimer coverings (perfect matchings) over the ensemble of random multiple chains by the transfer matrix approach. Our result shows that, with only two exceptions, the average of the logarithm of this expectation (i.e., the annealed entropy per dimer) is asymptotically nonzero when the fusing process goes to infinity and the length of the hexagonal chain is fixed, though it is zero when the fusing process and the length of the hexagonal chain go to infinity simultaneously. Some numerical results are provided to support our conclusion, from which we can see that the asymptotic behavior fits well to the theoretical results. We also apply the transfer matrix approach to the quenched entropy and reveal that the quenched entropy of random multiple chains has a close connection with the well-known Lyapunov exponent of random matrices. Using the theory of Lyapunov exponents we show that, for some random multiple chains, the quenched entropy per dimer is strictly smaller than the annealed one when the fusing process goes to infinity. Finally, we determine the expectation of the free energy per dimer over the ensemble of the random multiple chains in which the three types of dimers in different orientations are distinguished, and specify a series of non-random multiple chains whose free energy per dimer is asymptotically equal to this expectation. (paper)

  2. Glycine transporter dimers: evidence for occurrence in the plasma membrane.

    Science.gov (United States)

    Bartholomäus, Ingo; Milan-Lobo, Laura; Nicke, Annette; Dutertre, Sébastien; Hastrup, Hanne; Jha, Alok; Gether, Ulrik; Sitte, Harald H; Betz, Heinrich; Eulenburg, Volker

    2008-04-18

    Different Na(+)/Cl(-)-dependent neurotransmitter transporters of the SLC6a family have been shown to form dimers or oligomers in both intracellular compartments and at the cell surface. In contrast, the glycine transporters (GlyTs) GlyT1 and -2 have been reported to exist as monomers in the plasma membrane based on hydrodynamic and native gel electrophoretic studies. Here, we used cysteine substitution and oxidative cross-linking to show that of GlyT1 and GlyT2 also form dimeric complexes within the plasma membrane. GlyT oligomerization at the cell surface was confirmed for both GlyT1 and GlyT2 by fluorescence resonance energy transfer microscopy. Endoglycosidase treatment and surface biotinylation further revealed that complex-glycosylated GlyTs form dimers located at the cell surface. Furthermore, substitution of tryptophan 469 of GlyT2 by an arginine generated a transporter deficient in dimerization that was retained intracellulary. Based on these results and GlyT structures modeled by using the crystal structure of the bacterial homolog LeuT(Aa), as a template, residues located within the extracellular loop 3 and at the beginning of transmembrane domain 6 are proposed to contribute to the dimerization interface of GlyTs.

  3. Effects of Dimerization of Serratia marcescens Endonuclease on Water Dynamics.

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chuanying; Beck, Brian W.; Krause, Kurt; Weksberg, Tiffany E.; Pettitt, Bernard M.

    2007-02-15

    The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. The dynamics and structure of Serratia marcescens endonuclease and its neighboring solvent are investigated by molecular dynamics (MD). Comparisons are made with structural and biochemical experiments. The dimer form is physiologic and functions more processively than the monomer. We previously found a channel formed by connected clusters of waters from the active site to the dimer interface. Here, we show that dimerization clearly changes correlations in the water structure and dynamics in the active site not seen in the monomer. Our results indicate that water at the active sites of the dimer is less affected compared with bulk solvent than in the monomer where it has much slower characteristic relaxation times. Given that water is a required participant in the reaction, this gives a clear advantage to dimerization in the absence of an apparent ability to use both active sites simultaneously.

  4. Artificial light harvesting by dimerized Möbius ring

    Science.gov (United States)

    Xu, Lei; Gong, Z. R.; Tao, Ming-Jie; Ai, Qing

    2018-04-01

    We theoretically study artificial light harvesting by a Möbius ring. When the donors in the ring are dimerized, the energies of the donor ring are split into two subbands. Because of the nontrivial Möbius boundary condition, both the photon and acceptor are coupled to all collective-excitation modes in the donor ring. Therefore, the quantum dynamics in the light harvesting is subtly influenced by dimerization in the Möbius ring. It is discovered that energy transfer is more efficient in a dimerized ring than that in an equally spaced ring. This discovery is also confirmed by a calculation with the perturbation theory, which is equivalent to the Wigner-Weisskopf approximation. Our findings may be beneficial to the optimal design of artificial light harvesting.

  5. Characterization of oxygen dimer-enriched silicon detectors

    CERN Document Server

    Boisvert, V; Moll, M; Murin, L I; Pintilie, I

    2005-01-01

    Various types of silicon material and silicon p+n diodes have been treated to increase the concentration of the oxygen dimer (O2i) defect. This was done by exposing the bulk material and the diodes to 6 MeV electrons at a temperature of about 350 °C. FTIR spectroscopy has been performed on the processed material confirming the formation of oxygen dimer defects in Czochralski silicon pieces. We also show results from TSC characterization on processed diodes. Finally, we investigated the influence of the dimer enrichment process on the depletion voltage of silicon diodes and performed 24 GeV/c proton irradiations to study the evolution of the macroscopic diode characteristics as a function of fluence.

  6. Fano resonances in heterogeneous dimers of silicon and gold nanospheres

    Science.gov (United States)

    Zhao, Qian; Yang, Zhong-Jian; He, Jun

    2018-06-01

    We theoretically investigate the optical properties of dimers consisting of a gold nanosphere and a silicon nanosphere. The absorption spectrum of the gold sphere in the dimer can be significantly altered and exhibits a pronounced Fano profile. Analytical Mie theory and numerical simulations show that the Fano profile is induced by constructive and destructive interference between the incident electric field and the electric field of the magnetic dipole mode of the silicon sphere in a narrow wavelength range. The effects of the silicon sphere size, distance between the two spheres, and excitation configuration on the optical responses of the dimers are studied. Our study reveals the coherent feature of the electric fields of magnetic dipole modes in dielectric nanostructures and the strong interactions of the coherent fields with other nanophotonic structures.

  7. Pyrimidine dimers in Drosophila chromatin become increasingly accessible after irradiation

    International Nuclear Information System (INIS)

    Harris, P.V.; Boyd, J.B.

    1987-01-01

    A prokaryotic DNA-repair enzyme has been utilized as a probe for changes in the accessibility of pyrimidine dimers in Drosophila chromatin following UV irradiation. The results demonstrate a rapid cellular response to physiologically relevant doses of radiation which results in at least a 40% increase in accessible dimers. This increase occurs in two incision-deficient mutants which indicates that the excision-repair process, at or beyond the incision step, is not required or responsible for the increase. In the absence of excision the increase in accessibility persists for a least 2 days following irradiation. The observed increase in accessibility is inhibited by both novobiocin and coumermycin. These inhibitors do not inhibit the initial rate of incision, but do reduce dimer excision measured over more extended periods. A pre-incision process is proposed which actively exposes DNA lesions to excision repair. A fraction of the genome is postulated to be accessible without the intervention of that process. (Auth.)

  8. Disintegration and dimerization of δ-tocopherol under radiation effect

    International Nuclear Information System (INIS)

    Jasinska-Stepniak, A.; Gogolewski, M.; Zabielski, J.

    1996-01-01

    The goal of the work was to recognize scala changes of δ-tocopherol in model system (diluted in benzene, ethanol and ''in substantia'') after 2.5, 5, 10 and 20 kGy dose irradiation. δ-tocopherol and its mild oxidation products (dimers) after TLC separation were quantitatively determined with Emmerie-Engel method. Relations dose-effect have been defined and radiation capacity has been calculated. The results show that disintegration of δ-tocopherol diluted in ethanol is about ten times stronger the diluted in benzene. δ-tocopherol in benzene was dimerized. The most stable after irradiation was δ-tocopherol ''in substantia''. (author)

  9. Dimer-flipping-assisted diffusion on a Si(001) surface

    International Nuclear Information System (INIS)

    Zi, J.; Min, B. J.; Lu, Y.; Wang, C. Z.; Ho, K. M.

    2000-01-01

    The binding sites and diffusion pathways of Si adatoms on a c(4x2) reconstructed Si(001) surface are investigated by a tight-binding method with an environment-dependent silicon potential in conjunction with ab initio calculations using the Car--Parrinello method. A new diffusion pathway along the trough edge driven by dimer flipping is found with a barrier of 0.74 eV, comparable to that of 0.68 eV along the top of the dimer rows

  10. Pyrimidine dimer excision in human cells and skin cancer

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Smith, D.P.; Waters, R.

    1977-01-01

    We have compared three different methods for estimating the induction and removal of uv induced pyrimidine dimers from the DNA of human fibroblasts. Results indicate that after uv doses of 5-20 J/m 2 50% of the dimers are removed by 24 hours after irradiation. Almost complete excision can be observed if the cells are incubated for periods not less than 72 hours after 5 J/m 2 . After higher doses it probably takes even longer fr such complete removal to be seen

  11. Construction of covalently coupled, concatameric dimers of 7TM receptors

    DEFF Research Database (Denmark)

    Terpager, Marie; Scholl, D Jason; Kubale, Valentina

    2009-01-01

    -Ala repeats flanked by flexible spacers and positively charged residues to ensure correct inside-out orientation plus an extracellular HA-tag to construct covalently coupled dimers of 7TM receptors. Such 15 TM concatameric homo- and heterodimers of the beta(2)-adrenergic and the NK(1) receptors, which...... for either of the protomers, which was not observed upon simple coexpression of the two receptors. It is concluded that covalently joined 7TM receptor dimers with surprisingly normal receptor properties can be constructed with use of an artificial transmembrane connector, which perhaps can be used to fuse...

  12. Metal membrane with dimer slots as a universal polarizer

    DEFF Research Database (Denmark)

    Zhukovsky, Sergei; Zalkovskij, Maksim; Malureanu, Radu

    2014-01-01

    In this work, we show theoretically and confirm experimentally that thin metal membranes patterned with an array of slot dimers (or their Babinet analogue with metal rods) can function as a versatile spectral and polarization filter. We present a detailed covariant multipole theory for the electr......In this work, we show theoretically and confirm experimentally that thin metal membranes patterned with an array of slot dimers (or their Babinet analogue with metal rods) can function as a versatile spectral and polarization filter. We present a detailed covariant multipole theory...

  13. Synovitis in mice with inflammatory arthritis monitored with quantitative analysis of dynamic contrast-enhanced NIR fluorescence imaging using iRGD-targeted liposomes as fluorescence probes

    Directory of Open Access Journals (Sweden)

    Wu H

    2018-03-01

    Full Text Available Hao Wu,1,2,* Haohan Wu,1,2,* Yanni He,1 Zhen Gan,2 Zhili Xu,1,2 Meijun Zhou,1,2 Sai Liu,1,2 Hongmei Liu1 1Department of Ultrasonography, Guangdong Second Provincial General Hospital Affiliated to Southern Medical University, Guangzhou, China; 2Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China *These authors contributed equally to this work Background: Rheumatoid arthritis (RA is a common inflammatory disorder characterized primarily by synovitis and pannus formation in multiple joints, causing joints destruction and irreversible disability in most cases. Early diagnosis and effective therapy monitoring of RA are of importance for achieving the favorable prognosis. Methods: We first prepared the targeted fluorescence probes, and then explored the feasibility of near-infrared (NIR fluorescence molecular imaging to detect and evaluate the RA via the targeted fluorescence probes by quantitative analysis in this study. Results: The targeted fluorescence probes (indocyanine green-liposomes decorated with iRGD peptide [iLPs] was successfully prepared. The quantitative analysis found that strong fluorescence signal was detected in inflamed paws and the fluorescence signal in iLPs group was 3.03-fold higher than that in non-targeted (indocyanine green-liposomes decorated without iRGD peptide [LPs] group (P<0.01 at 15 min after injection, whereas the fluorescence signal from iLPs signal can almost not be observed in the non-inflamed paws, showing the high sensitivity and accuracy for arthritis by the NIR fluorescence imaging based on iLPs. Conclusion: The NIR fluorescence imaging by iLPs may facilitate improved arthritis diagnosis and early assessment of the disease progression by providing an in vivo characterization of angiogenesis in inflammatory joint diseases. Keywords: rheumatoid arthritis, synovitis, diagnosis, near-infrared fluorescence imaging, iRGD-targeted probes

  14. Synthesis and biological evaluation of a 99mTc-labelled cyclic RGD peptide for imaging the αvβ3 expression

    International Nuclear Information System (INIS)

    Haubner, F.; Bock, M.; Schwaiger, M.; Wester, H.J.; Bruchertseifer, F.; Kessler, H.

    2004-01-01

    Aim: The αvβ3 integrin is involved in tumour induced angiogenesis and tumour metastasis. We describe the synthesis and evaluation of a 99m Tc-labelled RGD analogue for the visualisation of αvβ3 integrin expression. Methods: The linear peptides were assembled on a solid support. Cyclisation was performed under high dilution conditions. For conjugation with the chelator peptide, a water soluble carbodiimide was used. Radiolabelling was carried out due to standard procedures with high radiochemical yield and radiochemical purity. For in vivo evaluation, nude mice bearing αvβ3-positive human melanoma M21 and αv-negative human melanoma M21-L or Balb / c mice bearing αv-positive murine osteosarcoma were used. Results: Activity accumulation of 99m Tc-DKCK-RGD 240 min p.i. was 1.1% ID/g in the αvβ3-positive melanoma and 0.3% ID/g in the negative control tumour. In the osteosarcoma model 2.2% ID/g was found 240 min p.i. Planar gamma camera images allowed contrasting visualisation of αvβ3-positive tumours 240 min p.i. Blocking of the tumour using the αvβ3-selective pentapeptide cyclo(-Arg-Gly-Asp-D-Phe-Val-) reduces activity accumulation in the tumour to background level. However, 240 min p.i. highest activity concentration was found in kidneys resulting in low tumour / kidney ratios. Metabolite analysis 240 min p.i. showed approximately 60% intact tracer in kidneys and 80% in the tumour. Only 24% intact tracer was found in blood 30 min p.i. Conclusion: 99m Tc-DKCK-RGD allows imaging of αvβ3-positive tumours in mice. However, pharmacokinetics as well as metabolic stability of the tracer have to be improved for potential clinical application. (orig.)

  15. Evaluation of technetium-99M labeled RGD-containing peptide as potential tumor imaging agents in tumor-bearing mice

    International Nuclear Information System (INIS)

    Hu Silong; Zeng Jun; Zhang Lihua

    2004-01-01

    Integrins (especially α v β 3 ) play a important role in angiogenesis, growth and metastasis of a solid tumor. Targeting tumor with radiolabeled ligands of the α V β 3 integrin may provide information about the receptor status and enable specific therapeutic strategy. A tripeptidic sequence Arg-Gly-Asp (RGD) is often the primary site of recognition by integrins. The aim of this study examine 99m Tc-labeled elevenfold peptide (GRGDSRGDSCY, GY11) that target the α V β 3 integrin to determine if this agent target tumors for diagnostic imaging and/or targeted radiotherapy of cancer. Methods: GY11 was radiolabelled with 99 Tc m via cystine residue by means of stannous chloride. 99 Tc m -GY11 was injected through tail vein into nude mice bearing A375 human melanoma. Biodistribution was investigated at 1,2,4 and 6 hours after injection. Percentage injected dose/gram of tissue (%ID/g) and tumor/non-tumor ratios were calculated. Planar images were acquired with SPECT at 1,2,4,6hrs, respectively. Results: 99 Tc m -GY11 was rapidly cleared from blood and excreted predominantly from the kidney. Tumor uptake at 2h postinjection was 3.1%ID/g. The ratios of tumor/blood and tumor/muscle increased from 0.9-6.2, 4.3-13.5 from 1-6hrs postinjection, respectively. Planar images confirmed that tumor could be visualized at 4h after administration of 99 Tc m -GY11. Conclusion: The results suggest that 99 Tc m -GY11 is a promising compound for noninvasive determining the α V β 3 integrin status. 99 Tc m -GY11 SPECT may be useful to imaging α V β 3 -positive tumor and also guide proper utility of α V β 3 antagonist therapy and radionuclide therapy for cancer. (authors)

  16. Analytical study of avian reticuloendotheliosis virus dimeric RNA generated in vivo and in vitro.

    Science.gov (United States)

    Darlix, J L; Gabus, C; Allain, B

    1992-12-01

    The retroviral genome consists of two identical RNA molecules associated at their 5' ends by a stable structure called the dimer linkage structure. The dimer linkage structure, while maintaining the dimer state of the retroviral genome, might also be involved in packaging and reverse transcription, as well as recombination during proviral DNA synthesis. To study the dimer structure of the retroviral genome and the mechanism of dimerization, we analyzed features of the dimeric genome of reticuloendotheliosis virus (REV) type A and identified elements required for its dimerization. Here we report that the REV dimeric genome extracted from virions and infected cells, as well as that synthesized in vitro, is more resistant to heat denaturation than avian sarcoma and leukemia virus, murine leukemia virus, or human immunodeficiency virus type 1 dimeric RNA. The minimal domain required to form a stable REV RNA dimer in vitro was found to map between positions 268 and 452 (KpnI and SalI sites), thus corresponding to the E encapsidation sequence (J. E. Embretson and H. M. Temin, J. Virol. 61:2675-2683, 1987). In addition, both the 5' and 3' halves of E are necessary in cis for RNA dimerization and the extent of RNA dimerization is influenced by viral sequences flanking E. Rapid and efficient dimerization of REV RNA containing gag sequences in addition to the E sequences and annealing of replication primer tRNA(Pro) to the primer-binding site necessitate the nucleocapsid protein.

  17. Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits

    OpenAIRE

    Norihisa Nishimichi; Nagako Kawashima; Yasuyuki Yokosaki

    2015-01-01

    Identification of epitopes for integrin-blocking monoclonal antibodies (mAbs) has aided our understanding of structure-function relationship of integrins. We mapped epitopes of chicken anti-integrin-α8-subunit-blocking mAbs by mutational analyses, examining regions that harboured all mapped epitopes recognized by mAbs against other α-subunits in the RGD-binding-integrin subfamily. Six mAbs exhibited blocking function, and these mAbs recognized residues on the same W2:41-loop on the top-face o...

  18. Biokinetics and dosimetry of a hybrid formulation of 9mTc-BN and 99mTc-RGD2 starting from optic images in a murine model

    International Nuclear Information System (INIS)

    Cornejo A, L. G.

    2015-01-01

    This work has the purpose of evaluate the biokinetics and absorbed dose of radiation of hybrid formulation 99m Tc-BN / 99m Tc-RGD 2 in a murine model by optical imaging techniques using the multimodal preclinical in vivo image system Xtreme. The used method were the 99m Tc-BN, 99m Tc-RGD 2 and 99m Tc-BN/ 99m Tc-RGD 2 formulas, with specific recognition for GRPr and the integrin s α(v)β(3) and α(v)β(5) respectively, was injected in the vein tail of three nude mousses with induce breast cancer tumors (cell line T-47-D), by the preclinical multimodal imaging system Xtreme (Bruker), optical images in different times was acquired (5, 10, 20 min, 2 and 24 h), using Images Processing Toolbox of MATLAB these images was transform from RGB format to gray scales and sectioned in five independent images corresponding to heart, kidneys, bladder and tumor areas. The intensity of each images was computed in counts per pixel, then those intensities was corrected for background, attenuation and scattering, using different factors for each phenomena previously calculated. Finally the activity values quantified vs time was fitted into a biokinetic model to obtain the disintegrations number and cumulate activities in each organ. With these data the radiation absorbed dose were calculated using MIRD methodology. Results: The number of disintegration and absorbed dose calculated in MBq h/MBq and mGy/MBq, of injected mouse with the 99m Tc-BN/ 99m Tc-RGD 2 formulation, was: 0.035 ± 0.65 E-02, 0.25 x 10 -5 ± 0.46 E-07; 0.393 ± 0.51 E-1, 2.85 E-05 ± 3.7 E-06; 0.306 ± 0.21 E-01, 2.11 E-05 ± 1.45 E-06 and 0.151 ± 0.19 E-01, 1.09 E-05 ± 1.42 E-06 , in heart, kidneys, bladder and tumor, respectively. The number of disintegration obtained in kidneys is comparable to those reported for Trinidad B. 2014 Conclusions: Our results demonstrated that using optical images and a code for image analyses development in MATLAB, could achieve comparable quantitative results as the conventional

  19. Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA

    OpenAIRE

    Dibrov, Sergey; McLean, Jaime; Hermann, Thomas

    2011-01-01

    An oligonucleotide representing a regulatory element of human thymidylate synthase mRNA has been crystallized as a dimer. The structure of the asymmetric dimer has been determined at 1.97 Å resolution.

  20. Adsorption, mobility, and dimerization of benzaldehyde on Pt(111)

    DEFF Research Database (Denmark)

    Rasmussen, Anton Michael Havelund; Hammer, Bjørk

    2012-01-01

    to have low energy barriers. Aggregation of molecules in dimers bound by aryl C–H⋯O hydrogen bonds is investigated, and specific configurations are found to be up to 0.15 eV more favorable than optimally configured, separated adsorbates. The binding is significantly stronger than what is found for gas...

  1. Synthesis and Dimerization Behavior of Five Metallophthalocyanines in Different Solvents

    Directory of Open Access Journals (Sweden)

    Zhenhua Cheng

    2014-01-01

    Full Text Available Metallophthalocyanine (MPc has become one of the metal organic compounds with the largest production and the most widely application, because of its excellent performance in catalytic oxidation. However, aggregation of the MPc in solution, resulting in decreased solubility, greatly limits the performance of application. Studying the behavior of dimerization of MPcs can provide a theoretical basis for solving the problem of the low solubility. So five metallophthalocyanines (FePc, CoPc, NiPc, CuPc, and ZnPc were prepared with improved method and characterized. Dimerization of the five MPcs was measured by UV-Vis spectroscopy separately in N,N-dimethyl formamide (DMF and dimethylsulfoxide (DMSO. The red-shift of maximum absorption wavelength and deviations from Lambert-Beer law with increasing the concentration were observed for all the five MPcs. The dimerization equilibrium constants (K of the five MPcs in DMF were arranged in order of CoPc > ZnPc > CuPc > FePc > NiPc, while in DMSO they were arranged in order of ZnPc > CoPc > FePc > CuPc > NiPc. The type of the central metal and nature of the solvent affect the dimerization of the MPcs.

  2. Unphosphorylated rhabdoviridae phosphoproteins form elongated dimers in solution.

    Science.gov (United States)

    Gerard, Francine C A; Ribeiro, Euripedes de Almeida; Albertini, Aurélie A V; Gutsche, Irina; Zaccai, Guiseppe; Ruigrok, Rob W H; Jamin, Marc

    2007-09-11

    The phosphoprotein (P) is an essential component of the replication machinery of rabies virus (RV) and vesicular stomatitis virus (VSV), and the oligomerization of P, potentially controlled by phosphorylation, is required for its function. Up to now the stoichiometry of phosphoprotein oligomers has been controversial. Size exclusion chromatography combined with detection by multiangle laser light scattering shows that the recombinant unphosphorylated phosphoproteins from VSV and from RV exist as dimers in solution. Hydrodynamic analysis indicates that the dimers are highly asymmetric, with a Stokes radius of 4.8-5.3 nm and a frictional ratio larger than 1.7. Small-angle neutron scattering experiments confirm the dimeric state and the asymmetry of the structure and yield a radius of gyration of about 5.3 nm and a cross-sectional radius of gyration of about 1.6-1.8 nm. Similar hydrodynamic properties and molecular dimensions were obtained with a variant of VSV phosphoprotein in which Ser60 and Thr62 are substituted by Asp residues and which has been reported previously to mimic phosphorylation by inducing oligomerization and activating transcription. Here, we show that this mutant also forms a dimer with hydrodynamic properties and molecular dimensions similar to those of the wild type protein. However, incubation at 30 degrees C for several hours induced self-assembly of both wild type and mutant proteins, leading to the formation of irregular filamentous structures.

  3. Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

    Directory of Open Access Journals (Sweden)

    Lukas P. Feilen

    2017-05-01

    Full Text Available Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs. The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

  4. Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

    Science.gov (United States)

    Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

    2017-01-01

    Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

  5. Core-to-core dimers forming switchable mesophase

    Czech Academy of Sciences Publication Activity Database

    Horčic, M.; Svoboda, J.; Novotná, Vladimíra; Pociecha, D.; Gorecka, E.

    2017-01-01

    Roč. 53, č. 18 (2017), s. 2721-2724 ISSN 1359-7345 R&D Projects: GA ČR GA15-02843S Institutional support: RVO:68378271 Keywords : liquid crystals * bent- core mesogens * dimers Subject RIV: JJ - Other Materials OBOR OECD: Nano-materials (production and properties) Impact factor: 6.319, year: 2016

  6. Plasma D-dimer concentration in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Montagnana Martina

    2006-01-01

    Full Text Available Abstract Background Systemic sclerosis (SSc is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis. Little is known so far on the activation of the hemostatic and fibrinolytic systems in SSc, and most preliminary evidences are discordant. Methods To verify whether SSc patients might display a prothrombotic condition, plasma D-dimer was assessed in 28 consecutive SSc patients and in 33 control subjects, matched for age, sex and environmental habit. Results and discussion When compared to healthy controls, geometric mean and 95% confidence interval (IC95% of plasma D-dimer were significantly increased in SSc patients (362 ng/mL, IC 95%: 361–363 ng/mL vs 229 ng/mL, IC95%: 228–231 ng/mL, p = 0.005. After stratifying SSc patients according to disease subset, no significant differences were observed between those with limited cutaneous pattern and controls, whereas patients with diffuse cutaneous pattern displayed substantially increased values. No correlation was found between plasma D-dimer concentration and age, sex, autoantibody pattern, serum creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and pulmonary involvement. Conclusion We demonstrated that SSc patients with diffuse subset are characterized by increased plasma D-dimer values, reflecting a potential activation of both the hemostatic and fibrinolytic cascades, which might finally predispose these patients to thrombotic complications.

  7. Dimeric Complexes of Tryptophan with M2+ Metal Ions

    NARCIS (Netherlands)

    Dunbar, R. C.; Steill, J. D.; Polfer, N. C.; Oomens, J.

    2009-01-01

    IRMPD spectroscopy using the FELIX free electron laser and a Fourier transform ICR mass spectrometer was used to characterize the structures of electrosprayed dimer complexes M(2+)Trp(2) of tryptophan with a series of eight doubly charged metal ions, including alkaline earths Ca, Sr, and Ba, and

  8. Density variations in a reactor during liquid full dimerization

    NARCIS (Netherlands)

    Golombok, M.; Bruijn, J.

    2000-01-01

    In a liquid full plug flow reactor during lower olefin dimerization, the assumption of constant density is not valid—the volume of a plug changes as it proceeds along the reactor. The observed kinetics depend on the density variation in the reactor as the conversion proceeds towards a distribution

  9. Cyclodextrin dimers as receptor molecules for steroid sensors

    NARCIS (Netherlands)

    de Jong, M.R.; Engbersen, Johannes F.J.; Huskens, Jurriaan; Reinhoudt, David

    2000-01-01

    The dansyl-modified dimer 9 complexes strongly with the steroidal bile salts. Relative to native -cyclodextrin, the binding of cholate (1 a) and deoxycholate (1 b) salts is especially enhanced. These steroids bind exclusively in a 1:1 fashion. For other bile salts (1 c-1 e) both 1:1 and 1:2

  10. Stepwise "Dark Photoswitching" of Photochromic Dimers in a Junction

    DEFF Research Database (Denmark)

    Olsen, Stine Tetzschner; Hansen, Thorsten; Nielsen, Mogens Brøndsted

    2017-01-01

    -induced switching) has been termed dark photoswitching and was observed for the dihydroazulene–vinylheptafulvene couple in a junction. In this theoretical study, we expand this concept to dimeric structures containing two dihydroazulene units linked through meta- or para-phenylene bridges and anchored...

  11. pi-Dimers of end-capped oligopyrrole cation radicals

    NARCIS (Netherlands)

    Haare, van J.A.E.H.; Groenendaal, L.; Havinga, E.E.; Janssen, R.A.J.; Meijer, E.W.

    1996-01-01

    In two consecutive one-electron oxidations, oligopyrroles substituted with phenyl capping groups (PhPynPh, n = 2–4) can be oxidized reversibly to give stable cation radicals and dications. Spectroelectrochemical studies give direct evidence that diamagnetic p-dimers of cation radicals are formed in

  12. Determining the nucleation rate from the dimer growth probability

    NARCIS (Netherlands)

    Ter Horst, J.H.; Kashchiev, D.

    2005-01-01

    A new method is proposed for the determination of the stationary one-component nucleation rate J with the help of data for the growth probability P2 of a dimer which is the smallest cluster of the nucleating phase. The method is based on an exact formula relating J and P2, and is readily applicable

  13. Dimerization of Carboxylic Acids: An Equation of State Approach

    DEFF Research Database (Denmark)

    Tsivintzelis, Ioannis; Kontogeorgis, Georgios; Panayiotou, Costas

    2017-01-01

    The association term of the nonrandom hydrogen bonding theory, which is an equation of state model, is extended to describe the dimerization of carboxylic acids in binary mixtures with inert solvents and in systems of two different acids. Subsequently, the model is applied to describe the excess...

  14. Designer interface peptide grafts target estrogen receptor alpha dimerization

    International Nuclear Information System (INIS)

    Chakraborty, S.; Asare, B.K.; Biswas, P.K.; Rajnarayanan, R.V.

    2016-01-01

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  15. Tricriticality for dimeric Coulomb molecular crystals in ground state

    Science.gov (United States)

    Travěnec, Igor; Šamaj, Ladislav

    2017-12-01

    We study the ground-state properties of a system of dimers. Each dimer consists in a pair of equivalent charges at a fixed distance, immersed in a neutralizing homogeneous background. All charges interact pairwisely by Coulomb potential. The dimer centers form a two-dimensional rectangular lattice with the aspect ratio α\\in [0, 1] and each dimer is allowed to rotate around its center. The previous numerical simulations, made for the more general Yukawa interaction, indicate that only two basic dimer configurations can appear: either all dimers are parallel or they have two different angle orientations within alternating (checkerboard) sublattices. As the dimer size increases, two second-order phase transitions, related to two kinds of the symmetry breaking in dimer’s orientations, were reported. In this paper, we use a recent analytic method based on an expansion of the interaction energy in Misra functions which converges quickly and provides an analytic derivation of the critical behaviour. Our main result is that there exists a specific aspect ratio of the rectangular lattice α^*=0.714 106 840 000 71\\ldots which divides the space of model’s phases onto two distinct regions. If the lattice aspect ratio α>α* , we recover both types of the second-order phase transitions and find that they are of mean-field type with the critical exponent β = 1/2 . If 0.711 535≤slantα<α* , the phase transition associated with the discontinuity of dimer’s angles on alternating sublattices becomes of first order. For α=α* , the first- and second-order phase transitions meet at the tricritical point, characterized by the different critical index β = 1/4 . Such phenomenon is known from literature about the Landau theory of one-component fields, but in our two-component version the scenario is more complicated: the component which is already in the symmetry-broken state at the tricritical point also interferes and exhibits unexpectedly the mean-field singular

  16. Designer interface peptide grafts target estrogen receptor alpha dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, S. [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Asare, B.K. [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States); Biswas, P.K., E-mail: pbiswas@tougaloo.edu [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Rajnarayanan, R.V., E-mail: rajendra@buffalo.edu [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States)

    2016-09-09

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  17. 2-Ethynylpyridine dimers: IR spectroscopic and computational study

    Science.gov (United States)

    Bakarić, Danijela; Spanget-Larsen, Jens

    2018-04-01

    2-ethynylpyridine (2-EP) presents a multifunctional system capable of participation in hydrogen-bonded complexes utilizing hydrogen bond donating (tbnd Csbnd H, Aryl-H) and hydrogen bond accepting functions (N-atom, Ctbnd C and pyridine π-systems). In this work, IR spectroscopy and theoretical calculations are used to study possible 2-EP dimer structures as well as their distribution in an inert solvent such as tetrachloroethene. Experimentally, the tbnd Csbnd H stretching vibration of the 2-EP monomer absorbs close to 3300 cm-1, whereas a broad band with maximum around 3215 cm-1 emerges as the concentration rises, indicating the formation of hydrogen-bonded complexes involving the tbnd Csbnd H moiety. The Ctbnd C stretching vibration of monomer 2-EP close to 2120 cm-1 is, using derivative spectroscopy, resolved from the signals of the dimer complexes with maximum around 2112 cm-1. Quantum chemical calculations using the B3LYP + D3 model with counterpoise correction predict that the two most stable dimers are of the π-stacked variety, closely followed by dimers with intermolecular tbnd Csbnd H⋯N hydrogen bonding; the predicted red shifts of the tbnd Csbnd H stretching wavenumbers due to hydrogen bonding are in the range 54-120 cm-1. No species with obvious hydrogen bonding involving the Ctbnd C or pyridine π-systems as acceptors are predicted. Dimerization constant at 25 °C is estimated to be K2 = 0.13 ± 0.01 mol-1 dm3.

  18. Dimerization of human immunodeficiency virus (type 1) RNA: stimulation by cations and possible mechanism.

    Science.gov (United States)

    Marquet, R; Baudin, F; Gabus, C; Darlix, J L; Mougel, M; Ehresmann, C; Ehresmann, B

    1991-05-11

    The retroviral genome consists of two identical RNA molecules joined close to their 5' ends by the dimer linkage structure. Recent findings indicated that retroviral RNA dimerization and encapsidation are probably related events during virion assembly. We studied the cation-induced dimerization of HIV-1 RNA and results indicate that all in vitro generated HIV-1 RNAs containing a 100 nucleotide domain downstream from the 5' splice site are able to dimerize. RNA dimerization depends on the concentration of RNA, mono- and multivalent cations, the size of the monovalent cation, temperature, and pH. Up to 75% of HIV-1 RNA is dimeric in the presence of spermidine. HIV-1 RNA dimer is fairly resistant to denaturing agents and unaffected by intercalating drugs. Antisense HIV-1 RNA does not dimerize but heterodimers can be formed between HIV-1 RNA and either MoMuLV or RSV RNA. Therefore retroviral RNA dimerization probably does not simply proceed through mechanisms involving Watson-Crick base-pairing. Neither adenine and cytosine protonation, nor quartets containing only guanines appear to determine the stability of the HIV-1 RNA dimer, while quartets involving both adenine(s) and guanine(s) could account for our results. A consensus sequence PuGGAPuA found in the putative dimerization-encapsidation region of all retroviral genomes examined may participate in the dimerization process.

  19. Functionalization of the PEG Corona of Nanoparticles by Clip Photochemistry in Water: Application to the Grafting of RGD Ligands on PEGylated USPIO Imaging Agent.

    Science.gov (United States)

    Pourcelle, Vincent; Laurent, Sophie; Welle, Alexandre; Vriamont, Nicolas; Stanicki, Dimitri; Vander Elst, Luce; Muller, Robert N; Marchand-Brynaert, Jacqueline

    2015-05-20

    The fast development of nanomedicines requires more and more reliable chemical tools in order to accurately design materials and control the surface properties of the nano-objects used in biomedical applications. In this study we describe a smooth and simple photografting technique, i.e., the clip photochemistry, that allows the introduction of molecules of interest in inert polymers or on stealth nanoparticles directly in aqueous solution. First we developed the methodology on polyethylene glycol (PEG) and looked for critical parameters of the process (irradiation times, concentrations, washings) by using several molecular probes and adapted analytical techniques ((19)F qNMR, EA, LSC). We found that the clip photochemistry in water is a robust and efficient method to functionalize PEG. Second we applied it on PEGylated USPIO (USPIO-PEG) magnetic resonance imaging agent and succeeded in introducing RGD peptide and homemade peptidomimetics on their PEG segments. The magnetic abilities of the conjugated nanoparticles were unchanged by the derivatization process as evidenced by their relaxometric properties and their NMRD profile. When tested on Jurkat lymphocyte T Cells, which express αvβ3 integrins, the USPIO conjugated with RGD ligands leads to an increase of the transverse relaxation rate (R2) by a factor 10 to 14 as compared to USPIO-PEG. Consequently, it makes them good candidates for targeted imaging technology in cancer therapy.

  20. Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces.

    Science.gov (United States)

    Sankaran, Shrikrishnan; Cavatorta, Emanuela; Huskens, Jurriaan; Jonkheijm, Pascal

    2017-09-05

    Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV 2+ ). The binding affinity of the knottins with CB[8] and MV 2+ surfaces was evaluated using surface plasmon resonance spectroscopy. Specific binding occurred, and the affinity increased with the valency of tryptophans on the knottin. Additionally, increased multilayer formation was observed, attributed to homoternary complex formation between tryptophan residues of different knottins and CB[8]. Thus, we were able to control the surface coverage of the knottins by valency and concentration. Cell experiments with mouse myoblast (C2C12) cells on the self-assembled knottin surfaces showed specific integrin recognition by the RGD-displaying knottins. Moreover, cells were observed to elongate more on the supramolecular knottin surfaces with a higher valency, and in addition, more pronounced focal adhesion formation was observed on the higher-valency knottin surfaces. We attribute this effect to the enhanced coverage and the enhanced affinity of the knottins in their interaction with the CB[8] surface. Collectively, these results are promising for the development of biomaterials including knottins via CB[8] ternary complexes for tunable interactions with cells.

  1. A first principles study of fluorescence quenching in rhodamine B dimers : how can quenching occur in dimeric species?

    NARCIS (Netherlands)

    Setiawan, Dani; Kazaryan, Andranik; Martoprawiro, Muhamad Abdulkadir; Filatov, Michael

    2010-01-01

    Rhodamine B (RhB) is widely used in chemistry and biology due to its high fluorescence quantum yield. In high concentrations, the quantum yield of fluorescence decreases considerably which is attributed to the formation of RhB dimers. In the present work, a possible mechanism of fluorescence

  2. The influence of proteasome inhibitor MG132, external radiation and unlabeled antibody on the tumor uptake and biodistribution of 188Re-labeled anti-E6 C1P5 antibody in cervical cancer in mice

    Science.gov (United States)

    Phaeton, Rébécca; Wang, Xing Guo; Einstein, Mark H.; Goldberg, Gary L.; Casadevall, Arturo; Dadachova, Ekaterina

    2009-01-01

    Background Human Papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer and >95% of all cervical cancers have detectable HPV sequences. We have recently demonstrated the efficacy of radioimmunotherapy (RIT) which targeted viral oncoprotein E6 in treatment of experimental cervical cancer We hypothesized that pre-treatment of tumor cells with various agents which cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors. Methods HPV-16 positive CasKi cells were treated in vitro with up to 6 Gy of external radiation, or proteasome inhibitor MG-132 or unlabeled anti-E6 antibody C1P5 and cell death was assessed. Biodistribution of 188Rhenium (188Re)-labeled C1P5 antibody was performed in both control and radiation MG-132 treated CasKi tumor-bearing nude mice. Results . 188Re-C1P5 antibody demonstrated tumor specificity and very low uptake and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG-132 but was unaffected by pre-treatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by our previous in vivo studies in CasKi tumor model. Conclusion We demonstrated that pre-treatment of cervical tumors with proteasome inhibitor MG-132 and with unlabeled antibody to E6 can serve as a means to generate non-viable cancer cells and to elevate the levels of target oncoproteins in the cells for increasing the accumulation of targeted radiolabeled antibodies in tumors. These results favor further development of RIT of cervical cancers targeting viral antigens. PMID:20127955

  3. Quantum-statistical mechanics of an atom-dimer mixture: Lee-Yang cluster expansion approach

    International Nuclear Information System (INIS)

    Ohkuma, Takahiro; Ueda, Masahito

    2006-01-01

    We use the Lee-Yang cluster expansion method to study quantum-statistical properties of a mixture of interconvertible atoms and dimers, where the dimers form in a two-body bound state of the atoms. We point out an infinite series of cluster diagrams whose summation leads to the Bose-Einstein condensation of the dimers below a critical temperature. Our theory captures some important features of a cold atom-dimer mixture such as interconversion of atoms and dimers and properties of the mixture at the unitarity limit

  4. Functional inhibition of NF-kappa B signal transduction in alpha v alpha beta 3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant I kappa B gene

    NARCIS (Netherlands)

    Ogawara, K; Kuldo, JM; Oosterhuis, K; Kroesen, BJ; Rots, MG; Trautwein, C; Kimura, T; Haisma, HJ; Molema, G

    2006-01-01

    In order to selectively block nuclear factor kappa B (NF-kappa B)-dependent signal transduction in angiogenic endothelial cells, we constructed an alpha v beta 3 integrin specific adenovirus encoding dominant negative I kappa B (dnI kappa B) as a therapeutic gene. By virtue of RGD modification of

  5. Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes

    Directory of Open Access Journals (Sweden)

    Carbone Maria

    2006-09-01

    Full Text Available Abstract Background Mammalian sperm-oocyte interaction at fertilization involves several combined interactions between integrins on the oocyte and integrin ligands (disintegrins on the sperm. Recent research has indicated the ability of peptides containing the RGD sequence that characterized several sperm disintegrins, to induce intracellular Ca2+ transients and to initiate parthenogenetic development in amphibian and bovine oocytes. In the present study, we investigate the hypothesis that an integrin-associated signalling may participate in oocyte activation signalling by determining the ability of a cyclic RGD-containing peptide to stimulate the activation of protein kinase C (PKC and the exocytosis of cortical granules in mouse oocytes. Methods An In-Vitro-Fertilization assay (IVF was carried in order to test the condition under which a peptide containing the RGD sequence, cyclo(Arg-Gly-Asp-D-Phe-Val, was able to inhibit sperm fusion with zona-free mouse oocytes at metaphase II stage. PKC activity was determined by means of an assay based on the ability of cell lysates to phosphorylate MARKS peptide, a specific PKC substrate. Loss of cortical granules was evaluated by measuring density in the oocyte cortex of cortical granules stained with LCA-biotin/Texas red-streptavidin. In all the experiments, effects of a control peptide containing a non RGD sequence, cyclo(Arg-Ala-Asp-D-Phe-Val, were evaluated. Results The IVF assay revealed that the fusion rate declined significantly when insemination was carried out in the presence of cyclic RGD peptide at concentrations > or = 250 microM (P Conclusion The presents results provide evidence that a cyclic RGD peptide highly effective in inhibiting sperm-oocyte interaction stimulates in mouse oocytes the activation of PKC and the exocytosis of cortical granules. These data support the view that RGD-binding receptors may function as signalling receptors giving rise integrated signalling not sufficient for

  6. MicroPET/CT imaging of {alpha}{sub v}{beta}{sub 3} integrin via a novel {sup 68}Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Menichetti, Luca; Kusmic, Claudia; Panetta, Daniele; Petroni, Debora; Salvadori, Piero A. [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Arosio, Daniela; Manzoni, Leonardo [CNR-Institute of Molecular Science and Technologies (ISTM), Milan (Italy); Matteucci, Marco [Scuola Superiore Sant' Anna, Pisa (Italy); Casagrande, Cesare [University of Milan, Department of Chemistry, Milan (Italy); L' Abbate, Antonio [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Scuola Superiore Sant' Anna, Pisa (Italy)

    2013-08-15

    The {alpha}{sub v}{beta}{sub 3} integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel {sup 68}Ga-2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI. A straightforward labelling chemistry to attach the radionuclide {sup 68}Ga to a NOTA-based chelating agent conjugated with a cyclic RGD peptidomimetic is described. Affinity for {alpha}{sub v}{beta}{sub 3} integrin was assessed by in vitro receptor binding assay. The proof-of-concept in vivo studies combined the {sup 68}Ga-NOTA-RGD with the flow tracer {sup 13}N-NH{sub 3} imaging in order to obtain positron emission tomography (PET)/CT imaging of both integrin expression and perfusion defect at 4 weeks after infarction. Hearts were then processed for immunostaining of integrin {beta}{sub 3}. NOTA-RGD conjugate displayed a binding affinity for {alpha}{sub v}{beta}{sub 3} integrin of 27.9 {+-} 6.8 nM. {sup 68}Ga-NOTA-RGD showed stability without detectable degradation or formation of by-products in urine up to 2 h following injection in the rat. MI hearts exhibited {sup 68}Ga-NOTA-RGD uptake in correspondence to infarcted and border zone regions. The tracer signal drew a parallel with vascular remodelling due to ischaemia-induced angiogenesis as assessed by immunohistochemistry. As compared to similar imaging approaches using the {sup 18}F-galacto-derivative, we documented for the first time with microPET/CT imaging the {sup 68}Ga-NOTA-RGD derivative that appears eligible for PET imaging in animal models of vascular remodelling during evolving MI. The simple chemistry employed to

  7. A short autocomplementary sequence plays an essential role in avian sarcoma-leukosis virus RNA dimerization.

    Science.gov (United States)

    Fossé, P; Motté, N; Roumier, A; Gabus, C; Muriaux, D; Darlix, J L; Paoletti, J

    1996-12-24

    Retroviral genomes consist of two identical RNA molecules joined noncovalently near their 5'-ends. Recently, two models have been proposed for RNA dimer formation on the basis of results obtained in vitro with human immunodeficiency virus type 1 RNA and Moloney murine leukemia virus RNA. It was first proposed that viral RNA dimerizes by forming an interstrand quadruple helix with purine tetrads. The second model postulates that RNA dimerization is initiated by a loop-loop interaction between the two RNA molecules. In order to better characterize the dimerization process of retroviral genomic RNA, we analyzed the in vitro dimerization of avian sarcoma-leukosis virus (ASLV) RNA using different transcripts. We determined the requirements for heterodimer formation, the thermal dissociation of RNA dimers, and the influence of antisense DNA oligonucleotides on dimer formation. Our results strongly suggest that purine tetrads are not involved in dimer formation. Data show that an autocomplementary sequence located upstream from the splice donor site and within a major packaging signal plays a crucial role in ASLV RNA dimer formation in vitro. This sequence is able to form a stem-loop structure, and phylogenetic analysis reveals that it is conserved in 28 different avian sarcoma and leukosis viruses. These results suggest that dimerization of ASLV RNA is initiated by a loop-loop interaction between two RNA molecules and provide an additional argument for the ubiquity of the dimerization process via loop-loop interaction.

  8. Effects of Dimers on Cooperation in the Spatial Prisoner's Dilemma Game

    International Nuclear Information System (INIS)

    Li Haihong; Cheng Hongyan; Dai Qionglin; Ju Ping; Yang Junzhong; Zhang Mei

    2011-01-01

    We investigate the evolutionary prisoner's dilemma game in structured populations by introducing dimers, which are defined as that two players in each dimer always hold a same strategy. We find that influences of dimers on cooperation depend on the type of dimers and the population structure. For those dimers in which players interact with each other, the cooperation level increases with the number of dimers though the cooperation improvement level depends on the type of network structures. On the other hand, the dimers, in which there are not mutual interactions, will not do any good to the cooperation level in a single community, but interestingly, will improve the cooperation level in a population with two communities. We explore the relationship between dimers and self-interactions and find that the effects of dimers are similar to that of self-interactions. Also, we find that the dimers, which are established over two communities in a multi-community network, act as one type of interaction through which information between communities is communicated by the requirement that two players in a dimer hold a same strategy. (general)

  9. Biodistribution and Radiation Dosimetry of the Integrin Marker 64Cu-BaBaSar-RGD2 Determined from Whole-Body PET/CT in a Non-Human Primate

    Science.gov (United States)

    Liu, Shuanglong; Vorobyova, Ivetta; Park, Ryan; Conti, Peter S.

    2017-10-01

    Introduction: 64Cu-BaBaSar-RGD2 is a positron emission radiotracer taken up by integrin αvβ3, which is overexpressed in many malignancies. The aim of this study was to evaluate the biodistribution of 64Cu-BaBaSar-RGD2 in a non-human primate with positron emission tomography and to estimate the absorbed doses in major organs for human. Materials and methods: Whole-body PET imaging was done in a Siemens Biograph scanner in a male macaque monkey. After an i.v. injection of 13.1–19.7 MBq/kg of 64Cu-BaBaSar-RGD2, whole body scan was collected for a total duration of 180 min. Attenuation and scatter corrections were applied to reconstruction of the whole-body emission scan. After image reconstruction, three-dimensional volumes of interest (VOI) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and residence time of each organ was calculated by integration of the time-activity curves. Human absorbed doses were estimated using the standard human model in OLINDA/EXM software. Results: Injection of 64Cu-BaBaSar-RGD2 was well tolerated in the macaque monkey, with no serious tracer-related adverse events observed. 64Cu-BaBaSar-RGD2 was cleared rapidly from the blood pool, with a 12.1-min biological half-time. Increased 64Cu-BaBaSar-RGD2 uptake was observed in the kidneys, and bladder, with mean percentage injected dose (ID%) values at 1 h after injection approximately 35.50 ± 6.47 and 36.89 ± 5.48, respectively. The calculated effective dose was 15.30 ± 2.21 µSv/MBq, and the kidneys had the highest absorbed dose at 108.43 ± 16.41 µGy/MBq using the non-voiding model. For an injected activity of 925 MBq 64Cu for human, the effective dose would be 14.2 ± 2.1 mSv. Discussion: Due to the limitation of the monkey number, we evaluated 64Cu-BaBaSar-RGD2 in the same monkey of three imaging sessions. Measured absorbed doses and effective doses of 64Cu-BaBaSar-RGD2 are

  10. Association of atoms into universal dimers using an oscillating magnetic field.

    Science.gov (United States)

    Langmack, Christian; Smith, D Hudson; Braaten, Eric

    2015-03-13

    In a system of ultracold atoms near a Feshbach resonance, pairs of atoms can be associated into universal dimers by an oscillating magnetic field with a frequency near that determined by the dimer binding energy. We present a simple expression for the transition rate that takes into account many-body effects through a transition matrix element of the contact. In a thermal gas, the width of the peak in the transition rate as a function of the frequency is determined by the temperature. In a dilute Bose-Einstein condensate of atoms, the width is determined by the inelastic scattering rates of a dimer with zero-energy atoms. Near an atom-dimer resonance, there is a dramatic increase in the width from inelastic atom-dimer scattering and from atom-atom-dimer recombination. The recombination contribution provides a signature for universal tetramers that are Efimov states consisting of two atoms and a dimer.

  11. Controlled Patterning of Plasmonic Dimers by Using an Ultrathin Nanoporous Alumina Membrane as a Shadow Mask.

    Science.gov (United States)

    Hao, Qi; Huang, Hao; Fan, Xingce; Yin, Yin; Wang, Jiawei; Li, Wan; Qiu, Teng; Ma, Libo; Chu, Paul K; Schmidt, Oliver G

    2017-10-18

    We report on design and fabrication of patterned plasmonic dimer arrays by using an ultrathin anodic aluminum oxide (AAO) membrane as a shadow mask. This strategy allows for controllable fabrication of plasmonic dimers where the location, size, and orientation of each particle in the dimer pairs can be independently tuned. Particularly, plasmonic dimers with ultrasmall nanogaps down to the sub-10 nm scale as well as a large dimer density up to 1.0 × 10 10 cm -2 are fabricated over a centimeter-sized area. The plasmonic dimers exhibit significant surface-enhanced Raman scattering (SERS) enhancement with a polarization-dependent behavior, which is well interpreted by finite-difference time-domain (FDTD) simulations. Our results reveal a facile approach for controllable fabrication of large-area dimer arrays, which is of fundamental interest for plasmon-based applications in surface-enhanced spectroscopy, biochemical sensing, and optoelectronics.

  12. GLYCOLALDEHYDE FORMATION VIA THE DIMERIZATION OF THE FORMYL RADICAL

    Energy Technology Data Exchange (ETDEWEB)

    Woods, Paul M.; Viti, Serena [Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom); Slater, Ben; Raza, Zamaan; Brown, Wendy A.; Burke, Daren J., E-mail: p.woods@qub.ac.uk [Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom)

    2013-11-10

    Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints.

  13. GLYCOLALDEHYDE FORMATION VIA THE DIMERIZATION OF THE FORMYL RADICAL

    International Nuclear Information System (INIS)

    Woods, Paul M.; Viti, Serena; Slater, Ben; Raza, Zamaan; Brown, Wendy A.; Burke, Daren J.

    2013-01-01

    Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints

  14. Acylphenols and dimeric acylphenols from Myristica maxima Warb.

    Science.gov (United States)

    Othman, Muhamad Aqmal; Sivasothy, Yasodha; Looi, Chung Yeng; Ablat, Abdulwali; Mohamad, Jamaludin; Litaudon, Marc; Awang, Khalijah

    2016-06-01

    Giganteone E (1), a new dimeric acylphenol was isolated as a minor constituent from the bark of Myristica maxima Warb. The structure of 1 was established on the basis of 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Malabaricones A-C (2-4), giganteones A and C (5 and 6), maingayones A and B (7 and 8), maingayic acid B (9) and β-sitosteryl oleate (10) were also characterized in this plant for the first time. Compound 10 was identified for the first time in the Myristicaceae. Compounds 2 and 5 were active against human prostate cancer cell-lines, thus making this the first report on the prostate cancer inhibiting potential of acylphenols and dimeric acylphenols. Compounds 1, 4, 5, 7 and 8 exhibited potent DPPH free radical scavenging activity. This is the first report on their free radical scavenging capacity. Copyright © 2016. Published by Elsevier B.V.

  15. Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook.

    Science.gov (United States)

    Xu, Feng-Qing; Xu, Fang-Cheng; Hou, Bo; Fan, Wei-Wei; Zi, Cheng-Ting; Li, Yan; Dong, Fa-Wu; Liu, Yu-Qing; Sheng, Jun; Zuo, Zhi-Li; Hu, Jiang-Miao

    2014-11-15

    The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 μM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Solution structure of the dimeric cytoplasmic domain of syndecan-4

    DEFF Research Database (Denmark)

    Shin, J; Lee, W; Lee, D

    2001-01-01

    The syndecans, transmembrane proteoglycans which are involved in the organization of cytoskeleton and/or actin microfilaments, have important roles as cell surface receptors during cell-cell and/or cell-matrix interactions. Since previous studies indicate that the function of the syndecan-4...... between peptides at physiological pH. Commensurately, the NMR structures demonstrate that syndecan-4L is a compact intertwined dimer with a symmetric clamp shape in the central variable V region with a root-mean-square deviation between backbone atom coordinates of 0.95 A for residues Leu(186)-Ala(195...... in the center of the dimeric twist similar to our previously reported 4V structure. The overall topology of the central variable region within the 4L structure is very similar to that of 4V complexed with the phosphatidylinositol 4,5-bisphosphate; however, the intersubunit interaction mode is affected...

  17. Antagonizing STAT3 dimerization with a rhodium(III) complex.

    Science.gov (United States)

    Ma, Dik-Lung; Liu, Li-Juan; Leung, Ka-Ho; Chen, Yen-Ting; Zhong, Hai-Jing; Chan, Daniel Shiu-Hin; Wang, Hui-Min David; Leung, Chung-Hang

    2014-08-25

    Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent anti-tumor activities in an in vivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti-tumor activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Stability of gold atoms and dimers adsorbed on graphene

    International Nuclear Information System (INIS)

    Varns, R; Strange, P

    2008-01-01

    We report density functional theory (DFT) calculations for gold atoms and dimers on the surface of graphene. The calculations were performed using the plane wave pseudopotential method. Calculations were performed for a variety of geometries, and both the graphene surface and gold atoms were allowed to fully relax. In agreement with experiment, our results show that the gold-gold interaction is considerably stronger than the gold-graphene interaction, implying that uniform coverage could not be attained. The minimum energy configuration for a single gold atom is found to be directly above a carbon atom, while for the dimer it is perpendicular to the surface and directly above a carbon-carbon bond. Our results are consistent with previous similar calculations

  19. Glycine transporter dimers: evidence for occurrence in the plasma membrane

    DEFF Research Database (Denmark)

    Bartholomäus, Ingo; Milan-Lobo, Laura; Nicke, Annette

    2008-01-01

    membrane based on hydrodynamic and native gel electrophoretic studies. Here, we used cysteine substitution and oxidative cross-linking to show that of GlyT1 and GlyT2 also form dimeric complexes within the plasma membrane. GlyT oligomerization at the cell surface was confirmed for both GlyT1 and GlyT2......Different Na(+)/Cl(-)-dependent neurotransmitter transporters of the SLC6a family have been shown to form dimers or oligomers in both intracellular compartments and at the cell surface. In contrast, the glycine transporters (GlyTs) GlyT1 and -2 have been reported to exist as monomers in the plasma...

  20. Data on dimer formation between importin α subtypes

    Directory of Open Access Journals (Sweden)

    Yoichi Miyamoto

    2016-06-01

    Full Text Available This article describes data related to the research article titled “Functional characterization of importin α8 as a classical nuclear localization signal receptor” [1]. A GST pull-down assay showed that both importin α1 and α8, which are classical nuclear localization signal (cNLS receptors, can form a dimer with importin α6, α7, or α8. Importin α8 has higher dimer-forming ability than importin α1. In addition, our data show that either importin α1 or importin α8 can form a heterodimer with importin α3, which exists in a preformed complex with cNLS substrates such as the conventional SV40TNLS or the p53 protein, resulting in the release of the cNLS substrates from importin α3.

  1. Photomonomerization of pyrimidine dimers by indoles and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.; Huang, C.W.; Hinman, L.; Gordon, M.P.; Deranleau, D.A.

    1976-01-01

    Model systems for the study of photoreactivation have been developed that utilize a variety of indole derivatives. These systems can split uracil cis-syn cyclobutadipyrimidine, either free or in RNA, when irradiated at wavelengths absorbed only by the indole moiety. The ability of indole compounds to split dimers is closely related to their electronic properties. Those of high electron-donor capacity such as indole, 3-methylindole, indole-3-acetic acid, 5-hydroxytryptophan and tryptophan are good photosensitizers, with efficacy in that order. Indoles with electron-withdrawing substituents such as indole-3-carboxylic acid, indole-3-aldehyde and oxindole are inactive in the monomerization reaction. These findings support the proposed mechanism that the photosensitized monomerization occurs as a result of electron transfer from the excited indole molecules to the pyrimidine bases. Proteins containing fully exposed tryptophan residues (chicken egg white lysozyme and bovine diisopropylphosphoryltrypsin) also cause the splitting of the /sup 14/C-labeled dimers under the same conditions. In the case of lysozyme the quantum yield of monomerization is similar to that of free tryptophan. Much of the monomerization ability of lysozyme was lost after the solvent-available tryptophan had been oxidized by treatment with N-bromosuccinimide. Bovine pancreatic ribonuclease A, a protein devoid of tryptophan, failed to exhibit photosensitized monomerization of uracil dimers. The biological implication of these reactions involving a protein with an exposed tryptophan residue is discussed. Although indoles are able to split the dimers in RNA, they fail to photoreactivate uv-damaged TMV-RNA. Indole-3-acetic acid, 3-methylindole and 5-hydroxytryptophan rapidly inactive viral RNA when irradiated at 313 nm, possibly because of side reactions.

  2. A new hydroxychavicol dimer from the roots of Piper betle.

    Science.gov (United States)

    Lin, Chwan-Fwu; Hwang, Tsong-Long; Chien, Chun-Chien; Tu, Huei-Yu; Lay, Horng-Liang

    2013-02-26

    A new hydroxychavicol dimer, 2-(g'-hydroxychavicol)-hydroxychavicol (1), was isolated from the roots of Piper betle Linn. along with five known compounds, hydroxychavicol (2), aristololactam A II (3), aristololactam B II (4), piperolactam A (5) and cepharadione A (6). The structures of these isolated compounds were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.

  3. A New Hydroxychavicol Dimer from the Roots of Piper betle

    Directory of Open Access Journals (Sweden)

    Huei-Yu Tu

    2013-02-01

    Full Text Available A new hydroxychavicol dimer, 2-(g'-hydroxychavicol-hydroxychavicol (1, was isolated from the roots of Piper betle Linn. along with five known compounds, hydroxychavicol (2, aristololactam A II (3, aristololactam B II (4, piperolactam A (5 and cepharadione A (6. The structures of these isolated compounds were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.

  4. Synthesis and anti-inflammatory activity of phenylbutenoid dimer analogs

    International Nuclear Information System (INIS)

    Kim, Sung Soo; Fang, Yuan Ying; Park, Hae Eil

    2015-01-01

    Several phenylbutenoid dimer (PBD) analogs were synthesized and evaluated for their inhibitory activities against nitric oxide (NO) production and TNF-α release. The PBD analogs were synthesized via Diels–Alder and subsequent Schlosser reactions as key steps. Among the tested compounds, two analogs (8c, 8f) exhibited much stronger inhibitory activity against LPS-stimulated NO production and TNF-α release in RAW 264.7 cells than that of wogonin

  5. Formation and Dimerization of NO2 A General Chemistry Experiment

    Science.gov (United States)

    Hennis, April D.; Highberger, C. Scott; Schreiner, Serge

    1997-11-01

    We have developed a general chemistry experiment which illustrates Gay-Lussac's law of combining volumes. Students are able to determine the partial pressures and equilibrium constant for the formation and dimerization of NO2. The experiment can be carried out in about 45 minutes with students working in groups of two. The experiment readily provides students with data that can be manipulated with a common spreadsheet.

  6. A new dimeric anthraquinone from endophytic Talaromyces sp. YE3016.

    Science.gov (United States)

    Xie, Xiao-Song; Fang, Xiao-Wei; Huang, Rong; Zhang, Shou-Peng; Wei, Hong-Xia; Wu, Shao-Hua

    2016-08-01

    A new unsymmetrical dimeric anthraquinone, 3-demethyl-3-(2-hydroxypropyl)-skyrin (1) was isolated from the solid-state fermentation extract of an endophytic fungal strain Talaromyces sp. YE 3016, together with five known compounds, skyrin (2), oxyskyrin (3), emodin (4), 1,3,6-trihydroxy-8-methyl-anthraquinone (5) and ergosterol (6). The structure of the new compound was elucidated on the basis of spectroscopic analysis. Compounds 1-3 exhibited moderate cytotoxic activities against MCF-7 cell line.

  7. Dimeric spectra analysis in Microsoft Excel: a comparative study.

    Science.gov (United States)

    Gilani, A Ghanadzadeh; Moghadam, M; Zakerhamidi, M S

    2011-11-01

    The purpose of this work is to introduce the reader to an Add-in implementation, Decom. This implementation provides the whole processing requirements for analysis of dimeric spectra. General linear and nonlinear decomposition algorithms were integrated as an Excel Add-in for easy installation and usage. In this work, the results of several samples investigations were compared to those obtained by Datan. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Theory and simulations of adhesion receptor dimerization on membrane surfaces.

    Science.gov (United States)

    Wu, Yinghao; Honig, Barry; Ben-Shaul, Avinoam

    2013-03-19

    The equilibrium constants of trans and cis dimerization of membrane bound (2D) and freely moving (3D) adhesion receptors are expressed and compared using elementary statistical-thermodynamics. Both processes are mediated by the binding of extracellular subdomains whose range of motion in the 2D environment is reduced upon dimerization, defining a thin reaction shell where dimer formation and dissociation take place. We show that the ratio between the 2D and 3D equilibrium constants can be expressed as a product of individual factors describing, respectively, the spatial ranges of motions of the adhesive domains, and their rotational freedom within the reaction shell. The results predicted by the theory are compared to those obtained from a novel, to our knowledge, dynamical simulations methodology, whereby pairs of receptors perform realistic translational, internal, and rotational motions in 2D and 3D. We use cadherins as our model system. The theory and simulations explain how the strength of cis and trans interactions of adhesive receptors are affected both by their presence in the constrained intermembrane space and by the 2D environment of membrane surfaces. Our work provides fundamental insights as to the mechanism of lateral clustering of adhesion receptors after cell-cell contact and, more generally, to the formation of lateral microclusters of proteins on cell surfaces. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. On the photophysics and photochemistry of the water dimer

    Energy Technology Data Exchange (ETDEWEB)

    Segarra-Marti, Javier; Merchan, Manuela [Instituto de Ciencia Molecular, Universitat de Valencia, P.O. Box 22085, 46071 Valencia (Spain); Roca-Sanjuan, Daniel; Lindh, Roland [Department of Chemistry - Angstroem, Theoretical Chemistry Program, Uppsala University, Box 518, 75120 Uppsala (Sweden)

    2012-12-28

    The photochemistry of the water dimer irradiated by UV light is studied by means of the complete active space perturbation theory//complete active space self-consistent field (CASPT2//CASSCF) method and accurate computational approaches like as minimum energy paths. Both electronic structure computations and ab initio molecular dynamics simulations are carried out. The results obtained show small shifts relative to a single water molecule on the vertical excitation energies of the dimer due to the hydrogen bond placed between the water donor (W{sub D}) and the water acceptor (W{sub A}). A red-shift and a blue-shift are predicted for the W{sub D} and W{sub A}, respectively, supporting previous theoretical and experimental results. The photoinduced chemistry of the water dimer is described as a process occurring between two single water molecules in which the effect of the hydrogen bond plays a minor role. Thus, the photoinduced decay routes correspond to two photodissociation processes, one for each water molecule. The proposed mechanism for the decay channels of the lowest-lying excited states of the system is established as the photochemical production of a hydrogen-bonded H{sub 2}O Horizontal-Ellipsis HO species plus a hydrogen H atom.

  10. Structures of closed and open conformations of dimeric human ATM

    Science.gov (United States)

    Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

    2017-01-01

    ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

  11. Dimerization effect of sucrose octasulfate on rat FGF1

    International Nuclear Information System (INIS)

    Kulahin, N.; Kiselyov, V.; Kochoyan, A.; Kristensen, O.; Kastrup, Jette S.; Berezin, V.; Bock, E.; Gajhede, M.

    2008-01-01

    The work describes the sucrose octasulfate-mediated dimerization of rat FGF1 by gel-filtration experiments and crystal structure determination. Fibroblast growth factors (FGFs) constitute a family of at least 23 structurally related heparin-binding proteins that are involved in regulation of cell growth, survival, differentiation and migration. Sucrose octasulfate (SOS), a chemical analogue of heparin, has been demonstrated to activate FGF signalling pathways. The structure of rat FGF1 crystallized in the presence of SOS has been determined at 2.2 Å resolution. SOS-mediated dimerization of FGF1 was observed, which was further supported by gel-filtration experiments. The major contributors to the sulfate-binding sites in rat FGF1 are Lys113, Lys118, Arg122 and Lys128. An arginine at position 116 is a consensus residue in mammalian FGF molecules; however, it is a serine in rat FGF1. This difference may be important for SOS-mediated FGF1 dimerization in rat

  12. Correlative SEM SERS for quantitative analysis of dimer nanoparticles.

    Science.gov (United States)

    Timmermans, F J; Lenferink, A T M; van Wolferen, H A G M; Otto, C

    2016-11-14

    A Raman microscope integrated with a scanning electron microscope was used to investigate plasmonic structures by correlative SEM-SERS analysis. The integrated Raman-SEM microscope combines high-resolution electron microscopy information with SERS signal enhancement from selected nanostructures with adsorbed Raman reporter molecules. Correlative analysis is performed for dimers of two gold nanospheres. Dimers were selected on the basis of SEM images from multi aggregate samples. The effect of the orientation of the dimer with respect to the polarization state of the laser light and the effect of the particle gap size on the Raman signal intensity is observed. Additionally, calculations are performed to simulate the electric near field enhancement. These simulations are based on the morphologies observed by electron microscopy. In this way the experiments are compared with the enhancement factor calculated with near field simulations and are subsequently used to quantify the SERS enhancement factor. Large differences between experimentally observed and calculated enhancement factors are regularly detected, a phenomenon caused by nanoscale differences between the real and 'simplified' simulated structures. Quantitative SERS experiments reveal the structure induced enhancement factor, ranging from ∼200 to ∼20 000, averaged over the full nanostructure surface. The results demonstrate correlative Raman-SEM microscopy for the quantitative analysis of plasmonic particles and structures, thus enabling a new analytical method in the field of SERS and plasmonics.

  13. Biokinetics and dosimetry of a hybrid formulation of {sup 9{sup m}}Tc-BN and {sup 99m}Tc-RGD{sub 2} starting from optic images in a murine model; Biocinetica y dosimetria de una formulacion hibrida de {sup 99m}Tc-BN y {sup 99m}Tc-RGD{sub 2} a partir de imagenes opticas en un modelo murino

    Energy Technology Data Exchange (ETDEWEB)

    Cornejo A, L. G.

    2015-07-01

    This work has the purpose of evaluate the biokinetics and absorbed dose of radiation of hybrid formulation {sup 99m}Tc-BN /{sup 99m}Tc-RGD{sub 2} in a murine model by optical imaging techniques using the multimodal preclinical in vivo image system Xtreme. The used method were the {sup 99m}Tc-BN, {sup 99m}Tc-RGD{sub 2} and {sup 99m}Tc-BN/{sup 99m}Tc-RGD{sub 2} formulas, with specific recognition for GRPr and the integrin s α(v)β(3) and α(v)β(5) respectively, was injected in the vein tail of three nude mousses with induce breast cancer tumors (cell line T-47-D), by the preclinical multimodal imaging system Xtreme (Bruker), optical images in different times was acquired (5, 10, 20 min, 2 and 24 h), using Images Processing Toolbox of MATLAB these images was transform from RGB format to gray scales and sectioned in five independent images corresponding to heart, kidneys, bladder and tumor areas. The intensity of each images was computed in counts per pixel, then those intensities was corrected for background, attenuation and scattering, using different factors for each phenomena previously calculated. Finally the activity values quantified vs time was fitted into a biokinetic model to obtain the disintegrations number and cumulate activities in each organ. With these data the radiation absorbed dose were calculated using MIRD methodology. Results: The number of disintegration and absorbed dose calculated in MBq h/MBq and mGy/MBq, of injected mouse with the {sup 99m}Tc-BN/{sup 99m}Tc-RGD{sub 2} formulation, was: 0.035 ± 0.65 E-02, 0.25 x 10{sub -5} ± 0.46 E-07; 0.393 ± 0.51 E-1, 2.85 E-05 ± 3.7 E-06; 0.306 ± 0.21 E-01, 2.11 E-05 ± 1.45 E-06 and 0.151 ± 0.19 E-01, 1.09 E-05 ± 1.42 E-06 , in heart, kidneys, bladder and tumor, respectively. The number of disintegration obtained in kidneys is comparable to those reported for Trinidad B. 2014 Conclusions: Our results demonstrated that using optical images and a code for image analyses development in MATLAB, could

  14. Optimization of the production process of hybrid and multivalent formulation Bombesin/RGD for the opportune detection of breast cancer; Optimizacion del proceso de fabricacion de la formulacion hibrida y multivalente Bombesina/RGD para la deteccion oportuna de cancer de mama

    Energy Technology Data Exchange (ETDEWEB)

    Robles M, M.

    2013-07-01

    The radiopharmaceuticals of third generation are used in nuclear medicine to obtain images of specific molecular targets, and they are unique in their capacity to detect in vivo specific biochemical sites as receptors that are over-expressed in diverse illness. In cancer cells several types of receptors are over-expressed, as the integrin s α(v)β(3) and α(v)β(5) that specifically recognize the sequence RGD (Arginine-Glycin-Ac. Aspartic) and gastrin-releasing peptide that recognizes specifically to the peptide Lys{sup 3}-Bombesin. The integrin s α(v)β(3) and α(v)β(5) are involved in the tumor angio genesis processes and the gastrin-releasing peptide is over-expressed in breast and prostate cancer. The molecular recognition of the specific receptors is the basis to be utilized as targets of the radiopharmaceuticals {sup 99m}Tc-HYNIC-Bombesin and {sup 99m}Tc-HYNIC-RGD. In this work was developed a lyophilized pharmaceutical formulation effective, stable and safe for the simultaneous obtaining of the radiopharmaceuticals {sup 99m}Tc-HYNIC-Bombesin ({sup 99m}Tc-EDDA/HYNIC-Lys{sup 3}-Bombesin) and {sup 99m}Tc-HYNIC-RGD ({sup 99m}Tc EDDA/HYNIC-E-[c(RGDfK)]{sub 2}). Later on the production process of the product HYNIC-Bombesin/RGD-Sn was optimized using a factorial design and the formulation was transferred to the production plant of radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ). The optimized formulation is described in the following chart: HYNIC-[Lys{sup 3}]-Bombesin - 12.5 μg; HYNIC-E-c[RGDfK]{sub 2} - 12.5 μg; Stannous chloride (SnCl{sub 2}) - 20 μg; Ethylenediamine diacetic acid (EDDA) - 10 mg; N-tris(hydroxymethyl)methyl glycin (Tricine) - 20 mg; Mannitol - 50 mg. The production process was validated and were carried out the stability studies under refrigeration conditions. (Author)

  15. Neutral dipole-dipole dimers: A new field in science

    Science.gov (United States)

    Kosower, Edward M.; Borz, Galina

    2018-03-01

    Dimer formation with dipole neutralization produces species such as low polarity water (LPW) compatible with hydrophobic surfaces (Phys. Chem. Chem. Phys. 2015, 17, 24895-24900) Dimerization and dipole neutralization occurs for N-methylacetamide on polyethylene, a behavior drastically different from its contortions in acetonitrile on AgBr:AgCl planar crystals (AgX) (ChemPhysChem 2014, 15, 3598-3607). The weak infrared absorption of the amide dimer on polyethylene is shown experimentally. Dimerization of palmitic acid is shown along with some of the many ramifications for intracellular systems. Polyoligomers of water are present on polyethylene surfaces. Some high resolution spectra of three of the polyoligomers of water are shown along with a mechanistic scheme for polyoligomer formation and dissolution. The structures of some of the oligomers are known from spectroscopic studies of water on AgX. The scope of the article begins with PE, generally accepted as hydrophobic. The IR of PE revealed not only that water was present but that it appeared in two forms, oligomers (O) and polyoligomers (PO). How did we recognize what they were? These species had been observed as especially strong "marker" peaks in the spectra1 of water placed on planar AgX, a platform developed by Katzir and his coworkers [6]. But there was a problem: the proximity to PE of oligomers with substantial (calculated) dipole moments and thus polarity, including cyclic hexamers of water (chair and boat forms), the cyclic pentamer, the books I and II, and the cyclic trimer [7a]. Another link was needed, a role perfectly fit by the already cited low polarity water (LPW). The choice was experimentally supported by the detection of low intensity absorption in the bending region.Some important generalities flow from these results. What other dimers might be present in the biological or chemical world? Palmitic acid dimer (PAD) would be a candidate for decreasing the polarity of the acid (PA). Another

  16. cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA.

    Science.gov (United States)

    Prats, A C; Roy, C; Wang, P A; Erard, M; Housset, V; Gabus, C; Paoletti, C; Darlix, J L

    1990-02-01

    The genetic material of all retroviruses examined so far consists of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Since the precise location of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analyzed the dimerization process of Moloney murine leukemia virus (MoMuLV) genomic RNA. For this purpose we derived an in vitro model for RNA dimerization. By using this model, murine leukemia virus RNA was shown to form dimeric molecules. Deletion mutagenesis in the 620-nucleotide leader of MoMuLV RNA showed that the dimer promoting sequences are located within the encapsidation element Psi between positions 215 and 420. Furthermore, hybridization assays in which DNA oligomers were used to probe monomer and dimer forms of MoMuLV RNA indicated that the DLS probably maps between positions 280 and 330 from the RNA 5' end. Also, retroviral nucleocapsid protein was shown to catalyze dimerization of MoMuLV RNA and to be tightly bound to genomic dimer RNA in virions. These results suggest that MoMuLV RNA dimerization and encapsidation are probably controlled by the same cis element, Psi, and trans-acting factor, nucleocapsid protein, and thus might be linked during virion formation.

  17. Comparison of radiolabeling efficiency of peptides containing the RGD domain using the Tc-99M and I-131 radioisotopes

    International Nuclear Information System (INIS)

    Sobral, Danielle V.; Cabral, Francisco Romero; Malavolta, Luciana

    2017-01-01

    Full text: Introduction: Radiolabeled peptides have become very important in nuclear medicine and oncology in recent years mainly because they represent the molecular basis for in vivo imaging and radiopharmaceutical therapy with high specificity and affinity for over expressed receptors in tumors (Thno 2(5):481-501, 2012 / Drug Discov. Today. 7:1224-1232, 2012). In this context, peptides containing the RGD domain which possess high affinity for the αvβ3 integrin receptor have become an important tool in a wide variety tumor, including glioblastoma (Exp. Opin. Drug Deliv. 8:1041- 1056, 2011). Objective: The goal of this work was to compare the radiolabeling efficiency of the GRGDYV and GRGDHV peptides when radiolabeled with the 131 I and 99m Tc radioisotopes, respectively, as well as, to evaluate the features of synthesized complexes. Methods: The GRGDYV and GRGDHV fragments were manually synthesized by peptide synthesis in solid phase accordingly to the Fmoc protocol and purified by preparative HPLC. The GRGDYV and GRGDHV peptides were radiolabeled with the I-131 and Tc-99m radioisotopes respectively, through of the direct method of radiolabeling. The radioiodination was evaluated and optimized using the methodology of Chloramine-T and for the peptide containing the histidine aminoacid the tricarbonyl method was used. Radiochemical yield analyses of [ 131 I]-GRGDYV and [ 99m Tc]-GRGDHV peptides were performed by thin layer chromatography on silica gel TLC-SG (Al) in ACN 95%. The radiolabeled peptides were purified by using solid phase extraction (Sep-Pak C18 filter). The stability studies were realized at 2, 24, 48 and 72 hours in room temperature and refrigerate (4 deg C) for [ 131 I]-GRGDYV and up to 6 hours for the fragment [ 99m Tc]-GRGDHV. Partition coefficient was determinate for both radiopeptides. Results: The peptides [ 131 I]-GRGDYV and [ 99m Tc]-GRGDHV were efficiently synthesized, radiolabeled and showed radiochemical yield of 91.02% ± 1.68 (n=5

  18. Comparison of radiolabeling efficiency of peptides containing the RGD domain using the Tc-99M and I-131 radioisotopes

    Energy Technology Data Exchange (ETDEWEB)

    Sobral, Danielle V.; Cabral, Francisco Romero; Malavolta, Luciana [Santa Casa de São Paulo, SP (Brazil). Faculdade de Ciências Médicas; Durante, Ana C. Ranucci; Miranda, Ana C. Camargo; Barbosa, Marycel R. F.Figols de [Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Radiolabeled peptides have become very important in nuclear medicine and oncology in recent years mainly because they represent the molecular basis for in vivo imaging and radiopharmaceutical therapy with high specificity and affinity for over expressed receptors in tumors (Thno 2(5):481-501, 2012 / Drug Discov. Today. 7:1224-1232, 2012). In this context, peptides containing the RGD domain which possess high affinity for the αvβ3 integrin receptor have become an important tool in a wide variety tumor, including glioblastoma (Exp. Opin. Drug Deliv. 8:1041- 1056, 2011). Objective: The goal of this work was to compare the radiolabeling efficiency of the GRGDYV and GRGDHV peptides when radiolabeled with the {sup 131}I and {sup 99m}Tc radioisotopes, respectively, as well as, to evaluate the features of synthesized complexes. Methods: The GRGDYV and GRGDHV fragments were manually synthesized by peptide synthesis in solid phase accordingly to the Fmoc protocol and purified by preparative HPLC. The GRGDYV and GRGDHV peptides were radiolabeled with the I-131 and Tc-99m radioisotopes respectively, through of the direct method of radiolabeling. The radioiodination was evaluated and optimized using the methodology of Chloramine-T and for the peptide containing the histidine aminoacid the tricarbonyl method was used. Radiochemical yield analyses of [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV peptides were performed by thin layer chromatography on silica gel TLC-SG (Al) in ACN 95%. The radiolabeled peptides were purified by using solid phase extraction (Sep-Pak C18 filter). The stability studies were realized at 2, 24, 48 and 72 hours in room temperature and refrigerate (4 deg C) for [{sup 131}I]-GRGDYV and up to 6 hours for the fragment [{sup 99m}Tc]-GRGDHV. Partition coefficient was determinate for both radiopeptides. Results: The peptides [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV were efficiently synthesized, radiolabeled and showed

  19. Effects of pressure and magnetic field on transport properties of Y1-xRxCo2 alloys (R=Gd, Tb, Dy, Ho and Er)

    International Nuclear Information System (INIS)

    Takaesu, Y; Nakama, T; Kinjyo, A; Yonamine, S; Hedo, M; Yagasaki, K; Uchima, K; Uwatoko, Y; Burkov, A T

    2010-01-01

    Electrical resistivity ρ and thermopower S of Y 1-x R x Co 2 (R=Gd, Tb, Dy, Ho and Er) Laves phase alloy systems were measured at temperatures from 1.5 K to 300 K in magnetic fields up to 15 T and under hydrostatic pressure up to 2 GPa. We show that there is a universal linear relation between the pressure and magnetic field derivatives of the resistivity, dρ/dP and dρ/dB, with gradient, determined by pressure derivative of the critical metamagnetic field of the cobalt 3d electron system. A similar scaling behavior was found for the thermopower dependencies on pressure and alloy composition.

  20. Angiopoietin-related growth factor (AGF) supports adhesion, spreading, and migration of keratinocytes, fibroblasts, and endothelial cells through interaction with RGD-binding integrins

    International Nuclear Information System (INIS)

    Zhang Yueqing; Hu Xiaobo; Tian Ruiyang; Wei Wangui; Hu Wei; Chen Xia; Han Wei; Chen Huayou; Gong Yi

    2006-01-01

    Angiopoietin-related growth factor (AGF) is a newly identified member of angiopoietin-related proteins (ARPs)/angiopoietin-like proteins (Angptls). AGF has been considered as a novel growth factor in accelerating cutaneous wound healing, as it is capable of stimulating keratinocytes proliferation as well as angiogenesis. But in our paper, we demonstrate that AGF stimulates keratinocytes proliferation only at high protein concentration, however, it can potently promote adhesion, spreading, and migration of keratinocytes, fibroblasts, and endothelial cells. Furthermore, we confirm that the adhesion and migration cellular events are mediated by RGD-binding integrins, most possibly the α v -containing integrins, by in vitro inhibition assays using synthetic competitive peptides. Our results strongly suggest that AGF is an integrin ligand as well as a mitogenic growth factor and theoretically participates in cutaneous wound healing in a more complex mechanism

  1. Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolism.

    Science.gov (United States)

    Takach Lapner, Sarah; Julian, Jim A; Linkins, Lori-Ann; Bates, Shannon; Kearon, Clive

    2017-10-05

    Two new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7 %) and the age-adjusted strategy (99.6 %) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1 % vs, 50.9 %; difference 5.2 %; 95 % CI 3.5 % to 6.8 %). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.

  2. Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri-Implantitis.

    Science.gov (United States)

    Diniz, Ivana M A; Chen, Chider; Ansari, Sahar; Zadeh, Homayoun H; Moshaverinia, Maryam; Chee, Daniel; Marques, Márcia M; Shi, Songtao; Moshaverinia, Alireza

    2016-02-01

    Peri-implantitis is one of the most common inflammatory complications in dental implantology. Similar to periodontitis, in peri-implantitis, destructive inflammatory changes take place in the tissues surrounding a dental implant. Bacterial flora at the failing implant sites resemble the pathogens in periodontal disease and consist of Gram-negative anaerobic bacteria including Aggregatibacter actinomycetemcomitans (Aa). Here we demonstrate the effectiveness of a silver lactate (SL)-containing RGD-coupled alginate hydrogel scaffold as a promising stem cell delivery vehicle with antimicrobial properties. Gingival mesenchymal stem cells (GMSCs) or human bone marrow mesenchymal stem cells (hBMMSCs) were encapsulated in SL-loaded alginate hydrogel microspheres. Stem cell viability, proliferation, and osteo-differentiation capacity were analyzed. Our results showed that SL exhibited antimicrobial properties against Aa in a dose-dependent manner, with 0.50 mg/ml showing the greatest antimicrobial properties while still maintaining cell viability. At this concentration, SL-containing alginate hydrogel was able to inhibit Aa growth on the surface of Ti discs and significantly reduce the bacterial load in Aa suspensions. Silver ions were effectively released from the SL-loaded alginate microspheres for up to 2 weeks. Osteogenic differentiation of GMSCs and hBMMSCs encapsulated in the SL-loaded alginate microspheres were confirmed by the intense mineral matrix deposition and high expression of osteogenesis-related genes. Taken together, our findings confirm that GMSCs encapsulated in RGD-modified alginate hydrogel containing SL show promise for bone tissue engineering with antimicrobial properties against Aa bacteria in vitro. © 2015 by the American College of Prosthodontists.

  3. In situ immobilization of proteins and RGD peptide on polyurethane surfaces via poly(ethylene oxide) coupling polymers for human endothelial cell growth.

    Science.gov (United States)

    Wang, Dong-an; Ji, Jian; Sun, Yong-hong; Shen, Jia-cong; Feng, Lin-xian; Elisseeff, Jennifer H

    2002-01-01

    A "CBABC"-type pentablock coupling polymer, mesylMPEO, was designed and synthesized to promote human endothelial cell growth on the surfaces of polyurethane biomaterials. The polymer was composed of a central 4,4'-methylenediphenyl diisocyanate (MDI) coupling unit and poly(ethylene oxide) (PEO) spacer arms with methanesulfonyl (mesyl) end groups pendent on both ends. As the presurface modifying additive (pre-SMA), the mesylMPEO was noncovalently introduced onto the poly(ether urethane) (PEU) surfaces by dip coating, upon which the protein/peptide factors (gelatin, albumin, and arginine-glycine-aspartic acid tripeptide [RGD]) were covalently immobilized in situ by cleavage of the original mesyl end groups. The pre-SMA synthesis and PEU surface modification were characterized using nuclear magnetic resonance spectroscopy ((1)H NMR), attenuated total reflection infrared spectroscopy (ATR-FTIR), and X-ray photoelectron spectroscopy (XPS). Human umbilical vein endothelial cells (HUVEC) were harvested manually by collagenase digestion and seeded on the modified PEU surfaces. Cell adhesion ratios (CAR) and cell proliferation ratios (CPR) were measured using flow cytometry, and the individual cell viability (ICV) was determined by MTT assay. The cell morphologies were investigated by optical inverted microscopy (OIM) and scanning electrical microscopy (SEM). The gelatin- and RGD-modified surfaces were HUVEC-compatible and promoted HUVEC growth. The albumin-modified surfaces were compatible but inhibited cell adhesion. The results also indicated that, for HUVEC in vitro cultivation, the cell adhesion stage was of particular importance and had a significant impact on the cell responses to the modified surfaces.

  4. Factors associated with D-dimer levels in HIV-infected individuals

    DEFF Research Database (Denmark)

    Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2014-01-01

    BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials...... with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6...... viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high...

  5. Photoreactivation of pyrimidine dimers in the DNA of normal and xeroderma pigmentosum cells

    International Nuclear Information System (INIS)

    Sutherland, B.M.; Oliver, R.; Fuselier, C.O.; Sutherland, J.C.

    1976-01-01

    Photoproducts formed in the DNA of human cells irradiated with ultraviolet light (uv) were identified as cyclobutyl pyrimidine dimers by their chromatographic mobility, reversibility to monomers upon short wavelength uv irradiation, and comparison of the kinetics of this monomerization with that of authentic cis--syn thymine--thymine dimers prepared by irradiation of thymine in ice. The level of cellular photoreactivation of these dimers reflects the level of photoreactivating enzyme measured in cell extracts. Action spectra for cellular dimer photoreactivation in the xeroderma pigmentosum line XP12BE agree in range (300 nm to at least 577 nm) and maximum (near 400 nm) with that for photoreactivation by purified human photoreactivating enzyme. Normal human cells can also photoreactivate dimers in their DNA. The action spectrum for the cellular monomerization of dimers is similar to that for photoreactivation by the photoreactivating enzyme in extracts of normal human fibroblasts

  6. Dimerization of 3He in 3He-4He mixture films

    International Nuclear Information System (INIS)

    Bashkin, E.

    1994-01-01

    3 He atoms dissolved in superfluid 4 He may form dimers ( 3 He) 2 in two-dimensional geometries. Dimer formation is studied in films of dilute 3 He- 4 He mixture. After designing a schematic 3 He- 3 He interaction potential, the dimer binding energy is calculated for various substrates. It is shown that 3 He impurity states localized near the substrate give rise to the highest magnitudes of the binding energy. (author). 32 refs., 6 figs.,; 1 tab

  7. Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation.

    Directory of Open Access Journals (Sweden)

    Hugo I Contreras-Treviño

    Full Text Available Species A rotavirus non-structural protein 3 (NSP3 is a translational regulator that inhibits or, under some conditions, enhances host cell translation. NSP3 binds to the translation initiation factor eIF4G1 and evicts poly-(A binding protein (PABP from eIF4G1, thus inhibiting translation of polyadenylated mRNAs, presumably by disrupting the effect of PABP bound to their 3'-ends. NSP3 has a long coiled-coil region involved in dimerization that includes a chaperone Hsp90-binding domain (HS90BD. We aimed to study the role in NSP3 dimerization of a segment of the coiled-coil region adjoining the HS90BD. We used a vaccinia virus system to express NSP3 with point mutations in conserved amino acids in the coiled-coil region and determined the effects of these mutations on translation by metabolic labeling of proteins as well as on accumulation of stable NSP3 dimers by non-dissociating Western blot, a method that separates stable NSP3 dimers from the monomer/dimerization intermediate forms of the protein. Four of five mutations reduced the total yield of NSP3 and the formation of stable dimers (W170A, K171E, R173E and R187E:K191E, whereas one mutation had the opposite effects (Y192A. Treatment with the proteasome inhibitor MG132 revealed that stable NSP3 dimers and monomers/dimerization intermediates are susceptible to proteasome degradation. Surprisingly, mutants severely impaired in the formation of stable dimers were still able to inhibit host cell translation, suggesting that NSP3 dimerization intermediates are functional. Our results demonstrate that rotavirus NSP3 acquires its function prior to stable dimer formation and remain as a proteasome target throughout dimerization.

  8. Electron-nuclear corellations for photoinduced dynamics in molecular dimers

    Science.gov (United States)

    Kilin, Dmitri S.; Pereversev, Yuryi V.; Prezhdo, Oleg V.

    2003-03-01

    Ultrafast photoinduced dynamics of electronic excitation in molecular dimers is drastically affected by dynamic reorganization of of inter- and intra- molecular nuclear configuration modelled by quantized nuclear degree of freedom [1]. The dynamics of the electronic population and nuclear coherence is analyzed with help of both numerical solution of the chain of coupled differential equations for mean coordinate, population inversion, electronic-vibrational correlation etc.[2] and by propagating the Gaussian wavepackets in relevant adiabatic potentials. Intriguing results were obtained in the approximation of small energy difference and small change of nuclear equilibrium configuration for excited electronic states. In the limiting case of resonance between electronic states energy difference and frequency of the nuclear mode these results have been justified by comparison to exactly solvable Jaynes-Cummings model. It has been found that the photoinduced processes in dimer are arranged according to their time scales:(i) fast scale of nuclear motion,(ii) intermediate scale of dynamical redistribution of electronic population between excited states as well as growth and dynamics of electronic -nuclear correlation,(iii) slow scale of electronic population approaching to the quasiequilibrium distribution, decay of electronic-nuclear correlation, and diminishing the amplitude of mean coordinate oscillations, accompanied by essential growth of the nuclear coordinate dispersion associated with the overall nuclear wavepacket width. Demonstrated quantum-relaxational features of photoinduced vibronic dinamical processess in molecular dimers are obtained by simple method, applicable to large biological systems with many degrees of freedom. [1] J. A. Cina, D. S. Kilin, T. S. Humble, J. Chem. Phys. (2003) in press. [2] O. V. Prezhdo, J. Chem. Phys. 117, 2995 (2002).

  9. Transport properties of a ladder with two random dimer chains

    International Nuclear Information System (INIS)

    Hu Dong-Sheng; Zhu Chen-Ping; Zhang Yong-Mei

    2011-01-01

    We investigate the transport properties of a ladder with two random dimer (RD) chains. It is found that there are two extended states in the ladder with identical RD chains and a critical state regarded as an extended state in the ladder with pairing RD chains. Such a critical state is caused by the chiral symmetry. The ladder with identical RD chains can be decoupled into two isolated RD chains and the ladder with pairing RD chains can not. The analytic expressions of the extended states are presented for the ladder with identical RD chains. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  10. Laccase-mediated dimerization of the flavonolignan silybin

    Czech Academy of Sciences Publication Activity Database

    Gažák, Radek; Sedmera, Petr; Marzorati, M.; Riva, S.; Křen, Vladimír

    2008-01-01

    Roč. 50, 2-4 (2008), s. 87-92 ISSN 1381-1177 R&D Projects: GA AV ČR KJB400200701; GA MŠk OC D25.001; GA MŠk(CZ) LC06010; GA MŠk OC 170; GA MŠk ME 922 Grant - others:CZ(CZ) Bilateral Czech-Italian inter-academic projec Institutional research plan: CEZ:AV0Z50200510 Keywords : silybin * silymarin * dimer formation Subject RIV: EE - Microbiology, Virology Impact factor: 2.015, year: 2008

  11. The (6-4) Dimeric Lesion as a DNA Photosensitizer

    OpenAIRE

    Vendrell Criado, Victoria; Rodríguez Muñiz, Gemma María; Lhiaubet ., Virginie Lyria; Cuquerella Alabort, Maria Consuelo; Miranda Alonso, Miguel Ángel

    2016-01-01

    [EN] Based on our previous investigations into the photophysical properties of the 5-methyl-2-pyrimidone (Pyo) chromophore, we now extend our studies to the photobehavior of the dimeric (6-4) thymine photoproducts (6-4 PP) to evaluate their capability to act as instrinsic DNA photosensitizers. The lesion presents significant absorption in the UVB/UVA region, weak fluorescence emission, a singlet-excited-state energy of approximately 351 kJ mol(-1), and a triplet-excited-state energy of 297 kJ...

  12. Revealing the Dimeric Crystal and Solution Structure of β-Lactoglobulin at pH 4 and Its pH and Salt Dependent Monomer–Dimer Equilibrium

    DEFF Research Database (Denmark)

    Khan, Sanaullah; Ipsen, Richard; Almdal, Kristoffer

    2018-01-01

    The dimeric structure of bovine β-lactoglobulin A (BLGA) at pH 4.0 was solved to 2.0 Å resolution. Fitting the BLGA pH 4.0 structure to SAXS data at low ionic strength (goodness of fit R-factor = 3.6%) verified the dimeric state in solution. Analysis of the monomer–dimer equilibrium at varying pH...... and ionic strength by SAXS and scattering modeling showed that BLGA is dimeric at pH 3.0 and 4.0, shifting toward a monomer at pH 2.2, 2.6, and 7.0 yielding monomer/dimer ratios of 80/20%, 50/50%, and 25/75%, respectively. BLGA remained a dimer at pH 3.0 and 4.0 in 50–150 mM NaCl, whereas the electrostatic...... shielding raised the dimer content at pH 2.2, 2.6, and 7.0, i.e., below and above the pI. Overall, the findings provide new insights into the molecular characteristics of BLGA relevant for dairy product formulations and for various biotechnological and pharmaceutical applications....

  13. Dimer and String Formation during Low Temperature Silicon Deposition on Si(100)

    DEFF Research Database (Denmark)

    Smith, A. P.; Jonsson, Hannes

    1996-01-01

    We present theoretical results based on density functional theory and kinetic Monte Carlo simulations of silicon deposition and address observations made in recently reported low temperature scanning tunneling microscopy studies. A mechanism is presented which explains dimer formation on top...... of the substrate's dimer rows at 160 K and up to room temperature, while between-row dimers and longer strings of adatoms (''diluted dimer rows'') form at higher temperature. A crossover occurs at around room temperature between two different mechanisms for adatom diffusion in our model....

  14. Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor

    International Nuclear Information System (INIS)

    Goffinont, S.; Davidkova, M.; Spotheim-Maurizot, M.

    2009-01-01

    The wild type lactose repressor of Escherichia coli is a tetrameric protein formed by two identical dimers. They are associated via a C-terminal 4-helix bundle (called tetramerization domain) whose stability is ensured by the interaction of leucine zipper motifs. Upon in vitro γ-irradiation the repressor losses its ability to bind the operator DNA sequence due to damage of its DNA-binding domains. Using an engineered dimeric repressor for comparison, we show here that irradiation induces also the change of repressor oligomerisation state from tetramer to dimer. The splitting of the tetramer into dimers can result from the oxidation of the leucine residues of the tetramerization domain.

  15. Solid-phase synthesis of 2{sup '}-O-methoxyethyl oligonucleotides using dimeric phosphoramidate blocks

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Gi Weon; Kang, Yong Han [Dept. of Applied Chemistry, Hanyang University, Ansan (Korea, Republic of)

    2016-11-15

    This research focused on the method of using dimeric phosphoramidite blocks to synthesize oligonucleotides for development as oligonucleotide drugs. A 16-mer oligonucleotide with the randomly selected sequence of C*C*T*C*G*C *T*C*T*C*G*C*C* C*G*C was synthesized using CC, GC, and TC dimers, a combination of monomers and dimers, or only monomers as building blocks. Using dimer blocks in this synthetic method provided a significant decrease in critical impurities that had similar properties to the main product, which was confirmed by LC-MS and HPLC analysis.

  16. Dimerization of a flocculent protein from Moringa oleifera: experimental evidence and in silico interpretation.

    Science.gov (United States)

    Pavankumar, Asalapuram R; Kayathri, Rajarathinam; Murugan, Natarajan A; Zhang, Qiong; Srivastava, Vaibhav; Okoli, Chuka; Bulone, Vincent; Rajarao, Gunaratna K; Ågren, Hans

    2014-01-01

    Many proteins exist in dimeric and other oligomeric forms to gain stability and functional advantages. In this study, the dimerization property of a coagulant protein (MO2.1) from Moringa oleifera seeds was addressed through laboratory experiments, protein-protein docking studies and binding free energy calculations. The structure of MO2.1 was predicted by homology modelling, while binding free energy and residues-distance profile analyses provided insight into the energetics and structural factors for dimer formation. Since the coagulation activities of the monomeric and dimeric forms of MO2.1 were comparable, it was concluded that oligomerization does not affect the biological activity of the protein.

  17. Magnetic and superconducting competition within the Hubbard dimer. Exact solution

    International Nuclear Information System (INIS)

    Matlak, M.; Slomska, T.; Grabiec, B.

    2005-01-01

    We express the Hubbard dimer Hamiltonian H d =Σ 16 α=1 E α vertical stroke E α right angle left angle E α vertical stroke in the second quantization with the use of the Hubbard and spin operators. We consider the case of positive and negative U. We decompose the resulting Hamiltonian into several parts collecting all the terms belonging to the same energy level. Such a decomposition visualizes explicitly all intrinsic interactions competing together and deeply hidden in the original form of the dimer Hamiltonian. Among them are competitive ferromagnetic and antiferromagnetic interactions. There are also hopping terms present which describe Cooper pairs hopping between sites 1 and 2 with positive and negative coupling constants (similar as in Kulik-Pedan, Penson-Kolb models). We show that the competition between intrinsic interactions strongly depends on the model parameters and the averaged occupation number of electrons n element of [0, 4] resulting in different regimes of the model (as e.g. t-J model regime, etc.). (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  18. Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

    Science.gov (United States)

    Ploier, Birgit; Caro, Lydia N.; Morizumi, Takefumi; Pandey, Kalpana; Pearring, Jillian N.; Goren, Michael A.; Finnemann, Silvia C.; Graumann, Johannes; Arshavsky, Vadim Y.; Dittman, Jeremy S.; Ernst, Oliver P.; Menon, Anant K.

    2016-10-01

    Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations--F45L, V209M and F220C--yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5.

  19. Pyrimidine dimers block simian virus 40 replication forks

    International Nuclear Information System (INIS)

    Berger, C.A.; Edenberg, H.J.

    1986-01-01

    UV light produces lesions, predominantly pyrimidine dimers, which inhibit DNA replication in mammalian cells. The mechanism of inhibition is controversial: is synthesis of a daughter strand halted at a lesion while the replication fork moves on and reinitiates downstream, or is fork progression itself blocked for some time at the site of a lesion? We directly addressed this question by using electron microscopy to examine the distances of replication forks from the origin in unirradiated and UV-irradiated simian virus 40 chromosomes. If UV lesions block replication fork progression, the forks should be asymmetrically located in a large fraction of the irradiated molecules; if replication forks move rapidly past lesions, the forks should be symmetrically located. A large fraction of the simian virus 40 replication forks in irradiated molecules were asymmetrically located, demonstrating that UV lesions present at the frequency of pyrimidine dimers block replication forks. As a mechanism for this fork blockage, we propose that polymerization of the leading strand makes a significant contribution to the energetics of fork movement, so any lesion in the template for the leading strand which blocks polymerization should also block fork movement

  20. Structures of DNA containing psoralen crosslink and thymine dimer

    International Nuclear Information System (INIS)

    Kim, S.H.; Pearlman, D.A.; Holbrook, S.R.; Pirkle, D.

    1985-01-01

    UV irradiation by itself or in conjunction with other chemicals can cause covalent damages to DNA in living cells. To overcome the detrimental effect of DNA damage, cells developed a repair mechanism by which damaged DNA is repaired. In the absence of such repair, cell malfunction or cell death can occur. Two most studied radiation-induced DNA damage are thymine dimer formation by UV irradiation and psoralen crosslink by combination of psoralens and UV: In the former, two adjacent thymine bases on a strand of DNA are fused by forming cyclobutane ring, and in the latter, one pyrimidine on one DNA strand is crosslinked to another pyrimidine on the other strand via a psoralen. The authors' objective is to deduce the structure of DNA segment which contains a psoralen crosslink or a thymine dimer using the combination of results of X-ray crystallographic studies, molecular model building, and energy minimization. These structural features may be important for understanding the biological effects of such damages and for the recognition by the repair enzymes

  1. How Does Thymine DNA Survive Ultrafast Dimerization Damage?

    Directory of Open Access Journals (Sweden)

    Hongjuan Wang

    2016-12-01

    Full Text Available The photodimerization reaction between the two adjacent thymine bases within a single strand has been the subject of numerous studies due to its potential to induce DNA mutagenesis and possible tumorigenesis in human skin cells. It is well established that the cycloaddition photoreaction takes place on a picosecond time scale along barrierless or low barrier singlet/triplet pathways. However, the observed dimerization quantum yield in different thymine multimer is considerable lower than might be expected. A reasonable explanation is required to understand why thymine in DNA is able to survive ultrafast dimerization damage. In this work, accurate quantum calculations based on the combined CASPT2//CASSCF/AMBER method were conducted to map the excited state relaxation pathways of the thymine monomer in aqueous solution and of the thymine oligomer in DNA. A monomer-like decay pathway, induced by the twisting of the methyl group, is found to provide a bypass channel to ensure the photostability of thymine in single-stranded oligomers. This fast relaxation path is regulated by the conical intersection between the bright SCT(1ππ* state with the intra-base charge transfer character and the ground state to remove the excess excitation energy, thereby achieving the ground-state recovery with high efficiency.

  2. A multistep single-crystal-to-single-crystal bromodiacetylene dimerization

    Science.gov (United States)

    Hoheisel, Tobias N.; Schrettl, Stephen; Marty, Roman; Todorova, Tanya K.; Corminboeuf, Clémence; Sienkiewicz, Andrzej; Scopelliti, Rosario; Schweizer, W. Bernd; Frauenrath, Holger

    2013-04-01

    Packing constraints and precise placement of functional groups are the reason that organic molecules in the crystalline state often display unusual physical or chemical properties not observed in solution. Here we report a single-crystal-to-single-crystal dimerization of a bromodiacetylene that involves unusually large atom displacements as well as the cleavage and formation of several bonds. Density functional theory computations support a mechanism in which the dimerization is initiated by a [2 + 1] photocycloaddition favoured by the nature of carbon-carbon short contacts in the crystal structure. The reaction proceeded up to the theoretical degree of conversion without loss of crystallinity, and it was also performed on a preparative scale with good yield. Moreover, it represents the first synthetic pathway to (E)-1,2-dibromo-1,2-diethynylethenes, which could serve as synthetic intermediates for the preparation of molecular carbon scaffolds. Our findings both extend the scope of single-crystal-to-single-crystal reactions and highlight their potential as a synthetic tool for complex transformations.

  3. Dimerization of a Viral SET Protein Endows its Function

    Energy Technology Data Exchange (ETDEWEB)

    H Wei; M Zhou

    2011-12-31

    Histone modifications are regarded as the most indispensible phenomena in epigenetics. Of these modifications, lysine methylation is of the greatest complexity and importance as site- and state-specific lysine methylation exerts a plethora of effects on chromatin structure and gene transcription. Notably, paramecium bursaria chlorella viruses encode a conserved SET domain methyltransferase, termed vSET, that functions to suppress host transcription by methylating histone H3 at lysine 27 (H3K27), a mark for eukaryotic gene silencing. Unlike mammalian lysine methyltransferases (KMTs), vSET functions only as a dimer, but the underlying mechanism has remained elusive. In this study, we demonstrate that dimeric vSET operates with negative cooperativity between the two active sites and engages in H3K27 methylation one site at a time. New atomic structures of vSET in the free form and a ternary complex with S-adenosyl homocysteine and a histone H3 peptide and biochemical analyses reveal the molecular origin for the negative cooperativity and explain the substrate specificity of H3K27 methyltransferases. Our study suggests a 'walking' mechanism, by which vSET acts all by itself to globally methylate host H3K27, which is accomplished by the mammalian EZH2 KMT only in the context of the Polycomb repressive complex.

  4. Monomer-dimer problem on random planar honeycomb lattice

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Haizhen [School of Mathematical Sciences, Xiamen University, Xiamen 361005, Fujian (China); Department of Mathematics, Qinghai Normal University, Xining 810008, Qinghai (China); Zhang, Fuji; Qian, Jianguo, E-mail: jqqian@xmu.edu.cn [School of Mathematical Sciences, Xiamen University, Xiamen 361005, Fujian (China)

    2014-02-15

    We consider the monomer-dimer (MD) problem on a random planar honeycomb lattice model, namely, the random multiple chain. This is a lattice system with non-periodic boundary condition, whose generating process is inspired by the growth of single walled zigzag carbon nanotubes. By applying algebraic and combinatorial techniques we establish a calculating expression of the MD partition function for bipartite graphs, which corresponds to the permanent of a matrix. Further, by using the transfer matrix argument we show that the computing problem of the permanent of high order matrix can be converted into some lower order matrices for this family of lattices, based on which we derive an explicit recurrence formula for evaluating the MD partition function of multiple chains and random multiple chains. Finally, we analyze the expectation of the number of monomer-dimer arrangements on a random multiple chain and the asymptotic behavior of the annealed MD entropy when the multiple chain becomes infinite in width and length, respectively.

  5. The (6-4) Dimeric Lesion as a DNA Photosensitizer.

    Science.gov (United States)

    Vendrell-Criado, Victoria; Rodríguez-Muñiz, Gemma M; Lhiaubet-Vallet, Virginie; Cuquerella, M Consuelo; Miranda, Miguel A

    2016-07-04

    Based on our previous investigations into the photophysical properties of the 5-methyl-2-pyrimidone (Pyo) chromophore, we now extend our studies to the photobehavior of the dimeric (6-4) thymine photoproducts (6-4 PP) to evaluate their capability to act as instrinsic DNA photosensitizers. The lesion presents significant absorption in the UVB/UVA region, weak fluorescence emission, a singlet-excited-state energy of approximately 351 kJ mol(-1) , and a triplet-excited-state energy of 297 kJ mol(-1) . Its triplet transient absorption has a maximum at 420-440 nm, a lifetime of around 7 μs, and a high formation quantum yield, ΦISC =0.86. This species is efficiently quenched by thymidine. Its DNA photosensitizing properties are demonstrated by a series of experiments run on a pBR322 plasmid. The lesion photoinduces both single-strand breaks and the formation of cyclobutane thymine dimers. Altogether, these results show that, the substitution of the pyrimidone ring at C4 by a 5-hydroxy-5,6-dihydrothymine does not cancel out the photosensitization properties of the chromophore. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Biocompatible Amphiphilic Hydrogel-Solid Dimer Particles as Colloidal Surfactants.

    Science.gov (United States)

    Chen, Dong; Amstad, Esther; Zhao, Chun-Xia; Cai, Liheng; Fan, Jing; Chen, Qiushui; Hai, Mingtan; Koehler, Stephan; Zhang, Huidan; Liang, Fuxin; Yang, Zhenzhong; Weitz, David A

    2017-12-26

    Emulsions of two immiscible liquids can slowly coalesce over time when stabilized by surfactant molecules. Pickering emulsions stabilized by colloidal particles can be much more stable. Here, we fabricate biocompatible amphiphilic dimer particles using a hydrogel, a strongly hydrophilic material, and achieve large contrast in the wetting properties of the two bulbs, resulting in enhanced stabilization of emulsions. We generate monodisperse single emulsions of alginate and shellac solution in oil using a flow-focusing microfluidics device. Shellac precipitates from water and forms a solid bulb at the periphery of the droplet when the emulsion is exposed to acid. Molecular interactions result in amphiphilic dimer particles that consist of two joined bulbs: one hydrogel bulb of alginate in water and the other hydrophobic bulb of shellac. Alginate in the hydrogel compartment can be cross-linked using calcium cations to obtain stable particles. Analogous to surfactant molecules at the interface, the resultant amphiphilic particles stand at the water/oil interface with the hydrogel bulb submerged in water and the hydrophobic bulb in oil and are thus able to stabilize both water-in-oil and oil-in-water emulsions, making these amphiphilic hydrogel-solid particles ideal colloidal surfactants for various applications.

  7. Proteolysis of truncated hemolysin A yields a stable dimerization interface

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Walter R.P.; Bhattacharyya, Basudeb; Grilley, Daniel P.; Weaver, Todd M. (Wabash); (UW)

    2017-02-21

    Wild-type and variant forms of HpmA265 (truncated hemolysin A) fromProteus mirabilisreveal a right-handed, parallel β-helix capped and flanked by segments of antiparallel β-strands. The low-salt crystal structures form a dimeric structureviathe implementation of on-edge main-chain hydrogen bonds donated by residues 243–263 of adjacent monomers. Surprisingly, in the high-salt structures of two variants, Y134A and Q125A-Y134A, a new dimeric interface is formedviamain-chain hydrogen bonds donated by residues 203–215 of adjacent monomers, and a previously unobserved tetramer is formed. In addition, an eight-stranded antiparallel β-sheet is formed from the flap regions of crystallographically related monomers in the high-salt structures. This new interface is possible owing to additional proteolysis of these variants after Tyr240. The interface formed in the high-salt crystal forms of hemolysin A variants may mimic the on-edge β-strand positioning used in template-assisted hemolytic activity.

  8. D-dimer: a useful tool in gauging optimal duration of oral anticoagulant therapy?

    Directory of Open Access Journals (Sweden)

    M. Silingardi

    2013-05-01

    Full Text Available BACKGROUND AND AIM OF THE STUDY Optimal duration of oral anticoagulant therapy (OAT in idiopathic venous thromboembolism (VTE is unknown. Indefinite OAT carries an unacceptable risk of major bleeding and prospective studies have demonstrated that OAT is no longer protective after its withdrawal. How to identify the patients at risk for recurrence? D-dimer is a marker of thrombin activity. Early prospective studies showed that elevated D-dimer levels after anticoagulation had a highly predictive value for a recurrent episode. Does D-dimer assay have a role in gauging the appropriate duration of anticoagulant therapy? The PROLONG study tries to answer this question. METHOD D-dimer assay was performed one month after stopping anticoagulation. Patiens with normal D-dimer levels did not resume anticoagulation while patients with elevated D-dimer levels were randomized to discontinue or resume anticoagulation. Study end-points was the composite of recurrent VTE and major bleeding during an average follow-up of 1.4 years. RESULTS The rate of recurrence is significantly higher in patients with elevated D-dimer levels who discontinued anticoagulation. Resuming anticoagulation in this cohort of patients markedly reduces recurrent events without increasing major bleeding. DISCUSSION AND CONCLUSIONS PROLONG study is provocative, because D-dimer assay is simple, thus not requiring dedicated laboratory facilities. D-dimer test has otherwise high sensitivity but low specificity in VTE diagnosis. Aspecifically elevated D-dimer levels are available in the elderly and the majority of patients included in the study were > 65 years old, thus introducing a possible selection bias. Nonetheless the results of the study are useful for the clinician. Prolongation of vitamin K antagonists in patients with elevated D-dimer levels one month after discontinuation of OAT for a first unprovoked episode of VTE results in a favourable risk-benefit relationship. Probably this

  9. Electron transfer reactions induced by the triplet state of thiacarbocyanine dimers

    International Nuclear Information System (INIS)

    Chibisov, Alexander K.; Slavnova, Tatyana D.; Goerner, Helmut

    2004-01-01

    The photoinduced electron transfer between either cationic 5,5 ' -dichloro-3,3 ' ,9-triethylthiacarbocyanine (1) or a structurally similar anionic dye (2) and appropriate donors, e.g. ascorbic acid, and acceptors, e.g. methyl viologen, was studied by ns-laser photolysis. In aqueous solution the dyes in the ground state are present as an equilibrated mixture of dimers and monomers, whereas the triplet state is mainly populated from dimers. The triplet states of both dimers and monomers are quenched by electron donors or acceptors and the rate constant for quenching is generally 2-4 times higher for dimers than for monomers. The kinetics of triplet decay and radical formation and decay as a result of primary and secondary electron transfer were analyzed. While the one-electron reduced dimer decays due to back reactions, the one-electron oxidized dimer rapidly dissociates into the monomer and the monomeric dye radical. For the dimeric dye/donor/acceptor systems the primary photoinduced electron transfer occurs either from the donor or to the acceptor yielding the dimeric dye radicals. The one-electron reduced dimer can be efficiently oxidized by acceptors, e.g. the rate constant for reaction of the dimeric dye radical of 1 with methyl viologen (photoreductive pathway of sensitization) is 1.6x10 9 M -1 s -1 . The photooxidative pathway of sensitization is more complicated; after dissociation of the dimeric dye radical, the monomeric dye radical is reduced in a secondary electron transfer from ascorbic acid, e.g. with a rate constant of 1x10 9 M -1 s -1 for 2, yielding the monomer. On increasing the donor concentration the photooxidative pathway of sensitization is switched to a photoreductive one

  10. D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

    Science.gov (United States)

    Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

    2004-01-01

    The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

  11. Multiple regions of Harvey sarcoma virus RNA can dimerize in vitro.

    Science.gov (United States)

    Feng, Y X; Fu, W; Winter, A J; Levin, J G; Rein, A

    1995-04-01

    Retroviruses contain a dimeric RNA consisting of two identical molecules of plus-strand genomic RNA. The structure of the linkage between the two monomers is not known, but they are believed to be joined near their 5' ends. Darlix and coworkers have reported that transcripts of retroviral RNA sequences can dimerize spontaneously in vitro (see, for example, E. Bieth, C. Gabus, and J. L. Darlix, Nucleic Acids Res. 18:119-127, 1990). As one approach to identification of sequences which might participate in the linkage, we have mapped sequences derived from the 5' 378 bases of Harvey sarcoma virus (HaSV) RNA which can dimerize in vitro. We found that at least three distinct regions, consisting of nucleotides 37 to 229, 205 to 272, and 271 to 378, can form these dimers. Two of these regions contain nucleotides 205 to 226; computer analysis suggests that this region can form a stem-loop with an inverted repeat in the loop. We propose that this hypothetical structure is involved in dimer formation by these two transcripts. We also compared the thermal stabilities of each of these dimers with that of HaSV viral RNA. Dimers of nucleotides 37 to 229 and 205 to 272 both exhibited melting temperatures near that of viral RNA, while dimers of nucleotides 271 to 378 are quite unstable. We also found that dimers of nucleotides 37 to 378 formed at 37 degrees C are less thermostable than dimers of the same RNA formed at 55 degrees C. It seems possible that bases from all of these regions participate in the dimer linkage present in viral RNA.

  12. Quantitative Experimental Determination of Primer-Dimer Formation Risk by Free-Solution Conjugate Electrophoresis

    Science.gov (United States)

    Desmarais, Samantha M.; Leitner, Thomas; Barron, Annelise E.

    2012-01-01

    DNA barcodes are short, unique ssDNA primers that “mark” individual biomolecules. To gain better understanding of biophysical parameters constraining primer-dimer formation between primers that incorporate barcode sequences, we have developed a capillary electrophoresis method that utilizes drag-tag-DNA conjugates to quantify dimerization risk between primer-barcode pairs. Results obtained with this unique free-solution conjugate electrophoresis (FSCE) approach are useful as quantitatively precise input data to parameterize computation models of dimerization risk. A set of fluorescently labeled, model primer-barcode conjugates were designed with complementary regions of differing lengths to quantify heterodimerization as a function of temperature. Primer-dimer cases comprised two 30-mer primers, one of which was covalently conjugated to a lab-made, chemically synthesized poly-N-methoxyethylglycine drag-tag, which reduced electrophoretic mobility of ssDNA to distinguish it from ds primer-dimers. The drag-tags also provided a shift in mobility for the dsDNA species, which allowed us to quantitate primer-dimer formation. In the experimental studies, pairs of oligonucleotide primer-barcodes with fully or partially complementary sequences were annealed, and then separated by free-solution conjugate CE at different temperatures, to assess effects on primer-dimer formation. When less than 30 out of 30 basepairs were bonded, dimerization was inversely correlated to temperature. Dimerization occurred when more than 15 consecutive basepairs formed, yet non-consecutive basepairs did not create stable dimers even when 20 out of 30 possible basepairs bonded. The use of free-solution electrophoresis in combination with a peptoid drag-tag and different fluorophores enabled precise separation of short DNA fragments to establish a new mobility shift assay for detection of primer-dimer formation. PMID:22331820

  13. A Model for Dimerization of the SOX Group E Transcription Factor Family.

    Directory of Open Access Journals (Sweden)

    Sarah N Ramsook

    Full Text Available Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.

  14. Field-based scanning tunneling microscope manipulation of antimony dimers on Si(001)

    NARCIS (Netherlands)

    Rogge, S.; Timmerman, R.H.; Scholte, P.M.L.O.; Geerligs, L.J.; Salemink, H.W.M.

    2001-01-01

    The manipulation of antimony dimers, Sb2, on the silicon (001) surface by means of a scanning tunneling microscope (STM) has been experimentally investigated. Directed hopping of the Sb2 dimers due the STM tip can dominate over the thermal motion at temperatures between 300 and 500 K. Statistics on

  15. A riboswitch regulates RNA dimerization and packaging in human immunodeficiency virus type 1 virions

    NARCIS (Netherlands)

    Ooms, Marcel; Huthoff, Hendrik; Russell, Rodney; Liang, Chen; Berkhout, Ben

    2004-01-01

    The genome of retroviruses, including human immunodeficiency virus type I (HIV-1), consists of two identical RNA strands that are packaged as noncovalently linked dimers. The core packaging and dimerization signals are located in the downstream part of the untranslated leader of HIV-1 RNA-the Psi

  16. Synthesis and Diels–Alder cycloaddition reaction of norbornadiene and benzonorbornadiene dimers

    Directory of Open Access Journals (Sweden)

    Bilal Nişancı

    2009-08-01

    Full Text Available Dimeric forms of norbornadiene and benzonorbornadiene were synthesized starting with known monobromide derivatives. The Diels–Alder cycloaddition reaction of dimers with TCNE and PTAD was investigated and new norbornenoid polycyclics were obtained. All compounds were characterized properly using NMR spectroscopy.

  17. Fabrication and characterization of terahertz anisotropic anti-rod dimer planar metamaterials

    DEFF Research Database (Denmark)

    Zalkovskij, Maksim; Malureanu, Radu; Novitsky, Andrey

    2012-01-01

    In this work we describe the fabrication and characterization of free-standing membranes with thick anti-rod dimers metamaterials for terahertz waves. Two different designs with parallel and V-shape anti-rods were analysed. Even though both structures consists of simple elements, namely anti......-rod dimers, they reveal interesting birefringent and dichroic transmission properties....

  18. The intrinsically disordered RNR inhibitor Sml1 is a dynamic dimer

    DEFF Research Database (Denmark)

    Danielsson, Jens; Liljedahl, Leena; Ba´ra´ny-Wallje, Elsa

    2008-01-01

    . Sml1 belongs to the class of intrinsically disordered proteins with a high degree of dynamics and very little stable structure. Earlier suggestions for a dimeric structure of Sml1 were confirmed, and from translation diffusion NMR measurements, a dimerization dissociation constant of 0.1 mM at 4...... natively disordered proteins....

  19. Study of structural stability and damaging effect on membrane for four Aβ42 dimers.

    Directory of Open Access Journals (Sweden)

    Wei Feng

    Full Text Available Increasing evidence shows that Aβ oligomers are key pathogenic molecules in Alzheimer's disease. Among Aβ oligomers, dimer is the smallest aggregate and toxic unit. Therefore, understanding its structural and dynamic properties is quite useful to prevent the formation and toxicity of the Aβ oligomers. In this study, we performed molecular dynamic simulations on four Aβ42 dimers, 2NCb, CNNC, NCNC and NCCN, within the hydrated DPPC membrane. Four Aβ42 dimers differ in the arrangements of two Aβ42 peptides. This study aims to investigate the impact of aggregation pattern of two Aβ peptides on the structural stability of the Aβ42 dimer and its disruption to the biological membrane. The MD results demonstrate that the NCCN, CNNC and NCNC have the larger structural fluctuation at the N-terminus of Aβ42 peptide, where the β-strand structure converts into the coil structure. The loss of the N-terminal β-strand further impairs the aggregate ability of Aβ42 dimer. In addition, inserting Aβ42 dimer into the membrane can considerably decrease the average APL of DPPC membrane. Moreover this decrease effect is largely dependent on the distance to the location of Aβ42 dimer and its secondary structure forms. Based on the results, the 2NCb is considered as a stable dimeric unit for aggregating the larger Aβ42 oligomer, and has a potent ability to disrupt the membrane.

  20. Mass spectrometric characterization of human serum albumin dimer: A new potential biomarker in chronic liver diseases.

    Science.gov (United States)

    Naldi, Marina; Baldassarre, Maurizio; Nati, Marina; Laggetta, Maristella; Giannone, Ferdinando Antonino; Domenicali, Marco; Bernardi, Mauro; Caraceni, Paolo; Bertucci, Carlo

    2015-08-10

    Human serum albumin (HSA) undergoes several structural alterations affecting its properties in pro-oxidant and pro-inflammatory environments, as it occurs during liver cirrhosis. These modifications include the formation of albumin dimers. Although HSA dimers were reported to be an oxidative stress biomarker, to date nothing is known about their role in liver cirrhosis and related complications. Additionally, no high sensitive analytical method was available for HSA dimers assessment in clinical settings. Thus the HSA dimeric form in human plasma was characterized by mass spectrometry using liquid chromatography tandem mass spectrometry (LC-ESI-Q-TOF) and matrix assisted laser desorption time of flight (MALDI-TOF) techniques. N-terminal and C-terminal truncated HSA, as well as the native HSA, undergo dimerization by binding another HSA molecule. This study demonstrated the presence of both homo- and hetero-dimeric forms of HSA. The dimerization site was proved to be at Cys-34, forming a disulphide bridge between two albumin molecules, as determined by LC-MS analysis after tryptic digestion. Interestingly, when plasma samples from cirrhotic subjects were analysed, the dimer/monomer ratio resulted significantly increased when compared to that of healthy subjects. These isoforms could represent promising biomarkers for liver disease. Additionally, this analytical approach leads to the relative quantification of the residual native HSA, with fully preserved structural integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha

    DEFF Research Database (Denmark)

    Jiang, G; den Hertog, J; Su, J

    1999-01-01

    that dimerization can negatively regulate activity, through the interaction of an inhibitory 'wedge' on one monomer with the catalytic cleft of domain 1 in the other monomer. Here we show that dimerization inhibits the activity of a full-length RPTP in vivo. We generated stable disulphide-bonded full...

  2. Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

    Science.gov (United States)

    Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

    2006-01-01

    The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus. PMID:16707664

  3. Analysis of hepatitis C virus RNA dimerization and core-RNA interactions.

    Science.gov (United States)

    Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

    2006-01-01

    The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3'-untranslated region (3'-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623-2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3'-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus.

  4. Fabrication and characterization of Au dimer antennas on glass pillars with enhanced plasmonic response

    DEFF Research Database (Denmark)

    Sadeghi, Pedram; Wu, Kaiyu; Rindzevicius, Tomas

    2017-01-01

    We report on the fabrication and dark-field spectroscopy characterization of Au dimer nanoantennas placed on top of SiO2 nanopillars. The reported process enables the fabrication of nanopillar dimers with gaps down to 15 nm and heights up to 1 μm. A clear dependence of the plasmonic resonance...

  5. Mutability of bacteriophage M13 by ultraviolet light: role of pyrimidine dimers

    International Nuclear Information System (INIS)

    Schaaper, R.M.; Glickman, B.W.

    1982-01-01

    The role of pyrimidine dimers in mutagenesis by ultraviolet light was examined by measuring the UV-induced reversion of six different bacteriophage M13 amber mutants for which the neighboring DNA sequences are known. The mutational response at amber (TAG) codons preceded by a guanine or adenine (where no pyrimidine dimer can be formed) were compared with those preceded by thymine or cytosine (where dimer formation is possible). Equivalent levels of UV-induced mutagenesis were observed at both kinds of sites. This observation demonstrates that there is no requirement for a pyrimidine dimer directly at the site of UV-induced mutation in this single-stranded DNA phage. UV irradiation of the phage was also performed in the presence of Ag + ions, which specifically sensitize the DNA to dimer formation. The two methods of irradiation, when compared at equal survival levels (and presumably equal dimer frequencies), produced equivalent frequencies of reversion of the amber phage. We believe these results indicate that while the presence of pyrimidine dimers may be a prerequisite for UV mutagenesis, the actual mutagenic event can occur at a site some distance removed from a dimer. (orig.)

  6. Variations in the heterogeneity of the decay of the fluorescence in six procyanidin dimers

    Science.gov (United States)

    Donghwan Cho; Rujiang Tian; Lawrence J. Porter; Richard W. Hemingway; Wayne L. Mattice

    1990-01-01

    The decay of the fluorescence has been measured in 1,4-dioxane for six dimers of (2R,3R)-(-)-epicatechin and (2R,3S)-(+)-catechin, hereafter denoted simply epicatechin and catechin. The dimers are epicatechin-(4β→8)-catechin, epicatechin-(4β→8)-epicatechin...

  7. Evaluation of Serum D-dimer Levels in Children with Pneumonia

    Directory of Open Access Journals (Sweden)

    Nilgün Selçuk Duru

    2016-03-01

    Full Text Available Aim: The aim of this study was to investigate the relationship of plasma D-dimer levels with duration of hospitalization and radiological and laboratory findings in patients with pneumonia. Methods: Forty-seven patients with pneumonia (31 boys and 16 girls, mean age: 4.2±4.7 years were included in the study. The patients were divided into two groups according to duration of hospitalization and three groups according to radiological findings. D-dimer and other laboratory findings were compared between the groups. Results: The mean serum D-dimer level was 1333.5±1364.4 ng/L. There was no statistically significant difference in D-dimer, leukocyte, erythrocyte sedimentation rate (ESR and C-reactive protein (CRP between the groups divided according to duration of hospitalization. In addition, there was no statistically difference in D-dimer levels between the groups divided according to radiological findings. Age, percentage of neutrophils, ESR and fibrinogen levels were higher in patients with lobar pneumonia when compared with the other groups and CRP level was higher in lobar pneumonia group when compared to interstitial pneumonia group. D-dimer levels were negatively correlated with age and positively correlated with ESR, CRP, and fibrinogen. Conclusion: In our study, D-dimer levels were high in patient with pneumonia. Further studies with a larger number of patients are necessary to determine the role of D-dimer levels as an acutephase reactant in patients with pneumonia

  8. Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Does a Normal Age-Adjusted D-Dimer Rule Out PE?

    Directory of Open Access Journals (Sweden)

    Jacob Ortiz

    2017-01-01

    Full Text Available Risk assessment for pulmonary embolism (PE currently relies on physician judgment, clinical decision rules (CDR, and D-dimer testing. There is still controversy regarding the role of D-dimer testing in low or intermediate risk patients. The objective of the study was to define the role of clinical decision rules and D-dimer testing in patients suspected of having a PE. Records of 894 patients referred for computed tomography pulmonary angiography (CTPA at a University medical center were analyzed. The clinical decision rules overall had an ROC of approximately 0.70, while signs of DVT had the highest ROC (0.80. A low probability CDR coupled with a negative age-adjusted D-dimer largely excluded PE. The negative predictive value (NPV of an intermediate CDR was 86–89%, while the addition of a negative D-dimer resulted in NPVs of 94%. Thus, in patients suspected of having a PE, a low or intermediate CDR does not exclude PE; however, in patients with an intermediate CDR, a normal age-adjusted D-dimer increases the NPV.

  9. Detection of cyclobutane thymine dimers in DNA of human cells with monoclonal antibodies raised against a thymine dimer-containing tetranucleotide

    Energy Technology Data Exchange (ETDEWEB)

    Roza, L; Wulp, K.J.M. van der; MacFarlane, S J; Lohman, P H.M.; Baan, R A

    1988-11-01

    A hybrid cell line (hybridoma) has been isolated after fusion between mouse-plasmacytoma cells and spleen cells from mice immunized with a thymine dimer-containing tetranucleotide coupled to a carrier protein. Monoclonal antibodies produced by this hybridoma were characterized by testing the effect of various inhibitors in a competitive enzyme-linked immunosorbent assay (ELISA). The antibodies have a high specificity for thymine dimers in single-stranded DNA or poly(dT), but do not bind UV-irradiated d(TpC)/sub 5/. Less binding is observed with short thymine dimer-containing sequences. In vitro treatment of UV-irradiated DNA with photoreactivating enzyme in the presence of light, or with Micrococcus luteus UV-endonuclease results in disappearance of antigenicity. Antibody-binding to DNA isolated from UV-irradiated human fibroblasts (at 254 nm) is linear with dose. Removal of thymine dimers in these cells during a post-irradiation incubation, as detected with the antibodies, is fast initially but the rate rapidly decreases (about 50% residual dimers at 20 h after 10 J/m/sup 2/). The induction of thymine dimers in human skin irradiated with low doses of UV-B, too, was demonstrated immunochemically, by ELISA as well as by quantitative immunofluorescence microscopy.

  10. Mechanism for Controlling the Dimer-Monomer Switch and Coupling Dimerization to Catalysis of the Severe Acute Respiratory Syndrome Coronavirus 3C-Like Protease

    Energy Technology Data Exchange (ETDEWEB)

    Shi,J.; Sivaraman, J.; Song, J.

    2008-01-01

    Unlike 3C protease, the severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CLpro) is only enzymatically active as a homodimer and its catalysis is under extensive regulation by the unique extra domain. Despite intense studies, two puzzles still remain: (i) how the dimer-monomer switch is controlled and (ii) why dimerization is absolutely required for catalysis. Here we report the monomeric crystal structure of the SARS-CoV 3CLpro mutant R298A at a resolution of 1.75 Angstroms . Detailed analysis reveals that Arg298 serves as a key component for maintaining dimerization, and consequently, its mutation will trigger a cooperative switch from a dimer to a monomer. The monomeric enzyme is irreversibly inactivated because its catalytic machinery is frozen in the collapsed state, characteristic of the formation of a short 310-helix from an active-site loop. Remarkably, dimerization appears to be coupled to catalysis in 3CLpro through the use of overlapped residues for two networks, one for dimerization and another for the catalysis.

  11. Anti-parallel dimer and tetramer formation of propylene carbonate

    Directory of Open Access Journals (Sweden)

    Ayana Tagawa

    2017-09-01

    Full Text Available Raman scattering and infrared (IR absorption spectra of enantiopure (R-propylene carbonate ((RPC and racemic propylene carbonate (PC were recorded at room temperature, 25 °C, in benzene (Bz solution and in the pure liquid state to investigate the presence of dimers and other higher order intermolecular associations. (RPC and PC both demonstrated a strong C=O stretching vibrational band. The band exhibited changes in its shape and resonance wavenumber highly dependent on the concentrations of PCs, whereas a difference between the chirality of (RPC and PC had little influence. In an extremely dilute condition, doubly split bands were observed at 1807 and 1820 cm-1 in both Raman and IR spectra, which are assigned to the characteristic bands of isolated monomeric PCs. An additional band appeared at 1795 cm-1 in a dilute to concentrated regime, and its magnitude strengthened with increasing concentrations accompanied with slight increasing in the magnitude of 1807 cm-1 band in Raman spectra, while an increase in the magnitude of 1807 cm-1 band was clearly greater than that of 1795 cm-1 band in IR spectra. The spectrum changes at 1795 and 1807 cm-1 were attributed to characteristics of anti-parallel dimer formation of PCs caused by strong dipole-dipole interactions between C=O groups. Moreover, another additional signal was clearly observed at 1780-1790 cm-1 in a concentrated regime, and became the primary signal in the pure liquid state with slight increasing in the intensity of 1795 cm-1 band in Raman spectra. On the other hand, in IR spectra the observed increasing of 1780-1790 cm-1 band was much less than that of 1795 cm-1 band. These newly found spectrum changes in the concentrated regime are attributed to the formation of anti-parallel tetramers of PCs based on the characteristics of band selection rule found in Raman and IR spectra. Equilibrium constants for the anti-parallel dimer (KD and tetramer formation (KT of PCs in Bz solution and in

  12. Conformational study of the protegrin-1 (PG-1 dimer interaction with lipid bilayers and its effect

    Directory of Open Access Journals (Sweden)

    Nussinov Ruth

    2007-04-01

    Full Text Available Abstract Background Protegrin-1 (PG-1 is known as a potent antibiotic peptide; it prevents infection via an attack on the membrane surface of invading microorganisms. In the membrane, the peptide forms a pore/channel through oligomerization of multiple subunits. Recent experimental and computational studies have increasingly unraveled the molecular-level mechanisms underlying the interactions of the PG-1 β-sheet motifs with the membrane. The PG-1 dimer is important for the formation of oligomers, ordered aggregates, and for membrane damaging effects. Yet, experimentally, different dimeric behavior has been observed depending on the environment: antiparallel in the micelle environment, and parallel in the POPC bilayer. The experimental structure of the PG-1 dimer is currently unavailable. Results Although the β-sheet structures of the PG-1 dimer are less stable in the bulk water environment, the dimer interface is retained by two intermolecular hydrogen bonds. The formation of the dimer in the water environment implies that the pathway of the dimer invasion into the membrane can originate from the bulk region. In the initial contact with the membrane, both the antiparallel and parallel β-sheet conformations of the PG-1 dimer are well preserved at the amphipathic interface of the lipid bilayer. These β-sheet structures illustrate the conformations of PG-1 dimer in the early stage of the membrane attack. Here we observed that the activity of PG-1 β-sheets on the bilayer surface is strongly correlated with the dimer conformation. Our long-term goal is to provide a detailed mechanism of the membrane-disrupting effects by PG-1 β-sheets which are able to attack the membrane and eventually assemble into the ordered aggregates. Conclusion In order to understand the dimeric effects leading to membrane damage, extensive molecular dynamics (MD simulations were performed for the β-sheets of the PG-1 dimer in explicit water, salt, and lipid bilayers

  13. Role of distonic dimer radical cations in the radiation-induced polymerisation of vinyl ethers

    International Nuclear Information System (INIS)

    Naumov, Sergej; Janovsky, Igor; Knolle, Wolfgang; Mehnert, Reiner

    2005-01-01

    The experimental low-temperature EPR results and the quantum chemical calculations suggest that dimer radical cations of cyclic and aliphatic vinyl ethers (VE) plays a key role in starting of radiation-induced polymerisation. The main species observed at high 2,3-dihydrofuran (DHF), 2,3-dihydropyran (DHP) and VE concentration is the dimer radical cation. In the case of cyclic VE the dimer radical cation transforms through H-abstraction from neutral molecule into a carbocation and radical, which could start both cationic and free-radical polymerisation. However, in the case of aliphatic VE no further reactive species, which could start polymerisation, were observed. This is caused (in agreement with experiment and quantum chemical calculations) by the very high stability of dimer radical cation and calculated endothermity of H-abstraction reaction by dimer radical cation from monomer

  14. Detectability of H2-Ar and H2-Ne Dimers in Jovian Atmospheres

    Directory of Open Access Journals (Sweden)

    Young-Key Minn

    1997-12-01

    Full Text Available The detection of jovian hydrogen-hydrogen dimers through the clear telluric 2-micron window(Kim et al. 1995, Trafton et al. 1997 suggests possibility to detect noble gases in the form of dimer with hydrogen in jovian atmospheres. Since noble gases do not have spectral structures in the infrared, it has been difficult to derive their abundances in the atmospheres of jovian planets. If there is a significant component of noble gases other than helium in the jovian atmospheres. it might be detected through its dimer spectrum with hydrogen molecule. The relatively sharp spectral structures of hydrogen-argon and hydrogen-neon dimers compared with those of hydrogen-hydrogen dimers are useful for the detection, if an adequate signal-to-noise (S/N is obtained. If we use a large telescope, such as the Keck telescope, with a long exposure time (>24 hours, then H2-Ar spectral structure may be detected.

  15. The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.

    Science.gov (United States)

    Washington, Ilyas; Saad, Leonide

    2016-01-01

    One of the earliest events preceding several forms of retinal degeneration is the formation and accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and underlying Bruch's membrane (BM). Such degenerations include Stargardt disease, Best disease, forms of retinitis pigmentosa, and age-related macular degeneration (AMD). Since their discovery in the 1990's, dimers of vitamin A, have been postulated as chemical triggers driving retinal senescence and degeneration. There is evidence to suggest that the rate at which vitamin A dimerizes and the eye's response to the dimerization products may dictate the retina's lifespan. Here, we present outstanding questions, finding the answers to which may help to elucidate the role of vitamin A dimerization in retinal degeneration.

  16. Anion Photoelectron Spectroscopy of the Homogenous 2-Hydroxypyridine Dimer Electron Induced Proton Transfer System

    Science.gov (United States)

    Vlk, Alexandra; Stokes, Sarah; Wang, Yi; Hicks, Zachary; Zhang, Xinxing; Blando, Nicolas; Frock, Andrew; Marquez, Sara; Bowen, Kit; Bowen Lab JHU Team

    Anion photoelectron spectroscopic (PES) and density functional theory (DFT) studies on the dimer anion of (2-hydroxypyridine)2-are reported. The experimentally measured vertical detachment energy (VDE) of 1.21eV compares well with the theoretically predicted values. The 2-hydroxypyridine anionic dimer system was investigated because of its resemblance to the nitrogenous heterocyclic pyrimidine nucleobases. Experimental and theoretical results show electron induced proton transfer (EIPT) in both the lactim and lactam homogeneous dimers. Upon electron attachment, the anion can serve as the intermediate between the two neutral dimers. A possible double proton transfer process can occur from the neutral (2-hydroxypyridine)2 to (2-pyridone)2 through the dimer anion. This potentially suggests an electron catalyzed double proton transfer mechanism of tautomerization. Research supported by the NSF Grant No. CHE-1360692.

  17. Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy

    DEFF Research Database (Denmark)

    Hansen, Anette Tarp; Andreasen, Birgitte Horst; Salvig, Jannie Dalby

    2010-01-01

    Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference...... intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women...... in gestational week 11–17, with normal current pregnancy. Blood samples were collected in gestational weeks 11–17, 21–27 and 34–37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution®. Results. A significant rise in D-dimer was found from first to second trimester (p...

  18. Spin quantum tunneling via entangled states in a dimer of exchange coupled single-molecule magnets

    Science.gov (United States)

    Tiron, R.; Wernsdorfer, W.; Aliaga-Alcalde, N.; Foguet-Albiol, D.; Christou, G.

    2004-03-01

    A new family of supramolecular, antiferromagnetically exchange-coupled dimers of single-molecule magnets (SMMs) has recently been reported [W. Wernsdorfer, N. Aliaga-Alcalde, D.N. Hendrickson, and G. Christou, Nature 416, 406 (2002)]. Each SMM acts as a bias on its neighbor, shifting the quantum tunneling resonances of the individual SMMs. Hysteresis loop measurements on a single crystal of SMM-dimers have now established quantum tunneling of the magnetization via entangled states of the dimer. This shows that the dimer really does behave as a quantum-mechanically coupled dimer. The transitions are well separated, suggesting long coherence times compared to the time scale of the energy splitting. This result is of great importance if such systems are to be used for quantum computing. It also allows the measurement of the longitudinal and transverse superexchange coupling constants [Phys. Rev. Lett. 91, 227203 (2003)].

  19. A discotic triphenylene dimer as organic hole transporting material for electroluminescence devices

    International Nuclear Information System (INIS)

    Mao Huaxiang; He Zhiqun; Wang Junling; Zhang Chunxiu; Xie, Ping; Zhang Rongben

    2007-01-01

    A triphenylene dimer, an intermediate between a discotic triphenylene molecule and the macromolecule, had been prepared by linking together two triphenylene units via phenylene carbamate linkages, which was formed through a reaction between one 1,4-phenylene diisocyanate and two hydroxyl end groups on flexible substituents of triphenylenes. The dimer exhibited good film-forming property. Its temperature-dependent phase transitions were investigated using differential scanning calorimetry and polarized optical microscopy. Room temperature microstructure of the dimer was analyzed by X-ray diffraction. Charge mobility of the triphenylene dimer was also measured. Our preliminary result using the materials in a sandwich light-emitting device is reported here. It demonstrates that the triphenylene dimer is a promising candidate as a hole transporting material

  20. Formation of thymine containing dimers in skin exposed to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, B E [Dundee Univ. (UK)

    1978-01-01

    Nuclear DNA appears to be the major molecular target for the inhibitory, mutagenic and lethal effects of ultraviolet radiation on cells in culture. Cyclobutyl dimers between adjacent pyrimidine bases, the major photochemical lesions for these effects in prokaryotes, also play a part in UVR effects on eukaryotes cells. Pyrimidine dimers have been isolated from in vivo UV-irradiated guinea pig and mouse skin. The wavelength dependence for dimer induction is similar to that for acute skin reactions but no direct causal relationship has been established. Sunlight UVR may induce dimers in skin DNA. Excision of dimers from mouse skin in vivo is deficient as it is for most rodent cells in culture; human cell excision is efficient and the difficulties in interpretation of UV-carcinogenesis results with mice in terms of human skin cancer are therefore increased.

  1. Visualization of multipolar longitudinal and transversal surface plasmon modes in nanowire dimers.

    Science.gov (United States)

    Alber, Ina; Sigle, Wilfried; Müller, Sven; Neumann, Reinhard; Picht, Oliver; Rauber, Markus; van Aken, Peter A; Toimil-Molares, Maria Eugenia

    2011-12-27

    We study the transversal and longitudinal localized surface plasmon resonances in single nanowires and nanowire dimers excited by the fast traveling electron beam in a transmission electron microscope equipped with high-resolution electron energy-loss spectroscopy. Bright and dark longitudinal modes up to the fifth order are resolved on individual metallic nanowires. On nanowire dimers, mode splitting into bonding and antibonding is measured up to the third order for several dimers with various aspect ratio and controlled gap size. We observe that the electric field maxima of the bonding modes are shifted toward the gap, while the electric field maxima of the antibonding modes are shifted toward the dimer ends. Finally, we observe that the transversal mode is not detected in the region of the dimer gap and decays away from the rod more rapidly than the longitudinal modes.

  2. The relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts in Escherichia coli cells

    International Nuclear Information System (INIS)

    Tang, Moon-shong; Hrncir, J.; Mitchell, D.; Ross, J.; Clarkson, J.

    1986-01-01

    In order to calculate the relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts, the authors have measured survival and mutation induction in UV-irradiated excision-deficient E. coli uvrA cells, with or without complete photoreactivation of the dimers. Radioimmunoassays with specificity for dimers or photoproducts have shown that maximum photoreactivation eliminates all of the dimers produce up to 10 Jm -2 254-nm light, while it has no effect on photoproducts. These results were confirmed by measuring the frequency of T4 endonuclease V-sensitive sites. Based on the best fit equations for survival and mutation induction, the authors have found that the calculated cytotoxicity of photoproducts is similar to that of dimers; however, the former is much more mutagenic than the latter. (Auth.)

  3. Initial in vitro and in vivo assessment of Au@DTDTPA-RGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tsoukalas, Charalmpos [National Center for Scientific Research ' Demokritos' (Greece); Laurent, Gautier; Jiménez Sánchez, Gloria [Université de Franche-Comté, Institut UTINAM (France); Tsotakos, Theodoros [National Center for Scientific Research ' Demokritos' (Greece); Bazzi, Rana [Université de Franche-Comté, Institut UTINAM (France); Stellas, Dimitris; Anagnostopoulos, Constantinos [Biomedical Research Foundation, Academy of Athens (Greece); Moulopoulos, Lia; Koutoulidis, Vasilis [Department of Radiology, Areteion Hospital, University of Athens Medical School (Greece); Paravatou-Petsotas, Maria; Xanthopoulos, Stavros [National Center for Scientific Research ' Demokritos' (Greece); Roux, Stephane [Université de Franche-Comté, Institut UTINAM (France); Bouziotis, Penelope [National Center for Scientific Research ' Demokritos' (Greece)

    2015-05-18

    Gadolinium chelate coated gold nanoparticles (Au@DTDTPA) can be applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. In this work, our aim was to radiolabel and evaluate this gold nanoparticle with Ga-68, in order to produce a dual modality PET/MRI imaging probe. For a typical preparation of 68Ga-labeled nanoparticles, the Au@DTDTPA nanoparticles (Au@DTDTPA/Au@DTDTPA-RGD) were mixed with ammonium acetate buffer, pH 5 and 40 MBq of 68Ga eluate. The mixture was then incubated for 45 min at 65 ÅãC. Radiochemical purity was determined by ITLC. In vitro stability of both radiolabeled species was assessed in saline and serum. In vitro cell binding experiments were performed on integrin ανβ3 receptor-positive U87MG cancer cells. Non-specific Au@DTDTPA was used for comparison. Ex vivo biodistribution studies and in vivo PET and MRI imaging studies in U87MG tumor-bearing SCID mice followed. The Au@DTDTPA nanoparticles were labeled with Gallium-68 at high radiochemical yield (>95%) and were stable at RT, and in the presence of serum, for up to 3 h. The cell binding assay on U87MG glioma cells proved that 68Ga-cRGD-Au@DTDTPA had specific recognition for these cells. Biodistribution studies in U87MG tumor-bearing SCID mice showed that the tumor to muscle ratio increased from 1 to 2 h p.i. (3,71 ± 0.22 and 4,69 ± 0.09 respectively), showing a clear differentiation between the affected and the non-affected tissue. The acquired PET and MRI images were in accordance to the ex vivo biodistribution results. The preliminary results of this study warrant the need for further development of Au@DTDTPA nanoparticles radiolabeled with Ga-68, as possible dual-modality PET/MRI imaging agents.

  4. Initial in vitro and in vivo assessment of Au@DTDTPA-RGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging

    International Nuclear Information System (INIS)

    Tsoukalas, Charalmpos; Laurent, Gautier; Jiménez Sánchez, Gloria; Tsotakos, Theodoros; Bazzi, Rana; Stellas, Dimitris; Anagnostopoulos, Constantinos; Moulopoulos, Lia; Koutoulidis, Vasilis; Paravatou-Petsotas, Maria; Xanthopoulos, Stavros; Roux, Stephane; Bouziotis, Penelope

    2015-01-01

    Gadolinium chelate coated gold nanoparticles (Au@DTDTPA) can be applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. In this work, our aim was to radiolabel and evaluate this gold nanoparticle with Ga-68, in order to produce a dual modality PET/MRI imaging probe. For a typical preparation of 68Ga-labeled nanoparticles, the Au@DTDTPA nanoparticles (Au@DTDTPA/Au@DTDTPA-RGD) were mixed with ammonium acetate buffer, pH 5 and 40 MBq of 68Ga eluate. The mixture was then incubated for 45 min at 65 ÅãC. Radiochemical purity was determined by ITLC. In vitro stability of both radiolabeled species was assessed in saline and serum. In vitro cell binding experiments were performed on integrin ανβ3 receptor-positive U87MG cancer cells. Non-specific Au@DTDTPA was used for comparison. Ex vivo biodistribution studies and in vivo PET and MRI imaging studies in U87MG tumor-bearing SCID mice followed. The Au@DTDTPA nanoparticles were labeled with Gallium-68 at high radiochemical yield (>95%) and were stable at RT, and in the presence of serum, for up to 3 h. The cell binding assay on U87MG glioma cells proved that 68Ga-cRGD-Au@DTDTPA had specific recognition for these cells. Biodistribution studies in U87MG tumor-bearing SCID mice showed that the tumor to muscle ratio increased from 1 to 2 h p.i. (3,71 ± 0.22 and 4,69 ± 0.09 respectively), showing a clear differentiation between the affected and the non-affected tissue. The acquired PET and MRI images were in accordance to the ex vivo biodistribution results. The preliminary results of this study warrant the need for further development of Au@DTDTPA nanoparticles radiolabeled with Ga-68, as possible dual-modality PET/MRI imaging agents.

  5. Evaluation of two novel {sup 64}Cu-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin α{sub v}β{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Reinier; Graves, Stephen A.; Nickles, Robert J. [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); Czerwinski, Andrzej; Valenzuela, Francisco [Peptides International, Inc., Louisville, KY (United States); Chakravarty, Rubel; Yang, Yunan; England, Christopher G. [University of Wisconsin, Department of Radiology, Madison, WI (United States); Cai, Weibo [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2015-11-15

    Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin α{sub v}β{sub 3}, may offer advantages in image contrast, time for imaging, and low uptake in nontarget tissues. Two cyclic RGDfK derivatives, (PEG){sub 2}-c(RGDfK) and PEG{sub 4}-SAA{sub 4}-c(RGDfK), were constructed and conjugated to NOTA for {sup 64}Cu labeling. Their integrin α{sub v}β{sub 3}-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the {sup 64}Cu-labeled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h after injection. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers. The IC{sub 50} values of NOTA-(PEG){sub 2}-c(RGDfK) and NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) were 444 ± 41 nM and 288 ± 66 nM, respectively. Dynamic PET data of {sup 64}Cu-NOTA-(PEG){sub 2}-c(RGDfK) and {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) showed similar circulation t{sub 1/2} and peak tumor uptake of about 4 %ID/g for both tracers. Due to its marked hydrophilicity, {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintained excellent tumor-to-background ratios. Static PET scans at later time-points corroborated the enhanced excretion of the tracer, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the integrin α{sub v}β{sub 3}-specificity of the peptides. Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed fast, high-contrast PET imaging of tumor-associated integrin α{sub v}β{sub 3}. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake. (orig.)

  6. Structural insights into lipid-dependent reversible dimerization of human GLTP

    International Nuclear Information System (INIS)

    Samygina, Valeria R.; Ochoa-Lizarralde, Borja; Popov, Alexander N.; Cabo-Bilbao, Aintzane; Goni-de-Cerio, Felipe; Molotkovsky, Julian G.; Patel, Dinshaw J.; Brown, Rhoderick E.; Malinina, Lucy

    2013-01-01

    It is shown that dimerization is promoted by glycolipid binding to human GLTP. The importance of dimer flexibility in wild-type protein is manifested by point mutation that ‘locks’ the dimer while diversifying ligand/protein adaptations. Human glycolipid transfer protein (hsGLTP) forms the prototypical GLTP fold and is characterized by a broad transfer selectivity for glycosphingolipids (GSLs). The GLTP mutation D48V near the ‘portal entrance’ of the glycolipid binding site has recently been shown to enhance selectivity for sulfatides (SFs) containing a long acyl chain. Here, nine novel crystal structures of hsGLTP and the SF-selective mutant complexed with short-acyl-chain monoSF and diSF in different crystal forms are reported in order to elucidate the potential functional roles of lipid-mediated homodimerization. In all crystal forms, the hsGLTP–SF complexes displayed homodimeric structures supported by similarly organized intermolecular interactions. The dimerization interface always involved the lipid sphingosine chain, the protein C-terminus (C-end) and α-helices 6 and 2, but the D48V mutant displayed a ‘locked’ dimer conformation compared with the hinge-like flexibility of wild-type dimers. Differences in contact angles, areas and residues at the dimer interfaces in the ‘flexible’ and ‘locked’ dimers revealed a potentially important role of the dimeric structure in the C-end conformation of hsGLTP and in the precise positioning of the key residue of the glycolipid recognition centre, His140. ΔY207 and ΔC-end deletion mutants, in which the C-end is shifted or truncated, showed an almost complete loss of transfer activity. The new structural insights suggest that ligand-dependent reversible dimerization plays a role in the function of human GLTP

  7. Engineering of a novel Ca2+-regulated kinesin molecular motor using a calmodulin dimer linker

    International Nuclear Information System (INIS)

    Shishido, Hideki; Maruta, Shinsaku

    2012-01-01

    Highlights: ► Engineered kinesin–M13 and calmodulin involving single cysteine were prepared. ► CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. ► Kinesin–M13 was dimerized via CaM dimer in the presence of calcium. ► Function of the engineered kinesin was regulated by a Ca 2+ -calmodulin dimer linker. -- Abstract: The kinesin–microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have “on–off” control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355–M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355–M13 dimerization with CaM dimers, we measured K355–M13 motility and found that it can be reversibly regulated in a Ca 2+ -dependent manner. We also found that velocities of K355–M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca 2+ -dependent dimerization of K355–M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  8. Numerical investigation of radiative properties and surface plasmon resonance of silver nanorod dimers on a substrate

    International Nuclear Information System (INIS)

    An, Wei; Zhu, Tong; Zhu, QunZhi

    2014-01-01

    When the distance between two silver nanoparticles is small enough, interparticle surface plasmon coupling has a great impact on their radiative properties. It is becoming a promising technique to use in the sensing and imaging. A model based on finite difference time domain method is developed to investigate the effect of the assembled parameters on the radiative properties and the field-enhancement effect of silver nanorod dimer. The numerical results indicate that the radiative properties of silver nanorod dimer are very sensitive to the assembled angle and the polarization orientation of incident wave. There is great difference on the intensity and location of field-enhancement effect for the cases of different assembled angle and polarization. The most intensive field-enhancement effect occurs in the middle of two nanorods when two nanorods is assembled head to head and the polarization orientation parallels to the length axis of nanorods. Moreover, compared with the single nanorod, the wavelength of extinction peak of dimer has a red-shift, and the intensity of field-enhancement effect on the dimer is more intensive than that of single particle. With the increasing of particle length, extinction cross-section of silver nanorod dimer rises, while extinction efficiency and scattering efficiency firstly increase then drop down gradually. In addition, the extinction peaks of silver nanorod dimer on the substrate are smaller than that without the substrate, and their extinction peaks has a red-shift compared with that without the substrate. -- Highlights: ► Radiative properties of silver nanorod dimer are very sensitive to the assembled angle. ► The projective length of nanorod dimer on the polarization orientation is crucial. ► Compared with single nanorod, wavelength of extinction peak of dimer has a red-shift. ► Extinction peaks of dimer on the substrate are smaller than that without the substrate

  9. Development of 68Ga ethyl cysteinate dimer for PET studies

    International Nuclear Information System (INIS)

    Alireza Mirzaei; Jalilian, A.R.; Gholamali Shabani; Ashraf Fakhari; Mehdi Akhlaghi; Davood Beiki

    2016-01-01

    In this work development of 68 Ga-ethyl cysteinate dimer ( 68 Ga-ECD) a 68 Ga tracer for possible cerebral blood flow based on 99m Tc ECD homolog is reported. 68 Ga-ECD was prepared using generator-based 68 GaCl 3 and ECD at optimized conditions. Quality control, stability, partition co-efficient and the biodistribution of the tracer (by tissue counting and PET/CT in rats) was studied. Significant metabolism of the lipophilic tracer into water soluble metabolite(s) led to urinary excretion of the tracer, un-comparable to that of homologous 99m Tc-compound. Cardiac uptake of the complex suggests formation of a possible lipophil cationic complex and/or metabolite. (author)

  10. A New Asymmetric ent-Kauranoid Dimer from Rabdosia rubescens

    Institute of Scientific and Technical Information of China (English)

    LU Hai-ying; LIANG Jing-yu

    2012-01-01

    Objective To study the ent-kaurane diterpenoids from Rabdosia rubescens.Methods The compounds were isolated by chromatographies and their structures were identified by spectral analyses.Results Four compounds were isolated,and they were identified as bisrubescensin E (1),2α,3α,24-trihydroxyurs-12-en-28-oic acid (2),2α,3α,24-trihydroxyurs-12,20-(30)-dien-28-oic acid (3),and 6,7-dihydroxycoumarin (4).Conclusion Compound 1 is a new asymmetric ent-kauranoid dimer.Compound 2 is isolated from the plant for the first time.Compounds 3 and 4 are isolated from the plants ofRabdosia (B1.) Hassk for the first time.

  11. Phosphorus Dimerization in Gallium Phosphide at High Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Lavina, Barbara [High Pressure Science and Engineering Center, University of Nevada, Las Vegas, Nevada 89154, United States; Department of Physics and Astronomy, University of Nevada, Las Vegas, Nevada 89154, United States; Kim, Eunja [Department of Physics and Astronomy, University of Nevada, Las Vegas, Nevada 89154, United States; Cynn, Hyunchae [Lawrence Livermore National Laboratory, Livermore, California 94550, United States; Weck, Philippe F. [Sandia National Laboratories, Albuquerque, New Mexico 87185, United States; Seaborg, Kelly [High Pressure Science and Engineering Center, University of Nevada, Las Vegas, Nevada 89154, United States; Department of Physics and Astronomy, University of Nevada, Las Vegas, Nevada 89154, United States; Siska, Emily [High Pressure Science and Engineering Center, University of Nevada, Las Vegas, Nevada 89154, United States; Meng, Yue [HPCAT, Carnegie Institution of Washington, Argonne, Illinois 60439, United States; Evans, William [Lawrence Livermore National Laboratory, Livermore, California 94550, United States

    2018-02-09

    Using combined experimental and computational approaches, we show that at 43 GPa and 1300 K gallium phosphide adopts the super-Cmcm structure, here indicated with its Pearson notation oS24. First-principles enthalpy calculations demonstrate that this structure is more thermodynamically stable above ~20 GPa than previously proposed polymorphs. Here, in contrast to other polymorphs, the oS24 phase shows a strong bonding differentiation and distorted fivefold coordination geometries of both P atoms. The shortest bond of the phase is a single covalent P–P bond measuring 2.171(11) Å at synthesis pressure. Phosphorus dimerization in GaP sheds light on the nature of the super-Cmcm phase and provides critical new insights into the high-pressure polymorphism of octet semiconductors. Bond directionality and anisotropy explain the relatively low symmetry of this high-pressure phase.

  12. Calculation of vibrational spectra for dioxouranium monochloride monomer and dimers

    Science.gov (United States)

    Umreiko, D. S.; Shundalau, M. B.; Zazhogin, A. P.; Komyak, A. I.

    2010-09-01

    Structural models were built and spectral characteristics were calculated based on ab initio calculations for the monomer and dimers of dioxouranium monochoride UO2Cl. The calculations were carried out in the effective core potential LANL2DZ approximation for the uranium atom and all-electron basis sets using DFT methods for oxygen and chlorine atoms (B3LYP/cc-pVDZ). The monomer UO2Cl was found to possess an equilibrium planar (close to T-shaped) configuration with C2v symmetry. The obtained spectral characteristics were analyzed and compared with experimental data. The adequacy of the proposed models and the qualitative agreement between calculation and experiment were demonstrated.

  13. Magnetostructural relationship for μ2-phenoxido bridged ferric dimers.

    Science.gov (United States)

    Yu, Fei; Cao, Zi-Heng; Ge, Jing-Yuan; Sun, Yi-Chen; Ouyang, Zhong-Wen; Zuo, Jing-Lin; Wang, Zhenxing; Kurmoo, Mohamedally

    2017-03-27

    Three Fe(iii) dimers, [Fe 2 (L-H) 2 ]·2CH 3 CN (1), [Fe 2 (L-OCH 3 ) 2 ] (2) and [Fe 2 (L-OC 2 H 5 ) 2 ]·2CH 3 CN (3), containing the pentadentate O,N,N,O,O-donor Schiff-base ligands with variable size pendants, were synthesized and structurally characterized. The three ligands were generated in situ from 2-(iminomethyl)phenol, 2-methoxy-6-(iminomethyl)phenol and 2-ethoxy-6-(iminomethyl)phenol, respectively. All three crystal structures contain centrosymmetric dimers of edge-sharing octahedra of Fe(iii) ions through a pair of μ 2 -phenoxido bridges. The exchange coupling is ferromagnetic for 1 (J = +0.47(1) cm -1 , ∠Fe-O-Fe = 98.02°) and 2 (J = +0.86(1) cm -1 , ∠Fe-O-Fe = 97.17°), but antiferromagnetic for 3 (J = -0.72(1) cm -1 , ∠Fe-O-Fe = 98.53°), which are correlated by high-field electron paramagnetic resonance revealing moderate magneto-anisotropy of D = -0.24(3) cm -1 , E = 0.08(1) cm -1 for 1, D = -0.38(1) cm -1 , E = 0.11(1) cm -1 for 2, and D = 0.30(3) cm -1 , E = 0.02(1) cm -1 for 3. The exchange couplings were further estimated by DFT calculations, which gave the finest Fe-O-Fe angle of 97.83° for the ferromagnetic-antiferromagnetic crossover.

  14. Amorphous Silica-Promoted Lysine Dimerization: a Thermodynamic Prediction

    Science.gov (United States)

    Kitadai, Norio; Nishiuchi, Kumiko; Nishii, Akari; Fukushi, Keisuke

    2018-03-01

    It has long been suggested that mineral surfaces played a crucial role in the abiotic polymerization of amino acids that preceded the origin of life. Nevertheless, it remains unclear where the prebiotic process took place on the primitive Earth, because the amino acid-mineral interaction and its dependence on environmental conditions have yet to be understood adequately. Here we examined experimentally the adsorption of L-lysine (Lys) and its dimer (LysLys) on amorphous silica over a wide range of pH, ionic strength, adsorbate concentration, and the solid/water ratio, and determined the reaction stoichiometries and the equilibrium constants based on the extended triple-layer model (ETLM). The retrieved ETLM parameters were then used, in combination with the equilibrium constant for the peptide bond formation in bulk water, to calculate the Lys-LysLys equilibrium in the presence of amorphous silica under various aqueous conditions. Results showed that the silica surface favors Lys dimerization, and the influence varies greatly with changing environmental parameters. At slightly alkaline pH (pH 9) in the presence of a dilute NaCl (1 mM), the thermodynamically attainable LysLys from 0.1 mM Lys reached a concentration around 50 times larger than that calculated without silica. Because of the versatility of the ETLM, which has been applied to describe a wide variety of biomolecule-mineral interactions, future experiments with the reported methodology are expected to provide a significant constraint on the plausible geological settings for the condensation of monomers to polymers, and the subsequent chemical evolution of life.

  15. Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from {sup 68}Ga-RGD PET/CT and {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai-Jeon [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Ewha Womans University School of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Chun, In Kook [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kangwon National University Hospital, Department of Nuclear Medicine, Chuncheon, Kangwon-Do (Korea, Republic of); Cho, Nariya [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Im, Seock-Ah [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Jeong, Sunjoo [Dankook University, Department of Molecular Biology, Yongin (Korea, Republic of); Lee, Song [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Jung, Kyeong Cheon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Lee, Yun-Sang [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul (Korea, Republic of); Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2014-08-15

    Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes. In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6 ± 7.5 years old). {sup 68}Ga-Labeled arginine-glycine-aspartic acid (RGD) and {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}) from RGD PET/CT and SUV{sub max} and SUV{sub avg} from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered. Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88 ± 8.73 vs 10.48 ± 6.01, p = 0.02 for SUV{sub max}; 9.40 ± 5.19 vs 5.92 ± 4.09, p = 0.02 for SUV{sub avg}) and the PR-negative group (8.37 ± 4.94 vs 4.79 ± 3.93, p = 0.03 for SUV{sub avg}). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42 ± 0.59 vs 2.90 ± 0.75, p = 0.04 for SUV{sub max}; 1.60 ± 0.38 vs 1.95 ± 0.53, p = 0.04 for SUV{sub avg}) and showed a significant positive correlation with the HER2/CEP17 ratio (r = 0.38, p = 0.03 for SUV{sub max} and r = 0.46, p < 0.01 for SUV{sub avg}). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER

  16. Preparation of the radiopharmaceutical {sup 99m} Tc-HYNIC-cyclo-Lys-D-Phe-RGD for In vivo image of integrines; Preparacion del radiofarmaco {sup 99m} Tc-HYNIC-ciclo-Lys-D-Phe-RGD para imagen In vivo de integrinas

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez H, E [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

    2007-07-01

    The diagnostic of some pathological processes by means of images constitutes one of the used methods in the determination of the origin, condition and/or evolution of one illness. The use of contrast agents in conjunction with other techniques help to the obtaining and visualization of complex systems, among these we can find to those radiopharmaceuticals used in nuclear medicine to visualize diverse organs and corporal systems. At the moment it is sought to develop a radiopharmaceutical of third generation that can be used for image In vivo of integrines with the purpose of detecting angio genesis processes, that which would allow to diagnose in way it specifies a wide range of primary tumors and their metastasis. Presently work it developed the radiopharmaceutical {sup 99m}Tc-HYNIC-cycle-Lys-D-Phe-RGD, likewise the good conditions were determined for the formation of this complex. The HYNIC was employee as chelating agent, using as co ligands EDDA and Tricine for to complete the sphere of coordination of the {sup 99m}Tc. The conjugated HYNIC-RGD was synthesized, purified, characterized and radiolabelled In situ with {sup 99m}Tc using High pressure liquid chromatography as analysis method in Reverse Phase (RP-HPLC). By this way it was developed the lyophilized formulation for its instantaneous labelled to which were carried out quality control tests. The one conjugated was obtained free of impurities, showing stability at same as their complex formed with {sup 99m}Tc. The analysis method was validated turning out to be necessary, exact, lineal and specific for the quantification of the analyte of interest. The lyophilized formulation showed a radiochemical purity bigger than 95%, besides being sterile and free of pyrogens. The biodistribution tests in athymic mice with induced tumors showed that the radiopharmaceutical was united mainly to the tumor and that this it was excreted mainly for renal via. (Author)

  17. Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism

    NARCIS (Netherlands)

    de Monyé, Wouter; Sanson, Bernd-Jan; Mac Gillavry, Melvin R.; Pattynama, Peter M. T.; Büller, Harry R.; van den Berg-Huysmans, Annette A.; Huisman, Menno V.

    2002-01-01

    D-dimer blood tests have been suggested to rule out pulmonary embolism. Despite evidence of the safety of withholding anticoagulant treatment in patients with suspected pulmonary embolism and a normal D-dimer assay result, clinicians remain reluctant to use a D-dimer assay as a sole diagnostic test.

  18. New developments in porphyrin-like macrocyclic chemistry: a novel family of dibenzotetraaza[14]annulene-based cofacial dimers.

    Science.gov (United States)

    Zwoliński, K M; Eilmes, J

    2016-03-14

    The first known homoleptic cofacial dimers, based on covalently linked dibenzotetraaza[14]annulenes, were synthesized in reasonable 35-40% yields, without recourse to high-dilution techniques. Dinuclear zinc(ii) dimer showed strong binding affinity toward DABCO. Site-selective monometallation of the dimer, triggered by the linkers' structure, was observed, allowing access to heterobimetallic co-receptors.

  19. Electronic and magnetic properties of R0.5A0.5MnO3 compounds (R=Gd, Dy, Ho, Er; A=Sr, Ca)

    International Nuclear Information System (INIS)

    Terai, T.; Sasaki, T.; Kakeshita, T.; Fukuda, T.; Saburi, T.; Kitagawa, H.; Kindo, K.; Honda, M.

    2000-01-01

    Electronic and magnetic properties of the perovskitelike compounds of R 0.5 A 0.5 MnO 3 (R=Gd, Dy, Ho, Er; A=Sr, Ca) have been studied by measuring lattice parameter, electrical resistivity, magnetic susceptibility, and magnetization. All the Sr-doped compounds show a transition from a paramagnetic insulator to a spin-glass-like insulator at T g , even though the manganite La 0.5 Ca 0.5 MnO 3 , with nearly the same tolerance factor t, have been shown by others, to have different transitions. On the other hand, all the Ca-doped compounds show a charge-ordering transition at T CO and show a transition from a paramagnetic insulator to a canted antiferromagnetic insulator and/or a spin-glass-like insulator at T CA below T CO . These transition temperatures decrease with decreasing t. In the compound of Gd 0.5 Ca 0.5 MnO 3 , the collapse of the charge ordering has been observed under a pulsed high magnetic field of 45 T at 4.2 K. On the other hand, in the compound of Gd 0.5 Sr 0.5 MnO 3 , the magnetization process depends on the strength of magnetic field. These electronic and magnetic properties depend not only on the tolerance factor but also the variance (second moment) of the A-site ion radii distribution

  20. In Situ Structural Characterization of Ferric Iron Dimers in Aqueous Solutions

    DEFF Research Database (Denmark)

    Zhu, Mengqiang; Puls, Brendan W.; Frandsen, Cathrine

    2013-01-01

    The structure of ferric iron (Fe3+) dimers in aqueous solutions has long been debated. In this work, we have determined the dimer structure in situ in aqueous solutions using extended X-ray absorption fine structure (EXAFS) spectroscopy. An Fe K-edge EXAFS analysis of 0.2 M ferric nitrate solutions...... at pH 1.28–1.81 identified a Fe–Fe distance at ∼3.6 Å, strongly indicating that the dimers take the μ-oxo form. The EXAFS analysis also indicates two short Fe–O bonds at ∼1.80 Å and ten long Fe–O bonds at ∼2.08 Å, consistent with the μ-oxo dimer structure. The scattering from the Fe–Fe paths interferes...... confirmed by Mössbauer analyses of analogous quick frozen solutions. This work also explores the electronic structure and the relative stability of the μ-oxo dimer in a comparison to the dihydroxo dimer using density function theory (DFT) calculations. The identification of such dimers in aqueous solutions...

  1. Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

    International Nuclear Information System (INIS)

    Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

    2013-01-01

    The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

  2. Chloroplast Preproteins Bind to the Dimer Interface of the Toc159 Receptor during Import1[OPEN

    Science.gov (United States)

    Chen, Lih-Jen; Yeh, Yi-Hung; Hsiao, Chwan-Deng

    2017-01-01

    Most chloroplast proteins are synthesized in the cytosol as higher molecular weight preproteins and imported via the translocons in the outer (TOC) and inner (TIC) envelope membranes of chloroplasts. Toc159 functions as a primary receptor and directly binds preproteins through its dimeric GTPase domain. As a first step toward a molecular understanding of how Toc159 mediates preprotein import, we mapped the preprotein-binding regions on the Toc159 GTPase domain (Toc159G) of pea (Pisum sativum) using cleavage by bound preproteins conjugated with the artificial protease FeBABE and cysteine-cysteine cross-linking. Our results show that residues at the dimer interface and the switch II region of Toc159G are in close proximity to preproteins. The mature portion of preproteins was observed preferentially at the dimer interface, whereas the transit peptide was found at both regions equally. Chloroplasts from transgenic plants expressing engineered Toc159 with a cysteine placed at the dimer interface showed increased cross-linking to bound preproteins. Our data suggest that, during preprotein import, the Toc159G dimer disengages and the dimer interface contacts translocating preproteins, which is consistent with a model in which conformational changes induced by dimer-monomer conversion in Toc159 play a direct role in facilitating preprotein import. PMID:28250068

  3. Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.

    Science.gov (United States)

    Rayaprolu, Vamseedhar; Royal, Perrine; Stengel, Karen; Sandoz, Guillaume; Kohout, Susy C

    2018-05-07

    Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P 3 or PI(3,4)P 2 Our results indicate that dimerization plays a significant role in Ci-VSP function. © 2018 Rayaprolu et al.

  4. The induction and repair of cyclobutane thymidine dimers in human skin

    International Nuclear Information System (INIS)

    Roza, L.; Erasmus Univ., Rotterdam; Vermeulen, W.; Schans, G.P. van der; Lohman, P.H.M.

    1987-01-01

    The most important detrimental effect of ultraviolet radiation (UV) on the living cell, so far known, is the induction of damage in the DNA. The major photoproducts induced in DNA by UV-C (200-280 nm) and UV-B (280-315 nm) are the cyclobutane-type pyrimidine dimers, which have been implicated in UV-induced mutagenesis and carcinogenesis. Dimer lesions in DNA of cells may be repaired in the dark by a multi-enzyme process (excision repair), or via a light dependent enzymatic reaction known as photoreactivation (phr) which is specific for pyrimidine dimers. Although phr has been found to occur in a wide range of organisms, studies on the presence of phr in mammalian cells have yielded conflicting results. To investigate repair of pyrimidine dimers in human skin cells irradiated in vivo, a specific and sensitive detection method was developed based on a monoclonal antibody directed against thymidine dimers. Application together with a fluorescent immunostaining permits the direct detection of thymidine dimers in human skin cells. The method is used in studies aimed at a better understanding of the role of these lesions in the process of carcinogenesis. A report is given on the isolation and characterization of the antibodies, and their application in a study on the induction of pyrimidine dimers in human skin and on photorepair in cultured cells. 10 refs.; 2 figs

  5. Thermal entanglement in an orthogonal dimer-plaquette chain with alternating Ising–Heisenberg coupling

    International Nuclear Information System (INIS)

    Paulinelli, H G; De Souza, S M; Rojas, Onofre

    2013-01-01

    In this paper we explore the entanglement in an orthogonal dimer-plaquette Ising–Heisenberg chain, assembled between plaquette edges, also known as orthogonal dimer plaquettes. The quantum entanglement properties involving an infinite chain structure are quite important, not only because the mathematical calculation is cumbersome but also because real materials are well represented by infinite chains. Using the local gauge symmetry of this model, we are able to map onto a simple spin-1 like Ising and spin-1/2 Heisenberg dimer model with single effective ion anisotropy. Thereafter this model can be solved using the decoration transformation and transfer matrix approach. First, we discuss the phase diagram at zero temperature of this model, where we find five ground states, one ferromagnetic, one antiferromagnetic, one triplet–triplet disordered and one triplet–singlet disordered phase, beside a dimer ferromagnetic–antiferromagnetic phase. In addition, we discuss the thermodynamic properties such as entropy, where we display the residual entropy. Furthermore, using the nearest site correlation function it is possible also to analyze the pairwise thermal entanglement for both orthogonal dimers. Additionally, we discuss the threshold temperature of the entangled region as a function of Hamiltonian parameters. We find a quite interesting thin reentrance threshold temperature for one of the dimers, and we also discuss the differences and similarities for both dimers. (paper)

  6. Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age Categories

    Directory of Open Access Journals (Sweden)

    G. Der Sahakian

    2010-01-01

    Full Text Available Background. Strategies combining pretest clinical assessment and D-dimers measurement efficiently and safely rule out venous thromboembolism events (VTE in low- and intermediate-risk patients. Objectives. As process of ageing is associated with altered concentrations of coagulation markers including an increase in D-dimers levels, we investigated whether D-dimers could reliably rule out VTE across age categories. Method. We prospectively assessed the test performance in 1,004 patients visiting the emergency department during the 6-month period with low or intermediate risk of VTE who also received additional diagnostic procedures. Results. 67 patients had VTE with D-dimers levels above the threshold, and 3 patients displayed D-dimers levels below the threshold. We observed that specificity of D-dimers test decreased in an age-dependent manner. However, sensitivity and negative predictive value remained at very high level in each age category including older patients. Conclusion. We conclude that, even though D-dimers level could provide numerous false positive results in elderly patients, its high sensitivity could reliably help physicians to exclude the diagnosis of VTE in every low- and intermediate-risk patient.

  7. Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits

    Directory of Open Access Journals (Sweden)

    Jackie Penn

    2015-02-01

    Full Text Available The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE and Bruch’s membrane (BM. However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.

  8. Structural features of the KPI domain control APP dimerization, trafficking, and processing.

    Science.gov (United States)

    Ben Khalifa, Naouel; Tyteca, Donatienne; Marinangeli, Claudia; Depuydt, Mathieu; Collet, Jean-François; Courtoy, Pierre J; Renauld, Jean-Christophe; Constantinescu, Stefan; Octave, Jean-Noël; Kienlen-Campard, Pascal

    2012-02-01

    The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.

  9. Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain

    Directory of Open Access Journals (Sweden)

    Cowburn David

    2011-05-01

    Full Text Available Abstract Background The C-terminal domain (CTD of HIV-1 capsid (CA, like full-length CA, forms dimers in solution and CTD dimerization is a major driving force in Gag assembly and maturation. Mutations of the residues at the CTD dimer interface impair virus assembly and render the virus non-infectious. Therefore, the CTD represents a potential target for designing anti-HIV-1 drugs. Results Due to the pivotal role of the dimer interface, we reasoned that peptides from the α-helical region of the dimer interface might be effective as decoys to prevent CTD dimer formation. However, these small peptides do not have any structure in solution and they do not penetrate cells. Therefore, we used the hydrocarbon stapling technique to stabilize the α-helical structure and confirmed by confocal microscopy that this modification also made these peptides cell-penetrating. We also confirmed by using isothermal titration calorimetry (ITC, sedimentation equilibrium and NMR that these peptides indeed disrupt dimer formation. In in vitro assembly assays, the peptides inhibited mature-like virus particle formation and specifically inhibited HIV-1 production in cell-based assays. These peptides also showed potent antiviral activity against a large panel of laboratory-adapted and primary isolates, including viral strains resistant to inhibitors of reverse transcriptase and protease. Conclusions These preliminary data serve as the foundation for designing small, stable, α-helical peptides and small-molecule inhibitors targeted against the CTD dimer interface. The observation that relatively weak CA binders, such as NYAD-201 and NYAD-202, showed specificity and are able to disrupt the CTD dimer is encouraging for further exploration of a much broader class of antiviral compounds targeting CA. We cannot exclude the possibility that the CA-based peptides described here could elicit additional effects on virus replication not directly linked to their ability to bind

  10. Dimerization of the Glucan Phosphatase Laforin Requires the Participation of Cysteine 329

    Science.gov (United States)

    Sánchez-Martín, Pablo; Raththagala, Madushi; Bridges, Travis M.; Husodo, Satrio; Gentry, Matthew S.; Sanz, Pascual; Romá-Mateo, Carlos

    2013-01-01

    Laforin, encoded by a gene that is mutated in Lafora Disease (LD, OMIM 254780), is a modular protein composed of a carbohydrate-binding module and a dual-specificity phosphatase domain. Laforin is the founding member of the glucan-phosphatase family and regulates the levels of phosphate present in glycogen. Multiple reports have described the capability of laforin to form dimers, although the function of these dimers and their relationship with LD remains unclear. Recent evidence suggests that laforin dimerization depends on redox conditions, suggesting that disulfide bonds are involved in laforin dimerization. Using site-directed mutagenesis we constructed laforin mutants in which individual cysteine residues were replaced by serine and then tested the ability of each protein to dimerize using recombinant protein as well as a mammalian cell culture assay. Laforin-Cys329Ser was the only Cys/Ser mutant unable to form dimers in both assays. We also generated a laforin truncation lacking the last three amino acids, laforin-Cys329X, and this truncation also failed to dimerize. Interestingly, laforin-Cys329Ser and laforin-Cys329X were able to bind glucans, and maintained wild type phosphatase activity against both exogenous and biologically relevant substrates. Furthermore, laforin-Cys329Ser was fully capable of participating in the ubiquitination process driven by a laforin-malin complex. These results suggest that dimerization is not required for laforin phosphatase activity, glucan binding, or for the formation of a functional laforin-malin complex. Cumulatively, these results suggest that cysteine 329 is specifically involved in the dimerization process of laforin. Therefore, the C329S mutant constitutes a valuable tool to analyze the physiological implications of laforin’s oligomerization. PMID:23922729

  11. Base Pair Opening in a Deoxynucleotide Duplex Containing a cis-syn Thymine Cyclobutane Dimer Lesion

    Science.gov (United States)

    Wenke, Belinda B.; Huiting, Leah N.; Frankel, Elisa B.; Lane, Benjamin F.; Núñez, Megan E.

    2014-01-01

    The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin cancer. We compared the stability of individual base pairs in thymine dimer-containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the thymine dimer lesion is locally and moderately destabilizing within an overall B-form duplex conformation. We measured the rates of exchange of individual imino protons by NMR using magnetization transfer from water and determined the equilibrium constant for the opening of each base pair Kop. In the normal duplex Kop decreases from the frayed ends of the duplex toward the center, such that the central TA pair is the most stable with a Kop of 8×10−7. In contrast, base pair opening at the 5’T of the thymine dimer is facile. The 5’T of the dimer has the largest equilibrium constant (Kop =3×10−4) in its duplex, considerably larger than even the frayed penultimate base pairs. Notably, base pairing by the 3’T of the dimer is much more stable than by the 5’T, indicating that the predominant opening mechanism for the thymine dimer lesion is not likely to be flipping out into solution as a single unit. The dimer asymmetrically affects the stability of the duplex in its vicinity, destabilizing base pairing on its 5’ side more than on the 3’ side. The striking differences in base pair opening between parent and dimer duplexes occur independently of the duplex-single strand melting transitions. PMID:24328089

  12. SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains.

    Science.gov (United States)

    Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S E; Prabhakar, Shyam; Jauch, Ralf

    2015-05-27

    The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins.

  13. SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains

    Science.gov (United States)

    Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S. E.; Prabhakar, Shyam; Jauch, Ralf

    2015-01-01

    The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins. PMID:26013289

  14. Characterization of topological phases of dimerized Kitaev chain via edge correlation functions

    Science.gov (United States)

    Wang, Yucheng; Miao, Jian-Jian; Jin, Hui-Ke; Chen, Shu

    2017-11-01

    We study analytically topological properties of a noninteracting modified dimerized Kitaev chain and an exactly solvable interacting dimerized Kitaev chain under open boundary conditions by analyzing two introduced edge correlation functions. The interacting dimerized Kitaev chain at the symmetry point Δ =t and the chemical potential μ =0 can be exactly solved by applying two Jordan-Wigner transformations and a spin rotation, which permits us to calculate the edge correlation functions analytically. We demonstrate that the two edge correlation functions can be used to characterize the trivial, Su-Schrieffer-Heeger-like topological and topological superconductor phases of both the noninteracting and interacting systems and give their phase diagrams.

  15. Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus

    DEFF Research Database (Denmark)

    Lauritsen, Iben; Willemoës, Martin; Jensen, Kaj Frank

    2011-01-01

    CTP synthase catalyzes the last committed step in de novo pyrimidine-nucleotide biosynthesis. Active CTP synthase is a tetrameric enzyme composed of a dimer of dimers. The tetramer is favoured in the presence of the substrate nucleotides ATP and UTP; when saturated with nucleotide, the tetramer...... completely dominates the oligomeric state of the enzyme. Furthermore, phosphorylation has been shown to regulate the oligomeric states of the enzymes from yeast and human. The crystal structure of a dimeric form of CTP synthase from Sulfolobus solfataricus has been determined at 2.5 Å resolution...

  16. Breaking symmetry in the structure determination of (large) symmetric protein dimers

    Energy Technology Data Exchange (ETDEWEB)

    Gaponenko, Vadim; Altieri, Amanda S.; Li, Jess; Byrd, R. Andrew [National Cancer Institute, Structural Biophysics Laboratory (United States)], E-mail: rabyrd@ncifcrf.gov

    2002-10-15

    We demonstrate a novel methodology to disrupt the symmetry in the NMR spectra of homodimers. A paramagnetic probe is introduced sub-stoichiometrically to create an asymmetric system with the paramagnetic probe residing on only one monomer within the dimer. This creates sufficient magnetic anisotropy for resolution of symmetry-related overlapped resonances and, consequently, detection of pseudocontact shifts and residual dipolar couplings specific to each monomeric component. These pseudocontact shifts can be readily incorporated into existing structure refinement calculations and enable determination of monomer orientation within the dimeric protein. This methodology can be widely used for solution structure determination of symmetric dimers.

  17. Alignment and Imaging of the CS2 Dimer Inside Helium Nanodroplets

    Science.gov (United States)

    Pickering, James D.; Shepperson, Benjamin; Hübschmann, Bjarke A. K.; Thorning, Frederik; Stapelfeldt, Henrik

    2018-03-01

    The carbon disulphide (CS2) dimer is formed inside He nanodroplets and identified using fs laser-induced Coulomb explosion, by observing the CS2+ ion recoil velocity. It is then shown that a 160 ps moderately intense laser pulse can align the dimer in advantageous spatial orientations which allow us to determine the cross-shaped structure of the dimer by analysis of the correlations between the emission angles of the nascent CS2+ and S+ ions, following the explosion process. Our method will enable fs time-resolved structural imaging of weakly bound molecular complexes during conformational isomerization, including formation of exciplexes.

  18. Analytical expressions for the correlation function of a hard sphere dimer fluid

    Science.gov (United States)

    Kim, Soonho; Chang, Jaeeon; Kim, Hwayong

    A closed form expression is given for the correlation function of a hard sphere dimer fluid. A set of integral equations is obtained from Wertheim's multidensity Ornstein-Zernike integral equation theory with Percus-Yevick approximation. Applying the Laplace transformation method to the integral equations and then solving the resulting equations algebraically, the Laplace transforms of the individual correlation functions are obtained. By the inverse Laplace transformation, the radial distribution function (RDF) is obtained in closed form out to 3D (D is the segment diameter). The analytical expression for the RDF of the hard dimer should be useful in developing the perturbation theory of dimer fluids.

  19. Giant magnetic anisotropy of rare-earth adatoms and dimers adsorbed by graphene oxide.

    Science.gov (United States)

    Zhang, Kai-Cheng; Li, Yong-Feng; Liu, Yong; Zhu, Yan; Shi, Li-Bin

    2017-05-24

    Nowadays, transition-metal adatoms and dimers with giant magnetic anisotropy have attracted much attention due to their potential applications in data storage, spintronics and quantum computations. Using density-functional calculations, we investigated the magnetic anisotropy of the rare-earth adatoms and dimers adsorbed by graphene oxide. Our calculations reveal that the adatoms of Tm, Er and Sm possess giant magnetic anisotropy, typically larger than 40 meV. When the dimers of (Tm,Er,Sm)-Ir are adsorbed onto graphene oxide, the magnetic anisotropy even exceeds 200 meV. The magnetic anisotropy can be tuned by the external electric field as well as the environment.

  20. Experimental Observation of Strongly Bound Dimers of Sulfuric Acid: Application to Nucleation in the Atmosphere

    DEFF Research Database (Denmark)

    Petaja, Tuukka; Sipila, Mikko; Paasonen, Pauli

    2011-01-01

    rate was clearly higher than the measured new particle formation rate at similar to 1.5 nmsuggesting that the rate limiting step for the nucleation takes place after the dimerization step. The quantum chemical calculations suggested that even in the ultraclean conditions there exist (a) stabilizing...... compound(s) with (a) concentration(s) high enough to prevent the dimer evaporation. Such a stabilizing compound should be abundant enough in any natural environment and would therefore not limit the formation of sulfuric acid dimers in the atmosphere....

  1. Spin Quantum Tunneling via Entangled States in a Dimer of Exchange-Coupled Single-Molecule Magnets

    Science.gov (United States)

    Tiron, R.; Wernsdorfer, W.; Foguet-Albiol, D.; Aliaga-Alcalde, N.; Christou, G.

    2003-11-01

    A new family of supramolecular, antiferromagnetically exchange-coupled dimers of single-molecule magnets (SMMs) has recently been reported. Each SMM acts as a bias on its neighbor, shifting the quantum tunneling resonances of the individual SMMs. Hysteresis loop measurements on a single crystal of SMM dimers have now established quantum tunneling of the magnetization via entangled states of the dimer. This shows that the dimer really does behave as a quantum mechanically coupled dimer, and also allows the measurement of the longitudinal and transverse superexchange coupling constants.

  2. Study of molybdenum(VI) dimerization equilibrium in strongly acidic medium

    International Nuclear Information System (INIS)

    Esbelin, E.

    2000-01-01

    Molybdenum (VI) was investigated spectro-photometrically in non complexing and strongly acidic medium for the first time by Krumenacker. Cationic species of molybdenum were identified by electrophoresis on cellulose paper in highly acidic solutions. From these early results using absorption spectrophotometry, Krumenacker postulated the condensation of molybdenum in this medium. He studied the polymeric species by measuring diffusion coefficients and identified the polymeric form as a dimer. He described the system by equations (1) and (2). Cruywagen later added two equations (3) and (4) to supplement the description of the system. The aim of this work was to re-examine the conditional dimerization equilibrium between the various species of molybdenum(VI) in strongly acid medium by focussing on the influence of the medium. All Mo solution concentrations were analyzed by ICP-AES. Absorbance of the solutions were measured with a VARIAN model CARY5 spectrophotometer in double beam mode with air as reference; blank solutions contained all reagents except molybdenum. The quartz cell path length was 1 mm. The dimerization of monomeric molybdenum(VI) was investigated spectro-photometrically at perchloric acid concentrations of 0.5, 1.0, 2.0 and 3 M at 25 deg C. Two absorption bands at 215 and 245 nm were observed and attributed to monomeric and dimeric forms respectively. The variations in the conditional molar absorption coefficient of molybdenum with total molybdenum(VI) concentration is indicative of several molybdenum forms involved in the total absorbance. Dimerization equilibrium is defined by equation (5). By using the additivity of absorbance and mass conservation of molybdenum, a descriptive equation of the 'spectrochemical' system is developed. This equation is linearized into two forms (6) et (7). From them, two refinement methods were used to estimate the conditional dimerization constant K' d for various medium concentrations. This numerical procedure offers

  3. Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

    Directory of Open Access Journals (Sweden)

    Yun Seong-Jo

    2012-01-01

    Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

  4. Analysis of the dimerized Sb/Si(001)-(2x1) surface by x-ray standing waves

    International Nuclear Information System (INIS)

    Lyman, P.F.; Qian, Y.; Bedzyk, M.J.

    1994-12-01

    X-ray standing wave measurements were undertaken to study the bonding position of Sb adatoms on the Sb-saturated Si(001)-(2x1) surface. Using the (004) and (022) Bragg reflections, the authors find that the Sb atoms form dimers, and that the center of the Sb ad-dimers lies 1.64 angstrom above the bulk-like Si(004) surface atomic plane. These in-plane results are compared to two structural models consisting of dimers whose bonds are parallel to the surface plane and whose centers are either shifted or unshifted (parallel to the dimer bond direction) relative to the underlying substrate planes. The authors thus find two special cases consistent with these data: one with symmetric (unshifted) dimers having a dimer bond length of 2.81 angstrom, and the other with midpoint-shifted dimers, having a bond length of 2.88 angstrom and a lateral shift of 0.21 angstrom

  5. Discovery of Deep Structure from Unlabeled Data

    Science.gov (United States)

    2014-11-01

    GPU processors . To evaluate the unsupervised learning component of the algorithms (which has become of less importance in the era of “big data...representations to those in biological visual, auditory, and somatosensory cortex ; and ran numerous control experiments investigating the impact of

  6. Electronic structure and chemical bond in technetium dimer

    International Nuclear Information System (INIS)

    Klyagina, A.P.; Fursova, V.D.; Levin, A.A.; Gutsev, G.L.

    1987-01-01

    DV-X α method is used to study electron structure and peculiarities of chemical bond in Tc 2 and Tc 2 2+ dimers. Electron state characteristics are calculated in the basis of numerical Hartree-Fock functions for d 6 s 1 - and d 5 s 2 -configurations of Tc atom and for Tc 2 2+ ion d 5 s 1 -configuration. Disposition order for valence MO in Tc and Tc 2 2+ calculated for the